Korlym

Abortifacients
Glucocorticoid Receptor Antagonists

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.

Oral Administration

Termination of early pregnancy (e.g., Mifeprex)
Administered orally as a single dose.
Prescribers must be certified with the Mifepristone REMS program by completing the Prescriber Agreement Form. Mifepristone must only be dispensed to patients by or under the supervision of a certified prescriber, or by certified pharmacies on prescriptions issued by certified prescribers; state laws may dictate further restrictions and requirements.
Prior to administration, complete the Patient Agreement Form (informed consent) and confirm pregnancy duration.
Record the serial number of the mifepristone package in the patient medical record to serve as a patient identification to maintain patient confidentiality.
For purposes of this treatment, pregnancy is dated from the first day of the last menstrual period. Pregnancy duration may be determined from menstrual history and clinical examination. If the duration is uncertain or ectopic pregnancy is suspected, assess the pregnancy by ultrasonographic scan.
Remove any intrauterine device (IUD) prior to treatment with mifepristone.
To complete the regimen, patients MUST take misoprostol within 24 to 48 hours after taking mifepristone.
Discuss an appropriate location for the patient to be when she takes misoprostol; expulsion could begin within 2 hours of administration, and typically occurs within 24 hours.
Give the treated patient the emergency contact numbers for healthcare providers and instruct the patient what to do if significant discomfort, excessive bleeding, or other adverse events occur.
Follow-up assessment to confirm complete pregnancy termination and evaluate bleeding should occur approximately 7 to 14 days after mifepristone administration. Termination can be confirmed by medical history, clinical examination, human Chorionic Gonadotropin (hCG) testing, or ultrasonographic scan. Lack of bleeding usually indicates treatment failure; however, prolonged or heavy bleeding is not proof of a complete abortion.
If complete expulsion has not occurred, but the pregnancy is not ongoing, women may be treated with another dose of misoprostol; a follow-up visit approximately 7 days later should occur to assess for complete termination.
Report failed terminations or other serious adverse reactions to the manufacturer.
For more information, call 1-877-432-7596 in the U.S. 24 hours a day, 7 days a week or visit www.earlyoptionpill.com.
 
Cushing's syndrome (Korlym)
Administered orally with food as a single daily dose.
Patients should swallow the tablet whole. Do not split, crush, or chew tablets.
 
Other indications (Korlym)
If administering mifepristone chronically; administer orally with food at roughly the same time daily.
Patients should swallow the tablet whole. Do not split, crush, or chew tablets.

Severe

infection / Delayed / 0.2-1.0
fetal death / Delayed / Incidence not known
endometritis / Early / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
angioedema / Rapid / Incidence not known
teratogenesis / Delayed / Incidence not known

Moderate

hypokalemia / Delayed / 34.0-44.0
peripheral edema / Delayed / 26.0-26.0
hypertension / Early / 24.0-24.0
dyspnea / Early / 16.0-16.0
constipation / Delayed / 10.0-10.0
hypoglycemia / Early / 5.0-10.0
edema / Delayed / 5.0-10.0
myasthenia / Delayed / 5.0-10.0
adrenocortical insufficiency / Delayed / 4.0-4.0
vaginal bleeding / Delayed / 10.0
uterine contractions / Early / 10.0
anemia / Delayed / Incidence not known
bleeding / Early / Incidence not known
stomatitis / Delayed / Incidence not known
endometrial hyperplasia / Delayed / Incidence not known
hot flashes / Early / Incidence not known
palpitations / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hypotension / Rapid / Incidence not known

Mild

abdominal pain / Early / 5.0-96.0
nausea / Early / 48.0-75.0
fever / Early / 48.0-48.0
vomiting / Early / 26.0-48.0
fatigue / Early / 0-48.0
headache / Early / 2.0-44.0
diarrhea / Early / 12.0-43.0
dizziness / Early / 9.0-41.0
xerostomia / Early / 18.0-18.0
sinusitis / Delayed / 14.0-14.0
pharyngitis / Delayed / 12.0-12.0
anorexia / Delayed / 10.0-10.0
polydipsia / Early / 5.0-10.0
gastroesophageal reflux / Delayed / 5.0-10.0
malaise / Early / 5.0-10.0
insomnia / Early / 5.0-10.0
anxiety / Delayed / 0-10.0
asthenia / Delayed / 1.0-10.0
pruritus / Rapid / 4.0-4.0
maculopapular rash / Early / 4.0-4.0
chills / Rapid / Incidence not known
leukocytosis / Delayed / Incidence not known
pelvic pain / Delayed / Incidence not known
dyspepsia / Early / Incidence not known
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known
menstrual irregularity / Delayed / Incidence not known
emotional lability / Early / Incidence not known
syncope / Early / Incidence not known

Bleeding, fever, infection, sepsis

Mifepristone, when used for medical abortion (e.g., Mifeprex), has been associated with cases of serious bacterial infection, including, although rare, fatal sepsis and septic shock. Patients should promptly report heavy vaginal bleeding, fever, or abdominal pain following treatment. A sustained fever 100.4 degrees F or above for more than 4 hours, severe abdominal pain, pelvic tenderness, syncope, or prolonged heavy vaginal bleeding, more than 24 hours after a medical abortion may be an indication of infection and warrant intervention; however, practitioners should also be alert to atypical presentations including leukocytosis, tachycardia, hemoconcentration, and general malaise (including weakness, nausea, vomiting, or diarrhea). Ensure the patient knows who to call and what to do if she experiences any of these symptoms. Uterine bleeding is expected during medical abortion; however, prolonged heavy bleeding (soaking through 2 thick full-size sanitary pads per hour for 2 consecutive hours) may be a sign of incomplete medical abortion or other complications. Heavy vaginal bleeding after a medical abortion should prompt the patient to seek immediate medical attention. Serious bacterial infections and sepsis, including fatalities, have occurred following the use of mifepristone and vaginal misoprostol and have been reported in the U.S. Clostridium sordellii has been identified as the causative organism in some cases; none of these patients presented with a fever, but they did present with sinus tachycardia, low blood pressure, leukocytosis, and very high red blood cell counts. The patients also had other atypical symptoms including weakness, nausea/vomiting, or diarrhea with or without abdominal pain. No causal relationship has been established between these events and the mifepristone-misoprostol regimen for termination of pregnancy. Patients with endogenous Cushing's syndrome are at risk for opportunistic infection such as Pneumocystis jiroveci pneumonia (PCP) during mifepristone treatment. Patients may present with respiratory distress shortly after initiation of the drug. Appropriate diagnostic tests should be undertaken and treatment for Pneumocystis jiroveci should be considered.

Contraception requirements, pregnancy, pregnancy testing, reproductive risk

Mifepristone has potent antiprogestational effects that will result in the termination of pregnancy. Mifepristone for treatment of Cushing's syndrome (e.g., Korlym) is contraindicated in women who are pregnant. Exclude pregnancy before the initiation of treatment and advise the female patient of the reproductive risk. Pregnancy testing should occur, and female patients of childbearing potential should have a negative pregnancy test before starting the chronic use of mifepristone and such women also must have a repeat negative pregnancy test if the drug is discontinued for more than 14 days. There are contraception requirements for female patients of reproductive potential during chronic treatment with mifepristone; all female patients of childbearing potential should use non-hormonal contraceptives during treatment and for 1 month after stopping treatment, unless the patient has had a surgical sterilization, in which case no additional contraception is needed. Should a woman become pregnant while taking mifepristone chronically, the woman should be apprised of the potential fetal risk. There are no data that assess the risk of birth defects in women exposed to mifepristone during pregnancy. Available data limited to exposure following a single dose of mifepristone during pregnancy showed a higher rate of major birth defects compared to the general population comparator. Animal studies also indicate a potential for fetal harm. Medical abortion with mifepristone (e.g., Mifeprex) is indicated when the objective is termination of the pregnancy at 70 days gestation or less, but should not be used for termination of later pregnancy. Mifepristone disrupts pregnancy, leading to the expulsion of the products of conception; mifepristone also has the pharmacologic effect of inducing uterine contractions and labor. Should the medication regimen fail to terminate a pregnancy as intended, the woman should be apprised of the potential fetal risks. The risk of adverse developmental outcomes with a continued pregnancy after a failed pregnancy termination with Mifepristone in a regimen with misoprostol is unknown; however, the process of a failed pregnancy termination could disrupt normal embryo-fetal development and result in adverse developmental effects. Cases of failed terminations and continued pregnancy should be reported to the manufacturer at: 1-855-MIFEINFO (1-855-643-3463). Conception can occur following termination and before resumption of normal menses, so appropriate contraception can be initiated as soon as the pregnancy termination has been confirmed, or before the woman resumes sexual intercourse.

Korlym, Mifeprex

Rx

Synthetic steroid with potent antiprogesterone and antiglucocorticoid activity; derivative of the synthetic progestin norethindrone
One product is used with a prostaglandin (e.g., misoprostol) as an abortifacent regimen via the Mifepristone REMS program (Mifeprex)
Another product (Korlym) is used to treat hyperglycemia in adults with Cushing's syndrome and is available via a limited distribution program since use is contraindicated during pregnancy

For pregnancy termination in combination with misoprostol, through 70 days (10 weeks) gestation dated from the first day of the last menstrual period. Oral dosage (FDA-approved regimen) Adults and Adolescents

On day 1, administer one 200 mg mifepristone tablet PO as a single dose. Between 24 to 48 hours later, administer misoprostol 800 mcg buccally; the patient should place two 200 mcg misoprostol tablets in each cheek pouch for 30 minutes and then swallow any remnants with water or another liquid. The duration of pregnancy may be determined from menstrual history and clinical examination. If the duration of pregnancy is uncertain or ectopic pregnancy is suspected, assess by ultrasonographic scan. Intrauterine devices (IUDs) should be removed prior to mifepristone treatment. Discuss an appropriate location for the patient to be when she takes misoprostol; expulsion could begin within 2 hours of administration, and typically occurs within 24 hours. Patients should be given emergency contact numbers for healthcare providers and instructed what to do if significant discomfort, excessive bleeding, or other adverse events occur. Follow-up assessment to confirm complete pregnancy termination and evaluate bleeding should occur approximately 7 to 14 days after mifepristone administration. If complete expulsion has not occurred, but the pregnancy is not ongoing, women may be treated with another dose of misoprostol 800 mcg buccally; a follow-up visit approximately 7 days later should occur to assess for complete termination.

For the treatment of hyperglycemia secondary to endogenous Cushing's syndrome in patients who have type 2 diabetes mellitus or glucose intolerance and have failed surgery or are not candidates for surgery.
Mifepristone has been designated an orphan drug for this indication by the FDA.
Oral dosage (Korlym only) Adults

Initially, 300 mg PO once daily with a meal. Increase dose in 300 mg increments, based on clinical response and tolerability. Do not increase more frequently than once every 2 to 4 weeks. Max: 1,200 mg/day and not to exceed 20 mg/kg/day PO. Review drug interactions and product label; specific dosage adjustments and a reduced max dosage are recommended based on the patient's current mifepristone dosage, response, and other treatments. Early symptom improvement, within 6 weeks, may guide dose escalation, later response may guide therapy beyond 2 months. If treatment is interrupted, reinitiate at 300 mg/day. If interruption of treatment is due to an adverse event, titrate to a dose lower than that which resulted in the interruption.

For emergency postcoital contraception†. Oral dosage Adults

600 mg PO given within 72 hours of intercourse was 100% effective in preventing pregnancy and was superior to an estrogen-progestin regimen; adverse effects were less in the mifepristone group; alternatively, 10 mg PO as a single dose, given within 72 hours of intercourse was found to be as effective as a levonorgestrel regimen (1.5% pregnancy rate in both groups); adverse effects did not differ greatly between the treatment groups. Mid-level doses of 25 mg, 50 mg, and 100 mg PO of mifepristone have also been successful; pregnancy rates are comparable to the 10 mg dose. Higher doses are associated with a higher incidence in the delay of the start of menses, which may increase patient anxiety.

For the treatment of uterine leiomyomata†. Oral dosage Adults

2.5 to 10 mg PO once daily.

†Indicates off-label use

Hepatic Impairment

Mifeprex (termination of early pregnancy): The effects of hepatic impairment have not been investigated.
 
Korlym (Cushing's disease treatment): Do not exceed 600 mg/day PO for mild to moderate hepatic impairment; patients with severe hepatic impairment have not been studied, therefore do not use.

Renal Impairment

Mifeprex (termination of early pregnancy): The effects of renal impairment have not been investigated.
 
Korlym (Cushing's disease treatment)
CrCl less than 90 mL/min: Do not exceed 600 mg/day PO in patients with renal impairment.

