Danocrine

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Danocrine

Classes

Androgens
Antigonadotropins and Similar Agents

Administration
Oral Administration

Administer with meals to minimize indigestion or GI irritation.

Adverse Reactions
Severe

hepatoma / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
Guillain-Barre syndrome / Delayed / Incidence not known
Stevens-Johnson syndrome / Delayed / Incidence not known
erythema multiforme / Delayed / Incidence not known
stroke / Early / Incidence not known
thrombosis / Delayed / Incidence not known
thromboembolism / Delayed / Incidence not known
myocardial infarction / Delayed / Incidence not known
teratogenesis / Delayed / Incidence not known
visual impairment / Early / Incidence not known
papilledema / Delayed / Incidence not known
erythrocytosis / Delayed / Incidence not known

Moderate

elevated hepatic enzymes / Delayed / 1.0-10.0
constipation / Delayed / 1.0-10.0
fluid retention / Delayed / 1.0-10.0
hypercholesterolemia / Delayed / 10.0
edema / Delayed / Incidence not known
anovulation / Delayed / Incidence not known
hematuria / Delayed / Incidence not known
peliosis hepatis / Delayed / Incidence not known
jaundice / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
hyperglycemia / Delayed / Incidence not known
palpitations / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
pseudotumor cerebri / Delayed / Incidence not known
depression / Delayed / Incidence not known
polycythemia / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known
leukopenia / Delayed / Incidence not known
thrombocytopenia / Delayed / Incidence not known
cataracts / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known

Mild

seborrhea / Delayed / 1.0-10.0
nausea / Early / 1.0-10.0
dizziness / Early / 1.0-10.0
headache / Early / 1.0-10.0
fatigue / Early / 1.0-10.0
hirsutism / Delayed / 10.0
acne vulgaris / Delayed / 10.0
weight gain / Delayed / 10.0
amenorrhea / Delayed / 10.0
menstrual irregularity / Delayed / 10.0
alopecia / Delayed / Incidence not known
oligospermia / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known
spermatogenesis inhibition / Delayed / Incidence not known
hoarseness / Early / Incidence not known
breakthrough bleeding / Delayed / Incidence not known
breast discharge / Delayed / Incidence not known
emotional lability / Early / Incidence not known
flushing / Rapid / Incidence not known
diaphoresis / Early / Incidence not known
vomiting / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
petechiae / Delayed / Incidence not known
vesicular rash / Delayed / Incidence not known
purpura / Delayed / Incidence not known
maculopapular rash / Early / Incidence not known
pruritus / Rapid / Incidence not known
urticaria / Rapid / Incidence not known
nasal congestion / Early / Incidence not known
chills / Rapid / Incidence not known
tremor / Early / Incidence not known
paresthesias / Delayed / Incidence not known
anxiety / Delayed / Incidence not known
weakness / Early / Incidence not known
pelvic pain / Delayed / Incidence not known
back pain / Delayed / Incidence not known
muscle cramps / Delayed / Incidence not known
carpal tunnel syndrome / Delayed / Incidence not known
leukocytosis / Delayed / Incidence not known
fever / Early / Incidence not known

Boxed Warning
Hepatic disease, hepatotoxicity, jaundice, peliosis hepatis

Do not use danazol in patients with severe hepatic disease. Danazol should be used with caution, if at all, in patients with milder grades of hepatic disease. Danazol use can cause hepatotoxicity including cholestatic jaundice, peliosis hepatis, and benign hepatic adenoma. Peliosis hepatis and adenoma may not be apparent until patients present with life-threatening intra-abdominal hemorrhage. Regular liver function tests (LFTs) should be carried out in all patients.

Contraception requirements, pregnancy, pregnancy testing

Danazol is contraindicated during pregnancy, so care should be taken to ensure that the patient is not pregnant and does not become pregnant during therapy. Sensitive pregnancy testing (e.g., beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy. Teratogenic effects have been associated with danazol treatment. Androgens have caused virilization of the external genitalia of the female fetus, including clitoromegaly, abnormal vaginal development, and fusion of genital folds to form a scrotal-like structure. The degree of masculinization is dependent on the amount of drug given and the age of the fetus; these effects are most likely to occur in the female fetus when the drugs are given in the first trimester. Females of childbearing potential should be advised of contraception requirements during therapy during treatment. A non-hormonal method of contraception should be used during therapy. If pregnancy occurs, the drug should be immediately discontinued and the patient should be counseled concerning the potential risks to the fetus.

Increased intracranial pressure, papilledema, pseudotumor cerebri

Danazol has been associated with cases of pseudotumor cerebri (benign increased intracranial pressure). Early signs and symptoms include headache, nausea/vomiting, visual disturbances, and papilledema. Patients with these signs and symptoms should be examined for papilledema, and if present, should discontinue the drug immediately and be referred for neurologic evaluation.

Stroke, thromboembolic disease, thromboembolism

Danazol is contraindicated in patients with active thrombosis or thromboembolic disease and history of such events. Thromboembolic disease such as thromboembolism or thrombotic events have occurred during danazol therapy. Cases of sagittal sinus thrombosis and fatal or life-threatening stroke have been reported.

Common Brand Names

Danocrine

Dea Class

Rx

Description

Synthetic steroid derived from ethisterone (ethinyl testosterone). Is antiestrogenic and weakly androgenic. Used for endometriosis, unless the process has advanced to the stage of surgical correction. Also used in the palliative treatment of fibrocystic breast disease and hereditary angioedema in both males and females.

Dosage And Indications
For the treatment of endometriosis. For mild cases. Oral dosage Adult females

200 to 400 mg/day PO in 2 divided doses. Begin therapy during menstruation to ensure the patient is not pregnant. Subsequent doses may be adjusted depending upon the patient's response. Continue uninterrupted therapy for 3 to 6 months; may extend to 9 months as necessary. If symptoms persist following termination of therapy, treatment can be reinstituted.

For moderate to severe cases. Oral dosage Adult females

Initially, 800 mg/day PO in 2 divided doses. Begin therapy during menstruation to ensure the patient is not pregnant. Subsequent doses may be gradually reduced depending upon the patient's response. Continue uninterrupted therapy for 3 to 6 months; may extend to 9 months as necessary. If symptoms persist following termination of therapy, treatment can be reinstituted.

For the treatment of fibrocystic breast disease. Oral dosage Adults

100 to 400 mg/day PO in 2 divided doses. Begin therapy during menstruation to ensure the patient is not pregnant. Dosage should be adjusted according to the individual patient's need and response. Although symptoms may be relieved, and even eliminated in 3 months, up to 6 months of uninterrupted therapy may be required to eliminate nodularity. Since ovulation may not be suppressed at these dosages, an effective non-hormonal method of contraception is recommended during therapy.

