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ZYDELIG
Classes
Small Molecule Antineoplastic Phosphatidylinositol-3-Kinase (PI3K) Inhibitors
Administration
Emetic Risk
Minimal/Low
Administer prn antiemetics as necessary.
Idelalisib may be taken with or without food.
Swallow tablets whole; do not crush or dissolve tablets.
If a dose is missed by less than 6 hours, take the missed as soon as possible and take the next dose at the usual time. If a dose is missed by more than 6 hours, skip that dose and take the next dose at the usual time.
Idelalisib should only be dispensed in the original container.
Adverse Reactions
neutropenia / Delayed / 42.0-58.0
infection / Delayed / 0-48.0
diarrhea / Early / 11.0-20.0
colitis / Delayed / 11.0-20.0
hepatotoxicity / Delayed / 16.0-16.0
fever / Early / 3.0-11.0
lymphopenia / Delayed / 10.0-10.0
elevated hepatic enzymes / Delayed / 5.0-9.0
leukopenia / Delayed / 8.0-8.0
rash / Early / 4.0-4.0
dyspnea / Early / 0-4.0
dehydration / Delayed / 0-3.0
stomatitis / Delayed / 2.0-2.0
anorexia / Delayed / 2.0-2.0
chills / Rapid / 2.0-2.0
nausea / Early / 1.0-1.0
gastroesophageal reflux / Delayed / 1.0-1.0
abdominal pain / Early / 1.0-1.0
GI perforation / Delayed / 0-1.0
arthralgia / Delayed / 1.0-1.0
anaphylactoid reactions / Rapid / 0-1.0
cough / Delayed / 1.0-1.0
Stevens-Johnson syndrome / Delayed / Incidence not known
toxic epidermal necrolysis / Delayed / Incidence not known
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known
pneumonitis / Delayed / 4.0-4.0
erythema / Early / Incidence not known
hypoxia / Early / Incidence not known
lymphocytosis / Delayed / Incidence not known
insomnia / Early / 9.0-9.0
sinusitis / Delayed / 8.0-8.0
lethargy / Early / 5.0-5.0
pruritus / Rapid / Incidence not known
Boxed Warning
Fatal and/or serious hepatotoxicity has been reported with idelalisib therapy. Use idelalisib with caution in patients with pre-existing hepatic disease; monitor these patients carefully for signs of toxicity. Elevated hepatic enzymes typically occurred within 12 weeks of starting therapy and were reversible if idelalisib was discontinued; this toxicity may recur when therapy is resumed following a dosage reduction. Monitor hepatic function (e.g., liver function tests) prior to starting idelalisib, every 2 weeks for the first 3 months, every 4 weeks for the next 3 months, and then every 1 to 3 months thereafter. Increase LFT monitoring to weekly if AST or ALT levels are more than 3-times the upper limit of normal (ULN) or bilirubin levels are more than 1.5-times the ULN. Therapy interruption, dosage reduction, and/or discontinuation may be necessary in patients who develop severe hepatotoxicity. Avoid the concurrent use of idelalisib in combination with other drugs that may cause hepatotoxicity.
Fatal and/or serious diarrhea or colitis and GI perforation have been reported with idelalisib therapy. Some patients with GI perforation also had moderate to severe diarrhea. Diarrhea can occur at any time during treatment and does not respond well to antimotility agents. The median time to diarrhea resolution was 1 week to 1 month after idelalisib therapy was stopped (with or without corticosteroid use). Monitor patients for signs and symptoms of diarrhea or colitis. In patients who develop moderate (4 to 6 stools/day over baseline) or severe (7 or more stools/day over baseline) diarrhea, increase monitoring to at least weekly until toxicity resolves. Therapy interruption and dosage reduction or discontinuation may be necessary in patients who develop severe diarrhea or colitis. Avoid the concurrent use of idelalisib in combination with other drugs that may cause diarrhea. Patients should be advised to report new or worsening abdominal pain, chills, fever, or nausea/vomiting. Discontinue therapy in patients who develop intestinal perforation.
Fatal and serious pneumonitis has been reported in patients treated with idelalisib in clinical trials. The time to onset of pneumonitis ranged from less than 1 month to 15 months. Monitor patients for pulmonary symptoms including cough, dyspnea, hypoxia, and bilateral interstitial infiltrates, or a decline in oxygen saturation by greater than 5%. If pneumonitis is suspected, hold idelalisib therapy. If symptomatic pneumonitis or organizing pneumonia is confirmed, discontinue idelalisib and initiate treatment with corticosteroids.
Serious infection has been reported with idelalisib therapy including sepsis, cytomegalovirus (CMV), and Pneumocystis jirovecii pneumonia (PJP); some infections were fatal. Treat active infections prior to starting idelalisib. Administer PJP prophylaxis in all patients during idelalisib therapy. Monitor patients for signs and symptoms of infection; perform clinical and laboratory monitoring for CMV infections in patients with a history of CMV or positive CMV serology. Hold idelalisib therapy in patients with suspected PJP infection; permanently discontinue therapy in patients with confirmed PJP. Hold therapy until the infection resolves in patients who develop a positive CMV PCR or antigen test and in patients who develop grade 3 or higher sepsis or pneumonia. Monitor for CMV reactivation (i.e., PCR or antigen test) at least monthly if therapy is resumed in patients who had confirmed CMV.
Common Brand Names
ZYDELIG
Dea Class
Rx
Description
Phosphatidylinositol 3-kinase inhibitor
Used in adults for relapsed chronic lymphocytic leukemia in combination with rituximab, and as a single-agent for relapsed follicular lymphoma or small lymphocytic lymphoma following at least 2 prior therapies
Boxed warning for fatal and/or serious cases of hepatotoxicity and severe diarrhea, colitis, infection, intestinal perforation, and pneumonitis
Dosage And Indications
NOTE: The FDA has designated idelalisib as an orphan drug for the treatment of CLL.
For the treatment of relapsed CLL in patients for whom rituximab alone would be considered appropriate due to other co-morbidities, in combination with rituximab. Oral dosage Adults
150 mg PO twice daily until disease progression or unacceptable toxicity, in combination with 8 doses of rituximab. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, dose reduction, and/or discontinuation may be necessary if severe toxicity occurs. A multicenter, randomized, double-blind, phase 3 study (n = 220) was stopped early when it was determined in a pre-specified interim analysis that treatment with idelalisib plus rituximab (median duration of therapy, 3.8 months; range, 0.3 to 16+ months) led to a significantly improved median progression-free survival time (primary endpoint) compared with placebo plus rituximab (median time not reached vs. 5.5 months; hazard ratio (HR) = 0.15; 95% CI, 0.08 to 0.28) in patients with relapsed chronic lymphocytic leukemia (CLL). In this study, idelalisib (150 mg PO twice daily until disease progression) was given in combination with rituximab administered as 375 mg/m2 IV on day 1 (week 0) followed 2 weeks later by 500 mg/m2 IV every 2 weeks for 4 doses (on day 1 of weeks 2, 4, 6, and 8) and then 500 mg/m2 IV every 4 weeks for 3 doses (on day 1 of weeks 12, 16, and 20). Eligible patients had CLL disease progression within 24 months of their last treatment, were not able to receive cytotoxic agents due to coexisting medical conditions, and had previously had either a CD20 antibody-based regimen or at least 2 previous cytotoxic regimens (median number of prior drugs, 3 drugs). The 12-month overall survival rate was 92% in the idelalisib plus rituximab arm compared with 80% in the placebo plus rituximab arm (HR = 0.28; 95% CI, 0.09 to 0.86).
NOTE: Idelalisib is not indicated and is not recommended in combination with bendamustine and/or rituximab for the treatment of follicular lymphoma, small lymphocytic lymphoma, or other indolent NHL.
For the treatment of relapsed B-cell follicular lymphoma (FL) in patients who have received at least 2 prior systemic therapies†.
NOTE: The FDA has designated idelalisib as an orphan drug for the treatment of FL.
NOTE: FDA approval was removed for this indication in February 2022 after initial accelerated approval due to a decision by the manufacturer to voluntarily withdraw the indication. Oral dosage Adults
Dosage not available. In a multinational, open-label, phase 2 trial (n = 125), treatment with single-agent idelalisib (median treatment duration, 6.6 months; range, 0.6 to 23.9 months) resulted in an overall response rate (ORR; primary endpoint) of 57% (95% CI, 48% to 66%) in patients with indolent NHL (i.e., follicular lymphoma [FL], n = 72; small lymphocytic lymphoma, n = 28; marginal-zone lymphoma, n = 15; and lymphoplasmacytic lymphoma, n = 10) who did not respond to or who relapsed within 6 months of treatment with rituximab and chemotherapy containing an alkylating agent. Patients received a median of 4 prior therapies (range, 2 to 12 therapies); 11% of patients had prior high-dose chemotherapy followed by an autologous stem-cell transplant. The median time to response was 1.9 months (range, 1.6 to 8.3 months) and the median response duration was 12.5 months (range, 0.03 to 14.8 months). At a median follow-up of 9.7 months, the median progression-free survival time was 11 months (range, 0.03 to 16.6 months); the median overall survival (OS) time was 20.3 months (range, 0.7 to 22 months) and the estimated 1-year OS rate was 80%. In patients with FL, the ORR rate was 54% (95% CI, 42% to 66%) with a complete response rate of 8% and a partial response rate of 46%.
NOTE: The FDA has designated idelalisib as an orphan drug for the treatment of SLL.
NOTE: FDA approval was removed for this indication in February 2022 after initial accelerated approval due to a decision by the manufacturer to voluntarily withdraw the indication. Oral dosage Adults
Dosage not available. In a multinational, open-label, phase 2 trial (n = 125), treatment with single-agent idelalisib (median treatment duration, 6.6 months; range, 0.6 to 23.9 months) resulted in an overall response rate (ORR; primary endpoint) of 57% (95% CI, 48% to 66%) in patients with indolent NHL (i.e., follicular lymphoma, n = 72; SLL, n = 28; marginal-zone lymphoma, n = 15; and lymphoplasmacytic lymphoma, n = 10) who did not respond to or who relapsed within 6 months of treatment with rituximab and chemotherapy containing an alkylating agent. Patients received a median of 4 prior therapies (range, 2 to 12 therapies); 11% of patients had prior high-dose chemotherapy followed by an autologous stem-cell transplant. The median time to response was 1.9 months (range, 1.6 to 8.3 months) and the median response duration was 12.5 months (range, 0.03 to 14.8 months). At a median follow-up of 9.7 months, the median progression-free survival time was 11 months (range, 0.03 to 16.6 months); the median overall survival time was 20.3 months (range, 0.7 to 22 months) and the estimated 1-year OS rate was 80%. In patients with SLL, the ORR rate was 61% (95% CI, 41% to 79%); all responses were partial responses.
Dosing Considerations
Baseline Hepatic Impairment: Specific guidelines for dosage adjustment in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Treatment-Related Hepatotoxicity
Elevated Hepatic Enzymes
AST/ALT level greater than 3- to 5-times the upper limit of normal (ULN): No dose adjustment needed; monitor transaminase levels at least weekly until levels are 1-time the ULN or less.
AST/ALT level greater than 5- to 20-times the ULN: Hold idelalisib treatment and monitor transaminase levels at least weekly. When levels are 1-time the ULN or less, resume idelalisib at a reduced dose of 100 mg PO twice daily.
AST/ALT level greater than 20-times the ULN: Permanently discontinue idelalisib.
Hyperbilirubinemia
Bilirubin level greater than 1.5- to 3-times the ULN: No dose adjustment needed; monitor bilirubin levels at least weekly until levels are 1-time the ULN or less.
Bilirubin level greater than 3- to 10-times the ULN: Hold idelalisib treatment and monitor bilirubin levels at least weekly. When levels are 1-time the ULN or less, resume idelalisib at a reduced dose of 100 mg PO twice daily.
Bilirubin level greater than 10-times the ULN: Permanently discontinue idelalisib.
Specific guidelines for dosage adjustment in renal impairment are not available; it appears that no dosage adjustments are needed.
Drug Interactions
Abacavir; Dolutegravir; Lamivudine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dolutegravir, a CYP3A substrate, as dolutegravir toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Abemaciclib: (Major) If coadministration with idelalisib is necessary, reduce the dose of abemaciclib to 100 mg PO twice daily in patients on either of the recommended starting doses of either 200 mg or 150 mg twice daily. In patients who have had already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg PO twice daily. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. If idelalisib is discontinued, increase the dose of abemaciclib to the original dose after 3 to 5 half-lives of idelalisib. Abemaciclib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 2.5-fold in cancer patients.
Acalabrutinib: (Major) Avoid the concomitant use of acalabrutinib and idelalisib; significantly increased acalabrutinib exposure may occur. Acalabrutinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In healthy subjects, the Cmax and AUC values of acalabrutinib were increased by 3.9-fold and 5.1-fold, respectively, when acalabrutinib was coadministered with another strong inhibitor for 5 days.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with idelalisib 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 idelalisib could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If idelalisib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Idelalisib is a strong inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Codeine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib 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 idelalisib 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 idelalisib 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 idelalisib is necessary. If idelalisib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like idelalisib 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 idelalisib 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.
Adagrasib: (Major) Avoid concomitant use of idelalisib with adagrasib and consider alternative therapy. Concomitant use may increase idelalisib exposure and the risk for idelalisib-related adverse reactions. Additionally, concomitant use during adagrasib therapy initiation before steady state is reached (approximately 8 days) may increase adagrasib exposure and the risk for adagrasib-related adverse reactions. If concomitant use is necessary, monitor patients frequently for signs and symptoms of adverse reactions from either drug (e.g., QT prolongation, hepatotoxicity, diarrhea, neutropenia, and infection). Both idelalisib and adagrasib are CYP3A substrates and strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold. Concomitant use of a single 200 mg dose of adagrasib with another strong CYP3A inhibitor increased adagrasib exposure by approximately 4-fold, however, no clinically significant differences in pharmacokinetics are predicted at steady state.
Ado-Trastuzumab emtansine: (Major) Avoid coadministration of idelalisib with ado-trastuzumab emtansine if possible due to the risk of elevated exposure to the cytotoxic component of ado-trastuzumab emtansine, DM1. Delay ado-trastuzumab emtansine treatment until idelalisib has cleared from the circulation (approximately 3 half-lives of idelalisib) when possible. If concomitant use is unavoidable, closely monitor patients for ado-trastuzumab emtansine-related adverse reactions. The cytotoxic component of ado-trastuzumab emtansine, DM1, is metabolized mainly by CYP3A4 and to a lesser extent by CYP3A5; idelalisib is a strong CYP3A4 inhibitor. Formal drug interaction studies with ado-trastuzumab emtansine have not been conducted.
