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  • CLASSES

    Protein Kinase Inhibitors

    BOXED WARNING

    Hepatic disease, hepatotoxicity

    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.

    Abdominal pain, colitis, diarrhea, GI perforation, nausea/vomiting

    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.

    Pneumonitis

    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 > 5%. If pneumonitis is suspected, hold idelalisib therapy. Permanently discontinue idelalisib treatment for pneumonitis and consider treatment with corticosteroids.

    Infection

    Serious infections have been reported with idelalisib therapy including sepsis, cytomegalovirus (CMV), and Pneumocystis jirovecii pneumonia (PJP); some infections were fatal. Consider PJP prophylaxis with idelalisib therapy. Monitor patients for signs and symptoms of infection. 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.

    DEA CLASS

    Rx

    DESCRIPTION

    Oral, selective, small molecule inhibitor of phosphatidylinositol 3-kinase
    FDA-approved for the treatment of relapsed chronic lymphocytic leukemia (CLL) in adults for whom rituximab alone would be considered appropriate therapy due to other co-morbidities. Also FDA-approved as monotherapy for the treatment of relapsed follicular lymphoma (FL) and small lymphocytic lymphoma (SLL) in adults who have received at least 2 prior therapies
    Not a first-line therapy for any indication; Boxed Warning for fatal and/or serious cases of hepatotoxicity, diarrhea, colitis, infection, intestinal perforation, and pneumonitis

    COMMON BRAND NAMES

    ZYDELIG

    HOW SUPPLIED

    ZYDELIG Oral Tab: 100mg, 150mg

    DOSAGE & INDICATIONS

    For the treatment of chronic lymphocytic leukemia (CLL).
    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. Avoid the concomitant use of strong CYP3A inducers and substrates; close monitoring for drug toxicity is recommended with concomitant use of strong CYP3A inhibitors. Interruption or discontinuation of therapy and/or a dose reduction may be necessary in patients who develop toxicities. 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).

    For the treatment of relapsed or refractory CLL, in combination with bendamustine and rituximab†.
    Oral dosage
    Adults

    150 mg orally twice daily until disease progression in combination with 6 cycles of bendamustine (70 mg/m2 IV on days 1 and 2) and rituximab (375 mg/m2 IV on day 1 in cycle 1; 500 mg/m2 IV on day 1 in cycles 2 to 6) was evaluated in a randomized, double-blind, placebo-controlled, phase III trial (n = 416). Cycles of bendamustine and rituximab were repeated every 28 days. According to the manufacturer, avoid the concomitant use of strong CYP3A inducers and substrates; close monitoring for drug toxicity is recommended with concomitant use of strong CYP3A inhibitors. Interruption or discontinuation of therapy and/or a dose reduction may be necessary in patients who develop toxicities.

    For the treatment of non-Hodgkin's lymphoma (NHL).
    NOTE: Idelalisib was granted accelerated approval from the FDA based on overall response rate; an improvement in patient survival or disease related symptoms has not been established.
    For the treatment of relapsed follicular B-cell non-Hodgkin lymphoma (FL) in patients who have received at least two prior systemic therapies.
    Oral dosage
    Adults

    150 mg PO twice daily until disease progression or unacceptable toxicity. Avoid the concomitant use of strong CYP3A inducers and substrates; close monitoring for drug toxicity is recommended with concomitant use of strong CYP3A inhibitors. Interruption or discontinuation of therapy and/or a dose reduction may be necessary in patients who develop toxicities. In a multinational, open-label, phase II 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%. The median response duration in patients with FL was not evaluable (range, 0 to 14.8+ months).

    For the treatment of small lymphocytic lymphoma (SLL) in patients who have received at least two prior systemic therapies.
    Oral dosage
    Adults

    150 mg PO twice daily until disease progression or unacceptable toxicity. Avoid the concomitant use of strong CYP3A inducers and substrates; close monitoring for drug toxicity is recommended with concomitant use of strong CYP3A inhibitors. Interruption or discontinuation of therapy and/or a dose reduction may be necessary in patients who develop toxicities. In a multinational, open-label, phase II 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 [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. The median response duration in patients with SLL was 11.9 months (range, up to 14.7+ months).

    MAXIMUM DOSAGE

    Adults

    150 mg PO bid.