For angioedema prophylaxis in patients with hereditary angioedema. Oral dosage Adults

Initially, 200 mg PO 2 to 3 times per day. If a favorable response is achieved, the dose may be reduced by half at intervals of 1 to 3 months. If there is an unfavorable response (in the form of an attack of angioedema during treatment), the dose may be increased by up to 200 mg per day. NOTE: If danazol therapy was initiated during an exacerbation of angioedema caused by trauma, stress, or other causes, periodic attempts to reduce or discontinue therapy should be considered.

For the treatment of chronic immune thrombocytopenic purpura (ITP)†. Oral dosage Adults

A dosage of 200 mg PO 4 times per day has been recommended. The drug should be administered for at least 6 months due to the slow response.

For the treatment of mastalgia† associated with premenstrual syndrome (PMS)†; or for PMS-associated bloating and weight gain, anxiety, depressive symptoms, and/or global complaints. Oral dosage Adults

The recommended dose is 50 to 100 mg PO twice daily. Dosages should be individually titrated to achieve desired effects. Danazol has also been found to decrease psychologic symptoms such as anxiety and depression, as well as global complaints. Therapy for weight gain and bloating should be limited to patients who demonstrate a premenstrual weight gain of more than 1.4 kg.

For emergency postcoital contraception†. Oral dosage Adults

Contradictory data exist regarding the efficacy of this drug for this use. A dosage of 800 to 1,200 mg PO every 12 hours for 2 doses and a dosage of 800 mg PO every 12 hours for 3 doses have been studied.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Mild to moderate hepatic impairment: No adjustment is needed; use with caution.
Severe hepatic impairment: Do not use.

Renal Impairment

CrCl >= 30 mL/min: No adjustment is needed.
CrCl < 30 mL/min: Do not use.