Albuterol; Budesonide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with budesonide, a CYP3A substrate, as budesonide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Alfentanil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with alfentanil, a CYP3A substrate, as alfentanil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Alfuzosin: (Contraindicated) Coadministration of alfuzosin and idelalisib is contraindicated due to increased alfuzosin exposure. Idelalisib is a strong CYP3A4 inhibitor. Alfuzosin is a CYP3A4 substrate. When coadministered with another strong CYP3A4 inhibitor, the AUC of alfuzosin was increased by 2.5-fold to 3.2-fold.
Aliskiren: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with aliskiren, a CYP3A substrate, as aliskiren toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Aliskiren; Hydrochlorothiazide, HCTZ: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with aliskiren, a CYP3A substrate, as aliskiren toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Almotriptan: (Moderate) The maximum recommended starting dose of almotriptan is 6.25 mg if coadministration with idelalisib is necessary; do not exceed 12.5 mg within a 24-hour period. Concomitant use of almotriptan and idelalisib should be avoided in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased almotriptan exposure by approximately 60%.
Alosetron: (Moderate) Coadministration of idelalisib and alosetron may increase alosetron concentrations resulting in alosetron-related adverse events. Idelalisib is a strong CYP3A4 inhibitor and alosetron is a CYP3A substrate.
Alprazolam: (Contraindicated) Coadministration of idelalisib and alprazolam is contraindicated due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with idelalisib, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased alprazolam exposure by 2.7- to 3.98-fold.
Amiodarone: (Moderate) Coadministration of idelalisib and amiodarone may increase amiodarone concentrations resulting in amiodarone-related adverse events. Idelalisib is a strong CYP3A4 inhibitor and amiodarone is a CYP3A substrate. If concomitant use is necessary, consider serial measurement of amiodarone serum concentrations.
Amitriptyline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amitriptyline, a CYP3A substrate, as amitriptyline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Amlodipine: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Amlodipine; Atorvastatin: (Major) Coadministration of idelalisib with atorvastatin may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin. If concomitant use of these drugs is required, consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness), particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Idelalisib is a strong CYP3A4 inhibitor; atorvastatin is a CYP3A4 substrate. (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Amlodipine; Benazepril: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Amlodipine; Celecoxib: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Amlodipine; Olmesartan: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Amlodipine; Valsartan: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with omeprazole, a CYP3A substrate, as omeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Coadministration of idelalisib with clarithromycin may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib and clarithromycin are both CYP3A4 substrates and strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold.
Apalutamide: (Major) Avoid coadministration of idelalisib with apalutamide due to decreased plasma concentrations of idelalisib; exposure to apalutamide may also increase. Idelalisib is a CYP3A4 substrate and strong CYP3A4 inhibitor. Apalutamide is a CYP3A4 substrate and strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased idelalisib exposure by 75%. Coadministration with one strong CYP3A4 inhibitor decreased the Cmax of single-dose apalutamide by 22% and the AUC remained similar. Concomitant use with another strong CYP3A4 inhibitor is predicted to increase the single-dose apalutamide AUC by 24% but have no effect on Cmax; the steady-state Cmax and AUC are predicted to increase by 38% and 51%, respectively, with this inhibitor. The predicted steady-state exposure of the active moieties (unbound apalutamide plus potency-adjusted unbound N-desmethyl apalutamide) is predicted to increase by 28%.
Apixaban: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with apixaban, a CYP3A substrate, as apixaban toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of idelalisib with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant; increased idelalisib exposure may also occur. If coadministration cannot be avoided, use caution and monitor for an increase in idelalisib- and aprepitant-related adverse effects for several days after administration of a multi-day aprepitant regimen. Idelalisib is a strong CYP3A4 inhibitor and aprepitant is a CYP3A4 substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Coadministration of a single oral dose of aprepitant (125 mg) on day 5 of a 10-day ketoconazole regimen (strong CYP3A4 inhibitor) increased the aprepitant AUC approximately 5-fold, and increased the mean terminal half-life by approximately 3-fold. Idelalisib is also a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of idelalisib. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Major) Recommendations for managing aripiprazole and idelalisib vary by aripiprazole dosage form and CYP2D6 metabolizer status. For aripiprazole oral dosage forms, administer half of the usual dose; administer a quarter of the usual dose to patients known to be poor metabolizers of CYP2D6. For monthly extended-release aripiprazole injections (Abilify Maintena), reduce the dosage from 400 mg to 300 mg/month or from 300 mg to 200 mg/month; administer 200 mg/month to patients known to be poor metabolizers of CYP2D6. For extended-release aripiprazole injections given once every 2 months (Abilify Asimtufii), reduce the dosage from 960 mg to 720 mg; avoid use in patients known to be poor metabolizers of CYP2D6. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; idelalisib is a strong CYP3A inhibitor. (Major) Recommendations for managing aripiprazole and idelalisib vary by aripiprazole dosage form and CYP2D6 metabolizer status. For extended-release aripiprazole lauroxil injections (Aristada), reduce the dose to the next lowest strength; no dosage adjustment is required for patients tolerating 441 mg. For extended-release aripiprazole lauroxil injections (Aristada) in patients who are known to be poor metabolizers of CYP2D6, reduce the dose to 441 mg; no dosage adjustment is necessary for patients already tolerating 441 mg. For fixed dose extended-release aripiprazole lauroxil injections (Aristada Initio), avoid concomitant use because the dose cannot be modified. Further dosage reductions may be required in patients who are also receiving a CYP2D6 inhibitor; see individual product prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is CYP3A and CYP2D6 substrate; idelalisib is a strong CYP3A inhibitor.
Artemether; Lumefantrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with artemether, a CYP3A substrate, as artemether toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Moderate) Coadministration of idelalisib with artemether; lumefantrine may increase the concentrations of artemether and lumefantrine resulting in an increased incidence of adverse events (e.g., QT prolongation). Idelalisib is a strong CYP3A4 inhibitor and artemether and lumefantrine are CYP3A substrates.
Asciminib: (Moderate) Closely monitor for asciminib-related adverse reactions if concurrent use of asciminib 200 mg twice daily with idelalisib is necessary as asciminib exposure may increase. Asciminib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Asenapine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with asenapine, a CYP3A substrate, as asenapine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Aspirin, ASA; Omeprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with omeprazole, a CYP3A substrate, as omeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib is necessary. If idelalisib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like idelalisib 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 idelalisib 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.
Atazanavir: (Major) Coadministration of idelalisib with atazanavir may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib and atazanavir are both CYP3A4 substrates and strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold. Atazanavir exposure was increased when administered with some strong CYP3A inhibitors but not others.
Atazanavir; Cobicistat: (Major) Coadministration of idelalisib with atazanavir may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib and atazanavir are both CYP3A4 substrates and strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold. Atazanavir exposure was increased when administered with some strong CYP3A inhibitors but not others. (Major) Coadministration of idelalisib with cobicistat may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. If use of both drugs is required, monitor for idelalisib- and cobicistat-related adverse reactions. Coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold.
Atogepant: (Major) Avoid use of atogepant and idelalisib when atogepant is used for chronic migraine. Limit the dose of atogepant to 10 mg PO once daily for episodic migraine if coadministered with idelalisib. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of CYP3A and idelalisib is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor resulted in a 5.5-fold increase in atogepant overall exposure and a 2.15-fold increase in atogepant peak concentration.
Atorvastatin: (Major) Coadministration of idelalisib with atorvastatin may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin. If concomitant use of these drugs is required, consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness), particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Idelalisib is a strong CYP3A4 inhibitor; atorvastatin is a CYP3A4 substrate.
Atorvastatin; Ezetimibe: (Major) Coadministration of idelalisib with atorvastatin may increase atorvastatin exposure resulting in atorvastatin-related toxicity; the risk may be increased with higher doses of atorvastatin. If concomitant use of these drugs is required, consider a lower starting and maintenance dose of atorvastatin and monitor patients carefully for signs and symptoms of myopathy/rhabdomyolysis (e.g., muscle pain, tenderness, or weakness), particularly during the initial months of therapy and during any periods of upward dosage titration of either drug. Idelalisib is a strong CYP3A4 inhibitor; atorvastatin is a CYP3A4 substrate.
Avacopan: (Major) Reduce the dose of avacopan to 30 mg once daily if concomitant use of idelalisib is necessary. Concomitant use may increase avacopan exposure and risk for avacopan-related adverse effects. Avacopan is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased avacopan overall exposure 2.19-fold.
Avanafil: (Major) Avoid the concomitant use of idelalisib and avanafil; significantly increased avanafil exposure may occur resulting in avanafil-related adverse events. Idelalisib is a strong CYP3A4 inhibitor and avanafil is a sensitive CYP3A substrate. Coadministration with other strong CYP3A4 inhibitors increased exposure to avanafil by 13-fold.
Avapritinib: (Major) Avoid coadministration of avapritinib with idelalisib due to the risk of increased avapritinib-related adverse reactions. Avapritinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 600% at steady-state.
Axitinib: (Major) Avoid coadministration of axitinib with idelalisib due to the risk of increased axitinib-related adverse reactions. If coadministration is unavoidable, decrease the dose of axitinib by approximately half; subsequent doses can be increased or decreased based on individual safety and tolerability. Resume the original dose of axitinib approximately 3 to 5 half-lives after idelalisib is discontinued. Axitinib is a CYP3A4/5 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4/5 inhibitor significantly increased the plasma exposure of axitinib in healthy volunteers.
Azelastine; Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and idelalisib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Bedaquiline: (Major) Avoid prolonged (greater than 14 days) concomitant use of idelalisib and bedaquiline unless the benefit outweighs the risk; increased bedaquiline exposure may occur resulting in bedaquiline-related adverse events. If concomitant use of these drugs is required, monitor patients for signs and symptoms of bedaquiline-related adverse reactions (e.g., QT prolongation and hepatotoxicity). Idelalisib is a strong CYP3A4 inhibitor and bedaquiline is a CYP3A substrate.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with idelalisib 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 idelalisib 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 idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Betamethasone: (Moderate) Monitor for corticosteroid-related adverse effects if coadministration is necessary. Consider using an alternative treatment to betametasone, such as a corticosteroid less affected by CYP3A4 (i.e., beclomethasone or prednisolone), particularly if long term use is indicated. Idelalisib is a strong CYP3A4 inhibitor and betamethasone is a CYP3A4 substrate. Another strong CYP3A4 inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Bortezomib: (Major) Coadministration of idelalisib with bortezomib may increase bortezomib exposure. If these drugs are used together, consider a bortezomib dose reduction and monitor patients for signs and symptoms of bortezomib-related adverse reactions (e.g., peripheral neuropathy and hematologic toxicity). Idelalisib is a strong CYP3A4 inhibitor and bortezomib is a CYP3A substrate. The mean bortezomib AUC value increased by 35% when bortezomib was administered with another strong CYP3A inhibitor in a drug interaction study (n = 12).
Bosentan: (Major) Coadministration of idelalisib with bosentan may increase bosentan exposure; monitor patients for signs and symptoms of bosentan-related adverse reactions (e.g., hepatotoxicity and anemia). Idelalisib is a strong CYP3A4 inhibitor and bosentan is a CYP3A substrate. The bosentan plasma concentration increased by 100% when bosentan was administered with another strong CYP3A inhibitor in a drug interaction study.
Bosutinib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bosutinib, a CYP3A substrate, as bosutinib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Brentuximab vedotin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with brentuximab vedotin, a CYP3A substrate, as brentuximab vedotin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Brexpiprazole: (Major) Because brexpiprazole is partially metabolized by CYP3A4, the manufacturer recommends that the brexpiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4 such as idelalisib. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. If these agents are used in combination, the patient should be carefully monitored for brexpiprazole-related adverse reactions. Because brexpiprazole is also metabolized by CYP2D6, patients classified as CYP2D6 poor metabolizers (PMs) who are receiving a strong CYP3A4 inhibitor or patients receiving a combination of a moderate to strong CYP3A4 inhibitor and moderate to strong CYP2D6 inhibitor should have their brexpiprazole dose reduced to one-quarter (25%) of the usual dose. If the co-administered CYP inhibitor is discontinued, adjust the brexpiprazole dose to its original level. 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 strong CYP3A4 inhibitor.
Brigatinib: (Major) Avoid coadministration of brigatinib with idelalisib if possible due to increased plasma exposure of brigatinib; an increase in brigatinib-related adverse reactions may occur. If concomitant use is unavoidable, reduce the dose of brigatinib by approximately 50% without breaking tablets (i.e., from 180 mg to 90 mg; from 90 mg to 60 mg); after discontinuation of idelalisib, resume the brigatinib dose that was tolerated prior to initiation of idelalisib. Brigatinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively.
Bromocriptine: (Major) When bromocriptine is used for diabetes, avoid coadministration with idelalisib ensuring adequate washout before initiating bromocriptine. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may significantly increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; idelalisib is a strong inhibitor of CYP3A4.
Budesonide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with budesonide, a CYP3A substrate, as budesonide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Budesonide; Formoterol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with budesonide, a CYP3A substrate, as budesonide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with budesonide, a CYP3A substrate, as budesonide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Bupivacaine Liposomal: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bupivacaine, a CYP3A substrate, as bupivacaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Bupivacaine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bupivacaine, a CYP3A substrate, as bupivacaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Bupivacaine; Epinephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bupivacaine, a CYP3A substrate, as bupivacaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Bupivacaine; Lidocaine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bupivacaine, a CYP3A substrate, as bupivacaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lidocaine, a CYP3A substrate, as lidocaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Bupivacaine; Meloxicam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bupivacaine, a CYP3A substrate, as bupivacaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with meloxicam, a CYP3A substrate, as meloxicam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Buprenorphine: (Major) The plasma concentrations of CYP3A4 substrates such as buprenorphine and its metabolite, norbuprenorphine, may be elevated when administered concurrently with strong CYP3A4 inhibitors such as idelalisib. During co-administration, use the lowest buprenorphine starting dose and slowly titrate to desired effect. Monitoring for adverse effects, such as CNS side effects or respiratory depression, is advisable. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Buprenorphine; Naloxone: (Major) The plasma concentrations of CYP3A4 substrates such as buprenorphine and its metabolite, norbuprenorphine, may be elevated when administered concurrently with strong CYP3A4 inhibitors such as idelalisib. During co-administration, use the lowest buprenorphine starting dose and slowly titrate to desired effect. Monitoring for adverse effects, such as CNS side effects or respiratory depression, is advisable. The effect of CYP3A4 inhibitors on buprenorphine implants has not been studied.