Abemaciclib: (Major) If coadministration with mifepristone is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If mifepristone is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of mifepristone. Abemaciclib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Acalabrutinib: (Major) Avoid use of these drugs together if possible. Significantly increased acalabrutinib exposure may occur when mifepristone is used chronically in the treatment of hormonal conditions, such as Cushing's syndrome. If mifepristone use is unavoidable, limit the dose of acalabrutinib to 100 mg once daily and monitor closely for drug-related toxicity and need for further adjustment or interruption of acalbrutinib therapy. Acalabrutinib is a CYP3A4 substrate; mifepristone is a CYP3A4 inhibitor. Mifepristone is expected to increase the exposure of CYP3A4 substrates. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with chronic mifepristone therapy may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Mifepristone is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Acetaminophen; Ibuprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If mifepristone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Adagrasib: (Major) Avoid concomitant use of adagrasib and mifepristone especially during the first 8 days of adagrasib therapy initiation. The concentrations of both medications may be increased and there is an additive risk for QT/QTc prolongation and torsade de pointes (TdP). If concomitant use is necessary, a mifepristone dosage adjustment may be required if it is being used in the treatment of Cushing's syndrome. Limit mifepristone to a maximum dosage of 900 mg per day. In a patient already receiving adagrasib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with adagrasib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with adagrasib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with adagrasib is initiated in a patient receiving already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. In a patient receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Additionally, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Mifepristone and adagrasib are CYP3A substrates and strong CYP3A inhibitors and both medications have been associated with QT interval prolongation. Concomitant use of a single 200 mg dose of adagrasib with another strong CYP3A inhibitor increased adagrasib exposure by approximately 4-fold, however, no clinically significant differences in pharmacokinetics are predicted at steady state.
Ado-Trastuzumab emtansine: (Major) Avoid coadministration of mifepristone with ado-trastuzumab emtansine if possible due to the risk of elevated exposure to the cytotoxic component of ado-trastuzumab emtansine, DM1. Delay ado-trastuzumab emtansine treatment until mifepristone has cleared from the circulation (approximately 3 half-lives of mifepristone) when possible. If concomitant use is unavoidable, closely monitor patients for ado-trastuzumab emtansine-related adverse reactions. The cytotoxic component of ado-trastuzumab emtansine, DM1, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5; mifepristone is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Afatinib: (Moderate) If the concomitant use of mifepristone and afatinib is necessary, monitor for afatinib-related adverse reactions. If the original dose of afatinib is not tolerated, consider reducing the daily dose of afatinib by 10 mg; resume the previous dose of afatinib as tolerated after discontinuation of mifepristone. The manufacturer of afatinib recommends permanent discontinuation of therapy for severe or intolerant adverse drug reactions at a dose of 20 mg per day, but does not address a minimum dose otherwise. Afatinib is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor; coadministration may increase plasma concentrations of afatinib. Administration with another P-gp inhibitor, given 1 hour before a single dose of afatinib, increased afatinib exposure by 48%; there was no change in afatinib exposure when the P-gp inhibitor was administered at the same time as afatinib or 6 hours later. In healthy subjects, the relative bioavailability for AUC and Cmax of afatinib was 119% and 104%, respectively, when coadministered with the same P-gp inhibitor, and 111% and 105% when the inhibitor was administered 6 hours after afatinib.
Alfentanil: (Major) Coadministration of alfentanil is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome or other hormonal conditions. Mifepristone inhibits CYP3A4. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates and that have a narrow therapeutic index, such as alfentanil. The increase in alfentanil concentrations can increase the risk for serious CNS depression and respiratory depression, particularly when mifepristone is added after a stable dose of alfentanil is achieved. A reduced dosage of alfentanil may be necessary if use together is not avoidable. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Alfuzosin: (Contraindicated) Alfuzosin is contraindicated for use with mifepristone due to the potential for serious/life-threatening reactions, including hypotension. Additive effects on the QT interval may also occur. Coadministration is expected to reduce the metabolism and increase systemic exposure to alfuzosin. Alfuzosin is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation; mifepristone is a strong CYP3A4 inhibitor that has also been associated with dose-dependent prolongation of the QT interval. Coadministration of another strong CYP3A4 inhibitor increased the alfuzosin AUC by 2.5-fold to 3.2-fold.
Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with chronic mifepristone therapy is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and mifepristone should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Alprazolam: (Contraindicated) Coadministration of mifepristone and alprazolam is contraindicated due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with mifepristone, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased alprazolam exposure by 2.7- to 3.98-fold.
Amiodarone: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Although specific drug interactions with mifepristone have not been studied, the use of mifepristone with CYP3A inhibitors may result in increased mifepristone concentrations and an increased risk of QT prolongation. Amiodarone is a CYP3A4 inhibitor and is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Concomitant use of amisulpride and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Atorvastatin: (Major) Coadministration of atorvastatin with mifepristone may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin. If concomitant use of these drugs is required, consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness), particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Atorvastatin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Celecoxib: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions. (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Valsartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid coadministration of mifepristone with clarithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving clarithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and clarithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Anagrelide: (Major) Concomitant use of anagrelide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Antithrombin III: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Apalutamide: (Major) Avoid coadministration of mifepristone (Korlym) with apalutamide due to possible decreases in the plasma concentrations of mifepristone; exposure to apalutamide may also increase. The impact of apalutamide on the efficacy of short-term mifepristone for termination of pregnancy is unknown; refer to the follow-up assessment to verify that treatment has been successful. Mifepristone is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. The concomitant use of CYP3A4 inducers with mifepristone has not been studied.
Apixaban: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Apomorphine: (Major) Concomitant use of apomorphine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Aprepitant, Fosaprepitant: (Major) The manufacturer of aprepitant recommends avoiding the concomitant use of mifepristone with aprepitant due to substantially increased exposure of aprepitant; increased mifepristone exposure may also occur. If coadministration cannot be avoided, use caution and monitor for an increase in mifepristone- and aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. When mifepristone is used in the treatment of Cushing's syndrome and coadministered with drugs that inhibit CYP3A4, it is recommended to limit the dose of mifepristone to 300 mg/day. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. In vitro, mifepristone is a CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Mifepristone is also a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of mifepristone. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose regimen, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction.
Aripiprazole: (Major) Concomitant use of aripiprazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, mifepristone is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation. (Major) Concomitant use of aripiprazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and increases aripiprazole exposure and risk for side effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, an aripiprazole dosage reduction is required; management recommendations vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Aripiprazole is CYP3A and CYP2D6 substrate, mifepristone is a strong CYP3A inhibitor, and both medications have been associated with QT/QTc prolongation.
Arsenic Trioxide: (Major) Concomitant use of arsenic trioxide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Artemether; Lumefantrine: (Major) Avoid use of mifepristone with artemether; lumefantrine if possible due to increased aremether; lumefantrine exposure and the potential for resultant drug toxicity, including QT prolongation. ECG monitoring is advised if use of drugs that prolong the QT interval is medically required. Both artemether; lumefantrine and mifepristone are associated with QT prolongation. Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, is a CYP3A4 inhibitor and is expected to significantly increase the exposure to CYP3A4 substrates, including both artemether and lumefantrine. (Moderate) Avoid use of mifepristone with artemether; lumefantrine if possible due to increased aremether; lumefantrine exposure and the potential for resultant drug toxicity, including QT prolongation. ECG monitoring is advised if use of drugs that prolong the QT interval is medically required. Both artemether; lumefantrine and mifepristone are associated with QT prolongation. Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, is a CYP3A4 inhibitor and is expected to significantly increase the exposure to CYP3A4 substrates, including both artemether and lumefantrine.
Asciminib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with mifepristone is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Asenapine: (Moderate) Concomitant use of mifepristone and asenapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If mifepristone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Atazanavir: (Major) Caution is advised when administering atazanavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with atazanavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving atazanavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with atazanavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and atazanavir are substrates and strong inhibitors of CYP3A4.
Atazanavir; Cobicistat: (Major) Caution is advised when administering atazanavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with atazanavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving atazanavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with atazanavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with atazanavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and atazanavir are substrates and strong inhibitors of CYP3A4. (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4.
Atogepant: (Major) Avoid use of atogepant and mifepristone when atogepant is used for chronic migraine. Limit the dose of atogepant to 10 mg PO once daily for episodic migraine if coadministered with mifepristone. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of CYP3A and mifepristone is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor resulted in a 5.5-fold increase in atogepant overall exposure and a 2.15-fold increase in atogepant peak concentration.
Atomoxetine: (Major) Concomitant use of atomoxetine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Atorvastatin: (Major) Coadministration of atorvastatin with mifepristone may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin. If concomitant use of these drugs is required, consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness), particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Atorvastatin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Atorvastatin; Ezetimibe: (Major) Coadministration of atorvastatin with mifepristone may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin. If concomitant use of these drugs is required, consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness), particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Atorvastatin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Avacopan: (Major) Reduce the dose of avacopan to 30 mg once daily if concomitant use of chronic mifepristone therapy is necessary. Concomitant use may increase avacopan exposure and risk for avacopan-related adverse effects. Avacopan is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased avacopan overall exposure 2.19-fold. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Avanafil: (Major) Do not use avanafil in patients receiving mifepristone due to the risk for increased avanafil serum concentrations and serious adverse reactions. Avanafil is a sensitive CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the avanafil AUC by 13-fold.
Avapritinib: (Major) Avoid coadministration of avapritinib with mifepristone due to the risk of increased avapritinib-related adverse reactions. Avapritinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 600% at steady-state. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), reduce the starting dose of avatrombopag to 20 mg PO 3 times weekly when used concomitantly with mifepristone. In patients starting mifepristone while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A4 substrate, and dual moderate or strong inhibitors such as mifepristone increase avatrombopag exposure, increasing the risk of avatrombopag toxicity.
Axitinib: (Major) Avoid coadministration of axitinib with mifepristone due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately half; subsequent doses can be increased or decreased based on individual safety and tolerability. Resume the original dose of axitinib approximately 3 to 5 half-lives after mifepristone is discontinued. Axitinib is a CYP3A4/5 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4/5 inhibitor significantly increased the plasma exposure of axitinib in healthy volunteers. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Azithromycin: (Major) Concomitant use of azithromycin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bedaquiline: (Major) Concurrent use of bedaquiline and a strong CYP3A4 inhibitor, such as mifepristone, for more than 14 days should be avoided unless the benefits justify the risks. Mifepristone may inhibit the metabolism of bedaquiline resulting in increased systemic exposure (AUC) and increased risk for adverse reactions. The activity of mifepristone on CYP3A4 inhibition may be prolonged due to its long half-life, particularly with chronic therapy. Furthermore, since both drugs are associated with QT prolongation, coadministration may result in additive effects on the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
Benzhydrocodone; Acetaminophen: (Major) Concurrent use of benzhydrocodone with chronic use of mifepristone for Cushing's syndrome may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider alternative therapy. If benzhydrocodone is used, administer the lowest possible dose and/or a decrease the dosing frequency. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of mifepristone in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Berotralstat: (Major) Reduce the berotralstat dose to 110 mg PO once daily in patients chronically taking mifepristone. Concurrent use may increase berotralstat exposure and the risk of adverse effects. Berotralstat is a P-gp substrate and mifepristone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased berotralstat exposure by 69%.
Betrixaban: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Concomitant use of metronidazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Bortezomib: (Moderate) Bortezomib is partially metabolized by CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Consider a bortezomib dose reduction if bortezomib is administered with a strong CYP3A4 inhibitor like mifepristone. The effects of mifepristone on drug metabolism may be prolonged due to its long half-life.
Bosentan: (Major) The use of mifepristone with bosentan is not recommended. Use of a strong CYP3A4 inhibitor like mifepristone will likely lead to large increases in bosentan plasma concentrations. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Bosentan may also induce mifepristone metabolism via CYP3A4. Avoid the use of mifepristone and potent CYP3A inducers due to the potential for reduced mifepristone exposure and reduced efficacy.
Brexpiprazole: (Moderate) Because brexpiprazole is primarily metabolized by CYP3A4 and CYP2D6, the manufacturer recommends that the brexpiprazole dose be reduced to one-quarter (25%) of the usual dose in patients receiving a moderate to strong inhibitor of CYP3A4 in combination with a moderate to strong inhibitor of CYP2D6. Mifepristone is a moderate inhibitor of CYP3A4 in vitro. If mifepristone is used in combination with brexpiprazole and a moderate to strong CYP2D6 inhibitor, reduce the brexpiprazole dose and carefully monitor the patient for brexpiprazole-related adverse reactions. A reduction of the brexpiprazole dose to 25% of the usual dose is also recommended in patients who are poor metabolizers of CYP2D6 and are receiving a moderate CYP3A4 inhibitor.
Brigatinib: (Major) Avoid coadministration of brigatinib with mifepristone if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 50% without breaking tablets (i.e., from 180 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of mifepristone, resume the brigatinib dose that was tolerated prior to initiation of mifepristone. Brigatinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively.
Bromocriptine: (Major) Concomitant use of strong CYP3A4 inhibitors like mifepristone should be avoided when bromocriptine is used for diabetes, and likely when used for other indications. Consider alternative treatments. Concurrent use may increase bromocriptine concentrations substantially, and increase the risk for side effects. Side effects associated with increased blood levels of bromocriptine include nausea, vomiting, constipation, diaphoresis, dizziness, pallor, severe hypotension, confusion, lethargy, drowsiness, and delusions or hallucinations. Bromocriptine is extensively metabolized in the liver via CYP3A4; mifepristone is a strong inhibitor of CYP3A4. Administration of bromocriptine with a moderate inhibitor of CYP3A4 increased the bromocriptine mean AUC and Cmax by 3.7-fold and 4.6-fold, respectively. The prolonged action and long half-life of mifepristone may result in prolonged inhibition of CYP3A4.
Bupivacaine; Meloxicam: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Buprenorphine: (Major) Concomitant use of buprenorphine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use can also increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when mifepristone is added after a stable buprenorphine dose is achieved. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping mifepristone, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If mifepristone is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a CYP3A4 substrate and mifepristone is a CYP3A4 inhibitor.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use can also increase the plasma concentration of buprenorphine, resulting in increased or prolonged opioid effects, particularly when mifepristone is added after a stable buprenorphine dose is achieved. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Additionally, consider dosage reduction of buprenorphine until stable drug effects are achieved. Monitor patient for respiratory depression and sedation at frequent intervals. When stopping mifepristone, the buprenorphine concentration may decrease, potentially resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependency. If mifepristone is discontinued, consider increasing buprenorphine dosage until stable drug effects are achieved. Monitor for signs of opioid withdrawal. Buprenorphine is a CYP3A4 substrate and mifepristone is a CYP3A4 inhibitor.
Bupropion: (Moderate) Monitor for an increase in bupropion-related adverse reactions during coadministration of mifepristone as concurrent use may increase bupropion exposure. A bupropion dose adjustment may be necessary. Bupropion is a sensitive substrate of CYP2B6; mifepristone is a moderate CYP2B6 inhibitor.
Bupropion; Naltrexone: (Moderate) Monitor for an increase in bupropion-related adverse reactions during coadministration of mifepristone as concurrent use may increase bupropion exposure. A bupropion dose adjustment may be necessary. Bupropion is a sensitive substrate of CYP2B6; mifepristone is a moderate CYP2B6 inhibitor.
Buspirone: (Moderate) A low dose of buspirone used cautiously is recommended when coadministered with mifepristone. If a patient has been titrated to a stable dosage of buspirone, a dose adjustment of buspirone may be necessary to avoid adverse events attributable to buspirone. Administering mifepristone with buspirone may increase buspirone concentration and risk for adverse events. Buspirone is a sensitive substrate of CYP3A; mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the buspirone AUC by 19-fold with an increased incidence of buspirone-related adverse effects.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with mifepristone if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Cabazitaxel is primarily metabolized by CYP3A4 and mifepristone is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Cabotegravir; Rilpivirine: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
Cabozantinib: (Major) Avoid concomitant use of cabozantinib and mifepristone due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with mifepristone 2 to 3 days after discontinuation of mifepristone. Cabozantinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Capmatinib: (Moderate) Monitor for an increase in capmatinib-related adverse reactions if coadministration with mifepristone is necessary. Capmatinib is a CYP3A substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%. The interaction is most likely when mifepristone is used chronically to treat hormonal conditions, such as Cushing's disease. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Carbamazepine: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of carbamazepine. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving carbamazepine. Monitor carbamazepine concentrations closely during coadministration of mifepristone; carbamazepine dose adjustments may be needed. Coadministration may decrease mifepristone exposure reducing efficacy and may increase carbamazepine concentrations. Mifepristone is a substrate and strong inhibitor of CYP3A; carbamazepine is a substrate and strong inducer of CYP3A.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Dosage reductions of cariprazine are recommended in patients taking strong CYP3A4 inhibitors, such as mifepristone. If a strong CYP3A4 inhibitor is initiated, reduce the current dosage of cariprazine by half. If the patient is already taking the CYP3A4 inhibitor and initiating cariprazine, an alternative initation regimen for cariprazine is recommended in the prescribing information. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
Celecoxib: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Celecoxib; Tramadol: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Ceritinib: (Major) Avoid concomitant use of mifepristone with ceritinib due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use is necessary for the treatment of Cushings syndrome, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for ceritinib-related adverse reactions. If mifepristone therapy is added for the treatment of Cushing's syndrome in a patient already receiving ceritinib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ceritinib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ceritinib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ceritinib are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold.
Chloramphenicol: (Major) Caution is advised when administering chloramphenicol with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with chloramphenicol should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving chloramphenicol, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with chloramphenicol is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with chloramphenicol is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Mifepristone is a CYP3A4 substrate; chloramphenicol is a strong CYP3A4 inhibitor.
Chloroquine: (Major) Concomitant use of mifepristone and chloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with chronic mifepristone therapy may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely

at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Mifepristone is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Cilostazol: (Moderate) Mifepristone is a strong inhibitor of CYP3A4. Use of mifepristone may lead to an increase in serum levels of drugs that are CYP3A4 substrates, such as cilostazol. Strong CYP3A4 inhibitors have significantly increased the systemic exposure of cilostazol and/or its major metabolites. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. If use together is medically necessary, use the lowest dose of cilostazol necessary (e.g., 50 mg PO twice daily), with appropriate monitoring and follow-up. Side effects of cilostazol may include unusual bleeding or bruising, diarrhea, dizziness, edema (such as swelling of the ankles or legs), headache, or upset stomach.
Cinacalcet: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of mifepristone and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Ciprofloxacin: (Major) Concomitant use of ciprofloxacin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cisapride: (Contraindicated) Avoid concomitant use of mifepristone and cisapride due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Citalopram: (Major) Concomitant use of mifepristone and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Avoid coadministration of mifepristone with clarithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving clarithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and clarithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of mifepristone as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; mifepristone is a strong inhibitor of CYP3A4.
Clofazimine: (Major) Concomitant use of clofazimine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clonazepam: (Moderate) Monitor for increased sedation and respiratory depression if clonazepam is coadministered with mifepristone; adjust the dose of clonazepam if necessary. The systemic exposure of clonazepam may be increased resulting in an increase in treatment-related adverse reactions. Clonazepam is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Clozapine: (Moderate) Avoid use together when possible. Use extreme caution when administering concomitant medications that prolong the QT interval or inhibit the metabolism of clozapine, such as mifepristone, which may do both. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Mifepristone has also been associated with QT prolongation. Mifepristone is an inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of clozapine. Elevated plasma concentrations of clozapine occurring through inhibition of CYP3A4 may potentially increase the risk of life-threatening arrhythmias or other clozapine-related adverse effects such as sedation, anticholinergic effects, seizures, orthostasis, or other adverse effects. According to the manufacturer, patients receiving clozapine in combination with a CYP3A4 inhibitor should be monitored for adverse reactions. Consideration should be given to reducing the clozapine dose if necessary. If the inhibitor is discontinued, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobicistat: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic mifepristone therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of mifepristone is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of mifepristone, resume cobimetinib at the previous dose. Use an alternative to mifepristone in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a P-glycoprotein (P-gp) substrate as well as a CYP3A substrate in vitro; mifepristone is a strong inhibitor of CYP3A as well as a P-gp inhibitor.
Codeine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of promethazine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Codeine; Promethazine: (Major) Concomitant use of promethazine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Concomitant use of codeine with chronic mifepristone therapy may increase codeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased morphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. It is recommended to avoid this combination when codeine is being used for cough. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of codeine until stable drug effects are achieved. Discontinuation of mifepristone could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If mifepristone is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A4 to norcodeine; norcodeine does not have analgesic properties. Mifepristone is a strong inhibitor of CYP3A4. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Colchicine: (Major) Avoid concomitant use of colchicine and mifepristone due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Conivaptan: (Contraindicated) Coadministration of conivaptan and mifepristone is contraindicated due to the potential for increased conivaptan exposure. Conivaptan is a CYP3A substrate; mifepristone is a strong CYP3A inhibitor. In a drug interaction study, coadministration of a strong CYP3A inhibitor increased the exposure of oral conivaptan by 11-fold.
Conjugated Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Conjugated Estrogens; Bazedoxifene: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Conjugated Estrogens; Medroxyprogesterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Corticosteroids: (Major) Mifepristone for termination of pregnancy is contraindicated in patients on long-term corticosteroid therapy and mifepristone for Cushing's disease or other chronic conditions is contraindicated in patients who require concomitant treatment with systemic corticosteroids for life-saving purposes, such as serious medical conditions or illnesses (e.g., immunosuppression after organ transplantation). For other situations where corticosteroids are used for treating non-life threatening conditions, mifepristone may lead to reduced corticosteroid efficacy and exacerbation or deterioration of such conditions. This is because mifepristone exhibits antiglucocorticoid activity that may antagonize corticosteroid therapy and the stabilization of the underlying corticosteroid-treated illness. Mifepristone may also cause adrenal insufficiency, so patients receiving corticosteroids for non life-threatening illness require close monitoring. Because serum cortisol levels remain elevated and may even increase during treatment with mifepristone, serum cortisol levels do not provide an accurate assessment of hypoadrenalism. Patients should be closely monitored for signs and symptoms of adrenal insufficiency, If adrenal insufficiency occurs, stop mifepristone treatment and administer systemic glucocorticoids without delay; high doses may be needed to treat these events. Factors considered in deciding on the duration of glucocorticoid treatment should include the long half-life of mifepristone (85 hours).
Crizotinib: (Major) Avoid concomitant use of mifepristone and crizotinib due to increased plasma concentrations of crizotinib, which may increase the incidence and severity of adverse reactions; QT prolongation and torsade de pointes (TdP) may also occur. If concomitant use is necessary for adults with non-small cell lung cancer (NSCLC) or inflammatory myofibroblastic tumor (IMT), reduce the dose of crizotinib to 250 mg PO once daily. If concomitant use is necessary for young adult or pediatric patients with anaplastic large cell lymphoma or pediatric patients with IMT, reduce the dose of crizotinib to 250 mg PO twice daily for BSA of 1.7 m2 or more; 200 mg PO twice daily for BSA of 1.17 to 1.69 m2; and 250 mg PO once daily for BSA of 0.81 to 1.16 m2; do not use this combination in patients with a BSA of 0.6 to 0.8 m2. Resume the original crizotinib dose after discontinuation of mifepristone. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Crizotinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with one strong CYP3A inhibitor increased the AUC of single-dose crizotinib by 216%. Concomitant use with another strong CYP3A inhibitor increased the steady-state AUC of crizotinib by 57% compared to crizotinib alone.
Cyclosporine: (Contraindicated) Coadministration of cyclosporine is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase cyclosporine concentrations and adverse effects, since cyclosporine is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Dabigatran: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding. It is not clear if mifepristone exhibits a pharmacokinetic interaction with dabigatran. Use together with caution when mifepristone is given chronically for other conditions, such as Cushing's syndrome. Increased serum concentrations of dabigatran might be possible as mifepristone may be an inhibitor of P-gp. Patients should be monitored for bleeding and increased adverse effects of dabigatran. P-gp inhibition and renal impairment are the major independent factors that result in increased exposure to dabigatran. Different recommendations may apply to the use of mifepristone with dabigatran when the patient is also renally impaired. Due to the slow eilimination of mifepristone, any interaction that does occur may be prolonged.
Daclatasvir: (Moderate) Administration of daclatasvir with mifepristone may increase daclatasvir serum concentrations. If these drugs are coadministered, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. Daclatasvir is a CYP3A4 and P-gp substrate, and mifepristone is a known CYP3A4 inhibitor and possibly a P-gp inhibitor. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Dalteparin: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Dapagliflozin; Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and mifepristone are used together; dosage reduction of saxagliptin may be needed in some patients. In patients taking CYP3A substrates, the manufacturer of mifepristone recommends that the lowest dose of the CYP3A substrate that achieves the proper clinical response and tolerability be used. When potent CYP3A inhibitors are used, the initial dose of saxagliptin should be limited to 2.5 mg/day; mifepristone is a CYP3A inhibitor and has been noted to increase concentrations of CYP3A substrates. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Daprodustat: (Major) Reduce the initial daprodustat dose by half during concomitant use of mifepristone unless the daprodustat dose is already 1 mg. Monitor hemoglobin and further adjust the daprodustat dose as appropriate. Concomitant use may increase daprodustat exposure and the risk for daprodustat-related adverse reactions. Daprodustat is a CYP2C8 substrate and mifepristone is a moderate CYP2C8 inhibitor. Concomitant use with a moderate CYP2C8 inhibitor is expected to increase daprodustat overall exposure by approximately 4-fold.
Daridorexant: (Major) Avoid concomitant use of daridorexant and mifepristone. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased daridorexant overall exposure by over 400%.
Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg/day PO in adults receiving mifepristone chronically for the treatment of hormonal conditions. The exposure of darifenacin, a sensitive CYP3A4 substrate, is expected to increase significantly with the administration of mifepristone when mifepristone is used chronically for hormonal conditions, such as Cushing's syndrome. Mifepristone is a CYP3A4 inhibitor. Due to the slow elimination of mifepristone from the body, any drug interactions that occur may be prolonged.
Darolutamide: (Moderate) Monitor patients more frequently for darolutamide-related adverse reactions if coadministration with mifepristone is necessary due to the risk of increased darolutamide exposure; decrease the dose of darolutamide for grade 3 or 4 adverse reactions or for otherwise intolerable adverse reactions. Mifepristone is a P-glycoprotein (P-gp) inhibitor and a strong CYP3A4 inhibitor; darolutamide is a CYP3A4 substrate. Concomitant use with another combined P-gp inhibitor and strong CYP3A4 inhibitor increased the mean AUC and Cmax of darolutamide by 1.7-fold and 1.4-fold, respectively.
Darunavir: (Major) Caution is advised when administering darunavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with darunavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving darunavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with darunavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and darunavir are substrates and strong inhibitors of CYP3A4.
Darunavir; Cobicistat: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4. (Major) Caution is advised when administering darunavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with darunavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving darunavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with darunavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and darunavir are substrates and strong inhibitors of CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4. (Major) Caution is advised when administering darunavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with darunavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving darunavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with darunavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with darunavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and darunavir are substrates and strong inhibitors of CYP3A4.
Dasatinib: (Major) Avoid coadministration of dasatinib and mifepristone due to the potential for increased dasatinib exposure and subsequent toxicity including QT prolongation and torsade de pointes (TdP). An alternative to mifepristone with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of mifepristone is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If mifepristone is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate that has the potential to prolong the QT interval; mifepristone is a strong CYP3A4 inhibitor that is associated with dose-dependent prolongation of the QT interval. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
Degarelix: (Major) Concomitant use of mifepristone and degarelix increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Delavirdine: (Major) Caution is advised when administering delavirdine with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with delavirdine should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving delavirdine, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with delavirdine is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with delavirdine is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with delavirdine is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with delavirdine is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and delavirdine are substrates and strong inhibitors of CYP3A4.
Desflurane: (Major) Concomitant use of mifepristone and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Deutetrabenazine: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range.
Dexmedetomidine: (Major) Concomitant use of dexmedetomidine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dextromethorphan; Bupropion: (Moderate) Monitor for an increase in bupropion-related adverse reactions during coadministration of mifepristone as concurrent use may increase bupropion exposure. A bupropion dose adjustment may be necessary. Bupropion is a sensitive substrate of CYP2B6; mifepristone is a moderate CYP2B6 inhibitor.
Dextromethorphan; Quinidine: (Contraindicated) Use of quinidine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase quinidine concentrations and adverse effects, since quinidine is a CYP3A4 substrate with a narrow therapeutic index. Increased quinidine concentrations are likely to cause proarrythmia and ECG changes, as well as symptoms of cinchonism. Both quinidine and mifepristone have been associated with QT prolongation and a risk for torsade de pointes (TdP). Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Diclofenac: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Diclofenac; Misoprostol: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Dienogest; Estradiol valerate: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
Diflunisal: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Diltiazem: (Moderate) Monitor blood pressure and heart rate if coadministration of diltiazem with mifepristone is necessary. Concurrent use may result in elevated diltiazem concentrations. Diltiazem is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Diphenhydramine; Ibuprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Diphenhydramine; Naproxen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Disopyramide: (Contraindicated) When mifepristone is used chronically for hormonal conditions, such as Cushing's disease, the concomitant use of CYP3A substrates with narrow therapeutic index, such as disopyramide, is contraindicated. Disopyramide administration is associated with QT prolongation and torsade de pointes (TdP). Disopyramide is a substrate for CYP3A4. Drugs with a possible risk for QT prolongation that are also CYP3A4 inhibitors include mifepristone. Life-threatening interactions have been reported with the coadministration of disopyramide with other CYP3A4 inhibitors with a potential to prolong the QT interval. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Docetaxel: (Major) Avoid coadministration of docetaxel with mifepristone if possible due to increased plasma concentrations of docetaxel. If concomitant use of docetaxel with chronic mifepristone is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Docetaxel is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
Dofetilide: (Major) Coadministration of dofetilide and mifepristone is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Mifepristone is associated with dose-related prolongation of the QT interval. Additionally, dofetilide is metabolized to a small extent by CYP3A4, and inhibitors of CYP3A4, such as mifepristone, could increase systemic dofetilide exposure, further increasing the risk for QT prolongation.
Dolasetron: (Major) Concomitant use of dolasetron and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dolutegravir; Rilpivirine: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
Donepezil: (Moderate) Concomitant use of mifepristone and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Donepezil; Memantine: (Moderate) Concomitant use of mifepristone and donepezil may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Doravirine: (Minor) Coadministration of doravirine and chronic mifepristone therapy may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; mifepristone is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant. The clinical significance of CYP450 inhibition with short-term use of mifepristone for termination of pregnancy is unknown.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Coadministration of doravirine and chronic mifepristone therapy may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; mifepristone is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant. The clinical significance of CYP450 inhibition with short-term use of mifepristone for termination of pregnancy is unknown.
Doxercalciferol: (Moderate) Cytochrome P450 enzyme inhibitors, such as mifepristone, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy.
Doxorubicin Liposomal: (Moderate) Avoid coadministration of mifepristone and doxorubicin if possible. Mifepristone is an inhibitor of CYP3A4 and may also inhibit P-glycoprotein (P-gp); doxorubicin is a major substrate of both P-gp and CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. When mifepristone is used chronically for hormonal conditions, as in the treatment of Cushing's disease, increased concentrations of CYP3A substrates are expected, and any drug interactions that do occur may be prolonged due to mifepristone's long duration of action. If not possible to avoid use of these drugs together, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Moderate) Avoid coadministration of mifepristone and doxorubicin if possible. Mifepristone is an inhibitor of CYP3A4 and may also inhibit P-glycoprotein (P-gp); doxorubicin is a major substrate of both P-gp and CYP3A4. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4 and/or P-gp, resulting in increased concentration and clinical effect of doxorubicin. When mifepristone is used chronically for hormonal conditions, as in the treatment of Cushing's disease, increased concentrations of CYP3A substrates are expected, and any drug interactions that do occur may be prolonged due to mifepristone's long duration of action. If not possible to avoid use of these drugs together, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with mifepristone is necessary; monitor for an increase in dronabinol-related CNS adverse reactions (e.g., cognitive impairment, euphoria, dizziness, confusion, somnolence, or changes in moods or behaviors) if mifepristone is used chronically for hormonal conditions such as Cushing's syndrome. A dose reduction of dronabinol may be needed in some patients to reduce the risk of central nervous system (CNS) symptoms. Dronabinol is a CYP2C9 and 3A4 substrate; mifepristone is an inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Dronedarone: (Contraindicated) Avoid concomitant use of mifepristone and dronedarone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Droperidol: (Major) Concomitant use of droperidol and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Dutasteride; Tamsulosin: (Major) Concurrent use of tamsulosin and mifepristone is not recommended due to the potential for elevated tamsulosin concentrations. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension, dizziness, and vertigo. Tamsulosin is extensively metabolized by CYP3A, and strong inhibitors of CYP3A, such as mifepristone, are expected to significantly raise tamsulosin concentrations. Concomitant treatment with another strong CYP3A inhibitor increased the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively.
Duvelisib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with chronic mifepristone therapy. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; mifepristone is a substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as mifepristone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Edoxaban: (Contraindicated) When mifepristone is used for the termination of pregnancy, the concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Efavirenz: (Major) Avoid use together when possible; consider alternatives to efavirenz. The use of these drugs together may increase the risk for QT prolongation or other efavirenz-induced side effects and may reduce mifepristone efficacy. Concurrent use will increase the systemic exposure of efavirenz and decrease mifepristone exposure. Efavirenz is a CYP2B6 substrate and CYP3A4 inducer, while mifepristone is a CYP3A4 substrate and CYP2B6 inhibitor. In addition, careful monitoring for mifepristone efficacy is necessary. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Also monitor for efavirenz-associated adverse reactions, such as nervous system or psychiatric symptoms, fast irregular heart rate, QT prolongation, hepatotoxicity, and rash. QT prolongation has been observed with use of efavirenz. Mifepristone, when given chronically for hormonal conditions such as Cushing's syndrome, has also been associated with dose-dependent prolongation of the QT interval.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid use together when possible; consider alternatives to efavirenz. The use of these drugs together may increase the risk for QT prolongation or other efavirenz-induced side effects and may reduce mifepristone efficacy. Concurrent use will increase the systemic exposure of efavirenz and decrease mifepristone exposure. Efavirenz is a CYP2B6 substrate and CYP3A4 inducer, while mifepristone is a CYP3A4 substrate and CYP2B6 inhibitor. In addition, careful monitoring for mifepristone efficacy is necessary. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Also monitor for efavirenz-associated adverse reactions, such as nervous system or psychiatric symptoms, fast irregular heart rate, QT prolongation, hepatotoxicity, and rash. QT prolongation has been observed with use of efavirenz. Mifepristone, when given chronically for hormonal conditions such as Cushing's syndrome, has also been associated with dose-dependent prolongation of the QT interval.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid use together when possible; consider alternatives to efavirenz. The use of these drugs together may increase the risk for QT prolongation or other efavirenz-induced side effects and may reduce mifepristone efficacy. Concurrent use will increase the systemic exposure of efavirenz and decrease mifepristone exposure. Efavirenz is a CYP2B6 substrate and CYP3A4 inducer, while mifepristone is a CYP3A4 substrate and CYP2B6 inhibitor. In addition, careful monitoring for mifepristone efficacy is necessary. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Also monitor for efavirenz-associated adverse reactions, such as nervous system or psychiatric symptoms, fast irregular heart rate, QT prolongation, hepatotoxicity, and rash. QT prolongation has been observed with use of efavirenz. Mifepristone, when given chronically for hormonal conditions such as Cushing's syndrome, has also been associated with dose-dependent prolongation of the QT interval.
Elacestrant: (Major) Avoid concomitant use of elacestrant and mifepristone due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Elagolix: (Major) Concomitant use of elagolix 200 mg twice daily and mifepristone for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and mifepristone to 6 months. Elagolix is a CYP3A substrate; mifepristone is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Elagolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of elagolix 200 mg twice daily and mifepristone for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and mifepristone to 6 months. Elagolix is a CYP3A substrate; mifepristone is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with mifepristone may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Mifepristone is a substrate and moderate inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity. (Moderate) Administering elbasvir; grazoprevir with mifepristone, RU-486 may cause the plasma concentrations of all three drugs to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Mifepristone is a substrate and moderate inhibitor of CYP3A. Both elbasvir and grazoprevir are metabolized by CYP3A, and grazoprevir is also a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of hepatotoxicity.