Drug Interactions

Abarelix: (Major) Concomitant use of androgens or estrogens with abarelix is relatively contraindicated, as both could counteract the therapeutic effect of abarelix.
Abciximab: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
Abemaciclib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with danazol is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with danazol. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
Acarbose: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Acetaminophen; Aspirin: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with danazol 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 danazol could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If danazol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Danazol is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol 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 danazol 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 danazol 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.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol is necessary. If danazol 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 moderate inhibitor like danazol 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 danazol 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.
Albuterol; Budesonide: (Moderate) Avoid coadministration of oral budesonide and danazol due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Alfentanil: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of drugs metabolized by this enzyme including alfentanil. A dose reduction of one or both drugs may be warranted. Close monitoring for oversedation and respiratory depression is warranted if a CYP3A4 inhibitor is used with alfentanil.
Alogliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Alogliptin; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Alogliptin; Pioglitazone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Alpha-glucosidase Inhibitors: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Alprazolam: (Major) Avoid coadministration of alprazolam and danazol due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with danazol, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased alprazolam exposure by 1.6- to 1.98-fold.
Alteplase: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with thrombolytic agents.
Amiodarone: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates, including amiodarone.
Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Atorvastatin: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required. (Moderate) The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with atorvastatin. Danazol is a CYP3A4 inhibitor and may inhibit the metabolism of atorvastatin, a CYP3A4 substrate. Until more data are available, danazol should be used very cautiously, if at all, in patients receiving statins which are CYP3A4 substrates.
Amlodipine; Benazepril: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Celecoxib: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Olmesartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Valsartan: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Anagrelide: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents.
Antithrombin III: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of danazol with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant. After administration, fosaprepitant is rapidly converted to aprepitant. Danazol is a moderate CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. Coadministration of daily oral aprepitant with a moderate CYP3A4 inhibitor, diltiazem, increased the aprepitant AUC 2-fold with a concomitant 1.7-fold increase in the diltiazem AUC; clinically meaningful changes in ECG, heart rate, or blood pressure beyond those induced by diltiazem alone did not occur.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of danazol. Patients receiving both a CYP2D6 inhibitor plus danazol may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; danazol is a moderate CYP3A inhibitor.
Artemether; Lumefantrine: (Moderate) Danazol is a inhibitor and artemether is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased artemether concentrations. Concomitant use warrants caution due to the potential for increased side effects. (Moderate) Danazol is a inhibitor and lumefantrine is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased lumefantrine concentrations. Concomitant use warrants caution due to the potential for increased side effects, including increased potentiation of QT prolongation.
Aspirin, ASA: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Caffeine: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Carisoprodol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4. (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Dipyridamole: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors. (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Omeprazole: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol is necessary. If danazol 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 moderate inhibitor like danazol 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 danazol 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. (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Atazanavir: (Moderate) Danazol is a CYP3A4 inhibitor, and serum concentrations of atazanavir, a CYP3A4 substrate, may increase with co-administration. Co-administer these drugs with caution due to the potential for atazanavir toxicity.
Atazanavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated cobicistat concentrations. Danazol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Danazol is a CYP3A4 inhibitor, and serum concentrations of atazanavir, a CYP3A4 substrate, may increase with co-administration. Co-administer these drugs with caution due to the potential for atazanavir toxicity.
Atorvastatin: (Moderate) The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with atorvastatin. Danazol is a CYP3A4 inhibitor and may inhibit the metabolism of atorvastatin, a CYP3A4 substrate. Until more data are available, danazol should be used very cautiously, if at all, in patients receiving statins which are CYP3A4 substrates.
Atorvastatin; Ezetimibe: (Moderate) The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with atorvastatin. Danazol is a CYP3A4 inhibitor and may inhibit the metabolism of atorvastatin, a CYP3A4 substrate. Until more data are available, danazol should be used very cautiously, if at all, in patients receiving statins which are CYP3A4 substrates.
Avapritinib: (Major) Avoid coadministration of avapritinib with danazol due to the risk of increased avapritinib-related adverse reactions. If concurrent use is unavoidable, reduce the starting dose of avapritinib from 300 mg PO once daily to 100 mg PO once daily in patients with gastrointestinal stromal tumor or from 200 mg PO once daily to 50 mg PO once daily in patients with advanced systemic mastocytosis. Avapritinib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration of avapritinib 300 mg PO once daily with a moderate CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 210% at steady-state.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with danazol may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of danazol 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 danazol 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. Danazol is an inhibitor of CYP3A4.
Bosentan: (Moderate) Danazol is a CYP3A4 inhibitor, and may reduce the hepatic metabolism of CYP3A4 substrates including bosentan. Excessive bosentan dosage can result in hypotension or elevated hepatic enzymes.
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. Danazol is a moderate inhibitor of CYP3A4. If danazol is used in combination with brexpiprazole and a moderate to strong CYP2D6 inhibitor, the brexpiprazole dose should be adjusted and the patient should be carefully monitored 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 danazol 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 40% without breaking tablets (i.e., from 180 mg to 120 mg; from 120 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of danazol, resume the brigatinib dose that was tolerated prior to initiation of danazol. Brigatinib is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase the AUC of brigatinib by approximately 40%.
Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of danazol. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; danazol is a moderate 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.
Budesonide: (Moderate) Avoid coadministration of oral budesonide and danazol due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Budesonide; Formoterol: (Moderate) Avoid coadministration of oral budesonide and danazol due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Avoid coadministration of oral budesonide and danazol due to the potential for increased budesonide exposure. Use caution with inhaled forms of budesonide as systemic exposure to the corticosteroid may also increase. Budesonide is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. In the presence of a strong CYP3A4 inhibitor, the systemic exposure to oral budesonide was increased by 8-fold.
Bupivacaine; Lidocaine: (Moderate) Danazol is a CYP3A4 inhibitor and may decrease the hepatic metabolism of lidocaine. Patients receiving lidocaine should be closely monitored for toxicity if danazol is added to therapy.
Buspirone: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of buspirone, a CYP3A4 substrate.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4. (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Cabotegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering danazol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Danazol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Canagliflozin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Canagliflozin; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Carbamazepine: (Moderate) Carbamazepine is metabolized by the hepatic isoenzyme CYP3A4. Danazol is known to inhibit CYP3A4 and may decrease carbamazepine metabolism and increase carbamazepine plasma concentrations.
Cariprazine: (Moderate) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. Danazol inhibits CYP3A4 and may reduce the hepatic metabolism of CYP3A4 substrates, although the impact of moderate CYP3A4 inhibitors on cariprazine metabolism has not been studied. Monitoring for adverse effects, such as CNS effects and extrapyramidal symptoms, is advisable during coadministration.
Chlordiazepoxide: (Moderate) Danazol is a CYP3A4 inhibitor and can theoretically reduce the metabolism of CYP3A4 substrates, including chlordiazepoxide.
Chlordiazepoxide; Amitriptyline: (Moderate) Danazol is a CYP3A4 inhibitor and can theoretically reduce the metabolism of CYP3A4 substrates, including chlordiazepoxide.
Chlordiazepoxide; Clidinium: (Moderate) Danazol is a CYP3A4 inhibitor and can theoretically reduce the metabolism of CYP3A4 substrates, including chlordiazepoxide.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with danazol 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 danazol could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If danazol is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Danazol is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol 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 danazol 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 danazol 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.
Cilostazol: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Cisapride: (Contraindicated) Cisapride is metabolized by the hepatic cytochrome P450 enzyme system, specifically the CYP3A4 isoenzyme. QT prolongation and ventricular arrhythmias, including torsade de pointes and death, have been reported when known and potent inhibitors of CYP3A4 are coadministered with cisapride. Danazol has the potential to inhibit the metabolism of cisapride through CYP3A4 and thus, should not be used with cisapride.