Buspirone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with buspirone, a CYP3A substrate, as buspirone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Cabazitaxel: (Major) Avoid coadministration of cabazitaxel with idelalisib if possible due to increased cabazitaxel exposure. If concomitant use is unavoidable, consider reducing the dose of cabazitaxel by 25%. Cabazitaxel is primarily metabolized by CYP3A4 and idelalisib is a strong CYP3A4 inhibitor. In a drug interaction study, coadministration with another strong CYP3A4 inhibitor increased cabazitaxel exposure by 25%.
Cabotegravir; Rilpivirine: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rilpivirine, a CYP3A substrate, as rilpivirine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Cabozantinib: (Major) Avoid concomitant use of cabozantinib and idelalisib due to the risk of increased cabozantinib exposure which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the dose of cabozantinib. For patients taking cabozantinib tablets, reduce the dose of cabozantinib by 20 mg; for patients taking cabozantinib capsules, reduce the dose of cabozantinib by 40 mg. Resume the cabozantinib dose that was used prior to initiating treatment with idelalisib 2 to 3 days after discontinuation of idelalisib. Cabozantinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased cabozantinib exposure by 38%.
Capmatinib: (Moderate) Monitor for an increase in capmatinib-related adverse reactions if coadministration with idelalisib is necessary. Capmatinib is a CYP3A substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased capmatinib exposure by 42%.
Carbamazepine: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as carbamazepine, as idelalisib exposure may be significantly reduced and efficacy compromised. Additionally, idelalisib is a strong CYP3A inhibitor while carbamazepine is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and carbamazepine.
Cariprazine: (Major) Cariprazine and its active metabolites are extensively metabolized by CYP3A4. When a strong CYP3A4 inhibitor, such as idelalisib, is initiated in a patient who is on a stable dose of cariprazine, reduce the cariprazine dosage by half. For adult patients taking cariprazine 4.5 mg daily, the dosage should be reduced to 1.5 mg or 3 mg daily. For adult patients taking cariprazine 1.5 mg daily, the dosing frequency should be adjusted to every other day. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased. When initiating cariprazine in a patient who is stable on a strong CYP3A4 inhibitor, the patient should be administered 1.5 mg of cariprazine on Day 1 and on Day 3 with no dose administered on Day 2. From Day 4 onward, the dose should be administered at 1.5 mg daily, then increased to a maximum dose of 3 mg daily. When the CYP3A4 inhibitor is withdrawn, the cariprazine dosage may need to be increased.
Celecoxib; Tramadol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tramadol, a CYP3A substrate, as tramadol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ceritinib: (Major) Avoid concomitant use of ceritinib with idelalisib due to increased exposure to both drugs which may increase the incidence and severity of adverse reactions. If concomitant use is necessary, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of 150 mg and monitor for treatment-related adverse reactions. After idelalisib is discontinued, resume the dose of ceritinib taken prior to initiating idelalisib. Both drugs are CYP3A substrates and strong CYP3A4 inhibitors. Coadministration with a strong CYP3A inhibitor increased ceritinib exposure by 2.9-fold. Coadministration with another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
Chloramphenicol: (Major) Coadministration of idelalisib with chloramphenicol may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib is a CYP3A4 substrate and chloramphenicol is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold.
Chlordiazepoxide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with chlordiazepoxide, a CYP3A substrate, as chlordiazepoxide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Chlordiazepoxide; Amitriptyline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amitriptyline, a CYP3A substrate, as amitriptyline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with chlordiazepoxide, a CYP3A substrate, as chlordiazepoxide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Chlordiazepoxide; Clidinium: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with chlordiazepoxide, a CYP3A substrate, as chlordiazepoxide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Chlorpheniramine; Codeine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with idelalisib 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 idelalisib could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If idelalisib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Idelalisib is a strong 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 idelalisib 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 idelalisib 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 idelalisib 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.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cilostazol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cilostazol, a CYP3A substrate, as cilostazol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Cinacalcet: (Moderate) Monitor for cinacalcet-related adverse effects during concomitant use of idelalisib and adjust dosage as appropriate based on response. Concomitant use may increase cinacalcet exposure. Cinacalcet is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased cinacalcet overall exposure by 127%.
Cisapride: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cisapride, a CYP3A substrate, as cisapride toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Clarithromycin: (Major) Coadministration of idelalisib with clarithromycin may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib and clarithromycin are both CYP3A4 substrates and strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold.
Clindamycin: (Moderate) Monitor for an increase in clindamycin-related adverse reactions with coadministration of idelalisib as concurrent use may increase clindamycin exposure. Clindamycin is a CYP3A4 substrate; idelalisib is a strong inhibitor of CYP3A4.
Clobazam: (Moderate) Monitor for increased clobazam-related adverse effects if coadministered with idelalisib due to potential for increased clobazam exposure. Clobazam is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of clobazam with another strong CYP3A4 inhibitor increased clobazam AUC by 54%, with an insignificant effect on clobazam Cmax.
Clomipramine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clomipramine, a CYP3A substrate, as clomipramine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Clonazepam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clonazepam, a CYP3A substrate, as clonazepam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Clorazepate: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clorazepate, a CYP3A substrate, as clorazepate toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Clozapine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clozapine, a CYP3A substrate, as clozapine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. In addition, it is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist.
Cobicistat: (Major) Coadministration of idelalisib with cobicistat may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. If use of both drugs is required, monitor for idelalisib- and cobicistat-related adverse reactions. Coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with idelalisib due to the risk of cobimetinib toxicity. Cobimetinib is a CYP3A substrate in vitro, and idelalisib is a strong 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), another 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).
Cocaine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cocaine, a CYP3A substrate, as cocaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Codeine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Codeine; Promethazine: (Moderate) Concomitant use of codeine with idelalisib 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 idelalisib could decrease codeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to codeine. If idelalisib 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. Idelalisib is a strong inhibitor of CYP3A4.
Colchicine: (Major) Avoid concomitant use of colchicine and idelalisib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Conivaptan: (Contraindicated) Coadministration of conivaptan and idelalisib is contraindicated due to the potential for increased conivaptan exposure. Conivaptan is a CYP3A substrate; idelalisib is a strong CYP3A inhibitor. In a drug interaction study, coadministration of a strong CYP3A inhibitor increased the exposure of oral conivaptan by 11-fold.
Conjugated Estrogens; Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with idelalisib, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
Copanlisib: (Major) Avoid the concomitant use of copanlisib and idelalisib if possible; increased copanlisib exposure may occur. If coadministration cannot be avoided, reduce the copanlisib dose to 45 mg and monitor patients for copanlisib-related adverse events (e.g., hypertension, infection, and skin rash). Copanlisib is a CYP3A substrate; idelalisib is a strong CYP3A inhibitor.
Crizotinib: (Major) Avoid
Cyclosporine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cyclosporine, a CYP3A substrate, as cyclosporine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Dabrafenib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dabrafenib, a CYP3A substrate, as dabrafenib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be reduced to 30 mg PO once daily when administered in combination with strong CYP3A4 inhibitors, such as idelalisib. Taking these drugs together may increase daclatasvir serum concentrations, and potentially increase the risk for adverse effects.
Dapsone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dapsone, a CYP3A substrate, as dapsone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Daridorexant: (Major) Avoid concomitant use of daridorexant and idelalisib. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use of another strong CYP3A inhibitor increased daridorexant overall exposure by over 400%.
Darifenacin: (Moderate) The daily dose of darifenacin should not exceed 7.5 mg PO when administered with idelalisib due to increased darifenacin exposure. Darifenacin is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor.
Darunavir: (Major) Coadministration of idelalisib with darunavir may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. The exposure of another sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Additionally, coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold.
Darunavir; Cobicistat: (Major) Coadministration of idelalisib with cobicistat may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. If use of both drugs is required, monitor for idelalisib- and cobicistat-related adverse reactions. Coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold. (Major) Coadministration of idelalisib with darunavir may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. The exposure of another sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Additionally, coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Coadministration of idelalisib with cobicistat may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. If use of both drugs is required, monitor for idelalisib- and cobicistat-related adverse reactions. Coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold. (Major) Coadministration of idelalisib with darunavir may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. The exposure of another sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Additionally, coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold.
Dasatinib: (Major) Avoid coadministration of dasatinib and idelalisib due to the potential for increased dasatinib exposure and subsequent toxicity. An alternative to idelalisib with no or minimal enzyme inhibition potential is recommended if possible. If coadministration cannot be avoided, consider a dasatinib dose reduction to 40 mg PO daily if original dose was 140 mg daily, 20 mg PO daily if original dose was 100 mg daily, or 20 mg PO daily if original dose was 70 mg daily. Concomitant use of idelalisib is not recommended in patients receiving dasatinib 60 mg or 40 mg daily. If dasatinib is not tolerated after dose reduction, consider alternative therapies. If idelalisib is stopped, allow a washout of approximately 1 week before increasing the dasatinib dose. Dasatinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of dasatinib by 4-fold and 5-fold, respectively.
Deflazacort: (Major) Avoid coadministration of deflazacort and idelalisib. If coadministration cannot be avoided, decrease deflazacort dose to one third of the recommended dosage when coadministered with idelalisib. 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; idelalisib is a strong inhibitor of CYP3A4. Administration of deflazacort with clarithromycin, a strong CYP3A4 inhibitor, increased total exposure to 21-desDFZ by about 3-fold.
Delavirdine: (Major) Coadministration of idelalisib with delavirdine may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib is a CYP3A4 substrate and delavirdine is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold.
Desogestrel; Ethinyl Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Dexamethasone: (Moderate) Monitor for steroid-related adverse reactions if coadministration of idelalisib with dexamethasone is necessary, due to increased dexamethasone exposure; Cushing's syndrome and adrenal suppression could potentially occur with long-term use. Consider the use of corticosteroids such as beclomethasone and prednisolone, whose concentrations are less affected by strong CYP3A inhibitors, especially for long-term use. Dexamethasone is primarily metabolized by CYP3A and idelalisib is a strong CYP3A inhibitor. Another strong CYP3A inhibitor has been reported to decrease the metabolism of certain corticosteroids by up to 60%, leading to increased risk of corticosteroid side effects.
Dextromethorphan; Quinidine: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quinidine, a CYP3A substrate, as quinidine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Diazepam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with diazepam, a CYP3A substrate, as diazepam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Diclofenac: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with diclofenac, a CYP3A substrate, as diclofenac toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Diclofenac; Misoprostol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with diclofenac, a CYP3A substrate, as diclofenac toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Dienogest; Estradiol valerate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Dihydroergotamine: (Contraindicated) Concomitant use of ergotamine with idelalisib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Diltiazem: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with diltiazem, a CYP3A substrate, as diltiazem toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Disopyramide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with disopyramide, a CYP3A substrate, as disopyramide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Disulfiram: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with disulfiram, a CYP3A substrate, as disulfiram toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Docetaxel: (Major) Avoid coadministration of docetaxel with idelalisib if possible due to increased plasma concentrations of docetaxel. If concomitant use is unavoidable, closely monitor for docetaxel-related adverse reactions and consider a 50% dose reduction of docetaxel. Docetaxel is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased docetaxel exposure by 2.2-fold.
Dolasetron: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dolasetron, a CYP3A substrate, as dolasetron toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Dolutegravir: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dolutegravir, a CYP3A substrate, as dolutegravir toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Dolutegravir; Lamivudine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dolutegravir, a CYP3A substrate, as dolutegravir toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Dolutegravir; Rilpivirine: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rilpivirine, a CYP3A substrate, as rilpivirine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dolutegravir, a CYP3A substrate, as dolutegravir toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Donepezil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with donepezil, a CYP3A substrate, as donepezil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Donepezil; Memantine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with donepezil, a CYP3A substrate, as donepezil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Doravirine: (Minor) Coadministration of doravirine and idelalisib may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; idelalisib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Minor) Coadministration of doravirine and idelalisib may result in increased doravirine plasma concentrations. Doravirine is a CYP3A4 substrate; idelalisib is a strong inhibitor. In drug interaction studies, concurrent use of strong CYP3A4 inhibitors increased doravirine exposure by more than 3-fold; however, this increase was not considered clinically significant.
Doxazosin: (Moderate) Monitor blood pressure and for signs of hypotension during coadministration. The plasma concentrations of doxazosin may be elevated when administered concurrently with idelalisib. Idelalisib is a strong CYP3A4 inhibitor; doxazosin is a CYP3A4 substrate. Coadministration of doxazosin with a moderate CYP3A4 inhibitor resulted in a 10% increase in mean AUC and an insignificant increase in mean Cmax and mean half-life of doxazosin. Although not studied in combination with doxazosin, strong CYP3A4 inhibitors may have a larger impact on doxazosin concentrations and therefore should be used with caution.
Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with idelalisib due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Idelalisib is a strong CYP3A4 inhibitor and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with idelalisib due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Idelalisib is a strong CYP3A4 inhibitor and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronabinol: (Major) Avoid the coadministration of dronabinol with idelalisib, due to the risk of serious dronabinol-related adverse reactions (e.g., cognitive impairment, psychosis, seizures, and hemodynamic instability, as well as feeling high, dizziness, confusion, somnolence). Dronabinol is a CYP2C9 and 3A4 substrate; idelalisib is a strong inhibitor of CYP3A4. Concomitant use may result in elevated plasma concentrations of dronabinol. In healthy subjects, the geometric mean Cmax of midazolam increased by 2.4-fold and the geometric mean AUC of midazolam by 5.4-fold when administered after idelalisib (150 mg by mouth for 15 doses).
Dronedarone: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dronedarone, a CYP3A substrate, as dronedarone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Droperidol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with droperidol, a CYP3A substrate, as droperidol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Drospirenone: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Drospirenone; Estetrol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Drospirenone; Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Drospirenone; Ethinyl Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Dutasteride: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like idelalisib are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
Dutasteride; Tamsulosin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tamsulosin, a CYP3A substrate, as tamsulosin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like idelalisib are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
Duvelisib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with idelalisib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; idelalisib is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as idelalisib.
Efavirenz: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with efavirenz, a CYP3A substrate, as efavirenz toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with efavirenz, a CYP3A substrate, as efavirenz toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with efavirenz, a CYP3A substrate, as efavirenz toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Elacestrant: (Major) Avoid concomitant use of elacestrant and idelalisib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased elacestrant overall exposure by 5.3-fold.
Elagolix: (Major) Concomitant use of elagolix 200 mg twice daily and idelalisib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and idelalisib to 6 months. Elagolix is a CYP3A substrate; idelalisib is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively.