Eletriptan: (Contraindicated) Eletriptan is contraindicated with recent use (i.e., within 72 hours) of chronic mifepristone therapy due to the potential for increased eletriptan exposure. The clinical significance of this interaction is not established when mifepristone is used for pregnancy termination. Eletriptan is a sensitive substrate of CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the Cmax and AUC of eletriptan by 3-fold and 6-fold, respectively.
Elexacaftor; tezacaftor; ivacaftor: (Major) If mifepristone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to twice a week in the morning, approximately 3 to 4 days apart (i.e., Day 1 and Day 4) when coadministered with mifepristone; omit the evening dose of ivacaftor. Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; mifepristone is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased elexacaftor exposure by 2.8- fold, tezacaftor exposure by 4.5-fold, and ivacaftor exposure by 15.6-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with mifepristone; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); mifepristone is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Eliglustat: (Major) Concomitant use of eliglustat and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Caution is advised when administering cobicistat with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with cobicistat should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving cobicistat, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with cobicistat is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with cobicistat is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and cobicistat are substrates and strong inhibitors of CYP3A4.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
Encorafenib: (Major) Avoid coadministration of encorafenib and mifepristone due to increased encorafenib exposure and QT prolongation. If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of mifepristone. Monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Use the lowest effective dose of mifepristone. If mifepristone is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of mifepristone. Encorafenib is a CYP3A4 substrate that has been associated with dose-dependent QT prolongation. When administered chronically, mifepristone is a strong CYP3A4 inhibitor that has been associated with dose-dependent QT prolongation. The clinical significance of mifepristone inhibition of CYP3A4 when used for pregnancy termination is not established. Coadministration of a strong CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 3-fold and 68%, respectively.
Enfortumab vedotin: (Moderate) Closely monitor for signs of enfortumab vedotin-related adverse reactions if concurrent use with mifepristone is necessary. Concomitant use may increase unconjugated monomethyl auristatin E (MMAE) exposure, which may increase the incidence or severity of enfortumab-vedotin toxicities. MMAE, the microtubule-disrupting component of enfortumab vedotin, is a CYP3A4 and P-gp substrate; mifepristone is a dual P-gp/strong CYP3A4 inhibitor. Based on physiologically-based pharmacokinetic (PBPK) modeling predictions, concomitant use of enfortumab vedotin with another dual P-gp/strong CYP3A4 inhibitor is predicted to increase the exposure of unconjugated MMAE by 38%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Enoxaparin: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Entrectinib: (Major) Avoid coadministration of entrectinib with mifepristone due to additive risk of QT prolongation and increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 100 mg PO once daily. If mifepristone is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of mifepristone. Entrectinib is a CYP3A4 substrate that has been associated with QT prolongation; mifepristone is a strong CYP3A4 inhibitor that is associated with dose-related prolongation of the QT interval. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Enzalutamide: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of enzalutamide. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving enzalutamide. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; enzalutamide is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
Eplerenone: (Contraindicated) Coadministration of mifepristone and eplerenone is contraindicated. Mifepristone potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and chronic mifepristone therapy due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If mifepristone is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a substrate of CYP3A4 and CYP2C9. Mifepristone is a moderate CYP2C9 inhibitor and a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Ergot alkaloids: (Contraindicated) Coadministration of ergot alkaloids and mifepristone is contraindicated due to the potential for increased ergot exposure. Increased plasma concentrations of ergot alkaloids are associated with risk of acute ergot toxicity which is characterized by peripheral vasospasm and ischemia of the extremities and other tissues. Ergot alkaloids are CYP3A substrates and mifepristone is a strong CYP3A inhibitor.
Eribulin: (Major) Concomitant use of eribulin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Erlotinib: (Major) Avoid coadministration of erlotinib with chronic mifepristone use if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Erlotinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Due to the slow elimination of mifepristone from the body, such interaction may be observed for a prolonged period after its administration. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure by 67%.
Erythromycin: (Major) Concomitant use of mifepristone and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase mifepristone concentrations. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Mifepristone is a CYP3A4 substrate and erythromycin is a moderate CYP3A4 inhibitor.
Escitalopram: (Major) Concomitant use of mifepristone and escitalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Estazolam: (Major) Estazolam should be used with mifepristone only with caution and consideration of appropriate estazolam dosage reduction. CNS depression, impaired motor and/or cognitive performance may occur due to increased estazolam exposure. In some patients, estazolam discontinuation may be necessary. Mifepristone inhibits CYP3A4 when it is used chronically in the treatment of hormonal conditions, such as Cushing's disease. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates like estazolam. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Esterified Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Esterified Estrogens; Methyltestosterone: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Estradiol: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
Estradiol; Progesterone: (Moderate) Use caution if coadministration of mifepristone with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Mifepristone is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone.
Estropipate: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as mifepristone may increase plasma concentrations of estrogens and cause estrogen-related side effects such as nausea and breast tenderness. Patients receiving estrogens should be monitored for an increase in adverse events.
Eszopiclone: (Major) The total dose of eszopiclone should not exceed 2 mg when administered with chronic mifepristone therapy. Coadministration may increase eszopiclone exposure resulting in increased risk of next-day psychomotor or memory impairment and decreased ability to perform tasks requiring full mental alertness such as driving. CYP3A4 is a primary metabolic pathway for eszopiclone; mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased eszopiclone exposure by 2.2-fold. The clinical significance of this interaction when mifepristone is used for pregnancy termination is not established.
Etodolac: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Etonogestrel: (Major) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
Etonogestrel; Ethinyl Estradiol: (Major) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
Everolimus: (Major) Avoid coadministration of everolimus with mifepristone due to the risk of increased everolimus-related adverse reactions. If concomitant use is unavoidable in patients receiving everolimus for either kidney or liver transplant, closely monitor everolimus whole blood trough concentrations. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Mifepristone is a strong CYP3A4 and P-gp inhibitor. Coadministration with another strong CYP3A4/P-gp inhibitor increased the AUC of everolimus by 15-fold. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Ezetimibe; Simvastatin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant simvastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of simvastatin therapy during use of mifepristone for pregnancy termination. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone is a strong CYP3A inhibitor; simvastatin is a sensitive CYP3A substrate. Coadministration of mifepristone and simvastatin increased simvastatin and simvastatin acid exposure by 10.4-fold and 15.7-fold, respectively, in drug interaction studies.
Fedratinib: (Major) Avoid coadministration of fedratinib with mifepristone as concurrent use may increase fedratinib exposure. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If mifepristone is discontinued, increase the fedratinib dose as follows: 300 mg PO once daily for 2 weeks and then 400 mg PO once daily thereafter as tolerated. Fedratinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. The significance of the interaction when mifepristone is used for pregnancy termination is unknown. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
Felodipine: (Moderate) Concurrent use of felodipine and mifepristone should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Concurrent use of another strong CYP3A4 inhibitor increased felodipine AUC and half-life by approximately 8-fold and 2-fold, respectively.
Fenoprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Fentanyl: (Contraindicated) Coadministration of fentanyl is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome or other hormonal conditions. Mifepristone inhibits CYP3A4. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates and that have a narrow therapeutic index, such as fentanyl. The increase in fentanyl concentrations can increase the risk for serious CNS depression and respiratory depression, particularly when mifepristone is added after a stable dose of fentanyl is achieved. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Fesoterodine: (Major) Limit the dose of fesoterodine to 4 mg once daily in adults and pediatric patients weighing more than 35 kg if coadministered with mifepristone. Avoid use of fesoterodine and mifepristone in pediatric patients weighing 25 to 35 kg. Concurrent use may increase fesoterodine exposure. Fesoterodine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor led to approximately a doubling of the overall exposure of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine.
Finasteride; Tadalafil: (Major) Avoid coadministration of tadalafil and mifepristone for the treatment of pulmonary hypertension. For the treatment of erectile dysfunction, do not exceed 10 mg tadalafil within 72 hours of mifepristone for the 'as needed' dose or 2.5 mg daily for the 'once-daily' dose. Tadalafil is metabolized predominantly by CYP3A4. Potent inhibitors of CYP3A4, such as mifepristone, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection.
Finerenone: (Contraindicated) Concomitant use of finerenone and mifepristone is contraindicated. Concomitant use may increase finerenone exposure and the risk for finerenone-related adverse reactions. Finerenone is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased overall exposure to finerenone by more than 400%.
Fingolimod: (Major) Concomitant use of fingolimod and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Flecainide: (Major) Concomitant use of flecainide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A inhibitors such as mifepristone is contraindicated due to increased flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following the use of mifepristone, start flibanserin at least 2 weeks after the last dose of mifepristone. If initiating mifepristone following flibanserin use, begin therapy at least 2 days after the last dose of flibanserin. In cases where the benefit of initiating mifepristone therapy within 2 days of stopping flibanserin clearly outweighs the risk of flibanserin-related hypotension and syncope, monitor the patient for signs of hypotension and syncope.
Fluconazole: (Contraindicated) Fluconazole has been associated with QT prolongation and rare cases of torsades de pointes (TdP). The concurrent use of fluconazole and other drugs that prolong the QT and are CYP3A4 substrates is contraindicated due to the risk of life-threatening arrhythmias such as TdP. Coadministration of fluconazole with drugs that are CYP3A4 substrates may result in an elevated plasma concentration of the interacting drug, causing an increased risk for adverse events, such as QT prolongation. Drugs that prolong QT and are substrates for CYP3A4 that are contraindicated with fluconazole include mifepristone.
Fluoxetine: (Major) Concomitant use of mifepristone and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fluphenazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and fluphenazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation that should be used cautiously with mifepristone include fluphenazine.
Flurbiprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Fluticasone; Salmeterol: (Major) Avoid concomitant use of salmeterol with mifepristone. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Fluvastatin: (Major) When mifepristone is used chronically in the treatment of hormonal conditions, such as Cushing's syndrome, and given with fluvastatin, the lowest dose of fluvastatin should be used and the patient monitored closely for an increased risk for fluvastatin-related adverse events, such as myopathy and rhabdomyolysis. Consider an alternative to fluvastatin if possible. Mifepristone inhibits CYP2C8/C9 and CYP3A4. In drug interaction studies, significantly increased the exposure of fluvastatin. Fluvastatin is primarily metabolized by CYP2C9, and to a lesser extent, CYP2C8 and CYP3A4. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Fluvoxamine: (Moderate) Coadministration of drugs that have been associated with QT prolongation, such as mifepristone and fluvoxamine, may increase the risk of QT prolongation or torsade de pointes. In addition, mifepristone is a CYP3A4 substrate and fluvoxamine is a moderate CYP3A4 inhibitor, which may further increase the risk of QT prolongation.
Fondaparinux: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Food: (Major) Advise patients to avoid cannabis use during mifepristone treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A and CYP2C9 substrates and mifepristone is a strong CYP3A and moderate CYP2C9 inhibitor. Concomitant use of a cannabinoid product containing THC and CBD at an approximate 1:1 ratio with another strong CYP3A inhibitor increased THC, 11-OH-THC, and CBD peak exposures by 1.3-, 3-, and 1.9-fold respectively.
Fosamprenavir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with mifepristone. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Foscarnet: (Major) Concomitant use of foscarnet and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fosphenytoin: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of fosphenytoin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving fosphenytoin. Monitor phenytoin concentrations during concomitant therapy with mifepristone due to risk for phenytoin toxicity. Coadministration may decrease mifepristone exposure reducing efficacy and increase phenytoin concentrations. Mifepristone is a CYP2C9 inhibitor and CYP3A4 substrate; phenytoin is a CYP2C9 substrate and strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
Fostamatinib: (Moderate) Monitor for fostamatinib toxicities that may require fostamatinib dose reduction (i.e., elevated hepatic enzymes, neutropenia, high blood pressure, severe diarrhea) if given concurrently with a strong CYP3A4 inhibitor. Concomitant use of fostamatinib with a strong CYP3A4 inhibitor increases exposure to the major active metabolite, R406, which may increase the risk of adverse reactions. R406 is extensively metabolized by CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
Fostemsavir: (Major) Concomitant use of fostemsavir and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. The degree of QT prolongation associated with fostemsavir is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with chronic mifepristone therapy is necessary. Gefitinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
Gemifloxacin: (Major) Concomitant use of gemifloxacin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Gemtuzumab Ozogamicin: (Moderate) Concomitant use of mifepristone and gemtuzumab ozogamicin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Gilteritinib: (Major) Consider an alternative to mifepristone during treatment with gilteritinib due to increased gilteritinib exposure and the potential for additive QT prolongation. If coadministration is required, frequently monitor for gilteritinib-related adverse effects and cardiac toxicity. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Interrupt therapy and reduce the gilteritinib dose if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study. Both drugs have been associated with QT prolongation. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Glasdegib: (Major) Consider an alternative to mifepristone during treatment with glasdegib due to the potential for additive QT prolongation and increased glasdegib exposure. If coadministration cannot be avoided, monitor for increased glasdegib-related adverse events and for increased risk of QT prolongation with more frequent ECG monitoring; use the lowest effective dose of mifepristone. Glasdegib is a CYP3A4 substrate that may cause QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Mifepristone is a strong CYP3A4 inhibitor that has been associated with dose-dependent prolongation of the QT interval. Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study. The clinical significance of inhibition of CYP3A4 with the short-term use of mifepristone for termination of pregnancy is unknown.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with the coadministration of glecaprevir and mifepristone as coadministration may increase serum concentrations of glecaprevir and increase the risk of adverse effects. Glecaprevir is a substrate of P-glycoprotein (P-gp); mifepristone is a P-gp inhibitor. (Moderate) Caution is advised with the coadministration of pibrentasvir and mifepristone as coadministration may increase serum concentrations of pibrentasvir and increase the risk of adverse effects. Pibrentasvir is a substrate of P-glycoprotein (P-gp); mifepristone is an inhibitor of P-gp.
Goserelin: (Major) Concomitant use of mifepristone and goserelin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Granisetron: (Major) Concomitant use of granisetron and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking mifepristone due to increased mifepristone exposure. Mifepristone is a CYP3A4 substrate and grapefruit juice is a strong CYP3A4 inhibitor.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Halogenated Anesthetics: (Major) Concomitant use of mifepristone and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Haloperidol: (Major) Avoid use together if possible due to an additive risk for QT prolongation and elevated haloperidol concentrations, which may lead to drug-related adverse events. Consider alternatives to haloperidol if possible. If use together is necessary, some patients may require haloperidol dose reduction; closely monitor for adverse events. Mifepristone inhibits CYP3A4 and has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Mild to moderate increases in haloperidol exposure have been reported during concurrent use with inhibitors of CYP3A4.
Heparin: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Histrelin: (Moderate) Concomitant use of mifepristone and androgen deprivation therapy (i.e., histrelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if chronic, concurrent use of mifepristone is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like mifepristone can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If mifepristone is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Hydroxychloroquine: (Major) Concomitant use of hydroxychloroquine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Major) Concomitant use of hydroxyzine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ibrexafungerp: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with mifepristone. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ibrutinib: (Major) Avoid concomitant use of ibrutinib and chronic mifepristone therapy; ibrutinib plasma concentrations may increase resulting in severe ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). Ibrutinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased ibrutinib exposure by 5.7-fold to 24-fold. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Ibuprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Ibuprofen; Famotidine: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If mifepristone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Ibuprofen; Pseudoephedrine: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Idelalisib: (Major) Caution is advised when administering idelalisib with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with idelalisib should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving idelalisib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with idelalisib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Additionally, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Both mifepristone and idelalisib are substrates and strong inhibitors of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
Iloperidone: (Major) Avoid coadministration of iloperidone and chronic mifepristone therapy due to the potential for QT prolongation; increased iloperidone exposure may also occur. If coadministration cannot be avoided, reduce the iloperidone dose by one-half and use the lowest effective dose of mifepristone. If mifepristone is discontinued, increase the iloperidone dose to the previous level. Iloperidone is a CYP3A4 substrate that has been associated with QT prolongation. Mifepristone is a strong CYP3A4 inhibitor that also prolongs the QT interval. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Imatinib: (Moderate) Monitor for an increase in imatinib-related adverse reactions if coadministration with mifepristone is necessary. Imatinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased imatinib exposure by 40%.
Indinavir: (Major) Caution is advised when administering indinavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with indinavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving indinavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with indinavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with indinavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with indinavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with indinavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and indinavir are substrates and strong inhibitors of CYP3A4.
Indomethacin: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Infigratinib: (Major) Avoid concomitant use of infigratinib and mifepristone. Coadministration may increase infigratinib exposure, increasing the risk for adverse effects. Infigratinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of infigratinib by 622%.
Inotuzumab Ozogamicin: (Major) Concomitant use of inotuzumab and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Irinotecan Liposomal: (Major) Avoid administration of mifepristone during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Mifepristone is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure to both irinotecan and SN-38. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Irinotecan: (Major) Avoid administration of mifepristone during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Mifepristone is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure to both irinotecan and SN-38. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with mifepristone may result in increased serum concentrations of both drugs. Mifepristone is a substrate and inhibitor of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoflurane: (Major) Concomitant use of mifepristone and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifampin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifampin. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
Isoniazid, INH; Rifampin: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifampin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifampin. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
Isradipine: (Moderate) Monitor blood pressure and heart rate if coadministration of isradipine with mifepristone is necessary. Concurrent use may result in elevated isradipine concentrations. Isradipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with mifepristone as istradefylline exposure and adverse effects may increase. Mifepristone is a strong CYP3A4 inhibitor. Istradefylline exposure was increased by 2.5-fold when administered with a strong inhibitor in a drug interaction study.
Itraconazole: (Major) Avoid coadministration of mifepristone with itraconazole due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving itraconazole, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with itraconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with itraconazole is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with itraconazole is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with itraconazole is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and itraconazole are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Ivabradine: (Major) Avoid coadministration of ivabradine and mifepristone as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; mifepristone inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances. Due to the slow elimination of mifepristone from the body, drug interactions may be prolonged.