Clevidipine: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Clonazepam: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of clonazepam, a CYP3A4 substrate.
Clorazepate: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of clorazepate, a CYP3A4 substrate.
Clozapine: (Moderate) Caution is advisable during concurrent use of danazol and clozapine. Danazol is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of clozapine. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Elevated plasma concentrations of clozapine occurring through CYP inhibition may potentially increase the risk of life-threatening arrhythmias, 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 after dose adjustments are made, monitor for lack of clozapine effectiveness and consider increasing the clozapine dose if necessary.
Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated cobicistat concentrations. Danazol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with chronic danazol therapy due to the risk of cobimetinib toxicity. If concurrent short-term (14 days or less) use of danazol is unavoidable, reduce the dose of cobimetinib to 20 mg once daily for patients normally taking 60 mg daily; after discontinuation of danazol, resume cobimetinib at the previous dose. Use an alternative to danazol in patients who are already taking a reduced dose of cobimetinib (40 or 20 mg daily). Cobimetinib is a CYP3A substrate in vitro, and danazol is a moderate inhibitor of CYP3A. In healthy subjects (n = 15), coadministration of a single 10 mg dose of cobimetinib with itraconazole (200 mg once daily for 14 days), a strong CYP3A4 inhibitor, increased the mean cobimetinib AUC by 6.7-fold (90% CI, 5.6 to 8) and the mean Cmax by 3.2-fold (90% CI, 2.7 to 3.7).
Codeine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with danazol 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 danazol could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If danazol 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. Danazol is a moderate inhibitor of CYP3A4.
Colchicine: (Major) Avoid concomitant use of colchicine and danazol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, 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 a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Conjugated Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as danazol 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 danazol 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 danazol 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.
Crizotinib: (Moderate) Monitor for an increase in crizotinib-related adverse reactions if coadministration with danazol is necessary. Crizotinib is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Cyclosporine: (Major) Close monitoring of cyclosporine concentrations is required when danazol is given concurrently with cyclosporine. Danazol has been reported to increase concentrations of cyclosporine. Danazol is an inhibitor of CYP3A4 while cyclosporine is a substrate of CYP3A4. In a patient stabilized on cyclosporine, the addition of danazol 200 mg every 8 hours yielded a 38% increase in the cyclosporine blood concentration and necessitated a cyclosporine dosage reduction from 250 mg twice daily to 200 mg twice daily.
Dabigatran: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Daclatasvir: (Moderate) Concurrent administration of daclatasvir, a CYP3A4 substrate, with danazol, a moderate CYP3A4 inhibitor, may increase daclatasvir serum concentrations. If these drugs are administered together, monitor patients for daclatasvir-related adverse effects, such as headache, fatigue, nausea, and diarrhea. The manufacturer does not recommend daclatasvir dose reduction for adverse reactions.
Dalteparin: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Dapagliflozin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Dapagliflozin; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Dapagliflozin; Saxagliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Darbepoetin Alfa: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to darbepoetin alfa, reducing the amount required to treat anemia.
Daridorexant: (Major) Limit the daridorexant dose to 25 mg if coadministered with danazol. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use of another moderate CYP3A inhibitor increased daridorexant overall exposure 2.4-fold.
Darunavir: (Moderate) Caution is warranted when darunavir is administered with danazol as there is a potential for elevated concentrations of darunavir. Danazol is a CYP3A4 inhibitor; darunavir is a substrate of CYP3A4.
Darunavir; Cobicistat: (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated cobicistat concentrations. Danazol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when darunavir is administered with danazol as there is a potential for elevated concentrations of darunavir. Danazol is a CYP3A4 inhibitor; darunavir is a substrate of CYP3A4.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated cobicistat concentrations. Danazol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when darunavir is administered with danazol as there is a potential for elevated concentrations of darunavir. Danazol is a CYP3A4 inhibitor; darunavir is a substrate of CYP3A4.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with danazol. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A4 substrate; danazol is a moderate inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Degarelix: (Major) Concomitant use of androgens with degarelix is relatively contraindicated, as androgens could counteract the therapeutic effect of degarelix.
Desirudin: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Dextromethorphan; Quinidine: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates including quinidine.
Diazepam: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of diazepam.
Dienogest; Estradiol valerate: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
Dihydroergotamine: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs, such as ergot alkaloids, and lead to ergot toxicity.
Diltiazem: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Dipyridamole: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Disopyramide: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of disopyramide. Patients receiving disoyramide should be closely monitored for toxicity if danazol is added to therapy.
Dofetilide: (Major) Danazol could significantly inhibit the CYP3A4 metabolism of dofetilide. The resultant increase in serum dofetilide concentrations could increase the risk of torsade de pointes.
Dolutegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering danazol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Danazol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Doxercalciferol: (Moderate) CYP450 enzyme inhibitors, like danazol, may inhibit the 25-hydroxylation of doxercalciferol, thereby decreasing the formation of the active metabolite and thus, decreasing efficacy. Patients should be monitored for a decrease in efficacy if CYP450 inhibitors are coadministered with doxercalciferol.
Doxorubicin Liposomal: (Major) Danazol is a CYP3A4 inhibitor and doxorubicin is a major CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of danazol and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) Danazol is a CYP3A4 inhibitor and doxorubicin is a major CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of danazol and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronabinol: (Major) Use caution if coadministration of dronabinol with danazol is necessary, and monitor for an increase in dronabinol-related adverse reactions (e.g., feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; danazol is a moderate inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol.
Dronedarone: (Moderate) Dronedarone and danazol should be coadministered with caution. Dronedarone is metabolized by CYP3A. Danazol is an inhibitor of CYP3A4. Concomitant use of dronedarone with danazol may increase dronedarone concentrations.
Drospirenone; Estradiol: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
Dutasteride; Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as danazol. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
Duvelisib: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with danazol. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; danazol is a moderate CYP3A inhibitor.
Elacestrant: (Major) Avoid concomitant use of elacestrant and danazol due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Elagolix; Estradiol; Norethindrone acetate: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
Elbasvir; Grazoprevir: (Moderate) Administering elbasvir; grazoprevir with danazol may cause the plasma concentrations of elbasvir and grazoprevir to increase; thereby increasing the potential for adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Danazol is a moderate CYP3A inhibitor. Both elbasvir and grazoprevir are metabolized by CYP3A. If these drugs are used together, closely monitor for signs of hepatotoxicity.
Eletriptan: (Moderate) Monitor for increased eletriptan-related adverse effects if coadministered with danazol. Systemic concentrations of eletriptan may be increased. Eletriptan is a substrate for CYP3A4, and danazol is a moderate CYP3A4 inhibitor. Coadministration of other moderate CYP3A4 inhibitors increased the eletriptan AUC by 2 to 4-fold.
Elexacaftor; tezacaftor; ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with danazol; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); danazol is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If danazol and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to every other day in the morning when coadministered with danazol; omit the ivacaftor evening dose and administer in the morning every other day alternating with elexacaftor; tezacaftor; ivacaftor (i.e., recommended dose of elexacaftor; tezacaftor; ivacaftor on day 1 in the morning and recommended dose of ivacaftor on day 2 in the morning). Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; danazol is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure by 2.9-fold. Simulation suggests a moderate inhibitor may increase elexacaftor and tezacaftor exposure by 2.3-fold and 2.1-fold, respectively.
Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of danazol and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of the agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both danazol and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Danazol is a moderate CYP3A inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration of eliglustat with CYP3A inhibitors may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated cobicistat concentrations. Danazol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated elvitegravir concentrations. Danazol is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated cobicistat concentrations. Danazol is a CYP3A4 inhibitor and cobicistat is a substrate of CYP3A4. (Moderate) Caution is warranted when cobicistat is administered with danazol as there is a potential for elevated elvitegravir concentrations. Danazol is a CYP3A4 inhibitor and elvitegravir is a substrate of CYP3A4.
Empagliflozin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Empagliflozin; Linagliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Empagliflozin; Linagliptin; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Empagliflozin; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring is advised when administering danazol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Danazol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Close clinical monitoring is advised when administering danazol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Danazol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Encorafenib: (Major) Avoid coadministration of encorafenib and danazol due to increased encorafenib exposure. If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of danazol. If danazol is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of danazol. Encorafenib is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 2-fold and 45%, respec