Elagolix; Estradiol; Norethindrone acetate: (Major) Concomitant use of elagolix 200 mg twice daily and idelalisib for more than 1 month is not recommended. Limit concomitant use of elagolix 150 mg once daily and idelalisib to 6 months. Elagolix is a CYP3A substrate; idelalisib is a strong inhibitor of CYP3A. Coadministration may increase elagolix plasma concentrations. In drug interaction studies, coadministration of elagolix with another strong CYP3A inhibitor increased the Cmax and AUC of elagolix by 77% and 120%, respectively. (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Elbasvir; Grazoprevir: (Major) Concurrent administration of elbasvir with idelalisib should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of elbasvir, and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Idelalisib is a strong inhibitor of the hepatic enzyme CYP3A, while elbasvir is metabolized by CYP3A. (Major) Concurrent administration of grazoprevir with idelalisib should be avoided if possible. Use of these drugs together is expected to significantly increase the plasma concentrations of grazoprevir, and may result in adverse effects (i.e., elevated ALT concentrations and hepatotoxicity). Idelalisib is a strong inhibitor of the hepatic enzyme CYP3A, while grazoprevir is metabolized by CYP3A. In addition, plasma concentrations of idelalisib (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
Eletriptan: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with eletriptan, a CYP3A substrate, as eletriptan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Eletriptan is contraindicated for use within 72 hours of usage of any drug that is a strong CYP3A4 inhibitor, including idelalisib.
Elexacaftor; tezacaftor; ivacaftor: (Major) If idelalisib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to twice a week in the morning, approximately 3 to 4 days apart (i.e., Day 1 and Day 4) when coadministered with idelalisib; omit the evening dose of ivacaftor. Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; idelalisib is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased elexacaftor exposure by 2.8- fold, tezacaftor exposure by 4.5-fold, and ivacaftor exposure by 15.6-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with idelalisib; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); idelalisib is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of idelalisib and eliglustat is contraindicated. In extensive CYP2D6 metabolizers (EMs), coadministration of these agents requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both idelalisib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Idelalisib is a strong CYP3A inhibitor and P-glycoprotein (P-gp) substrate in vitro; eliglustat is a CYP3A and CYP2D6 substrate and P-gp inhibitor. Coadministration of eliglustat with CYP3A inhibitors, such as idelalisib, 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. In addition, because idelalisib is a P-gp substrate and eliglustat is a P-gp inhibitor, exposure to idelalisib may be increased; monitor patients closely for idelalisib-related adverse events, such as elevated liver transaminases, neutropenia, thrombocytopenia, and severe diarrhea.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Coadministration of idelalisib with cobicistat may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. If use of both drugs is required, monitor for idelalisib- and cobicistat-related adverse reactions. Coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Coadministration of idelalisib with cobicistat may increase the exposure of both drugs; avoid use and use alternative agents if possible. Both drugs are CYP3A4 substrates and strong CYP3A4 inhibitors. If use of both drugs is required, monitor for idelalisib- and cobicistat-related adverse reactions. Coadministration with a strong CYP3A inhibitor increased idelalisib expoure by 1.8-fold.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rilpivirine, a CYP3A substrate, as rilpivirine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rilpivirine, a CYP3A substrate, as rilpivirine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Encorafenib: (Major) Avoid coadministration of encorafenib and idelalisib due to increased encorafenib exposure. If concurrent use cannot be avoided, reduce the encorafenib dose to one-third of the dose used prior to the addition of idelalisib. If idelalisib is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of idelalisib. Encorafenib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 3-fold and 68%, respectively.
Entrectinib: (Major) Avoid coadministration of entrectinib with idelalisib 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 100 mg PO once daily. If idelalisib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of idelalisib. Entrectinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of entrectinib by 6-fold in a drug interaction study.
Enzalutamide: (Major) Avoid coadministration of idelalisib with enzalutamide due to decreased plasma concentrations of idelalisib. Idelalisib is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased idelalisib exposure by 75%.
Eplerenone: (Contraindicated) Coadministration of idelalisib and eplerenone is contraindicated. Idelalisib potently inhibits the hepatic CYP3A4 isoenzyme and can increase the serum concentrations of eplerenone. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and idelalisib due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If idelalisib is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. The mean ratios for the Cmax and AUC of erdafitinib were 105% and 134%, respectively, when coadministered with another strong CYP3A4 inhibitor.
Ergotamine: (Contraindicated) Concomitant use of ergotamine with idelalisib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Ergotamine; Caffeine: (Contraindicated) Concomitant use of ergotamine with idelalisib is contraindicated due to an increased risk for vasospasm which may lead to cerebral or peripheral ischemia. Concomitant use may increase ergotamine exposure. Ergotamine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Erlotinib: (Major) Avoid coadministration of erlotinib with idelalisib if possible due to the increased risk of erlotinib-related adverse reactions. If concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased erlotinib exposure by 67%.
Erythromycin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with erythromycin, a CYP3A substrate, as erythromycin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Escitalopram: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with escitalopram, a CYP3A substrate, as escitalopram toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Esomeprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with esomeprazole, a CYP3A substrate, as esomeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Estazolam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor,with estazolam, a CYP3A substrate, as estazolam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Estradiol; Levonorgestrel: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Estradiol; Norethindrone: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Estradiol; Norgestimate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Estradiol; Progesterone: (Moderate) Use caution if coadministration of idelalisib with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Idelalisib is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Eszopiclone: (Major) The total dose of eszopiclone should not exceed 2 mg when administered with idelalisib. Coadministration may increase eszopiclone exposure resulting in increased risk of next-day psychomotor or memory impairment and decreased ability to perform tasks requiring full mental alertness such as driving. CYP3A4 is a primary metabolic pathway for eszopiclone; idelalisib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased eszopiclone exposure by 2.2-fold.
Ethinyl Estradiol; Norelgestromin: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Ethinyl Estradiol; Norethindrone Acetate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Ethinyl Estradiol; Norgestrel: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Ethosuximide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ethosuximide, a CYP3A substrate, as ethosuximide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ethynodiol Diacetate; Ethinyl Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Etonogestrel: (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as idelalisib may increase the serum concentration of etonogestrel.
Etonogestrel; Ethinyl Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as idelalisib may increase the serum concentration of etonogestrel.
Etravirine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with etravirine, a CYP3A substrate, as etravirine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Everolimus: (Major) Avoid coadministration of everolimus with idelalisib due to the risk of increased everolimus-related adverse reactions. If concomitant use is unavoidable in patients receiving everolimus for either kidney or liver transplant, closely monitor everolimus whole blood trough concentrations. Everolimus is a sensitive CYP3A4 substrate and P-glycoprotein (P-gp) substrate. Idelalisib is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4/P-gp inhibitor increased the AUC of everolimus by 15-fold.
Ezetimibe; Simvastatin: (Contraindicated) Coadministration of idelalisib, a strong CYP3A inhibitor, with simvastatin, a CYP3A substrate, is contraindicated as simvastatin toxicities, including the risk for myopathy, may be significantly increased. Consider an alternative to simvastatin.
Fedratinib: (Major) Avoid coadministration of fedratinib with idelalisib as concurrent use may increase fedratinib exposure. If concurrent use cannot be avoided, reduce the dose of fedratinib to 200 mg PO once daily. If idelalisib is discontinued, increase the fedratinib dose as follows: 300 mg PO once daily for 2 weeks and then 400 mg PO once daily thereafter as tolerated. Fedratinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased fedratinib exposure by 3-fold.
Felodipine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with felodipine, a CYP3A substrate, as felodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib is necessary. If idelalisib 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 idelalisib 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 idelalisib 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.
Fesoterodine: (Major) Limit the dose of fesoterodine to 4 mg once daily in adults and pediatric patients weighing more than 35 kg if coadministered with idelalisib. Avoid use of fesoterodine and idelalisib in pediatric patients weighing 25 to 35 kg. Concurrent use may increase fesoterodine exposure. Fesoterodine is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor led to approximately a doubling of the overall exposure of 5-hydroxymethyl tolterodine (5-HMT), the active metabolite of fesoterodine.
Finasteride; Tadalafil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tadalafil, a CYP3A substrate, as tadalafil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Finerenone: (Contraindicated) Concomitant use of finerenone and idelalisib is contraindicated. Concomitant use may increase finerenone exposure and the risk for finerenone-related adverse reactions. Finerenone is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased overall exposure to finerenone by more than 400%.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and strong CYP3A4 inhibitors, such as idelalisib, is contraindicated. Strong CYP3A4 inhibitors can increase flibanserin concentrations, which can cause severe hypotension and syncope. If initiating flibanserin following use of a strong CYP3A4 inhibitor, start flibanserin at least 2 weeks after the last dose of the CYP3A4 inhibitor. If initiating a strong CYP3A4 inhibitor following flibanserin use, start the strong CYP3A4 inhibitor at least 2 days after the last dose of flibanserin.
Flurazepam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with flurazepam, a CYP3A substrate, as flurazepam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Flutamide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with flutamide, a CYP3A substrate, as flutamide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Fluticasone: (Major) Coadministration of inhaled fluticasone propionate and idelalisib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Salmeterol: (Major) Avoid concomitant use of salmeterol with idelalisib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose. (Major) Coadministration of inhaled fluticasone propionate and idelalisib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Umeclidinium; Vilanterol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with umeclidinium; vilanterol, a CYP3A substrate, as umeclidinium; vilanterol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Coadministration of inhaled fluticasone propionate and idelalisib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Fluticasone; Vilanterol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with umeclidinium; vilanterol, a CYP3A substrate, as umeclidinium; vilanterol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Coadministration of inhaled fluticasone propionate and idelalisib is not recommended; use caution with inhaled fluticasone furoate. Increased systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression, may occur. Fluticasone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. In drug interaction studies, coadministration with strong inhibitors increased plasma fluticasone exposure resulting in 45% to 86% decreases in serum cortisol AUC. A strong inhibitor increased fluticasone furoate exposure by 1.33-fold with a 27% reduction in weighted mean serum cortisol; this change does not necessitate dose adjustment of fluticasone furoate.
Food: (Major) Advise patients to avoid cannabis use during idelalisib treatment. Concomitant use may alter the exposure of some cannabinoids and increase the risk for adverse reactions. The cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are CYP3A substrates and idelalisib is a strong CYP3A inhibitor. Concomitant use of a cannabinoid product containing THC and CBD at an approximate 1:1 ratio with another strong CYP3A inhibitor increased THC, 11-OH-THC, and CBD peak exposures by 1.3-, 3-, and 1.9-fold respectively.
Formoterol; Mometasone: (Moderate) Concomitant administration of idelalisib and mometasone or formoterol; mometasone may increase systemic exposure to mometasone. Mometasone is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. The risk of interaction in unclear; however, because of the potential for systemic absorption, avoidance of mometasone may be prudent. FDA-approved labeling for idelalisib warns against coadministration with CYP3A4 substrates. If these agents are given together, exercise caution with long-term concomitant use and monitor closely for hypercorticism and adrenal suppression.
Fosamprenavir: (Moderate) Monitor for increased fosamprenavir toxicity if coadministered with idelalisib. Concurrent use may increase the plasma concentrations of fosamprenavir. Fosamprenavir is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Fosphenytoin: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with strong CYP3A4 inducer such as phenytoin or fosphenytoin, as idelalisib exposure may be significantly reduced and efficacy compromised. Additionally, idelalisib is a strong CYP3A inhibitor while phenytoin is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and phenytoin or fosphenytoin.
Fostamatinib: (Moderate) Monitor for fostamatinib toxicities that may require fostamatinib dose reduction (i.e., elevated hepatic enzymes, neutropenia, high blood pressure, severe diarrhea) if given concurrently with a strong CYP3A4 inhibitor. Concomitant use of fostamatinib with a strong CYP3A4 inhibitor increases exposure to the major active metabolite, R406, which may increase the risk of adverse reactions. R406 is extensively metabolized by CYP3A4; idelalisib is a strong CYP3A4 inhibitor. Coadministration of fostamatinib with another strong CYP3A4 inhibitor increased R406 AUC by 102% and Cmax by 37%.
Gefitinib: (Moderate) Monitor for an increase in gefitinib-related adverse reactions if coadministration with idelalisib is necessary. Gefitinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased gefitinib exposure by 80%.
Gilteritinib: (Major) Consider an alternative to idelalisib during treatment with gilteritinib. Concurrent use may increase gilteritinib exposure resulting in treatment-related adverse events. If coadministration is required, frequently monitor for gilteritinib adverse reactions. Interrupt therapy and reduce the gilteritinib dose if serious or life-threatening toxicity occurs. Gilteritinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the gilteritinib AUC by 120% in a drug interaction study.
Glasdegib: (Major) Consider an alternative to idelalisib during treatment with glasdegib. Concurrent use may increase glasdegib exposure resulting in treatment-related adverse events including QT prolongation. If coadministration cannot be avoided, monitor for increased adverse events; more frequent ECG monitoring is recommended. Glasdegib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the glasdegib AUC by 2.4-fold in a drug interaction study.
Granisetron: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with granisetron, a CYP3A substrate, as granisetron toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib 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 idelalisib 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 idelalisib 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.
Guanfacine: (Major) Idelalisib may significantly increase guanfacine plasma concentrations. Guanfacine is primarily metabolized by CYP3A4, and idelalisib is a strong CYP3A4 inhibitor. FDA-approved labeling for extended-release (ER) guanfacine recommends that, if given with a strong CYP3A4 inhibitor, the guanfacine dosage should be decreased to half of the recommended dose. The labeling for idelalisib warns against coadministration with CYP3A4 substrates. If these agents are given together, reduce the guanfacine dosage as recommended and monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. If idelalisib is discontinued, the guanfacine ER dosage should be increased back to the recommended dose.
Haloperidol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with haloperidol, a CYP3A substrate, as haloperidol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Homatropine; Hy drocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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 idelalisib 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.
Ibrexafungerp: (Major) Decrease the ibrexafungerp dose to 150 mg PO every 12 hours for 1 day if administered concurrently with idelalisib. Coadministration may result in increased ibrexafungerp exposure and toxicity. Ibrexafungerp is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of ibrexafungerp by 5.8-fold and 2.5-fold, respectively.