Ivacaftor: (Major) If mifepristone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with mifepristone due to increased plasma concentrations of ivosidenib and additive QT prolongation. If concomitant use is unavoidable, reduce the dose of ivosidenib to 250 mg PO once daily. Monitor ECGs for QTc prolongation and monitor electrolytes, correcting any electrolyte abnormalities as clinically appropriate. If mifepristone is discontinued, wait at least 5 half-lives of mifepristone before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate that has been associated with QTc prolongation and ventricular arrhythmias. Mifepristone is a strong CYP3A4 inhibitor associated with dose-dependent QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased ivosidenib single-dose AUC to 269% of control, with no change in Cmax.
Ixabepilone: (Major) Avoid concurrent use of ixabepilone and mifepristone due to increased ixabepilone exposure, which may increase the risk of adverse reactions. If concomitant use is unavoidable, reduce the dose of ixabepilone to 20 mg/m2. Ixabepilone is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ixabepilone exposure by 79%.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and mifepristone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of both drugs, further increasing the risk for adverse effects. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ketoconazole should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ketoconazole, initiate mifepristone at a dose of 300 mg and titrate up to a maximum of 900 mg if clinically indicated. If ketoconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If ketoconazole is initiated in a patient already receiving mifepristone 600 mg, reduce mifepristone to 300 mg per day and titrate to a maximum of 600 mg if clinically indicated. If ketoconazole is initiated in a patient receiving already receiving 900 mg, reduce mifepristone to 600 mg per day and titrate up to a maximum of 900 mg if clinically indicated. In a patient receiving mifepristone 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ketoconazole are substrates and strong inhibitors of CYP3A4.
Ketoprofen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Ketorolac: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of mifepristone with clarithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving clarithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and clarithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Lapatinib: (Major) Avoid coadministration of lapatinib with mifepristone due to increased plasma concentrations of lapatinib; QT prolongation may also occur. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily; use the lowest effective dose of mifepristone to reduce the risk of QT prolongation. Monitor ECGs for QT prolongation and monitor electrolytes; correct any electrolyte abnormalities prior to treatment. If mifepristone is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have also been reported in postmarketing experience. Mifepristone is a strong CYP3A4 inhibitor that has also been associated with dose-dependent prolongation of the QT interval. Concomitant use with another strong CYP3A4 inhibitor increased lapatinib exposure by 3.6-fold and increased the half-life of lapatinib by 1.7-fold. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Larotrectinib: (Major) Avoid coadministration of larotrectinib with chronic mifepristone use due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If mifepristone is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of mifepristone. Larotrectinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of larotrectinib by 4.3-fold in a drug interaction study. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Lefamulin: (Major) Avoid coadministration of lefamulin with mifepristone as concurrent use may increase the risk of QT prolongation; concurrent use may also increase exposure from lefamulin tablets which may increase the risk of adverse effects. Lefamulin is a CYP3A4 and P-gp substrate that has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Mifepristone is a P-gp and strong CYP3A4 inhibitor that is also associated with QT prolongation. Coadministration of a combined P-gp and strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and mifepristone as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold. Due to the long half-life of mifepristone, a drug interaction is possible for a prolonged period after discontinuation of mifepristone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Leniolisib: (Major) Avoid concomitant use of leniolisib and mifepristone due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lenvatinib: (Major) Concomitant use of mifepristone and lenvatinib increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of mifepristone; monitor for potential reduction in efficacy. Mifepristone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of mifepristone; monitor for potential reduction in efficacy. Mifepristone is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Moderate) An increase in the plasma concentration of mifepristone may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Mifepristone is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor.
Leuprolide: (Moderate) Concomitant use of mifepristone and androgen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Leuprolide; Norethindrone: (Moderate) Concomitant use of mifepristone and a ndrogen deprivation therapy (i.e., leuprolide) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levamlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Levofloxacin: (Major) Concomitant use of levofloxacin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and mifepristone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation. Concomitant use may also increase the exposure of both drugs, further increasing the risk for adverse effects. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ketoconazole should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ketoconazole, initiate mifepristone at a dose of 300 mg and titrate up to a maximum of 900 mg if clinically indicated. If ketoconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If ketoconazole is initiated in a patient already receiving mifepristone 600 mg, reduce mifepristone to 300 mg per day and titrate to a maximum of 600 mg if clinically indicated. If ketoconazole is initiated in a patient receiving already receiving 900 mg, reduce mifepristone to 600 mg per day and titrate up to a maximum of 900 mg if clinically indicated. In a patient receiving mifepristone 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ketoconazole are substrates and strong inhibitors of CYP3A4.
Lithium: (Major) Concomitant use of mifepristone and lithium increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Lofexidine: (Moderate) Concomitant use of mifepristone and lofexidine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lonafarnib: (Contraindicated) Concomitant use of lonafarnib and mifepristone is contraindicated as use together increases the exposure and risk of adverse effects from both drugs. Consider alternatives. If concomitant use of mifepristone is absolutely necessary for the treatment of Cushing's syndrome in a patient already receiving lonafarnib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg/day if clinically indicated. Monitor closely for lonafarnib and mifepristone toxicity. If a patient is taking mifepristone daily and lonafarnib is necessary, consult the product literature for recommended dose adjustments. Lonafarnib is a sensitive CYP3A4 and CYP2C9 substrate and strong CYP3A4 inhibitor; mifepristone is a CYP3A4 substrate and strong CYP3A4 and moderate CYP2C9 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of lonafarnib by 425%.
Loperamide: (Moderate) Concomitant use of loperamide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a CYP3A4 and P-gp substrate and mifepristone is a strong CYP3A4 and P-gp inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Loperamide; Simethicone: (Moderate) Concomitant use of loperamide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Concomitant use may also increase loperamide exposure and the risk for other loperamide-related adverse effects; loperamide is a CYP3A4 and P-gp substrate and mifepristone is a strong CYP3A4 and P-gp inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with mifepristone due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Monitor patients for lopinavir-related adverse effects (e.g., diarrhea, nausea, vomiting, fast irregular heartbeat, hypokalemia, pancreatic or hepatic dysfunction). Mifepristone is a strong CYP3A4 inhibitor and may lead to an increase in serum concentrations of lopinavir, a CYP3A4 substrate. Mifepristone is also associated with dose-related prolongation of the QT interval. Lopinavir is associated with QT prolongation. (Major) Caution is advised when administering ritonavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ritonavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ritonavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ritonavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ritonavir are substrates and strong inhibitors of CYP3A4.
Lorlatinib: (Major) Avoid coadministration of lorlatinib with mifepristone due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the starting dose of lorlatinib from 100 mg to 75 mg once daily, or from 75 mg to 50 mg once daily. If mifepristone is discontinued, resume the original dose of lorlatinib after 3 half-lives of mifepristone. Lorlatinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lorlatinib exposure by 42%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Losartan: (Moderate) Closely monitor blood pressure during coadministration of losartan and mifepristone; adjust the dose of losartan as clinically appropriate. Concomitant use may decrease exposure to the active metabolite of losartan and decrease losartan efficacy. Losartan is a CYP2C9 substrate; mifepristone is a moderate CYP2C9 inhibitor. Coadministration with a moderate CYP2C9 inhibitor in two pharmacokinetic studies with healthy volunteers decreased concentrations of the active metabolite of losartan by 30% to 56%.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure during coadministration of losartan and mifepristone; adjust the dose of losartan as clinically appropriate. Concomitant use may decrease exposure to the active metabolite of losartan and decrease losartan efficacy. Losartan is a CYP2C9 substrate; mifepristone is a moderate CYP2C9 inhibitor. Coadministration with a moderate CYP2C9 inhibitor in two pharmacokinetic studies with healthy volunteers decreased concentrations of the active metabolite of losartan by 30% to 56%.
Lovastatin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant lovastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of lovastatin therapy during use of mifepristone for pregnancy termination. Mifepristone inhibits CYP3A4; lovastatin is a CYP3A4 substrate. Coadministration of mifepristone increases serum levels drugs metabolized via CYP3A4 with narrow therapeutic indexes, such as lovastatin. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after administration.
Low Molecular Weight Heparins: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Lumacaftor; Ivacaftor: (Major) If mifepristone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may decrease the therapeutic efficacy of mifepristone; avoid concurrent use if possible. If coadministration is necessary, monitor efficacy and adjust drug dosages as necessary. Lumacaftor; ivacaftor dosage adjustment is not required when mifepristone is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking mifepristone, reduce the dose of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking mifepristone. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Mifepristone is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Lumacaftor's induction of CYP3A may decrease the systemic exposure of mifepristone and decrease its therapeutic efficacy. Although mifepristone is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
Lumateperone: (Major) Reduce the dose of lumateperone to 10.5 mg once daily if concomitant use of mifepristone is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor increased lumateperone exposure by approximately 4-fold.
Lurasidone: (Major) Avoid use together if possible due to increased lurasidone exposure. The lurasidone adult dose should not exceed 40 mg/day if coadministered with moderate CYP3A4 inhibitors, such as mifepristone. Monitor closely for lurasidone-related adverse events, including increased CNS depression, changes in moods or behavirors, movement disorders, and leukopenia . Mifepristone, when used chronically for hormonal conditions such as Cushing's syndrome, inhibits CYP3A4. Lurasidone is primarily metabolized by CYP3A4 and use of mifepristone is expected to increase lurasidone exposure.
Lurbinectedin: (Major) Avoid concomitant use of lurbinectedin and mifepristone due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Macimorelin: (Major) Concomitant use of macimorelin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Maprotiline: (Major) Concomitant use of maprotiline and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with mifepristone is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A/P-glycoprotein (P-gp) substrate and mifepristone is a CYP3A4/P-gp inhibitor. Monitor for an increase in adverse effects with concomitant use.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with mifepristone due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Meclofenamate Sodium: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Mefenamic Acid: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Mefloquine: (Major) Concurrent use may increase the serum concentrations of mefloquine, further increasing the risk for mefloquine-related adverse effects, including dizziness, changes in moods or behaviors, vision changes, and QT prolongation. Mefloquine is metabolized by CYP3A4 and P-glycoprotein (P-gp). Mifepristone is a potent and prolonged inhibitor of CYP3A4 and P-gp. In addition, mifepristone may cause QT prolongation. Based on the long terminal half-life of mifepristone after reaching steady state, at least 2 weeks should elapse after cessation of mifepristone, when used for chronic conditions, before initiating or increasing the dose of any interacting concomitant medication. Discontinuation or dose reduction of mefloquine may be necessary if mifepristone must be used.
Meloxicam: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Metformin; Repaglinide: (Moderate) Repaglinide dose reductions and increased frequency of glucose monitoring may be required when mifepristone (for chronic conditions) is prescribed concurrently. When mifepristone is used chronically, such as with Cushing's syndrome, the lowest dose of repaglinide should be used that results in proper clinical response and tolerance. Monitor closely for hypoglycemia and adverse reactions. In some patients, a lower dose of repaglinide will be needed. Repaglinide is a CYP2C8 substrate. Mifepristone significantly increases exposure of drugs metabolized by CYP2C8, and can be expected to increase repaglinide exposure. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Metformin; Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and mifepristone are used together; dosage reduction of saxagliptin may be needed in some patients. In patients taking CYP3A substrates, the manufacturer of mifepristone recommends that the lowest dose of the CYP3A substrate that achieves the proper clinical response and tolerability be used. When potent CYP3A inhibitors are used, the initial dose of saxagliptin should be limited to 2.5 mg/day; mifepristone is a CYP3A inhibitor and has been noted to increase concentrations of CYP3A substrates. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Methadone: (Major) Avoid use together if possible. Coadministration of mifepristone may lead to a significant increase in serum concentrations of methadone. The increase in methadone concentrations can increase the risk for serious CNS and respiratory depression or QT prolongation, particularly when mifepristone is added after a stable dose of methadone is achieved. Methadone is a substrate for CYP3A4, CYP2B6, and P-glycoprotein (P-gp). Mifepristone, when used chronically for hormonal conditions such as Cushing's disease, inhibits CYP3A4, 2B6 and may inhibit P-gp. Methadone is associated with an increased risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (more than 200 mg/day but averaging approximately 400 mg/day in adult patients). Mifepristone use is also associated with QT prolongation; to minimize this risk, the lowest effective dose of mifepristone should always be used. Use of these drugs together may increase the risk for QT prolongation. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Metronidazole: (Major) Concomitant use of metronidazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Midazolam: (Major) Midazolam should be used with mifepristone only with caution, close monitoring, and consideration of appropriate midazolam dosage reduction. CNS depression, impaired motor and/or cognitive performance may occur due to increased midazolam exposure. Mifepristone inhibits CYP3A4 when it is used chronically in the treatment of hormonal conditions, such as Cushing's disease. Coadministration of mifepristone may lead to a significant increase in serum concentrations of drugs that are CYP3A4 substrates like midazolam. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and mifepristone due to the risk of increased midostaurin exposure which may increase the incidence and severity of adverse reactions; concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). If concomitant use cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity, particularly during the first week of midostaurin therapy for those with systemic mastocytosis/mast cell leukemia and during the first week of each cycle for those with acute myeloid leukemia. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Midostaurin is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration of one strong CYP3A4 inhibitor with a single dose of midostaurin increased the exposure of midostaurin and its active metabolites CGP62221 and CGP52421 by 10.4-fold, 3.5-fold, and 1.2-fold, respectively. Coadministration of another strong CYP3A4 inhibitor with twice daily doses of midostaurin increased Day 28 trough concentrations of midostaurin, CGP62221, and CGP52421 by 2.1-fold, 1.2-fold, and 1.3-fold respectively compared with day 21 trough levels with midostaurin alone.
Mirtazapine: (Major) Concomitant use of mifepristone and mirtazapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mirvetuximab Soravtansine: (Moderate) Closely monitor for mirvetuximab soravtansine-related adverse reactions if concomitant use of mifepristone is necessary. DM4, the cytotoxic component of mirvetuximab soravtansine, is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use may increase unconjugated DM4 exposure.
Mitapivat: (Major) Avoid coadministration of mitapivat with mifepristone due to increased risk of adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with other strong CYP3A inhibitors increased mitapivat overall exposure by 3.6 to 4.9-fold.
Mitotane: (Major) Avoid the concomitant use of mitotane with mifepristone due to duplication of pharmacodynamic effects and the potential for serious adrenalcortical insufficiency. The safe and effective use of these drugs together has not been established. Additionally, mitotane is a strong CYP3A4 inducer, and coadministration would be expected to decrease plasma concentrations of mifepristone. Avoid co-administration of mifepristone and CYP3A inducers such as mitotane. Use of mifepristone with CYP3A inducers has not been studied.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and mifepristone. Concomitant use increases the risk of QT/QTc prolongation and torsade de pointes (TdP) and may increase mobocertinib exposure and the risk for mobocertinib-related adverse reactions. Mobocertinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Use of a strong CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 374% to 419%. If concomitant use is necessary, consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring.
Moxifloxacin: (Major) Concomitant use of moxifloxacin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Nabumetone: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Naloxegol: (Contraindicated) Concomitant use of naloxegol with chronic mifepristone therapy is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as mifepristone, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. The clinical significance of this interaction when mifepristone is used for pregnancy termination is not established.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with mifepristone is necessary due to the risk of increased plasma concentrations of paclitaxel. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Nab-paclitaxel is a CYP3A4 and CYP2C8 substrate. Mifepristone is a strong CYP3A4 inhibitor and a moderate inhibitor of CYP2C8. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Contraindicated) Concomitant use of sirolimus and mifepristone is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Naproxen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Naproxen; Esomeprazole: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Naproxen; Pseudoephedrine: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Nefazodone: (Major) Caution is advised when administering nefazodone with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with nefazodone should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving nefazodone, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with nefazodone is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with nefazodone is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with nefazodone is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with nefazodone is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and nefazodone are substrates and strong inhibitors of CYP3A4.
Nelfinavir: (Major) Caution is advised when administering nelfinavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with nelfinavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving nelfinavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with nelfinavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with nelfinavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with nelfinavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with nelfinavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and nelfinavir are substrates and strong inhibitors of CYP3A4.
Neratinib: (Major) Avoid concomitant use of mifepristone with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 381%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Niacin; Simvastatin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant simvastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of simvastatin therapy during use of mifepristone for pregnancy termination. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone is a strong CYP3A inhibitor; simvastatin is a sensitive CYP3A substrate. Coadministration of mifepristone and simvastatin increased simvastatin and simvastatin acid exposure by 10.4-fold and 15.7-fold, respectively, in drug interaction studies.
Nicardipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nicardipine with mifepristone is necessary. Concurrent use may result in elevated nicardipine concentrations. Nicardipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Nifedipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nifedipine with mifepristone is necessary. Concurrent use may result in elevated nifedipine concentrations. Nifedipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and mifepristone; significant prolongation of the QT interval may occur. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Mifepristone has been associated with dose-dependent prolongation of the QT interval. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. If coadministration is required, monitor closely for prolongation of the QT interval and reduce the nilotinib dose to 300 mg once daily in adult patients with resistant or intolerant Ph+ CML or to 200 mg once daily in adult patients with newly diagnosed Ph+ CML. If mifepristone is discontinued, a washout period should be allowed before adjusting the nilotinib dosage upward to the indicated dose. Nilotinib is a substrate of CYP3A4 and mifepristone is a strong inhibitor of CYP3A4.
Nimodipine: (Moderate) Monitor blood pressure and heart rate if coadministration of nimodipine with mifepristone is necessary. Concurrent use may result in elevated nimodipine concentrations. Nimodipine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Nintedanib: (Moderate) Dual inhibitors of P-glycoprotein (P-gp) and CYP3A4, such as mifepristone, are expected to increase the exposure and clinical effect of nintedanib. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. If use together is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity (nausea, vomiting, diarrhea, abdominal pain, loss of appetite), headache, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of nintedanib therapy may be necessary. Mifepristone is a moderate inhibitor of P-gp and an inhibitor of CYP3A4; nintedanib is a P-gp substrate and a minor CYP3A4 substrate. In drug interactions studies, administration of nintedanib with a dual P-gp and CYP3A4 inhibitor increased nintedanib AUC by 60%.
Nirmatrelvir; Ritonavir: (Major) Caution is advised when administering ritonavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ritonavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ritonavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ritonavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ritonavir are substrates and strong inhibitors of CYP3A4.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with mifepristone due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and mifepristone is a CYP3A4 inhibitor.