tively.
Enoxaparin: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Entrectinib: (Major) Avoid coadministration of entrectinib with danazol due to 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 200 mg PO once daily. If danazol is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of danazol. Entrectinib is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with a CYP3A4 inhibitor in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving a concurrent CYP3A4 inhibitor, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. In addition, measure serum creatinine and serum potassium within 3 to 7 days of initiating a CYP3A4 inhibitor and periodically thereafter. Eplerenone is a CYP3A4 substrate. Danazol is a CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Epoetin Alfa: (Moderate) Androgens are known to stimulate erythropoiesis. Concurrent administration of androgens can increase the patient's response to epoetin alfa, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Eptifibatide: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Ergoloid Mesylates: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs, such as ergot alkaloids, and lead to ergot toxicity.
Ergot alkaloids: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs, such as ergot alkaloids, and lead to ergot toxicity.
Ergotamine: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs, such as ergot alkaloids, and lead to ergot toxicity.
Ergotamine; Caffeine: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs, such as ergot alkaloids, and lead to ergot toxicity.
Ertugliflozin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Ertugliflozin; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Ertugliflozin; Sitagliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Esterified Estrogens: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4 such as danazol 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 danazol 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: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
Estradiol; Levonorgestrel: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
Estradiol; Norethindrone: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
Estradiol; Norgestimate: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
Estradiol; Progesterone: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives. (Minor) The metabolism of progesterone may be inhibited by danazol, a known inhibitor of cytochrome P450 3A4 hepatic enzymes.
Estropipate: (Minor) Estrogens are partially metabolized by CYP3A4. Drugs that inhibit CYP3A4, such as danazol, 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.
Ethosuximide: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of ethosuximide, a CYP3A4 substrate. Patients receiving these agents should be closely monitored for toxicity if danazol is added to therapy. Conversely, a dose adjustment of either drug may be necessary if danazol therapy is discontinued.
Etonogestrel: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as danazol may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Minor) Coadministration of etonogestrel and moderate CYP3A4 inhibitors such as danazol may increase the serum concentration of etonogestrel.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with danazol is necessary. The dose of everolimus may need to be reduced. Everolimus is a sensitive CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Ezetimibe; Simvastatin: (Contraindicated) The use of simvastatin with danazol is contraindicated due to an increased risk of myopathy and rhabdomyolysis. A single case report has documented the onset of myositis that progressed to rhabdomyolysis with myoglobinuria after danazol was added to a regimen containing lovastatin. Although other drugs were in use concurrently, a drug interaction between danazol and lovastatin is suspected, as danazol (CYP3A4 inhibitor) is known to inhibit lovastatin metabolism.
Felodipine: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of danazol is necessary. If danazol is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like danazol can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If danazol is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or danazol; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased overall exposure to finerenone by 248%.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and moderate CYP3A4 inhibitors, such as danazol, is contraindicated. Moderate CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a moderate CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a moderate CYP3A4 inhibitor following flibanserin use, start the moderate CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Flurazepam: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of drugs metabolized by this enzyme, including flurazepam. Patients receiving these agents should be closely monitored for toxicity if danazol is added to therapy. Conversely, a dose adjustment of either drug may be necessary if danazol therapy is discontinued.
Fondaparinux: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Fosamprenavir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with danazol. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Glipizide; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Glyburide; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Goserelin: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as goserelin. Goserelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol 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 danazol 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 danazol 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.
Haloperidol: (Moderate) Danazol is an inhibitor of CYP3A4, one of the isoenzymes responsible for the metabolism of haloperidol. Mild to moderate increases in haloperidol plasma concentrations have been reported during concurrent use of haloperidol and inhibitors of CYP3A4. Until more data are available, it is advisable to closely monitor for adverse events when these medications are co-administered.
Heparin: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Histrelin: (Major) Avoid concurrent use of androgens with gonadotropin releasing hormone (GnRH) agonists such as histrelin. Histrelin inhibits steroidogenesis; concomitant use with androgens may counteract this therapeutic effect.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol 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 danazol 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 danazol 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.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol 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 danazol 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 danazol 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.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol 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 danazol 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 danazol 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.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol 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 danazol 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 danazol 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.
Ibrutinib: (Major) If ibrutinib is coadministered with danazol, reduce the ibrutinib dosage to 280 mg/day PO in patients receiving ibrutinib for B-cell malignancy. Resume ibrutinib at the previous dosage if danazol is discontinued. No initial ibrutinib dosage adjustment is necessary in patients receiving ibrutinib for chronic graft-versus-host disease. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection); modify the ibrutinib dosage as recommended if toxicity occurs. Ibrutinib is a CYP3A substrate; danazol is a moderate CYP3A inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A inhibitor, the AUC value of ibrutinib was increased by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol is necessary. If danazol 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 moderate inhibitor like danazol 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 danazol 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.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with danazol is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Danazol is a moderate CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Incretin Mimetics: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Infigratinib: (Major) Avoid concomitant use of infigratinib and danazol. Coadministration may increase infigratinib exposure, increasing the risk of adverse effects. Infigratinib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor.
Insulins: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with danazol may result in increased serum concentrations of isavuconazonium. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of the hepatic isoenzyme CYP3A4; danazol is an inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isradipine: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Ivabradine: (Major) Avoid coadminsitration of ivabradine and danazol as increased concentrations of ivabradine are possible. Ivabradine is primarily metabolized by CYP3A4; danazol inhibits CYP3A4. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If danazol and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with danazol due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. Ivosidenib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor is predicted to increase the ivosidenib single-dose AUC to 173% of control based on physiologically-based pharmacokinetic modeling, with no change in Cmax. Multiple doses of the moderate CYP3A4 inhibitor are predicted to increase the ivosidenib steady-state AUC to 152% of control and AUC to 190% of control.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of danazol is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Larotrectinib: (Moderate) Monitor for an increase in larotrectinib-related adverse reactions if concomitant use with danazol is necessary. Concomitant use may increase larotrectinib exposure. Larotrectinib is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase larotrectinib exposure by 2.7-fold.
Lefamulin: (Moderate) Monitor for lefamulin-related adverse effects if oral lefamulin is administered with danazol as concurrent use may increase exposure from lefamulin tablets; an interaction is not expected with intravenous lefamulin. Lefamulin is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor.
Lemborexant: (Major) Avoid coadministration of lemborexant and danazol as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Leuprolide: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Leuprolide; Norethindrone: (Major) Leuprolide inhibits steroidogenesis. While no drug interactions have been reported with leuprolide, therapy with androgens would be relatively contraindicated and would counteract the therapeutic effect of leuprolide.
Levamlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Lidocaine: (Moderate) Danazol is a CYP3A4 inhibitor and may decrease the hepatic metabolism of lidocaine. Patients receiving lidocaine should be closely monitored for toxicity if danazol is added to therapy.
Lidocaine; Epinephrine: (Moderate) Danazol is a CYP3A4 inhibitor and may decrease the hepatic metabolism of lidocaine. Patients receiving lidocaine should be closely monitored for toxicity if danazol is added to therapy.
Lidocaine; Prilocaine: (Moderate) Danazol is a CYP3A4 inhibitor and may decrease the hepatic metabolism of lidocaine. Patients receiving lidocaine should be closely monitored for toxicity if danazol is added to therapy.
Linagliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Linagliptin; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and danazol is contraindicated; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor.
Lovastatin: (Major) The risk of myopathy and rhabdomyolysis is increased if danazol is used with lovastatin. In adult patients taking danazol, the initial lovastatin dose should not exceed 10 mg/day PO, and the total lovastatin dose should not exceed 20 mg/day PO. A single case report has documented the onset of myositis which progressed to rhabdomyolysis with myoglobinuria after danazol was added to a regimen containing lovastatin. Although other drugs were in use concurrently, a drug interaction between danazol and lovastatin is suspected since danazol (CYP3A4 inhibitor) is known to inhibit lovastatin metabolism. If concurrent use of lovastatin and danazol is desired, carefully weigh the benefit of lovastatin against the risk of myopathy and rhabdomyolysis.