Ibrutinib: (Major) Avoid concomitant use of ibrutinib and idelalisib; ibrutinib plasma concentrations may increase resulting in severe ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection). Ibrutinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased ibrutinib exposure by 5.7-fold to 24-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib is necessary. If idelalisib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like idelalisib 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 idelalisib 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 idelalisib is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Idelalisib is a strong CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Iloperidone: (Major) Reduce the iloperidone dose by one-half if coadministered with idelalisib. If idelalisib is discontinued, increase the iloperidone dose to the previous level. Increased iloperidone exposure may occur with concurrent use. Iloperidone is a CYP3A4 substrate. Idelalisib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the AUC of iloperidone and its metabolites P88 and P95 by 57%, 55% and 35%, respectively.
Imatinib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with imatinib, STI-571, a CYP3A substrate, as imatinib, STI-571 toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Imipramine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with imipramine, a CYP3A substrate, as imipramine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Indinavir: (Major) Coadministration of idelalisib with indinavir may increase the exposure of both drugs; use alternative agents if possible. Although specific recommendations are unavailable for use with idelalisib, a reduced dose of indinavir 600 mg PO every 8 hours is recommended when coadministered with other strong CYP3A inhibitors. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib- and indinavir-related adverse reactions. Idelalisib and atazanavir are both CYP3A4 substrates and strong CYP3A4 inhibitors. Exposure of another sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Additionally, coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold.
Infigratinib: (Major) Avoid concomitant use of infigratinib and idelalisib. Coadministration may increase infigratinib exposure, increasing the risk for adverse effects. Infigratinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the AUC of infigratinib by 622%.
Irinotecan Liposomal: (Major) Avoid administration of idelalisib during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Idelalisib is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure to both irinotecan and SN-38.
Irinotecan: (Major) Avoid administration of idelalisib during treatment with irinotecan and for at least 1 week prior to starting therapy unless there are no therapeutic alternatives. Irinotecan and its active metabolite, SN-38, are CYP3A4 substrates. Idelalisib is a strong CYP3A4 inhibitor. Concomitant use may increase systemic exposure to both irinotecan and SN-38.
Isavuconazonium: (Contraindicated) Concomitant use of isavuconazonium with idelalisib is contraindicated due to the risk for increased isavuconazole serum concentrations and serious adverse reactions, such as hepatic toxicity. Isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate of hepatic isoenzyme CYP3A4; idelalisib is a strong inhibitor of this enzyme. According to the manufacturer, coadministration of isavuconazole with strong CYP3A4 inhibitors is contraindicated. Isavuconazole serum concentrations were increased 5-fold when coadministered with ketoconazole, another strong CYP3A4 inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as rifampin, as idelalisib exposure may be significantly reduced and efficacy compromised. In healthy subjects, rifampin 600 mg once daily for 8 days administered with a single dose of idelalisib 150 mg resulted in a decrease of the geometric mean idelalisib AUC by 75% and geometric mean Cmax by 58% compared wtih idelalisib administered alone.
Isoniazid, INH; Rifampin: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as rifampin, as idelalisib exposure may be significantly reduced and efficacy compromised. In healthy subjects, rifampin 600 mg once daily for 8 days administered with a single dose of idelalisib 150 mg resulted in a decrease of the geometric mean idelalisib AUC by 75% and geometric mean Cmax by 58% compared wtih idelalisib administered alone.
Isradipine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with isradipine, a CYP3A substrate, as isradipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Istradefylline: (Major) Do not exceed 20 mg once daily of istradefylline if administered with idelalisib as istradefylline exposure and adverse effects may increase. Idelalisib is a strong CYP3A4 inhibitor. Istradefylline exposure was increased by 2.5-fold when administered with a strong inhibitor in a drug interaction study.
Itraconazole: (Moderate) Monitor for increased idelalisib and itraconazole adverse reactions if coadministration is necessary. A dose reduction of either agent may be necessary. Both itraconazole and idelalisib are strong CYP3A4 inhibitors and substrates.
Ivabradine: (Contraindicated) Coadministration of ivabradine and idelalisib is contraindicated. Ivabradine is primarily metabolized by CYP3A4; idelalisib is a strong CYP3A4 inhibitor. Coadministration will increase the plasma concentrations of ivabradine. Increased ivabradine concentrations may result in bradycardia exacerbation and conduction disturbances.
Ivacaftor: (Major) If idelalisib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Ivermectin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ivermectin, a CYP3A substrate, as ivermectin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with idelalisib if possible due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, reduce the dose of ivosidenib to 250 mg PO once daily. Monitor ECGs for QTc prolongation and monitor electrolytes, correcting any electrolyte abnormalities as clinically appropriate. If idelalisib is discontinued, wait at least 5 half-lives of idelalisib before increasing the dose of ivosidenib to the recommended dose of 500 mg PO once daily. Ivosidenib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ivosidenib single-dose AUC to 269% of control, with no change in Cmax.
Ixabepilone: (Major) Avoid concurrent use of ixabepilone and idelalisib due to increased ixabepilone exposure, which may increase the risk of adverse reactions. If concomitant use is unavoidable, reduce the dose of ixabepilone to 20 mg/m2. Ixabepilone is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ixabepilone exposure by 79%.
Ketoconazole: (Major) Avoid idelalisib for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may increase exposure of both drugs and increase the risk of adverse effects. If concomitant use is necessary, monitor closely for adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection); a ketoconazole dose reduction may be necessary. Both ketoconazole and idelalisib are CYP3A substrates and strong CYP3A inhibitors. Coadministration with ketoconazole increased increased idelalisib exposure by 1.8-fold.
Lansoprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lansoprazole, a CYP3A substrate, as lansoprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lansoprazole, a CYP3A substrate, as lansoprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Coadministration of idelalisib with clarithromycin may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib and clarithromycin are both CYP3A4 substrates and strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold.
Lapatinib: (Major) Avoid coadministration of lapatinib with idelalisib due to increased plasma concentrations of lapatinib. If concomitant use is unavoidable, decrease the dose of lapatinib to 500 mg PO once daily. If idelalisib is discontinued, increase lapatinib to the indicated dose after a washout period of approximately 1 week. Lapatinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Concomitant use with another strong CYP3A4 inhibitor increased lapatinib exposure by 3.6-fold and increased the half-life of lapatinib by 1.7-fold.
Larotrectinib: (Major) Avoid coadministration of larotrectinib with idelalisib due to increased larotrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided, reduce the larotrectinib dose by 50%. If idelalisib is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of idelalisib. Larotrectinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the AUC of larotrectinib by 4.3-fold in a drug interaction study.
Lefamulin: (Major) Avoid coadministration of idelalisib with oral lefamulin due to increased lefamulin exposure; idelalisib may be administered with intravenous lefamulin. Lefamulin is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration of a strong CYP3A4 inhibitor increased the exposure of oral and intravenous lefamulin by 165% and 31%, respectively.
Lemborexant: (Major) Avoid coadministration of lemborexant and idelalisib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of lemborexant with another strong/moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Leniolisib: (Major) Avoid concomitant use of leniolisib and idelalisib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of idelalisib; monitor for potential reduction in efficacy. Idelalisib is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of idelalisib; monitor for potential reduction in efficacy. Idelalisib is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Moderate) An increase in the plasma concentration of idelalisib may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. If idelalisib is coadministered with both letermovir and cyclosporine, monitor for adverse reactions and modify idelalisib dose as needed. Idelalisib is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. Concurrent use with a strong CYP3A inhibitor increased exposure of idelalisib by 1.8-fold.
Leuprolide; Norethindrone: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Levamlodipine: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Levoketoconazole: (Major) Avoid idelalisib for 2 weeks prior to and during treatment with ketoconazole. Concomitant use may increase exposure of both drugs and increase the risk of adverse effects. If concomitant use is necessary, monitor closely for adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection); a ketoconazole dose reduction may be necessary. Both ketoconazole and idelalisib are CYP3A substrates and strong CYP3A inhibitors. Coadministration with ketoconazole increased increased idelalisib exposure by 1.8-fold.
Levonorgestrel: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Levonorgestrel; Ethinyl Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Lidocaine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lidocaine, a CYP3A substrate, as lidocaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Lidocaine; Epinephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lidocaine, a CYP3A substrate, as lidocaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Lidocaine; Prilocaine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lidocaine, a CYP3A substrate, as lidocaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and idelalisib is contraindicated; concurrent use may increase the exposure of both drugs and the risk of adverse effects. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; idelalisib is a CYP3A4 substrate and strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of lonafarnib by 425% and increased idelalisib exposure by 1.8-fold.
Loperamide: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with idelalisib. Concurrent use may increase loperamide exposure. Loperamide is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Loperamide; Simethicone: (Moderate) Monitor for loperamide-associated adverse reactions, such as CNS effects and cardiac toxicities (i.e., syncope, ventricular tachycardia, QT prolongation, torsade de pointes, cardiac arrest), if coadministered with idelalisib. Concurrent use may increase loperamide exposure. Loperamide is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 and P-gp inhibitor increased loperamide exposure by 3.8-fold.
Lopinavir; Ritonavir: (Contraindicated) Concomitant use of idelalisib, a CYP3A4 substrate, and ritonavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while ritonavir is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and ritonavir. (Moderate) Avoid concurrent use of idelalisib and lopinavir when possible. Use of idelalisib, a strong CYP3A4 inhibitor, and lopinavir, a CYP3A4 substrate, may increase lopinavir plasma concentrations. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Lorlatinib: (Major) Avoid coadministration of lorlatinib with idelalisib due to increased plasma concentrations of lorlatinib, which may increase the incidence and severity of adverse reactions. If concomitant use is unavoidable, reduce the starting dose of lorlatinib from 100 mg to 75 mg once daily, or from 75 mg to 50 mg once daily. If idelalisib is discontinued, resume the original dose of lorlatinib after 3 half-lives of idelalisib. Lorlatinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A4 inhibitor increased lorlatinib exposure by 42%.
Losartan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with losartan, a CYP3A substrate, as losartan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Losartan; Hydrochlorothiazide, HCTZ: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with losartan, a CYP3A substrate, as losartan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Lovastatin: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lovastatin, a CYP3A substrate, as lovastatin toxicities, such as myopathy, may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Consider an alternative to lovastatin. A single dose of 10 mg of rosuvastatin was administered alone and after idelailsib 150 mg for 12 doses in healthy subjects and no changes in exposure to rosuvastatin were observed.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of idelalisib and lumacaftor; ivacaftor as idelalisib exposure may be significantly reduced and efficacy compromised. Additionally, the exposure of ivacaftor may be increased. Lumacaftor; ivacaftor dosage adjustment is not required when idelalisib is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking idelalisib, reduce the dose of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking idelalisib. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Idelalisib is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Lumacaftor's induction of CYP3A may decrease the systemic exposure of idelalisib and decrease its therapeutic efficacy. Although idelalisib is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold. (Major) If idelalisib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of idelalisib and lumacaftor; ivacaftor as idelalisib exposure may be significantly reduced and efficacy compromised. Additionally, the exposure of ivacaftor may be increased. Lumacaftor; ivacaftor dosage adjustment is not required when idelalisib is started in a patient already taking lumacaftor; ivacaftor. However, if lumacaftor; ivacaftor is initiated in a patient already taking idelalisib, reduce the dose of lumacaftor; ivacaftor to 1 tablet PO daily or 1 packet of oral granules every other day for the first week of treatment, and then increase to the usual recommended daily dose. This dosage adjustment is also necessary if lumacaftor; ivacaftor therapy has been interrupted for more than 1 week and re-initiated while the patient is taking idelalisib. The 1-week lead-in period at the lower lumacaftor; ivacaftor dosage allows for lumacaftor's induction of CYP3A to reach steady state. Idelalisib is a substrate and strong inhibitor of CYP3A. Ivacaftor is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer. Lumacaftor's induction of CYP3A may decrease the systemic exposure of idelalisib and decrease its therapeutic efficacy. Although idelalisib is a strong CYP3A4 inhibitor, net ivacaftor exposure at steady state is not expected to exceed that achieved with ivacaftor monotherapy (i.e., 150 mg PO every 12 hours) because of lumacaftor's CYP3A induction. In pharmacokinetic studies, coadministration of lumacaftor; ivacaftor with another strong CYP3A4 inhibitor increased ivacaftor exposure by 4.3-fold.
Lumateperone: (Major) Reduce the dose of lumateperone to 10.5 mg once daily if concomitant use of idelalisib is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor increased lumateperone exposure by approximately 4-fold.
Lurasidone: (Contraindicated) Concurrent use of lurasidone with strong CYP3A4 inhibitors, such as idelalisib, is contraindicated. Lurasidone is primarily metabolized by CYP3A4. Increased lurasidone plasma concentrations are expected when the drug is co-administered with strong inhibitors of CYP3A4.
Lurbinectedin: (Major) Avoid concomitant use of lurbinectedin and idelalisib due to the risk of increased lurbinectedin exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of lurbinectedin by 50%. Lurbinectedin is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of lurbinectedin by 2.7-fold.
Maprotiline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with maprotiline, a CYP3A substrate, as maprotiline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Maraviroc: (Major) Coadministration of idelalisib, a strong CYP3A4 inhibitor, and maraviroc, a CYP3A4 substrate, may result in elevated maraviroc concentrations. According to the manufacturer of idelalisib, concomitant use of idelalisib and CYP3A substrates should be avoided. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. According to the manufacturer of maraviroc, a reduced adult maraviroc dose of 150 mg PO twice daily is recommended when it is administered in the presence of a CYP3A inhibitor, with or without a concomitant CYP3A inducer. Coadministration of maraviroc with strong CYP3A inhibitors is contraindicated in patients with CrCl less than 30 mL/min. Dose recommendations in pediatrics are: 150 mg PO twice daily for children weighing 40 kg or more, 100 mg PO twice daily for children weighing 30 to 39 kg, 75 mg PO twice daily (or 80 mg PO twice daily for solution) for children weighing 20 to 29 kg, 50 mg PO twice daily for children weighing 10 to 19 kg, and use is not recommended in children weighing 2 to 9 kg.
Mavacamten: (Contraindicated) Mavacamten is contraindicated for use with idelalisib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Medroxyprogesterone: (Major) Coadministration of medroxyprogesterone, a CYP3A substrate with idelalisib, a strong CYP3A inhibitor should be avoided since it is expected to increase concentrations of medroxyprogesterone acetate. Formal drug interaction studies have not been conducted; however, medroxyprogesterone is metabolized primarily by hydroxylation via the CYP3A4 in vitro.