Nonsteroidal antiinflammatory drugs: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Ofloxacin: (Major) Concomitant use of ofloxacin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Olanzapine: (Moderate) Concomitant use of mifepristone and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Fluoxetine: (Major) Concomitant use of mifepristone and fluoxetine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. (Moderate) Concomitant use of mifepristone and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine; Samidorphan: (Moderate) Concomitant use of mifepristone and olanzapine may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olaparib: (Major) Avoid coadministration of olaparib with mifepristone due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after mifepristone is discontinued. Olaparib is a CYP3A substrate and mifepristone is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and mifepristone is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and mifepristone may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If mifepristone is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and mifepristone. If concomitant use is necessary, decrease omaveloxolone dose to 50 mg once daily. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased omaveloxolone overall exposure by 4-fold.
Ondansetron: (Major) Concomitant use of ondansetron and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oral Contraceptives: (Major) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
Oritavancin: (Moderate) Mifepristone is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of mifepristone may be reduced if these drugs are administered concurrently. Specific drug interactions with mifepristone have not been studied; it is not known if lowered mifepristone serum concentrations would lead to therapeutic failures.
Osilodrostat: (Major) Concomitant use of osilodrostat and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Osimertinib: (Major) Concomitant use of osimertinib and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaliplatin: (Major) Concomitant use of oxaliplatin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Oxaprozin: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Oxybutynin: (Moderate) Monitor for an increase in oxybutynin-related adverse reactions if coadministration with mifepristone is necessary. Oxybutynin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased mean oxybutynin plasma concentrations by approximately 2-fold.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If mifepristone is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking mifepristone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Mifepristone is associated with dose-related prolongation of the QT interval.
Pacritinib: (Contraindicated) Concurrent use of pacritinib with mifepristone is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Concomitant use may also increase the risk for QT/QTc prolongation and torsade de pointes (TdP). Pacritinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Palbociclib: (Major) Avoid coadministration of chronic mifepristone with palbociclib due to increased palbociclib exposure. If concomitant use is unavoidable, reduce the dose of palbociclib to 75 mg once daily. If mifepristone is discontinued, wait 3 to 5 half-lives of mifepristone and then increase palbociclib to its original dose. Palbociclib is a CYP3A substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A inhibitor increased palbociclib exposure after a single dose by approximately 87%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Paliperidone: (Major) Concomitant use of paliperidone and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Palovarotene: (Major) Avoid concomitant use of palovarotene and mifepristone due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. Palovarotene is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased palovarotene overall exposure by 3-fold.
Panobinostat: (Major) The co-administration of panobinostat with mifepristone is not recommended; QT prolongation has been reported with both agents. Mifepristone is a CYP3A4 inhibitor and panobinostat is a CYP3A4 substrate. The panobinostat Cmax and AUC (0-48hr) values were increased by 62% and 73%, respectively, in patients with advanced cancer who received a single 20 mg-dose of panobinostat after taking 14 days of a strong CYP3A4 inhibitor. Although an initial panobinostat dose reduction is recommended in patients taking concomitant strong CYP3A4 inhibitors, no dose recommendations with mild or moderate CYP3A4 inhibitors are provided by the manufacturer. If concomitant use of mifepristone and panobinostat cannot be avoided, closely monitor electrocardiograms and for signs and symptoms of panobinostat toxicity such as cardiac arrhythmias, diarrhea, bleeding, infection, and hepatotoxicity. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve.
Pasireotide: (Major) Concomitant use of pasireotide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as mifepristone, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and the other drug must be continued, closely monitor the patient for QT interval prolongation. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Although specific drug interactions with mifepristone have not been studied, the use of mifepristone with CYP3A inhibitors may result in increased mifepristone concentrations and an increased risk of QT prolongation.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and mifepristone due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If mifepristone is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of mifepristone. Pemigatinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased pemigatinib exposure by 88%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Pentamidine: (Major) Concomitant use of pentamidine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Pentosan: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the increased risk of serious bleeding.
Perindopril; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Perphenazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and perphenazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include perphenazine.
Perphenazine; Amitriptyline: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and perphenazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include perphenazine.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and mifepristone due to the risk of increased pexidartinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pexidartinib dosage as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. If mifepristone is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of mifepristone. Pexidartinib is a CYP3A substrate; mifepristone is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Phenobarbital: (Major) Avoid the use of mifepristone and potent CYP3A inducers such as phenobarbital. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid the use of mifepristone and potent CYP3A inducers such as phenobarbital. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
Phenytoin: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of phenytoin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving phenytoin. Monitor phenytoin concentrations during concomitant therapy with mifepristone due to risk for phenytoin toxicity. Coadministration may decrease mifepristone exposure reducing efficacy and increase phenytoin concentrations. Mifepristone is a CYP2C9 inhibitor and CYP3A4 substrate; phenytoin is a CYP2C9 substrate and strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as mifepristone, due to a potential increased risk of QT prolongation. In addition, because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends that the pimavanserin dose be reduced to 10 mg/day PO in patients receiving strong inhibitors of CYP3A4 such as mifepristone. If these agents are used in combination, the patient should be carefully monitored for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, loss of balance or coordination, and QT prolongation.
Pimozide: (Contraindicated) Avoid concomitant use of pimozide and mifepristone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Piroxicam: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Pirtobrutinib: (Major) Avoid concomitant use of pirtobrutinib and mifepristone due to the risk of increased pirtobrutinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pirtobrutinib dose by 50 mg. If the current pirtobrutinib dosage is 50 mg once daily, interrupt pirtobrutinib treatment for the duration of mifepristone use. Resume the previous dose of pirtobrutinib after mifepristone is discontinued for 5 half-lives. Pirtobrutinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant with another strong CYP3A inhibitor increased pirtobrutinib overall exposure by 49%.
Pitolisant: (Major) Concomitant use of pitolisant and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of mifepristone due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; mifepristone is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Ponatinib: (Major) Avoid coadministration of ponatinib and mifepristone due to the potential for increased ponatinib exposure. If concurrent use cannot be avoided, reduce the ponatinib dose to the next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg). If the patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid the use of mifepristone and consider alternative therapy. After mifepristone has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting mifepristone. Ponatinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking mifepristone due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Mifepristone is associated with dose-related prolongation of the QT interval.
Posaconazole: (Contraindicated) Coadministration of posaconazole and mifepristone is contraindicated due to the risk of additive QT prolongation and life threatening arrhythmias such as torsades de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving posaconazole, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg daily if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with posaconazole is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with posaconazole is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg/day. Both mifepristone and posaconazole are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Pralsetinib: (Major) Avoid concomitant use of mifepristone with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Primaquine: (Major) Avoid use together if possible; consider alternative therapies to primaquine. Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include mifepristone. Mifepristone, when used chronically for hormonal conditions, such as Cushing's syndrome, has been associated with QT prolongation. To limit the risk for QT prolongation, the lowest effective dose of mifepristone should be used. Closely monitor.
Primidone: (Major) Avoid the use of mifepristone and potent CYP3A inducers such as primidone. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and mifepristone due to the risk for increased colchicine exp osure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Procainamide: (Major) Concomitant use of procainamide and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Prochlorperazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and prochlorperazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include prochlorperazine.
Progesterone: (Moderate) Use caution if coadministration of mifepristone with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Mifepristone is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone.
Promethazine: (Major) Concomitant use of promethazine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Dextromethorphan: (Major) Concomitant use of promethazine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Promethazine; Phenylephrine: (Major) Concomitant use of promethazine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Propafenone: (Major) Concomitant use of mifepristone and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of quetiapine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of quetiapine, further increasing the risk for adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concomitant use is necessary, reduce the dose of quetiapine to one-sixth the original dose and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Quetiapine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Quinidine: (Contraindicated) Use of quinidine with mifepristone is contraindicated when mifepristone is used chronically for hormonal conditions, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase quinidine concentrations and adverse effects, since quinidine is a CYP3A4 substrate with a narrow therapeutic index. Increased quinidine concentrations are likely to cause proarrythmia and ECG changes, as well as symptoms of cinchonism. Both quinidine and mifepristone have been associated with QT prolongation and a risk for torsade de pointes (TdP). Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Quinine: (Major) Concurrent use of quinine and mifepristone should generally be avoided due to an increased risk for elevated concentrations of either drug and an increased risk for QT prolongation and torsade de pointes (TdP). Consider alternative drug therapy if possible. Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. In addition, both drugs are inhibitors and substrates of CYP3A4; coadministration may result in increased concentration of both drugs. Monitor for quinine-related "cinchonism". Monitor for adrenal suppression from Mifepristone. To minimize the risk for QT prolongation, the lowest effective dose of mifepristone should be used.
Quizartinib: (Major) Avoid concomitant use of mifepristone with quizartinib due to the risk of increased quizartinib exposure which may increase the risk of adverse reactions. Concomitant use may also increase the risk for torsade de pointes (TdP) and QT/QTc prolongation. If concomitant use is necessary, reduce the dose of quizartinib to 26.5 mg for patients taking a daily dose of 53 mg, and to 17.7 mg for patients taking a daily dose of 35.4 mg or 26.5 mg; interrupt quizartinib therapy for the duration of the strong CYP3A inhibitor use for patients already taking a daily dose of 17.7 mg. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Quizartinib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of quizartinib by 94%.
Ramelteon: (Moderate) Ramelteon should be administered with caution in subjects taking strong CYP3A4 inhibitors. Because ramelteon is partially metabolized via CYP3A4, an increase in exposure of ramelteon is expected. An increase in ramelteon AUC by approximately 84% and Cmax by 36% was noted when coadministered with a strong CYP3A4 inhibitor (ketoconazole). Similar increases were noted in M-II pharmacokinetics. Patients should be monitored for increased ramelteon side effects. Examples of CYP3A4 inhibitors include: chloramphenicol, conivaptan, cyclosporine, dalfopristin; quinupristin, delavirdine, diltiazem, erythromycin, ethinyl estradiol, imatinib, STI-571, itraconazole, systemic miconazole, mifepristone, troleandomycin, verapamil, voriconazole, and zafirlukast. This list is not inclusive of all CYP3A4 inhibitors. Imatinib, voriconazole, and zafirlukast are also CYP2C9 inhibitors, and when administered with ramelteon may result in multiple hepatic enzyme inhibition interactions, although the significance of these interactions has not been studied. The patient should be monitored closely for ramelteon-associated toxicity.
Ranolazine: (Major) Avoid use together if possible. Both drugs may prolong the QT interval and may increase the risk for arrhythmia. If use together is necessary, limit the ranolazine dosage to 500 mg PO twice daily. Monitor for ranolazine-related adverse reactions such as dizziness, headache, constipation, and nausea. Limit the mifepristone to the lowest effective dose to reduce QT prolongation risk. Ranolazine is metabolized mainly by CYP3A4 and to an extent by P-glycoprotein (P-gp) and mifepristone is known to inhibit CYP3A4 and may also inhibit P-glycoprotein (P-gp); use together is expected to increase ranolazine concentrations. Due to the slow elimination of mifepristone from the body, drug interactions that occur may be prolonged.
Red Yeast Rice: (Major) Advise patients not to take red yeast rice with mifepristone. Certain red yeast rice dietary supplement products contain lovastatin. Mifepristone is a CYP3A4 inhibitor and is contraindicated with lovastatin due to the expected increase in serum concentrations of lovastatin and the potential for myopathy, rhabdomyolysis or other serious HMG-CoA reductase inhibitor effects. Due to the slow elimination of mifepristone from the body, any interactions that do occur may be prolonged.
Regorafenib: (Major) Avoid coadministration of regorafenib with mifepristone due to increased plasma concentrations of regorafenib and decreased plasma concentrations of the active metabolites M-2 and M-5, which may lead to increased toxicity. Regorafenib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased regorafenib exposure by 33% and decreased exposure of M-2 and M-5 by 93% each. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Relugolix: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Concomitant use may also increase relugolix exposure and the risk of other relugolix-related adverse effects. If concomitant use is unavoidable, administer mifepristone at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of mifepristone is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor.
Relugolix; Estradiol; Norethindrone acetate: (Major) Avoid use of mifepristone with QT interval prolonging drugs. Mifepristone is associated with dose-related prolongation of the QT interval. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval. Concomitant use may also increase relugolix exposure and the risk of other relugolix-related adverse effects. If concomitant use is unavoidable, administer mifepristone at least 6 hours after relugolix and monitor for adverse reactions. Alternatively, relugolix therapy may be interrupted for up to 14 days if a short course of mifepristone is required; if treatment is interrupted for more than 7 days, resume relugolix with a 360 mg loading dose followed by 120 mg once daily. Relugolix is a P-glycoprotein (P-gp) substrate and mifepristone is a P-gp inhibitor.
Repaglinide: (Moderate) Repaglinide dose reductions and increased frequency of glucose monitoring may be required when mifepristone (for chronic conditions) is prescribed concurrently. When mifepristone is used chronically, such as with Cushing's syndrome, the lowest dose of repaglinide should be used that results in proper clinical response and tolerance. Monitor closely for hypoglycemia and adverse reactions. In some patients, a lower dose of repaglinide will be needed. Repaglinide is a CYP2C8 substrate. Mifepristone significantly increases exposure of drugs metabolized by CYP2C8, and can be expected to increase repaglinide exposure. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as chronic mifepristone therapy, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ribociclib: (Major) Avoid coadministration of mifepristone with ribociclib due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving ribociclib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ribociclib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ribociclib are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of mifepristone with ribociclib due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving ribociclib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ribociclib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ribociclib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ribociclib are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Rifampin: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifampin. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifampin. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifampin is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
Rifapentine: (Major) When mifepristone is administered for the treatment of Cushing's syndrome, avoid coadministration of rifapentine. When mifepristone is administered for pregnancy termination, follow-up assessment to verify that treatment has been successful is recommended in patients receiving rifapentine. Coadministration may decrease mifepristone exposure reducing efficacy. Mifepristone is a CYP3A4 substrate; rifapentine is a strong CYP3A4 inducer. The impact of CYP3A4 inducers on mifepristone efficacy is unknown.
Rifaximin: (Moderate) Monitor for an increase in rifaximin-related adverse reactions if coadministration with mifepristone is necessary. Concomitant use may increase rifaximin exposure. In patients with hepatic impairment, a potential additive effect of reduced metabolism may further increase systemic rifaximin exposure. Rifaximin is a P-gp substrate and mifepristone is a P-gp inhibitor. Coadministration with another P-gp inhibitor increased rifaximin overall exposure by 124-fold.
Rilpivirine: (Major) Avoid use together if possible due to the risk of elevated rilpivirine exposure and a combined risk for QT prolongation. Consider alternatives to rilpivirine when coadministered with a drug with a known risk of QT prolongation and torsade de pointes (TdP), such as mifepristone when it is used for chronic hormonal conditions, such as Cushing's syndrome. Mifepristone is an inhibitor of CYP3A4; rilpivirine is a CYP3A4 substrate. Coadministration is likely to increase rilpivirine plasma concentrations. Monitor for rilpivirine-related side effects, including rash, mood changes or depression, fast, irregular heart rate, and hepatotoxicity. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used.
Rimegepant: (Major) Avoid coadministration of rimegepant with mifepristone; concurrent use may significantly increase rimegepant exposure. Rimegepant is a CYP3A4 and P-gp substrate; mifepristone is a strong CYP3A4 inhibitor and P-gp inhibitor. Coadministration of rimegepant with another strong CYP3A4 inhibitor increased rimegepant exposure by 4-fold.
Ripretinib: (Moderate) Monitor patients more frequently for ripretinib-related adverse reactions if coadministered with mifepristone. Coadministration may increase the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions. Ripretinib and DP-5439 are metabolized by CYP3A4 and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ripretinib and DP-5439 exposure by 99%.
Risperidone: (Major) Concomitant use of risperidone and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ritonavir: (Major) Caution is advised when administering ritonavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with ritonavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving ritonavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with ritonavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with ritonavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and ritonavir are substrates and strong inhibitors of CYP3A4.
Rivaroxaban: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Romidepsin: (Major) Avoid use together if possible. Both romidepsin and mifepristone have been reported to prolong the QT interval. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment. To minimize the risk of QT prolongation, the lowest effect dose of mifepristone should always be used when it is given chronically for hormonal conditions, such as Cushing's syndrome. In addition, romidepsin is a substrate for CYP3A4 and P-glycoprotein (P-gp). Mifepristone is a CYP3A4 inhibitor and may inhibit P-gp. Concurrent administration of romidepsin with an inhibitor of CYP3A4 and P-gp may cause an increase in systemic romidepsin concentrations. Monitor for toxicity related to increased romidepsin exposure, including hematologic and non-hematologic toxicity and follow the romidepsin dose modifications for toxicity as clinically indicated.
Ruxolitinib: (Major) Reduce the ruxolitinib dosage when coadministered with mifepristone in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur. No dose adjustments are necessary for patients with graft-versus-host disease; however, monitor blood counts more frequently for toxicity and adjust ruxolitinib dosage for adverse reactions. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Avoid the use of mifepristone in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily; alternatively, ruxolitinib therapy may be interrupted for the duration of mifepristone use. Ruxolitinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor.
Salmeterol: (Major) Avoid concomitant use of salmeterol with mifepristone. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Saquinavir: (Contraindicated) Coadministration of saquinavir and mifepristone is contraindicated due to the risk of additive QT prolongation and life-threatening arrhythmias such as torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving saquinavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg daily if clinically indicated. If therapy with saquinavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with saquinavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with saquinavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with saquinavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg/day. Both mifepristone and saquinavir are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Saxagliptin: (Moderate) Monitor patients for hypoglycemia if saxagliptin and mifepristone are used together; dosage reduction of saxagliptin may be needed in some patients. In patients taking CYP3A substrates, the manufacturer of mifepristone recommends that the lowest dose of the CYP3A substrate that achieves the proper clinical response and tolerability be used. When potent CYP3A inhibitors are used, the initial dose of saxagliptin should be limited to 2.5 mg/day; mifepristone is a CYP3A inhibitor and has been noted to increase concentrations of CYP3A substrates. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Segesterone Acetate; Ethinyl Estradiol: (Contraindicated) Mifepristone is a progesterone-receptor antagonist and will interfere with the effectiveness of hormonal contraceptives. Therefore, non-hormonal contraceptive methods should be used in Cushing's patients taking mifepristone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and mifepristone due to the risk of additive QT prolongation and increased selpercatinib exposure resulting in increased treatment-related adverse effects. If coadministration is unavoidable, reduce the dose of selpercatinib to 40 mg PO twice daily if original dose was 120 mg twice daily, and to 80 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If mifepristone is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of mifepristone. Selpercatinib is a CYP3A4 substrate that has been associated with concentration-dependent QT prolongation; mifepristone is a strong CYP3A4 inhibitor that is associated with dose-related prolongation of the QT interval. Coadministration with another strong CYP3A4 inhibitor increased selpercatinib exposure by 133%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Selumetinib: (Major) Avoid coadministration of selumetinib and mifepristone due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If mifepristone is discontinued, resume the original selumetinib dose after 3 elimination half-lives of mifepristone. Selumetinib is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selumetinib exposure by 49%.