Lumacaftor; Ivacaftor: (Major) If danazol and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Lumateperone: (Major) Reduce the dose of lumateperone to 21 mg once daily if concomitant use of danazol is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased lumateperone exposure by approximately 2-fold.
Lurasidone: (Major) Danazol is a moderate inhibitor of CYP3A4 and has the potential for interactions with substrates of CYP3A4 such as lurasidone. Concurrent use of these medications may lead to an increased risk of lurasidone-related adverse reactions. If a moderate inhibitor of CYP3A4 is being prescribed and lurasidone is added in an adult patient, the recommended starting dose of lurasidone is 20 mg/day and the maximum recommended daily dose of lurasidone is 80 mg/day. If a moderate CYP3A4 inhibitor is added to an existing lurasidone regimen, reduce the lurasidone dose to one-half of the original dose. Patients should be monitored for efficacy and toxicity.
Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and danazol due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with danazol is necessary, due to a possible increase in maraviroc exposure. Maraviroc is a CYP3A substrate and danazol is a CYP3A4 inhibitor. Monitor for an increase in adverse effects with concomitant use.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting danazol therapy. Avoid initiation of danazol in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable danazol therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Mefloquine: (Moderate) Mefloquine is metabolized by CYP3A4. Danazol is an inhibitor of this enzyme and may decrease the clearance of mefloquine and increase mefloquine systemic exposure.
Meglitinides: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin; Repaglinide: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin; Rosiglitazone: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin; Saxagliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Metformin; Sitagliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Methadone: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of drugs that are CYP3A4 substrates including methadone.
Methoxy polyethylene glycol-epoetin beta: (Moderate) Androgens are known to stimulate erythropoiesis. Despite the fact that endogenous generation of erythropoietin is depressed in patients with chronic renal failure, other tissues besides the kidney can synthesize erythropoietin, albeit in small amounts. Concurrent administration of androgens can increase the patient's response to MPG-epoetin beta, reducing the amount required to treat anemia. Because adverse reactions have been associated with an abrupt increase in blood viscosity, this drug combination should be avoided, if possible. Further evaluation of this combination needs to be made.
Methylergonovine: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs, such as ergot alkaloids, and lead to ergot toxicity.
Midazolam: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of some drugs that are CYP3A4 substrates including midazolam.
Miglitol: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Mitapivat: (Moderate) Do not exceed mitapivat 20 mg PO twice daily during coadministration with danazol and monitor hemoglobin and for adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased mitapivat overall exposure by 2.6-fold.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and danazol; reduce the dose of mobocertinib by approximately 50% and monitor the QT interval more frequently if use is necessary. Concomitant use may increase mobocertinib exposure and the risk for adverse reactions. Mobocertinib is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Use of a moderate CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 100% to 200%.
Nafarelin: (Major) Gonadotropin releasing hormone (GnRH) agonists (i.e.,nafarelin) inhibit steroidogenesis, therefore the concomitant use of these agents with androgens may counteract this therapeutic effect. Avoid concurrent use of androgens with GnRH agonists.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with danazol. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor.
Naloxegol: (Major) Avoid concomitant administration of naloxegol and danazol due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with danazol is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. 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: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of danazol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Neratinib: (Major) Avoid concomitant use of danazol with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibition on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inhibitor increased neratinib exposure by 481%. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure.
Niacin; Simvastatin: (Contraindicated) The use of simvastatin with danazol is contraindicated due to an increased risk of myopathy and rhabdomyolysis. A single case report has documented the onset of myositis that progressed to rhabdomyolysis with myoglobinuria after danazol was added to a regimen containing lovastatin. Although other drugs were in use concurrently, a drug interaction between danazol and lovastatin is suspected, as danazol (CYP3A4 inhibitor) is known to inhibit lovastatin metabolism.
Nicardipine: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Nifedipine: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Nilotinib: (Moderate) Concomitant use of nilotinib, a substrate and moderate CYP3A4 inhibitor, and danazol, a CYP3A4 inhibitor, may result in increased nilotinib levels. Monitor patients for nilotinib toxicity (e.g., QT interval prolongation) if these drugs are used together.
Nimodipine: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with danazol 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 danazol is a CYP3A4 inhibitor.
Olaparib: (Major) Avoid coadministration of olaparib with danazol due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after danazol is discontinued. Olaparib is a CYP3A substrate and danazol is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
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 danazol is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and danazol may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If danazol 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 danazol is a moderate CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and danazol. If concomitant use is necessary, decrease omaveloxolone dose to 100 mg once daily; additional dosage reductions may be necessary. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased omaveloxolone overall exposure by 1.25-fold.
Oxybutynin: (Moderate) Oxybutynin is metabolized by CYP3A4. Serum concentrations of oxybutynin may be increased if coadministered with inhibitors of CYP3A4 including danazol. The manufacturer recommends that caution when oxybutynin is co-administered with CYP3A4 inhibitors.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of danazol is necessary. If danazol 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 moderate inhibitor like danazol 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 danazol 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.
Pacritinib: (Major) Avoid concurrent use of pacritinib with danazol due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Palovarotene: (Major) Avoid concomitant use of palovarotene and danazol due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. If concomitant use is necessary, decrease the palovarotene dose by half. Palovarotene is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased palovarotene overall exposure by 2.5-fold.
Paricalcitol: (Moderate) Care should be taken when dosing paricalcitol with strong CYP3A4 inhibitors, such as danazol. Dose adjustments of paricalcitol may be required. Monitor plasma PTH and serum calcium and phosphorous concentrations if a patient initiates or discontinues therapy with this combination.
Pazopanib: (Moderate) Pazopanib is a substrate for CYP3A4. Danazol is an inhibitor of CYP3A4. Concurrent administration may result in increased pazopanib concentrations. Dose reduction of pazopanib may be necessary when coadministration of pazopanib and danazol is required.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and danazol 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 danazol is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of danazol. Pemigatinib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase pemigatinib exposure by approximately 50% to 80%.
Pentosan: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Perindopril; Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and danazol 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 danazol is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of danazol. Pexidartinib is a CYP3A substrate; danazol is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%.
Pimozide: (Major) Concurrent use of pimozide and danazol should be avoided. Pimozide is metabolized primarily through CYP3A4, and danazol is a CYP3A4 inhibitor. Elevated pimozide concentrations occurring through inhibition of CYP3A4 can lead to QT prolongation, ventricular arrhythmias, and sudden death.
Pioglitazone; Metformin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Pralsetinib: (Major) Avoid concomitant use of danazol 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 danazol is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Pramlintide: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Prasugrel: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and danazol due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, 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 a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Progesterone: (Minor) The metabolism of progesterone may be inhibited by danazol, a known inhibitor of cytochrome P450 3A4 hepatic enzymes.
Quazepam: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of benzodiazepines metabolized by oxidation, such as quazepam.
Quinidine: (Moderate) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates including quinidine.
Red Yeast Rice: (Major) Since certain red yeast rice products contain lovastatin, clinicians should use red yeast rice cautiously in combination with drugs known to interact with lovastatin. Danazol is a CYP3A4 inhibitor. CYP3A4 inhibitors have been shown to increase HMG-CoA reductase activity and potential for myopathy when coadministered with lovastatin. Because of these potential risks, red yeast rice is best avoided by patients taking CYP3A4 inhibitors.
Relugolix; Estradiol; Norethindrone acetate: (Minor) As danazol inhibits CYP3A4 activity, serum estrogen concentrations and estrogenic-related side effects (e.g., nausea, breast tenderness) may potentially increase when coadministered with either estrogens or combined hormonal contraceptives, including oral contraceptives.
Reteplase, r-PA: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with thrombolytic agents.
Rilpivirine: (Moderate) Close clinical monitoring is advised when administering danazol with rilpivirine due to an increased potential for rilpivirine-related adverse events. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Danazol is an inhibitor of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in increased rilpivirine plasma concentrations.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with danazol; concurrent use may increase rimegepant exposure. Rimegepant is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor.
Rivaroxaban: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants. Coadministration of rivaroxaban and danazol may result in increases in rivaroxaban exposure and may also increase bleeding risk. Danazol is an inhibitor of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs and symptoms of bleeding.
Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4. Danazol is an inhibitor of CYP3A4. Concurrent administration of romidepsin with an inhibitor of CYP3A4 may cause an increase in systemic romidepsin concentrations. Use caution when concomitant administration of these agents is necessary.
Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are mild or moderate inhibitors of CYP3A4 such as danazol, a dose adjustment is not necessary, but monitoring patients for toxicity may be prudent. There was an 8% and 27% increase in the Cmax and AUC of a single dose of ruxolitinib 10 mg, respectively, when the dose was given after a short course of erythromycin 500 mg PO twice daily for 4 days. The change in the pharmacodynamic marker pSTAT3 inhibition was consistent with the increase in exposure.
Saquinavir: (Moderate) Both saquinavir boosted with ritonavir and danazol are inhibitors of CYP3A4; an isoenzyme responsible for the metabolism of saquinavir. The use of saquinavir/ritonavir with danazol may result in large increases in saquinavir plasma concentrations, which could cause adverse events such as life threatening cardiac arrhythmias (e.g., torsades de pointes [TdP]).
Saw Palmetto, Serenoa repens: (Major) Drug interactions with Saw palmetto, Serenoa repens have not been specifically studied or reported. Saw palmetto extracts appear to have antiandrogenic effects. The antiandrogenic effects of Saw palmetto, Serenoa repens would be expected to antagonize the actions of androgens; it would seem illogical for patients taking androgens to use this herbal supplement.
Saxagliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Coadministration of segesterone and moderate CYP3A4 inhibitors such as danazol may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and danazol due to the risk of increased selpercatinib exposure which may increase the risk of adverse reactions, including QT prolongation. If coadministration is unavoidable, reduce the dose of selpercatinib to 80 mg PO twice daily if original dose was 120 mg twice daily, and to 120 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If danazol is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of danazol. Selpercatinib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase selpercatinib exposure by 60% to 99%.
Selumetinib: (Major) Avoid coadministration of selumetinib and danazol 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 danazol is discontinued, resume the original selumetinib dose after 3 elimination half-lives of danazol. Selumetinib is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase selumetinib exposure by 41%.
SGLT2 Inhibitors: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Sildenafil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with danazol is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A4 substrate and danazol is a CYP3A4 inhibitor.
Silodosin: (Moderate) Silodosin is extensively metabolized by hepatic cytochrome P450 3A4. In theory, drugs that inhibit CYP3A4, such as danazol, may cause significant increases in silodosin plasma concentrations.
Simvastatin: (Contraindicated) The use of simvastatin with danazol is contraindicated due to an increased risk of myopathy and rhabdomyolysis. A single case report has documented the onset of myositis that progressed to rhabdomyolysis with myoglobinuria after danazol was added to a regimen containing lovastatin. Although other drugs were in use concurrently, a drug interaction between danazol and lovastatin is suspected, as danazol (CYP3A4 inhibitor) is known to inhibit lovastatin metabolism.
Siponimod: (Moderate) Concomitant use of siponimod and danazol may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of danazol. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sirolimus overall exposure 1.6-fold.
Sitagliptin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with danazol. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Danazol is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with danazol. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Danazol is a CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Sotagliflozin: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Soy Isoflavones: (Moderate) Theoretically, the soy isoflavones may counteract the activity of the androgens.
Sparsentan: (Moderate) Monitor for an increase in sparsentan-related adverse effects if concomitant use with danazol is necessary. Concomitant use may increase sparsentan exposure. Sparsentan is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sparsentan overall exposure by 70%.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if danazol must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of danazol is necessary. If danazol 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 moderate CYP3A4 inhibitor like danazol 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 danazol 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.
Sulfonylureas: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Tacrolimus: (Moderate) Danazol has been reported to increase tacrolimus whole blood concentrations. Patients receiving tacrolimus should be closely monitored for toxicity if danazol is added to therapy. Conversely, a dose adjustment of tacrolimus may be necessary if danazol therapy is discontinued.
Tamsulosin: (Moderate) Use caution when administering tamsulosin with a moderate CYP3A4 inhibitor such as danazol. Tamsulosin is extensively metabolized by CYP3A4 hepatic enzymes. In clinical evaluation, concomitant treatment with a strong CYP3A4 inhibitor resulted in significant increases in tamsulosin exposure; interactions with moderate CYP3A4 inhibitors have not been evaluated. If concomitant use in necessary, monitor patient closely for increased side effects.
Tasimelteon: (Moderate) Caution is recommended during concurrent use of tasimelteon and danazol. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as danazol, may increase exposure to tasimelteon with the potential for adverse reactions.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with danazol as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If danazol is discontinued, wait at least 3 half-lives of danazol before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telmisartan; Amlodipine: (Moderate) Coadministration of CYP3A4 inhibitors with amlodipine can theoretically decrease the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inhibitors, such as danazol , are coadministered with calcium-channel blockers. Monitor therapeutic response; a dose reduction of amlodipine may be required.
Tenecteplase: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with thrombolytic agents.
Terbinaf ine: (Moderate) Due to the risk for terbinafine related adverse effects, caution is advised when coadministering danazol. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may increase the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; danazol is an inhibitor of this enzyme. Monitor patients for adverse reactions if these drugs are coadministered.
Tezacaftor; Ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with danazol; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); danazol is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If danazol and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Thiazolidinediones: (Moderate) Changes in insulin sensitivity or glycemic control may occur in patients treated with androgens. In diabetic patients, the metabolic effects of androgens may decrease blood glucose and, therefore, may decrease antidiabetic agent dosage requirements. Monitor blood glucose and HbA1C when these drugs are used together.
Thrombolytic Agents: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with thrombolytic agents.
Ticagrelor: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Tirofiban: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Tolvaptan: (Major) Avoid coadministration of danazol when tolvaptan is administered for hyponatremia. In patients with autosomal dominant polycystic kidney disease (ADPKD), reduce tolvaptan dosage if administered with danazol. In ADPKD patients receiving tolvaptan 90mg every morning and 30 mg every evening, reduce the dose to 45 mg every morning and 15 mg every evening; for those receiving tolvaptan 60 mg every morning and 30 mg every evening, reduce the dose to 30 mg every morning and 15 mg every evening; for those receiving tolvaptan 45 mg every morning and 15 mg every evening, reduce the dose to 15 mg every morning and 15 mg every evening. Consider additional dosage reduction if the reduced dose is not tolerated. Tolvaptan is a sensitive CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased the tolvaptan AUC by 200%.
Trandolapril; Verapamil: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
Tretinoin, ATRA: (Moderate) The concomitant use of systemic tretinoin, ATRA and danazol should be done cautiously due to the potential for increased intracranial pressure and an increased risk of pseudotumor cerebri (benign intracranial hypertension). Early signs and symptoms of pseudotumor cerebri include papilledema, headache, nausea, vomiting, and visual disturbances.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with danazol and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and danazol is a moderate CYP3A inhibitor.
Triptorelin: (Major) Gonadotropin releasing hormone (GnRH) agonists (i.e.,triptorelin) inhibit steroidogenesis, therefore the concomitant use of these agents with androgens may counteract this therapeutic effect. Avoid concurrent use of androgens with GnRH agonists.
Ubrogepant: (Major) Limit the initial dose of ubrogepant to 50 mg and avoid a second dose within 24 hours if coadministered with danazol. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor resulted in a 3.5-fold increase in the exposure of ubrogepant.
Ulipristal: (Minor) Ulipristal is a substrate of CYP3A4 and danazol is a CYP3A4 inhibitor. Concomitant use may increase the plasma concentration of ulipristal resulting in an increased risk for adverse events.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with danazol due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; danazol is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Vemurafenib: (Moderate) Concomitant use of vemurafenib and danazol may result in increased vemurafenib concentrations. Vemurafenib is CYP3A4 substrate and danazol is a CYP3A4 inhibitor. Use caution and monitor patients for increased side effects.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with danazol due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of danazol. Venetoclax is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor.
Verapamil: (Minor) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of CYP3A4 substrates like calcium-channel blockers.
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 danazol is necessary. Vinblastine is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with danazol is necessary. Vinorelbine is a CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor.
Voclosporin: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with danazol. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and danazol is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Vorapaxar: (Moderate) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with platelet inhibitors.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with danazol is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Danazol is a moderate 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.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with danazol. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of danazol, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; danazol is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Ziprasidone: (Major) Danazol is a CYP3A4 inhibitor and can decrease the hepatic metabolism of ziprasidone. Patients receiving ziprasidone should be closely monitored for toxicity if danazol is added to therapy.
Zolpidem: (Moderate) It is advisable to closely monitor zolpidem tolerability and safety during concurrent use of danazol, a moderate CYP3A4 inhibitor, since CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism. There is evidence of an increase in pharmacodynamics effects and systemic exposure of zolpidem during co-administration with some potent inhibitors of CYP3A4, such as azole antifungals.