Mefloquine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with mefloquine, a CYP3A substrate, as mefloquine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Meloxicam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with meloxicam, a CYP3A substrate, as meloxicam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Metformin; Repaglinide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with repaglinide, a CYP3A substrate, as repaglinide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Methadone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with methadone, a CYP3A substrate, as methadone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Methylprednisolone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with methylprednisolone, a CYP3A substrate, as methylprednisolone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Midazolam: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with midazolam, a CYP3A substrate, as midazolam toxicities may be significantly increased. In healthy subjects, a single oral dose of midazolam 5 mg administered after idelalisib 150 mg by mouth for 15 doses increased the geometric mean Cmax of midazolam by 2.4-fold and the geometric mean AUC of midazolam by 5.4-fold.
Midostaurin: (Major) Avoid the concomitant use of midostaurin and idelalisib due to the risk of increased midostaurin exposure which may increase the incidence and severity of adverse reactions. If concomitant use cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity, particularly during the first week of midostaurin therapy for those with systemic mastocytosis/mast cell leukemia and during the first week of each cycle for those with acute myeloid leukemia. Midostaurin is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration of one strong CYP3A4 inhibitor with a single dose of midostaurin increased the exposure of midostaurin and its active metabolites CGP62221 and CGP52421 by 10.4-fold, 3.5-fold, and 1.2-fold, respectively. Coadministration of another strong CYP3A4 inhibitor with twice daily doses of midostaurin increased Day 28 trough concentrations of midostaurin, CGP62221, and CGP52421 by 2.1-fold, 1.2-fold, and 1.3-fold respectively compared with day 21 trough levels with midostaurin alone.
Mifepristone: (Major) Caution is advised when administering idelalisib with mifepristone because increased serum concentrations of either drug may occur. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with idelalisib should be done only when necessary, and in such cases the dose of mifepristone should be limited to a maximum dose of 900 mg per day. In a patient already receiving idelalisib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving mifepristone 300 mg, dosage adjustments are not required. If therapy with idelalisib is initiated in a patient already receiving mifepristone 600 mg, reduce dose of mifepristone to 300 mg and titrate to a maximum of 600 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving 900 mg, reduce dose of mifepristone to 600 mg and titrate to a maximum of 900 mg if clinically indicated. If therapy with idelalisib is initiated in a patient already receiving 1,200 mg, reduce the mifepristone dose to 900 mg. Additionally, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Both mifepristone and idelalisib are substrates and strong inhibitors of CYP3A4. Coadministration with another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
Mirtazapine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with mirtazapine, a CYP3A substrate, as mirtazapine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Mirvetuximab Soravtansine: (Moderate) Closely monitor for mirvetuximab soravtansine-related adverse reactions if concomitant use of idelalisib is necessary. DM4, the cytotoxic component of mirvetuximab soravtansine, is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use may increase unconjugated DM4 exposure.
Mitapivat: (Major) Avoid coadministration of mitapivat with idelalisib due to increased risk of adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with other strong CYP3A inhibitors increased mitapivat overall exposure by 3.6 to 4.9-fold.
Mitotane: (Major) Avoid the concomitant use of mitotane with idelalisib; consider alternative agents with less CYP3A4 induction. Mitotane is a strong CYP3A4 inducer and idelalisib is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of idelalisib. In healthy subjects, coadministration of another strong CYP3A inducer, rifampin (600 mg daily for 8 days) with idelalisib (single dose) resulted in a decrease of the geometric mean idelalisib AUC by 75% and geometric mean Cmax by 58% compared with idelalisib alone.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and idelalisib. Concomitant use may increase mobocertinib exposure and the risk for adverse reactions such as QT prolongation. Mobocertinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Use of a strong CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 374% to 419%.
Modafinil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with modafinil, a CYP3A substrate, as modafinil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Mometasone: (Moderate) Concomitant administration of idelalisib and mometasone or formoterol; mometasone may increase systemic exposure to mometasone. Mometasone is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. The risk of interaction in unclear; however, because of the potential for systemic absorption, avoidance of mometasone may be prudent. FDA-approved labeling for idelalisib warns against coadministration with CYP3A4 substrates. If these agents are given together, exercise caution with long-term concomitant use and monitor closely for hypercorticism and adrenal suppression.
Naldemedine: (Major) Monitor for potential naldemedine-related adverse reactions if coadministered with idelalisib. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor.
Naloxegol: (Contraindicated) Concomitant use of naloxegol with idelalisib is contraindicated. Naloxegol is metabolized primarily by CYP3A. Strong CYP3A4 inhibitors, such as idelalisib, can significantly increase exposure to naloxegol which may precipitate opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with idelalisib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and idelalisib is a strong 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) Avoid concomitant use of sirolimus and idelalisib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Naproxen; Esomeprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with esomeprazole, a CYP3A substrate, as esomeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Nefazodone: (Contraindicated) Concomitant use of idelalisib, a CYP3A4 substrate, and nefazodone, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while nefazodone is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and nefazodone.
Nelfinavir: (Contraindicated) Concomitant use of idelalisib, a CYP3A4 substrate, and nelfinavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while nelfinavir is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and nelfinavir.
Neratinib: (Major) Avoid concomitant use of idelalisib with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased neratinib exposure by 381%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Netupitant is mainly metabolized by CYP3A4. Coadministration of netupitant; palonosetron with a strong CYP3A4 inhibitor (e.g., idelalisib) can significantly increase the systemic exposure to netupitant. However, no dosage adjustment is necessary for single dose administration.
Nevirapine: (Moderate) Monitor for an increase in nevirapine-related adverse reactions if coadministration with idelalisib is necessary. Nevirapine is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased nevirapine exposure by 100%; concomitant use with a strong CYP3A4 inhibitor may also increase nevirapine exposure.
Niacin; Simvastatin: (Contraindicated) Coadministration of idelalisib, a strong CYP3A inhibitor, with simvastatin, a CYP3A substrate, is contraindicated as simvastatin toxicities, including the risk for myopathy, may be significantly increased. Consider an alternative to simvastatin.
Nifedipine: (Moderate) Careful monitoring and dose adjustment of nifedipine may be necessary if administered with idelalisib as nifedipine exposure and adverse effects may be increased. Consider initiating nifedipine at the lowest dose. Nifedipine is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and idelalisib. If coadministration is required, monitor patients closely for prolongation of the QT interval and reduce the nilotinib dose to 300 mg once daily in patients with resistant or intolerant Ph+ CML or to 200 mg once daily in patients with newly diagnosed Ph+ CML. If idelalisib is discontinued, a washout period should be allowed before adjusting the nilotinib dosage upward to the indicated dose. Nilotinib is a substrate of CYP3A4 and idelalisib is a strong inhibitor of CYP3A4.
Nimodipine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with nimodipine, a CYP3A substrate, as nimodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Nirmatrelvir; Ritonavir: (Contraindicated) Concomitant use of idelalisib, a CYP3A4 substrate, and ritonavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while ritonavir is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and ritonavir.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with idelalisib 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 idelalisib is a strong CYP3A4 inhibitor.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Norethindrone: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Norethindrone; Ethinyl Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Norgestimate; Ethinyl Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Norgestrel: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Nortriptyline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with nortriptyline, a CYP3A substrate, as nortriptyline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Olaparib: (Major) Avoid coadministration of olaparib with idelalisib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 100 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after idelalisib is discontinued. Olaparib is a CYP3A substrate and idelalisib is a strong CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with another strong CYP3A inhibitor increased the olaparib Cmax by 42% and the AUC by 170%.
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 idelalisib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and idelalisib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If idelalisib 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 idelalisib is a strong CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Olopatadine; Mometasone: (Moderate) Concomitant administration of idelalisib and mometasone or formoterol; mometasone may increase systemic exposure to mometasone. Mometasone is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. The risk of interaction in unclear; however, because of the potential for systemic absorption, avoidance of mometasone may be prudent. FDA-approved labeling for idelalisib warns against coadministration with CYP3A4 substrates. If these agents are given together, exercise caution with long-term concomitant use and monitor closely for hypercorticism and adrenal suppression.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and idelalisib. If concomitant use is necessary, decrease omaveloxolone dose to 50 mg once daily. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased omaveloxolone overall exposure by 4-fold.
Omeprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with omeprazole, a CYP3A substrate, as omeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Omeprazole; Amoxicillin; Rifabutin: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rifabutin, a CYP3A substrate, as rifabutin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with omeprazole, a CYP3A substrate, as omeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Omeprazole; Sodium Bicarbonate: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with omeprazole, a CYP3A substrate, as omeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ondansetron: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ondansetron, a CYP3A substrate, as ondansetron toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Oral Contraceptives: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Osilodrostat: (Major) Reduce the dose of osilodrostat by one-half during coadministration of idelalisib; concurrent use may increase osilodrostat exposure and the risk of osilodrostat-related adverse reactions. Osilodrostat is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor.
Oxybutynin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with oxybutynin, a CYP3A substrate, as oxybutynin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib is necessary. If idelalisib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like idelalisib 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 idelalisib 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.
Paclitaxel: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with paclitaxel, a CYP3A substrate, as paclitaxel toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Pacritinib: (Contraindicated) Concurrent use of pacritinib with idelalisib is contraindicated due to increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Palbociclib: (Major) Avoid coadministration of idelalisib with palbociclib; significantly increased palbociclib exposure may occur. If concomitant use cannot be avoided, reduce the dose of palbociclib to 75 mg PO once daily and monitor for increased adverse reactions. If idelalisib is discontinued, increase the palbociclib dose (3 to 5 half-lives of idelalisib) to the dose used before the initiation of idelalislib. Palbociclib is primarily metabolized by CYP3A4 and idelalisib is a strong CYP3A4 inhibitor. In a drug interaction trial, coadministration with another strong CYP3A4 inhibitor increased the AUC and Cmax of palbociclib by 87% and 34%, respectively.
Palovarotene: (Major) Avoid concomitant use of palovarotene and idelalis ib due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. Palovarotene is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased palovarotene overall exposure by 3-fold.
Paricalcitol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with paricalcitol, a CYP3A substrate, as paricalcitol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and idelalisib 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 idelalisib is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of idelalisib. Pemigatinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased pemigatinib exposure by 88%.
Perampanel: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with perampanel, a CYP3A substrate, as perampanel toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Perindopril; Amlodipine: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Perphenazine; Amitriptyline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amitriptyline, a CYP3A substrate, as amitriptyline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and idelalisib 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 idelalisib is discontinued, increase the pexidartinib dose to the original dose after 3 plasma half-lives of idelalisib. Pexidartinib is a CYP3A substrate; idelalisib is a strong CYP3A inhibitor. Coadministration of another strong CYP3A inhibitor increased pexidartinib exposure by 70%.
Phenobarbital: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as phenobarbital, as idelalisib exposure may be significantly reduced and efficacy compromised.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as phenobarbital, as idelalisib exposure may be significantly reduced and efficacy compromised.
Phenytoin: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with strong CYP3A4 inducer such as phenytoin, as idelalisib exposure may be significantly reduced and efficacy compromised. Additionally, idelalisib is a strong CYP3A inhibitor while phenytoin is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and phenytoin.
Pimavanserin: (Major) Because pimavanserin is primarily metabolized by CYP3A4 and CYP3A5, the manufacturer recommends that the pimavanserin dose be reduced to 10 mg/day PO in patients receiving strong inhibitors of CYP3A4 such as idelalisib. If these agents are used in combination, the patient should be carefully monitored for pimavanserin-related adverse reactions, including nausea, vomiting, confusion, loss of balance or coordination, and QT prolongation.
Pimozide: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pimozide, a CYP3A substrate, as pimozide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Pirtobrutinib: (Major) Avoid concomitant use of pirtobrutinib and idelalisib due to the risk of increased pirtobrutinib exposure which may increase the risk for adverse effects. If concomitant use is necessary, reduce the pirtobrutinib dose by 50 mg. If the current pirtobrutinib dosage is 50 mg once daily, interrupt pirtobrutinib treatment for the duration of idelalisib use. Resume the previous dose of pirtobrutinib after idelalisib is discontinued for 5 half-lives. Pirtobrutinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant with another strong CYP3A inhibitor increased pirtobrutinib overall exposure by 49%.
Polatuzumab Vedotin: (Moderate) Monitor for increased polatuzumab vedotin toxicity during coadministration of idelalisib due to the risk of elevated exposure to the cytotoxic component of polatuzumab vedotin, MMAE. MMAE is metabolized by CYP3A4; idelalisib is a strong CYP3A4 inhibitor. Strong CYP3A4 inhibitors are predicted to increase the exposure of MMAE by 45%.
Ponatinib: (Major) Avoid coadministration of ponatinib and idelalisib due to the potential for increased ponatinib exposure. If concurrent use cannot be avoided, reduce the ponatinib dose to the next lower dose level (45 mg to 30 mg; 30 mg to 15 mg; 15 mg to 10 mg). If the patient is taking ponatinib 10 mg once daily prior to concurrent use, avoid the use of idelalisib and consider alternative therapy. After idelalisib has been discontinued for 3 to 5 half-lives, resume the dose of ponatinib that was tolerated prior to starting idelalisib. Ponatinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ponatinib AUC by 78%.
Pralsetinib: (Major) Avoid concomitant use of idelalisib 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 idelalisib is a strong CYP3A inhibitor. Coadministration with a strong CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 122%.
Prasugrel: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with prasugrel, a CYP3A substrate, as prasugrel toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Pravastatin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pravastatin, a CYP3A substrate, as pravastatin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Prednisolone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with prednisolone, a CYP3A substrate, as prednisolone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. In addition, because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections. If coadministration is necessary, close clinical monitoring is advised and therapy should be accompanied by appropriate antimicrobial therapies as indicated.
Prednisone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with prednisone, a CYP3A substrate, as prednisone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. In addition, because systemically administered corticosteroids exhibit immunosuppressive effects when given in high doses and/or for extended periods, additive effects may be seen with other immunosuppressives or antineoplastic agents. While therapy is designed to take advantage of this effect, patients may be predisposed to over-immunosuppression resulting in an increased risk for the development of severe infections. If coadministration is necessary, close clinical monitoring is advised and therapy should be accompanied by appropriate antimicrobial therapies as indicated.
Primidone: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as primidone, as idelalisib exposure may be significantly reduced and efficacy compromised.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and idelalisib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. Concomitant use is contraindicated in patients with renal or hepatic impairment. Additionally, this combination is contraindicated if colchicine is being used for cardiovascular risk reduction. If concomitant use is necessary outside of these scenarios, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce the dose from 0.6 mg twice daily to 0.3 mg once daily or from 0.6 mg once daily to 0.3 mg once every other day. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 0.6 mg followed by 0.3 mg. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 0.6 mg. Colchicine is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Progesterone: (Moderate) Use caution if coadministration of idelalisib with progesterone is necessary, as the systemic exposure of progesterone may be increased resulting in an increase in treatment-related adverse reactions. Idelalisib is a strong CYP3A4 inhibitor. Progesterone is metabolized primarily by hydroxylation via a CYP3A4. This interaction does not apply to vaginal preparations of progesterone (e.g., Crinone, Endometrin).