Sertraline: (Major) Concomitant use of sertraline and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sevoflurane: (Major) Concomitant use of mifepristone and halogenated anesthetics increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sildenafil: (Major) Coadministration with mifepristone is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving mifepristone. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Sildenafil is a sensitive CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Silodosin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4 and is a P-glycoprotein (P-gp) substrate. In theory, drugs that inhibit CYP3A4 and P-gp such as mifepristone may cause significant increases in silodosin plasma concentrations.
Simvastatin: (Contraindicated) When mifepristone is used in the treatment of Cushing's syndrome, coadministration is contraindicated based on studies demonstrating significant simvastatin exposure increases which may lead to an increased risk of myopathy and rhabdomyolysis. Consider interruption of simvastatin therapy during use of mifepristone for pregnancy termination. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Mifepristone is a strong CYP3A inhibitor; simvastatin is a sensitive CYP3A substrate. Coadministration of mifepristone and simvastatin increased simvastatin and simvastatin acid exposure by 10.4-fold and 15.7-fold, respectively, in drug interaction studies.
Siponimod: (Major) Concomitant use of siponimod and mifepristone is not recommended due to a significant increase in siponimod exposure. Additionally, both drugs are associated with QT prolongation. Siponimod is a CYP2C9 and CYP3A4 substrate; mifepristone is a moderate CYP2C9/strong CYP3A4 dual inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Contraindicated) Concomitant use of sirolimus and mifepristone is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor.
Sodium Stibogluconate: (Major) Concomitant use of sodium stibogluconate and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with mifepristone. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); mifepristone is an inhibitor of P-gp. Mifepristone is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with mifepristone. Taking these drugs together may increase the plasma concentrations of velpatasvir, potentially resulting in adverse events. Velpatasvir is a substrate of the drug transporter P-glycoprotein (P-gp); mifepristone is an inhibitor of P-gp. Mifepristone is also an inhibitor of the hepatic enzyme CYP3A4. Velpatasvir is a CYP3A4 substrate.
Solifenacin: (Moderate) Concomitant use of mifepristone and solifenacin may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Sonidegib: (Major) Avoid concomitant use of sonidegib and chronic use of mifepristone as increased sonidegib plasma are expected, resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Mifepristone is a strong CYP3A4 inhibitor and may significantly increase the level of the CYP3A4 substrate, sonidegib. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of sonidegib by 2.2-fold and 1.5-fold, respectively.
Sorafenib: (Major) Concomitant use of sorafenib and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sotalol: (Major) Concomitant use of sotalol and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Sparsentan: (Major) Avoid concomitant use of sparsentan and mifepristone. Concomitant use may increase sparsentan exposure and the risk for sparsentan-related adverse effects. Sparsentan is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased sparsentan overall exposure by 174%.
St. John's Wort, Hypericum perforatum: (Major) Avoid the use of potent CYP3A inducers such as St. John's wort with mifepristone due to the potential for reduced mifepristone exposure and reduced efficacy. It is not known if lowered mifepristone serum levels would lead to reduced response or therapeutic failure. If use together is medically necessary, monitor the patient closely to ensure the proper therapeutic response is obtained.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if mifepristone must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of mifepristone is necessary. If mifepristone is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like mifepristone can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If mifepristone is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Sulindac: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Sumatriptan; Naproxen: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Sunitinib: (Major) Avoid use of mifepristone with sunitinib due to the risk of QT prolongation; increased sunitinib exposure may also occur. Sunitinib is a CYP3A4 substrate that can prolong the QT interval. Mifepristone is a strong CYP3A4 inhibitor that is associated with dose-related prolongation of the QT interval. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Suvorexant: (Major) Coadministration of suvorexant and chronic mifepristone therapy is not recommended due to the potential for significantly increased suvorexant exposure. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Suvorexant is a CYP3A4 substrate. Mifepristone is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
Tacrolimus: (Contraindicated) Coadministration of systemic tacrolimus is contraindicated when mifepristone is used chronically, such as in the treatment of Cushing's syndrome. Mifepristone, a CYP3A4 inhibitor, is likely to increase tacrolimus concentrations and adverse effects, since tacrolimus is a CYP3A4 substrate with a narrow therapeutic index. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Tadalafil: (Major) Avoid coadministration of tadalafil and mifepristone for the treatment of pulmonary hypertension. For the treatment of erectile dysfunction, do not exceed 10 mg tadalafil within 72 hours of mifepristone for the 'as needed' dose or 2.5 mg daily for the 'once-daily' dose. Tadalafil is metabolized predominantly by CYP3A4. Potent inhibitors of CYP3A4, such as mifepristone, may reduce tadalafil clearance. Increased systemic exposure to tadalafil may result in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection.
Tamoxifen: (Major) Concomitant use of tamoxifen and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tamsulosin: (Major) Concurrent use of tamsulosin and mifepristone is not recommended due to the potential for elevated tamsulosin concentrations. Such increases in tamsulosin concentrations may be expected to produce clinically significant and potentially serious side effects, such as hypotension, dizziness, and vertigo. Tamsulosin is extensively metabolized by CYP3A, and strong inhibitors of CYP3A, such as mifepristone, are expected to significantly raise tamsulosin concentrations. Concomitant treatment with another strong CYP3A inhibitor increased the Cmax and AUC of tamsulosin by a factor of 2.2 and 2.8, respectively.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with mifepristone as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telavancin: (Major) Concomitant use of telavancin and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Telmisartan; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with mifepristone is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. Strong CYP3A4 inhibitors may increase the plasma concentrations of amlodipine to a greater extent.
Temsirolimus: (Major) Avoid chronic coadministration of mifepristone with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider reducing the dose of temsirolimus to 12.5 mg per week. Allow a washout period of approximately 1 week after discontinuation of mifepristone before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor did not significantly affect temsirolimus exposure, but increased the AUC and Cmax of sirolimus by 3.1-fold and 2.2-fold, respectively. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Tetrabenazine: (Major) Concomitant use of tetrabenazine and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Tezacaftor; Ivacaftor: (Major) If mifepristone and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with mifepristone; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); mifepristone is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Thioridazine: (Contraindicated) Avoid concomitant use of thioridazine and mifepristone due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Thiotepa: (Major) Avoid the concomitant use of thiotepa and chronic use of mifepristone if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; mifepristone is a strong CYP3A4 inhibitor.
Thrombin Inhibitors: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Ticagrelor: (Moderate) Use together with caution and monitor for evidence of increased antiplatelet effect, as well as side effects such as bleeding and dyspnea. CYP3A inhibitors may increase ticagrelor exposure and so increase the risk of dyspnea, bleeding, and other adverse events. No dose adjustment has been recommended. Ticagrelor is a CYP3A4 and P-glycoprotein (P-gp) substrate. Mifepristone inhibits CYP3A4 and may be a P-gp inhibitor. Due to the slow elimination of mifepristone from the body, any interactions that occur may be prolonged.
Tipranavir: (Major) Caution is advised when administering tipranavir with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with tipranavir should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving tipranavir, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with tipranavir is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with tipranavir is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with tipranavir is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with tipranavir is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and tipranavir are substrates and strong inhibitors of CYP3A4.
Tisotumab Vedotin: (Moderate) Monitor for tisotumab vedotin-related adverse reactions if concomitant use with mifepristone is necessary due to increased monomethyl auristatin E (MMAE) exposure which may increase the incidence and severity of adverse reactions. MMAE, the active component of tisotumab vedotin, is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Clinical drug interaction studies have not been conducted for tisotumab vedotin. However, coadministration of another antibody-drug conjugate that contains MMAE with a strong CYP3A inhibitor increased unconjugated MMAE exposure by 34%.
Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with chronic mifepristone therapy. In patients receiving 5 mg or less twice daily, reduce to once daily dosing; in patients receiving 10 mg twice daily, reduce to 5 mg twice daily; in patients receiving 22 mg once daily of the extended-release (XR) formulation, switch to 11 mg XR once daily; in patients receiving 11 mg XR once daily, switch to the immediate-release formulation at a dose of 5 mg once daily. Tofacitinib exposure is increased when coadministered with mifepristone. Mifepristone is a strong CYP3A4 inhibitor; tofacitinib is a CYP3A4 substrate. When mifepristone is given chronically, the half-life of the drug is prolonged, and drug-interaction potential is extended. Coadministration with another strong CYP3A4 inhibitor increased tofacitinib exposure by 2-fold. The clinical significance of this interaction when mifepristone is used in a regimen for pregnancy termination is unknown.
Tolmetin: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Tolterodine: (Major) Reduce the dose of immediate-release tolterodine to 1 mg twice daily and extended-release tolterodine to 2 mg once daily and monitor for evidence of QT prolongation if coadministered with chronic mifepristone therapy. Concurrent use may increase tolterodine exposure. Mifepristone has been associated with dose-dependent prolongation of the QT interval and when administered chronically is a strong CYP3A4 inhibitor. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. In CYP2D6 poor metabolizers, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor CYP2D6 metabolizers, reduced doses of tolterodine are advised when administered with strong CYP3A4 inhibitors. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the tolterodine AUC by 2.5-fold in CYP2D6 poor metabolizers. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Tolvaptan: (Contraindicated) The concomitant use of tolvaptan and chronic mifepristone therapy is contraindicated. Concurrent use is expected to increase tolvaptan exposure. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Tolvaptan is a sensitive CYP3A4 substrate; mifepristone is a strong inhibitor of CYP3A4. Coadministration of another strong CYP3A4 inhibitor increased tolvaptan exposure 5-fold. No data exists regarding the appropriate dose adjustment needed to allow safe administration of tolvaptan with strong CYP3A4 inhibitors.
Topotecan: (Major) Avoid coadministration of mifepristone with oral topotecan due to increased topotecan exposure; mifepristone may be administered with intravenous topotecan. Oral topotecan is a substrate of P-glycoprotein (P-gp) and mifepristone is a P-gp inhibitor. Oral administration within 4 hours of another P-gp inhibitor increased the dose-normalized AUC of topotecan lactone and total topotecan 2-fold to 3-fold compared to oral topotecan alone.
Toremifene: (Major) Avoid coadministration of mifepristone with toremifene if possible due to increased plasma concentrations of toremifene which may result in QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. To minimize the risk of QT prolongation, the lowest effective dose of mifepristone should always be used. Toremifene is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner. Mifepristone is a strong CYP3A4 inhibitor that has also been associated with dose-dependent prolongation of the QT interval. Coadministration with another strong CYP3A4 inhibitor increased toremifene exposure by 2.9-fold; exposure to N-demethyltoremifene was reduced by 20%. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with chronic use of mifepristone due to the risk of increased trabectedin exposure. If short-term mifepristone (less than 14 days) cannot be avoided, begin administration 1 week after the trabectedin infusion and discontinue it the day prior to the next trabectedin infusion. Trabectedin is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
Trandolapril; Verapamil: (Moderate) Monitor blood pressure and heart rate during coadministration of verapamil and mifepristone. Coadministration may increase the exposure of verapamil. Verapamil is a CYP3A4 substrate and mifepristone is a strong inhibitor of CYP3A4.
Trazodone: (Major) Concomitant use of trazodone and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Concomitant use may also increase the exposure of trazodone, further increasing the risk for adverse effects. Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. If concomitant use is necessary, consider a reduced dose of trazodone based on tolerability and consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Trazodone is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of trazodone alone.
Triazolam: (Contraindicated) Coadministration of triazolam, a primary CYP3A4 substrate, with strong CYP3A4 inhibitors, such as mifepristone, is contraindicated by the manufacturer of triazolam due to the risk for increased and prolonged sedation and respiratory depression. Concurrent use is expected to produce large increases in systemic exposure to triazolam, with the potential for serious adverse effects. Mifepristone inhibits CYP3A4 when it is used chronically in the treatment of hormonal conditions, such as Cushing's disease. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Triclabendazole: (Major) Concomitant use of triclabendazole and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Trifluoperazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and trifluoperazine should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. Drugs with a possible risk for QT prolongation and torsades de pointes that should be used cautiously with mifepristone include trifluoperazine.
Triptorelin: (Moderate) Concomitant use of mifepristone and androgen deprivation therapy (i.e., triptorelin) may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Tucatinib: (Major) Caution is advised when administering tucatinib with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with tucatinib should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving tucatinib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with tucatinib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with tucatinib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with tucatinib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with tucatinib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Mifepristone is a CYP3A4 substrate, a strong CYP3A4 inhibitor, and a moderate CYP2C8 inhibitor; tucatinib is a CYP2C8 substrate and strong CYP3A4 inhibitor.
Ubrogepant: (Contraindicated) Coadministration of ubrogepant and mifepristone is contraindicated as concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor resulted in a 9.7-fold increase in the exposure of ubrogepant.
Upadacitinib: (Major) During concomitant use of upadacitinib and mifepristone reduce the upadacitinib dosage to 15 mg once daily. During induction for ulcerative colitis and Crohn's disease reduce the upadacitinib dosage to 30 mg once daily. Concomitant use may increase upadacitinib exposure and risk for adverse effects. Concomitant use with another strong CYP3A inhibitor increased upadacitinib overall exposure 1.75-fold.
Valdecoxib: (Moderate) Mifepristone significantly increased exposure of drugs metabolized by CYP2C8/2C9 in interaction studies. Therefore, when mifepristone is used chronically, as in the treatment of Cushing's syndrome, use caution with coadministered CYP2C8/2C9 substrates, including the NSAIDs. Use the lowest doses of the substrate and patients should be monitored closely for adverse reactions.
Vandetanib: (Major) Concomitant use of vandetanib and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with mifepristone due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Concomitant use also increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Vardenafil is primarily metabolized by CYP3A and mifepristone is a strong CYP3A inhibitor. Coadministration with other strong CYP3A inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Vemurafenib: (Major) Avoid vemurafenib in patients receiving medications known to prolong the QT interval such as mifepristone. Vemurafenib has been shown to prolong the QT interval in a concentration-dependent manner. The ECG changes occurred within the first month of treatment. Mifepristone has also been associated with dose-dependent prolongation of the QT interval. Additionally, coadministration may result in increased vemurafenib exposure and an increased risk of adverse events, including QT prolongation. Vemurafenib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. Because of the prolonged action of mifepristone, the effects on CYP3A may be prolonged. Coadministration with another strong CYP3A4 inhibitor increased the exposure of vemurafenib by 40%.
Venetoclax: (Major) Coadministration of mifepristone with venetoclax is contraindicated during the initiation and ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); consider an alternative medication or adjust the venetoclax dose with close monitoring for toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) in patients receiving a steady daily dose of venetoclax if concurrent use is necessary. In patients with acute myeloid leukemia (AML), reduce the venetoclax dose and monitor for toxicity during concurrent use. Resume the original venetoclax dose 2 to 3 days after discontinuation of mifepristone. Specific venetoclax dosage adjustments are as follows: CLL/SLL patients at steady daily dose: 100 mg/day. AML patients: 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, then 100 mg/day starting on day 4. Venetoclax is a CYP3A4 and P-glycoprotein (P-gp) substrate; mifepristone is a CYP3A4 (strong) and P-gp inhibitor Coadministration of strong CYP3A4 inhibitors increased the venetoclax AUC by 90% to 690% in drug interaction studies, while coadministration with a single dose of another P-gp inhibitor increased venetoclax exposure by 78% in a drug interaction study. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Venlafaxine: (Major) Concomitant use of mifepristone and venlafaxine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Verapamil: (Moderate) Monitor blood pressure and heart rate during coadministration of verapamil and mifepristone. Coadministration may increase the exposure of verapamil. Verapamil is a CYP3A4 substrate and mifepristone is a strong inhibitor of CYP3A4.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with mifepristone is necessary. Vinblastine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Vincristine Liposomal: (Moderate) Increased concentrations of vincristine are likely if chronic mifepristone therapy is given concurrently; exercise caution and monitor for vincristine-related side effects, including neurotoxicity. Mifepristone is an inhibitor of CYP3A4 and possibly an inhibitor of P-gp. Vincristine is a CYP3A4 and P-gp substrate. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Use the lowest dose of vincristine necessary, with appropriate monitoring and follow-up.
Vincristine: (Moderate) Increased concentrations of vincristine are likely if chronic mifepristone therapy is given concurrently; exercise caution and monitor for vincristine-related side effects, including neurotoxicity. Mifepristone is an inhibitor of CYP3A4 and possibly an inhibitor of P-gp. Vincristine is a CYP3A4 and P-gp substrate. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration. Use the lowest dose of vincristine necessary, with appropriate monitoring and follow-up.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with chronic mifepristone therapy is necessary. Vinorelbine is a CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor. Due to the slow elimination of mifepristone from the body, such interactions may be observed for a prolonged period after mifepristone administration.
Voclosporin: (Contraindicated) Concomitant use of voclosporin and mifepristone is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Additive QT prolongation may also occur. Voclosporin is a sensitive CYP3A4 substrate and mifepristone is a strong CYP3A4 inhibitor that has been associated with QT prolongation. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid coadministration of mifepristone with clarithromycin due to the risk of additive QT prolongation and torsade de pointes (TdP); the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving clarithromycin, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with clarithromycin is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with clarithromycin is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and clarithromycin are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and mifepristone. Increased serum concentrations of vorapaxar are possible when vorapaxar, a CYP3A4 and CYP2J2 substrate, is coadministered with mifepristone, a CYP3A inhibitor. Increased exposure to vorapaxar may increase the risk of bleeding complications.
Voriconazole: (Major) Avoid coadministration of mifepristone with voriconazole due to the risk of additive QT prolongation; the exposure of both drugs may also be increased. If concomitant use of mifepristone is necessary for the treatment of Cushing's syndrome in a patient already receiving voriconazole, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with voriconazole is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with voriconazole is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with voriconazole is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with voriconazole is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Both mifepristone and voriconazole are substrates and strong inhibitors of CYP3A4 that are associated with QT prolongation.
Vorinostat: (Moderate) Concomitant use of mifepristone and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Warfarin: (Major) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding. Use with caution in other circumstances due to increased warfarin exposure. Closely monitor the INR if coadministration of warfarin with mifepristone is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Mifepristone is a moderate CYP2C9 inhibitor and the S-enantiomer, the active metabolite of warfarin, is a CYP2C9 substrate. Mifepristone is a strong CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance. The lowest effective dose of warfarin should be used. Due to the slow elimination of mifepristone from the body, such an interaction may be observed for a prolonged period after its administration.
Zaleplon: (Moderate) Monitor for an increase in zaleplon-related adverse reactions, including excessive sedation and confusion, if coadministered with mifepristone. Routine dosage adjustments of zaleplon are not required. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Zaleplon is partially metabolized by CYP3A. Mifepristone is a strong CYP3A inhibitor. Coadministration with a single dose of another strong CYP3A inhibitor increased the AUC of zaleplon by 20%.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with mifepristone. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of mifepristone, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; mifepristone is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Ziprasidone: (Major) Concomitant use of ziprasidone and mifepristone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Zolpidem: (Moderate) Consider decreasing the dose of zolpidem if coadministration with mifepristone is necessary. Concurrent use may increase zolpidem exposure. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown. Zolpidem is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Coadministration with other strong CYP3A inhibitors increased the AUC of zolpidem by 34% to 70%.