    Geriatric

    150 mg PO bid.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    Neonates

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Idelalisib exposure is increased in patients with ALT, AST, or bilirubin greater than the upper limit of normal. Patients with a baseline AST or ALT > 2.5 times the upper limit of normal (ULN) or bilirubin > 1.5 x ULN were excluded from clinical studies. Specific guidelines for patients with baseline hepatic impairment are not available; it appears that no dose adjustments are needed.
    •Treatment-related increases in AST / ALT:
    AST / ALT > 3—5 x ULN: No dose adjustment necessary. Monitor AST / ALT at least weekly until <= 1 x ULN.
    AST / ALT > 5—20 x ULN: Hold idelalisib treatment and monitor AST / ALT at least weekly. When AST / ALT are <= 1 x ULN, resume idelalisib treatment at 100 mg by mouth twice daily.
    AST / ALT > 20 x ULN: Permanently discontinue idelalisib treatment.
    •Treatment-related increases in bilirubin:
    Bilirubin > 1.5—3 x ULN: No dose adjustment necessary. Monitor bilirubin at least weekly until <= 1 x ULN.
    Bilirubin > 3—10 x ULN: Hold idelalisib treatment and monitor bilirubin at least weekly. When bilirubin is <= 1 x ULN, resume idelalisib treatment at 100 mg by mouth twice daily.
    Bilirubin > 10 x ULN: Permanently discontinue idelalisib treatment.

    Renal Impairment

    No dose adjustment is necessary for patients with creatinine clearance (CrCL) >= 15 mL/min; data is not available for patients with CrCL < 15 mL/min.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Idelalisib may be taken with or without food.
    Swallow tablets whole; do not crush or dissolve tablets.
    Do not take 2 doses at the same time if a dose is missed. If a dose is missed by less than 6 hours, take the missed dose right away and take the next dose as usual. 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.

    STORAGE

    ZYDELIG:
    - Excursions permitted to 59 to 86 degrees F
    - Store and dispense in original container
    - Store between 68 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Hepatic disease, hepatotoxicity

    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.

    Abdominal pain, colitis, diarrhea, GI perforation, nausea/vomiting

    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.

    Pneumonitis

    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 > 5%. If pneumonitis is suspected, hold idelalisib therapy. Permanently discontinue idelalisib treatment for pneumonitis and consider treatment with corticosteroids.

    Serious rash

    Idelalisib is contraindicated in patients with a history of serious allergic reactions including anaphylaxis and toxic epidermal necrolysis (TEN). Serious rash has been reported with idelalisib therapy; fatal cases of Stevens-Johnson syndrome (SJS) and TEN have occurred. Monitor patients for the development of severe cutaneous reactions; discontinue therapy if serious rash occurs. Hold idelalisib if SJS or TEN is suspected; permanently discontinue therapy if a SJS or TEN diagnosis is confirmed. Permanently discontinue idelalisib in patients who develop a serious allergic reaction and institute supportive measures.

    Neutropenia

    Severe neutropenia has been reported with idelalisib therapy. Monitor complete blood counts at least every 2 weeks for the first 6 months of therapy, and at least weekly if neutrophil counts are less than 1,000 cells/mm3. Therapy interruption and a dosage reduction may be necessary in patients who develop severe neutropenia.

    Infection

    Serious infections have been reported with idelalisib therapy including sepsis, cytomegalovirus (CMV), and Pneumocystis jirovecii pneumonia (PJP); some infections were fatal. Consider PJP prophylaxis with idelalisib therapy. Monitor patients for signs and symptoms of infection. 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.

    Pregnancy

    Idelalisib is designated as pregnancy category D according to the manufacturer. Fetal harm may occur if idelalisib is administered during pregnancy, based on findings in animal studies. Females of childbearing potential should avoid becoming pregnant during therapy. Women who become pregnant while receiving idelalisib should be apprised of the potential reproductive risk. 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).

    Breast-feeding

    Advise female patients not to breast-feed while taking idelalisib. Breast-feeding should be discontinued while taking the drug because of the potential for serious adverse reactions in nursing infants from idelalisib. It is not known if idelalisib is excreted into human milk.

    Contraception requirements, infertility, reproductive risk

    Counsel patients about the reproductive risk and contraception requirements during idelalisib treatment. Female patients of reproductive potential should use effective contraception during and for at least 1 month after the last idelalisib dose. Women who become pregnant while receiving idelalisib should be apprised of the potential hazard to the fetus. Idelalisib may cause infertility in both men and women. In a fertility study in male rats, decreased epididymidal and testicular weights were observed at all dose levels and reduced sperm concentration at mid- and high doses; however, there were no adverse effects on fertility parameters. In a separate fertility study in females, there were no adverse effects on fertility parameters in female rats; however, there was a decrease in the number of live embryos at the high dose (AUC approximately 17 times the exposure in patients at the recommended daily dosing).