How Supplied

Danazol/Danocrine Oral Cap: 50mg, 100mg, 200mg

Maximum Dosage
Adults

800 mg/day PO; 2400 mg/day PO has been used for off-label emergency postcoital contraception.

Geriatric

Safety and efficacy have not been established.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism Of Action

Through its action on the pituitary, danazol indirectly reduces estrogen production by lowering the output of follicle-stimulating hormone and luteinizing hormone. There is also evidence that danazol binds to sex hormone receptors in target tissues, thereby exibiting anabolic, antiestrognic and weakly androgenic activity. With higher doses, amenorrhea generally occurs after about 6 weeks of therapy; ovulation and cyclic bleeding returns to normal 60—90 days after therapy is discontinued. Danazol is used to treat endometriosis because it causes atrophy of ectopic endometrial tissue, which relieves symptoms completely. It also decreases the growth rate of abnormal breast tissue, making it useful in fibrocystic breast disease. Heriditary angioedema is an inherited disorder characterized by a deficiency in C1 esterase inhibitor (C1 INH), a serum inhibitor of the activated first component of complement. Danazol increases circulating levels of C1 INH and therby increases C4 of the complement system, which also is deficient in hereditary angioedema. Consequently, danazol prevents attacks of hereditary angioedema in both males and females. The exact mechanism by which danazol increases C1 INH is not known. Danazol does not possess any progestogenic activity, and does not suppress normal pituitary release of corticotropin, or release of cortisol by the adrenal glands.

Pharmacokinetics

Danazol is administered orally. Distribution data are limited, but extensive hepatic metabolism produces the primary metabolite, 2-hydroxymethylethisterone. Danazol is excreted in the urine and has an elimination half-life of 4—5 hours.
 
Affected cytochrome P450 isoenzymes: CYP3A4
Danazol inhibits the cytochrome P450 system isoenzyme CYP3A4, and may reduce the hepatic metabolism of CYP3A4 substrates.

Oral Route

The bioavailability of danazol is not directly dose-related; dosage increases are not proportional to increases in plasma concentrations. For example, doubling the dose may yield only a 30—40% increase in plasma concentration. Peak concentrations occur within 2 hours, but the onset of a therapeutic effect (anovulation or amenorrhea) does not occur for approximately 6—8 weeks after taking daily doses. Pain reduction in fibrocystic breast disease will begin to be realized at 1 month, with a peak effect at 2—3 months.

Pregnancy And Lactation
Pregnancy

Danazol is contraindicated during pregnancy, so care should be taken to ensure that the patient is not pregnant and does not become pregnant during therapy. Sensitive pregnancy testing (e.g., beta subunit test if available) capable of determining early pregnancy is recommended immediately prior to start of therapy. Teratogenic effects have been associated with danazol treatment. Androgens have caused virilization of the external genitalia of the female fetus, including clitoromegaly, abnormal vaginal development, and fusion of genital folds to form a scrotal-like structure. The degree of masculinization is dependent on the amount of drug given and the age of the fetus; these effects are most likely to occur in the female fetus when the drugs are given in the first trimester. Females of childbearing potential should be advised of contraception requirements during therapy during treatment. A non-hormonal method of contraception should be used during therapy. If pregnancy occurs, the drug should be immediately discontinued and the patient should be counseled concerning the potential risks to the fetus.