Korlym/Mifeprex/Mifepristone (RU-486) Oral Tab: 200mg, 300mg

Adults

200 mg PO as a single dose is the FDA-approved maximum dose for termination of pregnancy; 1,200 mg/day PO for Cushing's syndrome and not to exceed 20 mg/kg/day PO; otherwise maximum dose is dependent on the indication for use.

Geriatric

Safety and efficacy have not been established.

Adolescents

200 mg PO as a single dose is the FDA-approved maximum dose for termination of pregnancy; safety and efficacy have not been established for Cushing's syndrome.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mifepristone is a potent antagonist of glucocorticoid and progesterone receptors. Mifepristone is a competitive antagonist with progesterone at the progesterone receptor. The drug has varied actions that contribute to its efficacy for selected indications.
Cushing's disease: Mifepristone acts as a cortisol receptor blocker. Mifepristone is a selective antagonist of the progesterone receptor at low doses and blocks the glucocorticoid receptor (GR-II) at higher doses. Mifepristone has high affinity for the GR-II receptor but little affinity for the GR-I (MR, mineralocorticoid) receptor. Mifepristone appears to have little or no affinity for estrogen, muscarinic, histaminic, or monoamine receptors. Because mifepristone acts at the receptor level to block the effects of cortisol, its antagonistic actions affect the hypothalamic-pituitary-adrenal (HPA) axis in such a way as to further increase circulating cortisol levels while, at the same time, blocking their effects. Mifepristone and the 3 active metabolites have greater affinity for the glucocorticoid receptor [100% (mifepristone), 61% (metabolite 1), 48% (metabolite 2), and 45% (metabolite 3)] than either dexamethasone (23%) or cortisol (9%).
termination of pregnancy: In the termination of pregnancy, mifepristone interrupts progesterone support to the endometrium and sensitizes the myometrium to prostaglandins. In addition, mifepristone increases the synthesis and decreases the metabolism of prostaglandins. By administering mifepristone a few days before administering exogenous prostaglandins (e.g., misoprostol), the effects of the prostaglandins can be increased. This results in menstrual bleeding, disruption of placental function, and, eventually, termination of pregnancy. When given during the first trimester of pregnancy, uterine activity is increased within 36 to 48 hours after administration of mifepristone. In addition, mifepristone causes softening or ripening of the cervix, which contributes to its activity. Clinical examination is necessary to confirm the complete termination of pregnancy after using the mifepristone regimen. Changes in quantitative human Chorionic Gonadotropin (hCG) levels will not be decisive until at least 10 days after administration. A continuing pregnancy can be confirmed by ultrasound.
postcoital contraception: If given within 72 hours after unprotected intercourse, mifepristone acts as a postcoital contraceptive by inhibiting implantation. When given in the late follicular phase of a menstrual cycle, mifepristone inhibits ovulation by preventing the development of a normal luteinizing hormone (LH) surge and delaying a new surge for approximately 15 days. Menses occurs at the expected time in most (66%) of women to whom the drug is administered; a delay in menses may be noted in some women receiving larger doses. Menses usually occurs within 1 to 3 days if mifepristone is given during the late luteal phase. Efficacy is similar to levonorgestrel-containing emergency contraceptive regimens.

Mifepristone is administered orally. Protein binding is approximately 98%, mostly to alpha-1-acid glycoprotein and to albumin. Mifepristone and its metabolites are distributed to other tissues, including the central nervous system (CNS). It readily crosses the placenta with a maternal:fetal ratio in plasma of 9.1 for mifepristone and 17.1 for the monodemethylated metabolite. Following a distribution phase, elimination is slow at first (50% of a single-dose eliminated in 12 to 17 hours) and then becomes more rapid. Mifepristone is metabolized to demethylated and hydroxylated active metabolites, primarily via hepatic microsomal isoenzyme CYP3A4. The 3 major metabolites are RU-42-433 (a N-monodemethylated metabolite most widely found in the plasma); RU-42-848 (demethylated metabolite); and RU-42-698 (hydroxylated metabolite). Excretion is primarily (approximately 90%) via the fecal route. The half-life after a single 200 mg dose is approximately 18 hours; serum concentrations are undetectable 11 days after administration is discontinued.[ Time to steady state is within 2 weeks following chronic dosing, and the mean (SD) half-life of the parent mifepristone was 85 (61) hours following multiple doses of 600 mg/day.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP3A4, CYP2C8/2C9, and CYP2B6
Because mifepristone is an inhibitor of CYP3A, concurrent use of mifepristone with a drug whose metabolism is largely or solely mediated by CYP3A is likely to result in increased plasma concentrations of that drug, especially with drugs that also have high first-pass effect. Discontinuation or dose reduction of such medications may be necessary with mifepristone use. In addition, Medications that inhibit CYP3A could increase plasma mifepristone concentrations and dose reduction of mifepristone may be required; when used with strong CYP3A inhibitors, the maximum dose of mifepristone must be limited. Mifepristone also inhibits CYP2C8, 2C9 and 2B6, and therefore may increase the concentrations of drugs largely dependent on these CYP enzymes for drug metabolism. Based on the long terminal half-life of mifepristone after reaching steady state when used in chronic dosing regimens, at least 2 weeks should elapse after cessation of mifepristone before initiating or increasing the dose of any interacting concomitant medication.
 
In vitro studies also indicate an interaction potential for drugs metabolized by CYP2A6, 2C19, 1A2, 2D6 and 2E1, by mifepristone and/or its metabolites. However, clinical in vivo drug-drug interaction studies have not been performed. Additionally, mifepristone binds P-glycoprotein (P-gp), inhibiting P-gp activity and breast cancer resistance protein (BCRP).

Oral Route

The absolute bioavailability of mifepristone after a 20 mg dose is 69%. Following oral administration, time to peak plasma concentrations (Tmax) of mifepristone occurred between 1 and 2 hours following a single dose, and between 1 and 4 hours following multiple doses of 600 mg of mifepristone in healthy volunteers. After ingestion of a single 200 mg dose, mean Cmax of 1.77 +/- 0.7 mg/L occurs; mean AUC was 25.8 +/- 6.2 mg x hour/L. After ingestion of a single 600 mg dose, a Cmax of 1.98 +/- 1 mg/L was attained. Mean plasma concentrations of the 3 active metabolites of mifepristone peak between 2 and 8 hours after multiple doses of 600 mg/day, and the combined concentrations of the metabolites exceed that of the parent mifepristone. Exposure to mifepristone is substantially less than dose proportional.

Pregnancy

Mifepristone is present in human milk. Limited data demonstrate undetectable to low levels of the drug in human milk with the relative weight-adjusted infant dose 0.5% or less as compared to maternal dosing. The effects in a nursing infant or on milk production are unknown. The drug's antiprogestogen and glucocorticoid antagonist effects could be harmful to a nursing infant. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. To minimize exposure to a breastfed infant, women who discontinue or interrupt chronic mifepristone treatment may consider pumping and discarding breast milk during treatment and for 18 to 21 days (5 to 6 half-lives) after the last dose, before breast-feeding.