Propafenone: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with propafenone, a CYP3A substrate, as propafenone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Quazepam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quazepam, a CYP3A substrate, as quazepam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Quetiapine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quetiapine, a CYP3A substrate, as quetiapine toxicities may be significantly increased. If coadministration cannot be avoided, the manufacturer of quetiapine recommends reducing the dose of quetiapine to one sixth of the current dose in combination with a potent CYP3A4 inhibitor. When the CYP3A4 inhibitor is discontinued, the dose of quetiapine should be increased by 6-fold. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Quinidine: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quinidine, a CYP3A substrate, as quinidine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Quinine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with quinine, a CYP3A substrate, as quinine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Quizartinib: (Major) Avoid concomitant use of idelalisib with quizartinib due to the risk of increased quizartinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the dose of quizartinib to 26.5 mg for patients taking a daily dose of 53 mg, and to 17.7 mg for patients taking a daily dose of 35.4 mg or 26.5 mg; interrupt quizartinib therapy for the duration of the strong CYP3A inhibitor use for patients already taking a daily dose of 17.7 mg. Quizartinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the overall exposure of quizartinib by 94%.
Rabeprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rabeprazole, a CYP3A substrate, as rabeprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ramelteon: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ramelteon, a CYP3A substrate, as ramelteon toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ranolazine: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ranolazine, a CYP3A substrate, as ranolazine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Regorafenib: (Major) Avoid coadministration of regorafenib with idelalisib due to increased plasma concentrations of regorafenib and decreased plasma concentrations of the active metabolites M-2 and M-5, which may lead to increased toxicity. Regorafenib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased regorafenib exposure by 33% and decreased exposure of M-2 and M-5 by 93% each.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly.
Repaglinide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with repaglinide, a CYP3A substrate, as repaglinide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Retapamulin: (Moderate) Coadministration of retapamulin with strong CYP3A4 inhibitors, such as idelalisib, in patients younger than 24 months is not recommended. Systemic exposure of topically administered retapamulin may be higher in patients younger than 24 months than in patients 2 years and older. Retapamulin is a CYP3A4 substrate.
Ribociclib: (Major) Avoid coadministration of idelalisib with ribociclib if possible due to increased ribociclib exposure resulting in a risk of QT prolongation; exposure to idelalisib may also be increased. If concomitant use is unavoidable, reduce the dose of ribociclib to 400 mg PO once daily. Monitor ECGs for QT prolongation and monitor electrolytes; also monitor for idelalisib-related adverse reactions. If idelalisib is discontinued, the original dose of ribociclib may be resumed after at least 5 half-lives of idelalisib. Ribociclib is a CYP3A4 substrate and strong inhibitor that has been shown to prolong the QTc interval in a dose- and concentration-related manner. Idelalisib is also a CYP3A4 substrate and strong inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ribociclib exposure in healthy subjects by 3.2-fold, while another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
Ribociclib; Letrozole: (Major) Avoid coadministration of idelalisib with ribociclib if possible due to increased ribociclib exposure resulting in a risk of QT prolongation; exposure to idelalisib may also be increased. If concomitant use is unavoidable, reduce the dose of ribociclib to 400 mg PO once daily. Monitor ECGs for QT prolongation and monitor electrolytes; also monitor for idelalisib-related adverse reactions. If idelalisib is discontinued, the original dose of ribociclib may be resumed after at least 5 half-lives of idelalisib. Ribociclib is a CYP3A4 substrate and strong inhibitor that has been shown to prolong the QTc interval in a dose- and concentration-related manner. Idelalisib is also a CYP3A4 substrate and strong inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ribociclib exposure in healthy subjects by 3.2-fold, while another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
Rifabutin: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rifabutin, a CYP3A substrate, as rifabutin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Rifampin: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as rifampin, as idelalisib exposure may be significantly reduced and efficacy compromised. In healthy subjects, rifampin 600 mg once daily for 8 days administered with a single dose of idelalisib 150 mg resulted in a decrease of the geometric mean idelalisib AUC by 75% and geometric mean Cmax by 58% compared wtih idelalisib administered alone.
Rifapentine: (Major) Avoid coadministration of idelalisib with rifapentine due to the risk of decreased idelalisib exposure and reduced efficacy. Idelalisib is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased idelalisib exposure by 75%.
Rilpivirine: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rilpivirine, a CYP3A substrate, as rilpivirine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Rimegepant: (Major) Avoid coadministration of rimegepant with idelalisib; concurrent use may significantly increase rimegepant exposure. Rimegepant is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration of rimegepant with another strong CYP3A4 inhibitor increased rimegepant exposure by 4-fold.
Ripretinib: (Moderate) Monitor patients more frequently for ripretinib-related adverse reactions if coadministered with idelalisib. Coadministration may increase the exposure of ripretinib and its active metabolite (DP-5439), which may increase the risk of adverse reactions. Ripretinib and DP-5439 are metabolized by CYP3A4 and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased ripretinib and DP-5439 exposure by 99%.
Ritonavir: (Contraindicated) Concomitant use of idelalisib, a CYP3A4 substrate, and ritonavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while ritonavir is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and ritonavir.
Rivaroxaban: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with rivaroxaban, a CYP3A substrate, as rivaroxaban toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ropivacaine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ropivacaine, a CYP3A substrate, as ropivacaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ruxolitinib: (Major) Reduce the ruxolitinib dosage when coadministered with idelalisib in patients with myelofibrosis (MF) or polycythemia vera (PV) as increased ruxolitinib exposure and toxicity may occur. No dose adjustments are necessary for patients with graft-versus-host disease; however, monitor blood counts more frequently for toxicity and adjust ruxolitinib dosage for adverse reactions. In MF patients, reduce the initial dose to 10 mg PO twice daily for platelet count of 100,000 cells/mm3 or more and 5 mg PO once daily for platelet count of 50,000 to 99,999 cells/mm3. In PV patients, reduce the initial dose to 5 mg PO twice daily. In MF or PV patients stable on ruxolitinib dose of 10 mg PO twice daily or more, reduce dose by 50%; in patients stable on ruxolitinib dose of 5 mg PO twice daily, reduce ruxolitinib to 5 mg PO once daily. Avoid the use of idelalisib in MF or PV patients who are stable on a ruxolitinib dose of 5 mg PO once daily. Ruxolitinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor.
Salmeterol: (Major) Avoid concomitant use of salmeterol with idelalisib. Concomitant use increases salmeterol exposure and may increase the incidence and severity of salmeterol-related adverse effects. Signs and symptoms of excessive beta-adrenergic stimulation commonly include tachyarrhythmias, hypertension, and tremor. Salmeterol is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased salmeterol overall exposure 16-fold mainly due to increased bioavailability of the swallowed portion of the dose.
Saquinavir: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and saquinavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while saquinavir is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and saquinavir.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Segesterone Acetate; Ethinyl Estradiol: (Moderate) Idelalisib is a strong CYP3A inhibitor, and ethinyl estradiol (EE) is a CYP3A substrate. Use caution in dose selection, as the hormonal side effects of ethinyl estradiol may be increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Females of reproductive potential should avoid becoming pregnant during idelalisib therapy, using effective contraception during treatment and for at least 1 month after the last dose. Thus, use idelalisib with caution in combination with any combination oral contraceptives, most of which contain EE or mestranol (which is converted to EE). In addiiton, drospirenone has antimineralocorticoid effects; the progestin may increase serum potassium. Consider monitoring serum potassium concentrations during the first month of dosing in high-risk patients who take strong CYP3A4 inhibitors long-term and concomitantly. (Minor) Coadministration of segesterone, a CYP3A4 substrate and a strong CYP3A4 inhibitor, such as idelalisib may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and idelalisib 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 40 mg PO twice daily if original dose was 120 mg twice daily, and to 80 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If idelalisib is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of idelalisib. Selpercatinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selpercatinib exposure by 133%.
Selumetinib: (Major) Avoid coadministration of selumetinib and idelalisib 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 idelalisib is discontinued, resume the original selumetinib dose after 3 elimination half-lives of idelalisib. Selumetinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased selumetinib exposure by 49%.
Sertraline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with sertraline, a CYP3A substrate, as sertraline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Sildenafil: (Major) Coadministration of idelalisib is not recommended in patients receiving sildenafil for pulmonary arterial hypertension (PAH). When sildenafil is used for erectile dysfunction, consider a starting dose of 25 mg for patients receiving idelalisib. Concurrent use may increase sildenafil plasma concentrations resulting in increased associated adverse events including hypotension, syncope, visual changes, and prolonged erection. Idelalisib is a strong CYP3A4 inhibitor; sildenafil is a sensitive CYP3A4 substrate. Coadministration of other strong CYP3A4 inhibitors increased the sildenafil AUC between 3- and 11-fold.
Silodosin: (Contraindicated) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with silodosin, a CYP3A substrate, as silodosin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Simvastatin: (Contraindicated) Coadministration of idelalisib, a strong CYP3A inhibitor, with simvastatin, a CYP3A substrate, is contraindicated as simvastatin toxicities, including the risk for myopathy, may be significantly increased. Consider an alternative to simvastatin.
Siponimod: (Moderate) Concomitant use of siponimod and idelalisib 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; idelalisib is a strong CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Major) Avoid concomitant use of sirolimus and idelalisib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor.
Sofosbuvir; Velpatasvir: (Moderate) Use caution when administering velpatasvir with idelalisib. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Idelalisib is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Moderate) Use caution when administering velpatasvir with idelalisib. Taking these drugs together may increase velpatasvir plasma concentrations, potentially resulting in adverse events. Idelalisib is a potent CYP3A4 inhibitor; velpatasvir is a substrate of CYP3A4.
Solifenacin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with solifenacin, a CYP3A substrate, as solifenacin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Sonidegib: (Major) Avoid concomitant use of sonidegib and idelalisib as increased sonidegib plasma are expected, resulting in an increased risk of adverse events, particularly musculoskeletal toxicity. Idelalisib is a strong CYP3A4 inhibitor and may significantly increase the level of the CYP3A4 substrate, sonidegib. Coadministration of another strong CYP3A4 inhibitor increased the mean Cmax and AUC of sonidegib by 2.2-fold and 1.5-fold, respectively.
Sparsentan: (Major) Avoid concomitant use of sparsentan and idelalisib. Concomitant use may increase sparsentan exposure and the risk for sparsentan-related adverse effects. Sparsentan is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased sparsentan overall exposure by 174%.
St. John's Wort, Hypericum perforatum: (Contraindicated) Avoid concomitant use of idelalisib, a CYP3A4 substrate, with a strong CYP3A4 inducer such as St. John's Wort, Hypericum perforatum, as idelalisib exposure may be significantly reduced and efficacy compromised.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if idelalisib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of idelalisib is necessary. If idelalisib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a strong CYP3A4 inhibitor like idelalisib 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 idelalisib 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.
Sunitinib: (Major) Avoid coadministration of idelalisib with sunitinib if possible due to increased sunitinib exposure, which may increase the risk of QT prolongation. If concomitant use is unavoidable, monitor the QT interval more frequently and consider reducing the daily dose of sunitinib to a minimum of 37.5 mg for patients with GIST or RCC, and to a minimum of 25 mg for patients with pNET. Sunitinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased exposure to sunitinib and its primary active metabolite by 51%.
Suvorexant: (Major) Coadministration of suvorexant and idelalisib is not recommended due to the potential for significantly increased suvorexant exposure. Suvorexant is a CYP3A4 substrate. Idelalisib is a strong CYP3A4 inhibitor. Coadministration of another strong CYP3A4 inhibitor increased the suvorexant AUC by 2.8-fold.
Tacrolimus: (Major) The manufacturer of idelalisib recommends avoiding concomitant use with sensitive 3A4 substrates such as tacrolimus. If coadministration is unavoidable, decrease tacrolimus dose and closely monitor tacrolimus serum concentrations; additional dosage reductions may be required. Concurrent use may increase tacrolimus serum concentrations and increase the risk of toxicity. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic index; idelalisib is a strong CYP3A4 inhibitor. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Tadalafil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tadalafil, a CYP3A substrate, as tadalafil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Tamsulosin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tamsulosin, a CYP3A substrate, as tamsulosin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with idelalisib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. Tazemetostat is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telmisartan; Amlodipine: (Moderate) Coadministration of idelalisib with amlodipine may increase the systemic exposure of amlodipine resulting in amlodipine-related adverse events. Consider an amlodipine dose reduction if these agents are administered together and monitor for symptoms of hypotension and edema.
Temsirolimus: (Major) Avoid coadministration of idelalisib with temsirolimus due to increased plasma concentrations of the primary active metabolite of temsirolimus (sirolimus). If concomitant use is unavoidable, consider reducing the dose of temsirolimus to 12.5 mg per week. Allow a washout period of approximately 1 week after discontinuation of idelalisib before increasing temsirolimus to its original dose. Temsirolimus is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor did not significantly affect temsirolimus exposure, but increased the AUC and Cmax of sirolimus by 3.1-fold and 2.2-fold, respectively.
Teniposide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with teniposide, a CYP3A substrate, as teniposide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Terbinafine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with terbinafine, a CYP3A substrate, as terbinafine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Tezacaftor; Ivacaftor: (Major) If idelalisib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to twice weekly. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased ivacaftor exposure by 8.5-fold. (Major) Reduce the dosing frequency of tezacaftor; ivacaftor when coadministered with idelalisib; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet twice a week, approximately 3 to 4 days apart (i.e., Day 1 and Day 4). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); idelalisib is a strong CYP3A inhibitor. Coadministration of a strong CYP3A inhibitor increased tezacaftor and ivacaftor exposure 4- and 15.6-fold, respectively.
Theophylline, Aminophylline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with theophylline, aminophylline, a CYP3A substrate, as theophylline, aminophylline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Thiotepa: (Major) Avoid the concomitant use of thiotepa and idelalisib if possible; reduced metabolism to the active thiotepa metabolite may result in decreased thiotepa efficacy. Consider an alternative agent with no or minimal potential to inhibit CYP3A4. If coadministration is necessary, monitor patients for signs of reduced thiotepa efficacy. In vitro, thiotepa is metabolized via CYP3A4 to the active metabolite, TEPA; idelalisib is a strong CYP3A4 inhibitor.
Tiagabine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tiagabine, a CYP3A substrate, as tiagabine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Ticagrelor: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ticagrelor, a CYP3A substrate, as ticagrelor toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Tinidazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tinidazole, a CYP3A substrate, as tinidazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Tipranavir: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and tipranavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while tipranavir is a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and tipranavir.
Tisotumab Vedotin: (Moderate) Monitor for tisotumab vedotin-related adverse reactions if concomitant use with idelalisib is necessary due to increased monomethyl auristatin E (MMAE) exposure which may increase the incidence and severity of adverse reactions. MMAE, the active component of tisotumab vedotin, is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Clinical drug interaction studies have not been conducted for tisotumab vedotin. However, coadministration of another antibody-drug conjugate that contains MMAE with a strong CYP3A inhibitor increased unconjugated MMAE exposure by 34%.
Tofacitinib: (Major) A dosage reduction of tofacitinib is necessary if coadministered with idelalisib. In patients receiving 5 mg or less twice daily, reduce to once daily dosing; in patients receiving 10 mg twice daily, reduce to 5 mg twice daily; in patients receiving 22 mg once daily of the extended-release (XR) formulation, switch to 11 mg XR once daily; in patients receiving 11 mg XR once daily, switch to the immediate-release formulation at a dose of 5 mg once daily. Tofacitinib exposure is increased when coadministered with idelalisib. Idelalisib is a strong CYP3A4 inhibitor; tofacitinib is a CYP3A4 substrate. Coadministration with another strong CYP3A4 inhibitor increased tofacitinib exposure by 2-fold.
Tolterodine: (Major) Reduce the dose of immediate-release tolterodine to 1 mg twice daily and extended-release tolterodine to 2 mg once daily if coadministered with idelalisib. Concurrent use may increase tolterodine exposure. Idelalisib is a strong CYP3A4 inhibitor. In CYP2D6 poor metabolizers, the CYP3A4 pathway becomes important in tolterodine elimination. Because it is difficult to assess which patients will be poor CYP2D6 metabolizers, reduced doses of tolterodine are advised when administered with strong CYP3A4 inhibitors. In a drug interaction study, coadministration of a strong CYP3A4 inhibitor increased the tolterodine AUC by 2.5-fold in CYP2D6 poor metabolizers.
Tolvaptan: (Contraindicated) The concomitant use of tolvaptan and idelalisib is contraindicated. Concurrent use is expected to increase tolvaptan exposure. Tolvaptan is a sensitive CYP3A4 substrate; idelalisib is a strong inhibitor of CYP3A4. Coadministration of another strong CYP3A4 inhibitor increased tolvaptan exposure 5-fold. No data exists regarding the appropriate dose adjustment needed to allow safe administration of tolvaptan with strong CYP3A4 inhibitors.
Toremifene: (Major) Avoid coadministration of idelalisib with toremifene if possible due to increased plasma concentrations of toremifene which may result in QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene is a CYP3A4 substrate that has been shown to prolong the QTc interval in a dose- and concentration-related manner, and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased toremifene exposure by 2.9-fold; exposure to N-demethyltoremifene was reduced by 20%.
Trabectedin: (Major) Avoid the concomitant use of trabectedin with idelalisib due to the risk of increased trabectedin exposure. Trabectedin is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% compared to a single dose of trabectedin (1.3 mg/m2) given alone.
Tramadol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tramadol, a CYP3A substrate, as tramadol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Tramadol; Acetaminophen: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tramadol, a CYP3A substrate, as tramadol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Trandolapril; Verapamil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with verapamil, a CYP3A substrate, as verapamil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Trazodone: (Major) Avoid coadministration of trazodone with idelalisib due to the potential for increased trazodone exposure and associated adverse effects including QT prolongation. If concurrent use cannot be avoided, consider a reduced dose of trazodone based on tolerability. Trazodone is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of other strong CYP3A4 inhibitors increased the exposure of trazodone compared to the use of trazodone alone.
Triamcinolone: (Moderate) Idelalisib may inhibit the CYP3A4 metabolism of triamcinolone, resulting in increased plasma triamcinolone concentrations and reduced serum cortisol concentrations. There have been reports of clinically significant drug interactions in patients receiving another strong CYP3A4 inhibitor with triamcinolone, resulting in systemic corticosteroid effects including, but not limited to, Cushing syndrome and adrenal suppression. Consider the benefit-risk of concomitant use and monitor for systemic corticosteroid side effects. Consider using an alternative treatment to triamcinolone, such as a corticosteroid not metabolized by CYP3A4 (i.e., beclomethasone or prednisolone). In some patients, a corticosteroid dose adjustment may be needed. If corticosteroid therapy is to be discontinued, consider tapering the dose over a period of time to decrease the potential for withdrawal.
Triazolam: (Contraindicated) Coadministration of triazolam, a primary CYP3A4 substrate, with strong CYP3A4 inhibitors, such as idelalisib, is contraindicated by the manufacturer of triazolam due to the risk for increased and prolonged sedation and respiratory depression. Concurrent use is expected to produce large increases in systemic exposure to triazolam, with the potential for serious adverse effects.
Tucatinib: (Major) Coadministration of idelalisib with tucatinib may increase idelalisib exposure; use alternative agents if possible. If concomitant use is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
Ubrogepant: (Contraindicated) Coadministration of ubrogepant and idelalisib is contraindicated as concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor resulted in a 9.7-fold increase in the exposure of ubrogepant.
Ulipristal: (Moderate) Use of ulipristal and idelalisib may increase the plasma concentration of ulipristal but is not likely to be significant for single-dose emergency contraceptive use. Avoid idelalisib if ulipristal is given chronically for hormonal conditions. Concomitant use of ulipristal, a CYP3A4 substrate and idelalisib, a potent CYP3A4 inhibitor may increase the plasma concentration of ulipristal resulting in an increased risk for ulipristal-related adverse events.
Umeclidinium; Vilanterol: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with umeclidinium; vilanterol, a CYP3A substrate, as umeclidinium; vilanterol toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Upadacitinib: (Major) During concomitant use of upadacitinib and idelalisib reduce the upadacitinib dosage to 15 mg once daily. During induction for ulcerative colitis and Crohn's disease reduce the upadacitinib dosage to 30 mg once daily. Concomitant use may increase upadacitinib exposure and risk for adverse effects. Concomitant use with another strong CYP3A inhibitor increased upadacitinib overall exposure 1.75-fold.
Valbenazine: (Major) The dose of valbenazine should be reduced to 40 mg once daily during co-administration with a strong CYP3A4 inhibitor, such as idelalisib. QT prolongation is not clinically significant at valbenazine concentrations expected with recommended dosing; however, valbenazine concentrations may be higher in patients taking a strong CYP3A4 inhibitor and QT prolongation may become clinically significant.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with idelalisib due to increased vardenafil exposure; do not exceed a single dose of 2.5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; idelalisib is a strong CYP3A4 inhibitor. Coadministration with other strong CYP3A4 inhibitors increased the AUC of vardenafil by 10- to 16-fold.
Vemurafenib: (Major) Avoid the concomitant use of vemurafenib and idelalisib; vemurafenib exposure may be increased resulting in an increased risk of adverse events, including QT prolongation. If use with idelalisib cannot be avoided, consider a vemurafenib dose reduction; monitor patients closely for the development of adverse events and dose reduce or discontinue therapy based on manufacturer guidance. Vemurafenib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the exposure of vemurafenib by 40%.
Venetoclax: (Major) Coadministration of idelalisib with venetoclax is contraindicated during the initiation and ramp-up phase in patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL); consider an alternative medication or adjust the venetoclax dose with close monitoring for toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) in patients receiving a steady daily dose of venetoclax if concurrent use is necessary. In patients with acute myeloid leukemia (AML), reduce the venetoclax dose and monitor for toxicity during concurrent use. Resume the original venetoclax dose 2 to 3 days after discontinuation of idelalisib. Specific venetoclax dosage adjustments are as follows: CLL/SLL patients at steady daily dose: 100 mg/day. AML patients: 10 mg on day 1, 20 mg on day 2, 50 mg on day 3, then 100 mg/day starting on day 4. Venetoclax is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration of strong CYP3A4 inhibitors increased the venetoclax AUC by 90% to 690% in drug interaction studies.
Venlafaxine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with venlafaxine, a CYP3A substrate, as venlafaxine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Verapamil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with verapamil, a CYP3A substrate, as verapamil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Vilazodone: (Major) Because CYP3A4 is the primary isoenzyme involved in the metabolism of vilazodone, the manufacturer of vilazodone recommends that the daily dose not exceed 20 mg/day during concurrent use of a strong CYP3A4 inhibitor, such as idelalisib. The original vilazodone dose can be resumed when the CYP3A4 inhibitor is discontinued.
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 idelalisib is necessary. Vinblastine is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor.
Vincristine Liposomal: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with vincristine, a CYP3A substrate, as vincristine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Vincristine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with vincristine, a CYP3A substrate, as vincristine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with idelalisib is necessary. Vinorelbine is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor.
Voclosporin: (Contraindicated) Concomitant use of voclosporin and idelalisib is contraindicated; concomitant use may increase the exposure of voclosporin and the risk of voclosporin-related adverse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased voclosporin exposure by approximately 19-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Coadministration of idelalisib with clarithromycin may increase idelalisib exposure; use alternative agents if possible. If concomitant use of these drugs is required, monitor patients frequently for signs and symptoms of idelalisib-related adverse reactions (e.g., hepatotoxicity, diarrhea, neutropenia, and infection). Idelalisib and clarithromycin are both CYP3A4 substrates and strong CYP3A inhibitors. Coadministration with another strong CYP3A inhibitor increased idelalisib exposure by 1.8-fold.
Voriconazole: (Major) Avoid coadministration of idelalisib with voriconazole if possible due to increased exposure of both drugs, potentially resulting in adverse reactions. Voriconazole is a CYP3A4 substrate and strong inhibitor that has been associated with QT prolognation. Idelalisib is also a CYP3A4 substrate and strong inhibitor. Coadministration with another strong CYP3A4 inhibitor increased idelalisib exposure by 1.8-fold.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with idelalisib is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Idelalisib is a strong CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zaleplon: (Moderate) Zaleplon is partially metabolized by CYP3A4, and concurrent use of strong CYP3A4 inhibitors, such as idelalisib, may decrease the clearance of zaleplon. Routine dosage adjustments of zaleplon are not required. Dosage adjustments should be made on an individual basis according to efficacy and tolerability.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO once daily if coadministered with idelalisib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Interrupt zanubrutinib therapy as recommended for adverse reactions. After discontinuation of idelalisib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. The AUC of zanubrutinib was increased by 278% when coadministered with another strong CYP3A4 inhibitor.
Ziprasidone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ziprasidone, a partial CYP3A substrate, since ziprasidone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. If concurrent use is required, monitor for ziprasidone-induced adverse effects including QT prolongation, CNS effects, and extrapyramidal symptoms.
Zolmitriptan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with zolmitriptan, a CYP3A substrate, as zolmitriptan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Zolpidem: (Moderate) Consider decreasing the dose of zolpidem if coadministration with idelalisib is necessary. Zolpidem is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with strong CYP3A4 inhibitors increased the AUC of zolpidem by 34% to 70%.
How Supplied
ZYDELIG Oral Tab: 100mg, 150mg
Maximum Dosage
150 mg PO twice daily.
Geriatric150 mg PO twice daily.
AdolescentsSafety and efficacy have not been established.
ChildrenSafety and efficacy have not been established.
InfantsSafety and efficacy have not been established.
NeonatesSafety and efficacy have not been established.
Mechanism Of Action
Idelalisib is an oral, selective, small molecule inhibitor of phosphatidylinositol 3-kinase, which is expressed in both normal and malignant B-cells. In cell lines derived from malignant B-cells and in primary tumor cells, it induced apoptosis and inhibited proliferation. Additionally, idelalisib inhibits several cell signaling pathways, including B-cell receptor (BCR) signaling and the CXCR4 and CXCR5 signaling, which are involved in trafficking and homing of B-cells to the lymph nodes and bone marrow. Inhibition of chemotaxis and adhesion, as well as reduced cell viability occurred with idelalisib treatment of lymphoma cells.
Pharmacokinetics
Idelalisib is administered orally. It is 84% or greater bound to plasma proteins, without dependence on concentration. The mean blood-to-plasma ratio is 0.7. Based on population parameters, the apparent central volume of distribution at steady state is 23 L (coefficient of variance (CV), about 85%). Idelalisib is metabolized by aldehyde oxidase and CYP3A to its major metabolite which is inactive, GS-563117; additionally, it undergoes minor metabolism by UGT1A4. The systemic clearance at steady state is 14.9 L/hour (CV, about 38%), and the elimination half-life is 8.2 hours. Following a single radiolabeled dose of 150 mg orally, 78% of the dose was excreted in the feces and 14% in the urine.
Affected cytochrome P450 isoenzymes: CYP3A4
Idelalisib is metabolized via CYP3A4; it is also a strong CYP3A4 inhibitor. Avoid coadministration of idelalisib with strong CYP3A inducers and sensitive CYP3A substrates. If idelalisib is administered with a strong CYP3A inhibitor, monitor for signs of idelalisib toxicity. Idelalisib may inhibit CYP2C8, CYP2C19, and UGT1A1 and may induce CYP2B6 based on in vitro studies; additionally, it is an in vitro substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters.
Idelalisib exposure increases in a less than dose-proportional manner at doses of 50 to 350 mg by mouth twice daily. The steady-state Cmax and AUC values were 1,861 ng/mL (CV, 43%) and 10,598 ng X hour/mL (CV, 41%), respectively, following idelalisib 150 mg twice daily. The median Tmax of idelalisib is 1.5 hours.
Effect of food: Administration of a single dose of idelalisib with a high-fat meal increased the AUC 1.4-fold relative to fasting conditions; therefore, it may be administered without regard to food.
Pregnancy And Lactation
Idelalisib may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant during and for at least 1 month after idelalisib therapy. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. Idelalisib caused embryo-fetal toxicity at doses of 75 and 150 mg/kg/day (AUC 12 and 30 times the human exposure at the recommended dose, respectively) including decreased fetal weight, external malformations (short tail), and skeletal variations such as delayed ossification and/or unossification of the skull, vertebrae, and sternebrae. Reductions in maternal weight gain were also observed. At doses of 150 mg/kg/day, additional findings included urogenital blood loss, complete resorption, increased post-implantation loss, and malformations (vertebral agenesis with anury, hydrocephaly, and microphthalmia/anophthalmia).
It is not known if idelalisib or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during idelalisib therapy and for 1 month after the last dose.