    ADVERSE REACTIONS

    Severe

    enterocolitis / Delayed / 0-47.0
    neutropenia / Delayed / 25.0-46.0
    infection / Delayed / 0-36.0
    diarrhea / Early / 14.0-19.0
    colitis / Delayed / 14.0-19.0
    elevated hepatic enzymes / Delayed / 5.0-19.0
    chills / Rapid / 0-16.0
    fever / Early / 2.0-11.0
    lymphopenia / Delayed / 0-10.0
    leukopenia / Delayed / 0-8.0
    thrombocytopenia / Delayed / 0-6.0
    exfoliative dermatitis / Delayed / 0-4.0
    rash (unspecified) / Early / 3.0-4.0
    maculopapular rash / Early / 0-4.0
    dyspnea / Early / 0-4.0
    dehydration / Delayed / 0-3.0
    abdominal pain / Early / 1.0-2.0
    anorexia / Delayed / 1.0-2.0
    stomatitis / Delayed / 0-2.0
    peripheral edema / Delayed / 0-2.0
    asthenia / Delayed / 0-2.0
    anemia / Delayed / 0-2.0
    GI perforation / Delayed / 0-1.0
    gastroesophageal reflux / Delayed / 0-1.0
    nausea / Early / 1.0-1.0
    vomiting / Early / 0-1.0
    Stevens-Johnson syndrome / Delayed / 0-1.0
    toxic epidermal necrolysis / Delayed / 0-1.0
    fatigue / Early / 0-1.0
    arthralgia / Delayed / 0-1.0
    anaphylactoid reactions / Rapid / 0-1.0
    headache / Early / 1.0-1.0
    cough / Delayed / 1.0-1.0

    Moderate

    pneumonitis / Delayed / 4.0-4.0
    hypoxia / Early / Incidence not known

    Mild

    insomnia / Early / 9.0-12.0
    night sweats / Early / 0-12.0
    sinusitis / Delayed / 0-8.0
    lethargy / Early / 0-5.0

    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) A dose reduction of abemaciclib is required if coadministration with idelalisib is necessary due to increased plasma concentrations of abemaciclib. In patients at the recommended starting doses of either 200 mg or 150 mg twice daily, reduce the dose of abemaciclib to 100 mg twice daily. In patients who have already had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the dose of abemaciclib to 50 mg twice daily. If idelalisib is discontinued, resume the original dose of abemaciclib after 3 to 5 half-lives of idelalisib. Abemaciclib is a CYP3A4 substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with another strong CYP3A inhibitor was predicted to increase exposure to unbound abemaciclib and its active metabolites by 1.7-fold to 2.2-fold.
    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; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; Dextromethorphan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; Dextromethorphan; Doxylamine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; Hydrocodone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; Oxycodone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with oxycodone, a CYP3A substrate, as oxycodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Acetaminophen; 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.
    Ado-Trastuzumab emtansine: (Major) Avoid concomitant use of ado-trastuzumab emtansine with idelalisib, as plasma exposure to the cytotoxic small molecule of ado-trastuzumab emtansine, DM1, may be increased. Treatment with ado-trastuzumab emtansine should be delayed until idelalisib is cleared from the circulation (approximately 3 elimination half-lives), or an alternate medication with less potential to inhibit CYP3A4 should be considered. If co-administration is necessary, monitor for an increase in ado-trastuzumab emtansine-related adverse events. Idelalisib is a strong CYP3A4 inhibitor; the Cmax of another sensitive CYP3A4 substrate, midazolam, was increased by 2.4-fold and the AUC by 5.4-fold when coadministered with idelalisib. While formal drug interaction studies have not been conducted, DM1 is mainly metabolized by CYP3A4 (and to a lesser extent, CYP3A5) in vitro. Coadministration may result in potentially increased DM1 exposure and toxicity.
    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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with alfuzosin, a CYP3A substrate, as alfuzosin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Aliskiren: (Severe) 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; Amlodipine: (Severe) 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. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Severe) 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. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Severe) 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; Valsartan: (Severe) 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: (Major) Idelalisib may increase the systemic exposure of almotriptan. If coadministered, the recommended starting dose of almotriptan is 6.25 mg; do not exceed 12.5 mg within a 24-hour period. Avoid coadministration in patients with renal or hepatic impairment. Almotriptan is a CYP3A4 substrate and idelalisib is a potent CYP3A4 inhibitor. In a drug interaction study, coadministration of almotriptan and ketoconazole, another potent CYP3A4 inhibitor, resulted in an approximately 60% increase in almotriptan exposure.
    Alogliptin; Pioglitazone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pioglitazone, a CYP3A substrate, as pioglitazone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Alprazolam: (Major) Coadministration of alprazolam and idelalisib is not recommended. If coadministration cannot be avoided, a dosage reduction of alprazolam should be considered. Idealalisib is a potent CYP3A4 inhibitor. The initial step in alprazolam metabolism is hydroxylation catalyzed by cytochrome CYP3A. Drugs that inhibit this metabolic pathway may profoundly decrease alprazolam clearance, resulting in increased potential for serious alprazolam-related adverse events, such as respiratory depression and prolonged sedation. Consequently, alprazolam should be avoided in patients receiving very potent inhibitors of CYP3A isoenzymes.
    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.
    Amitriptyline; Chlordiazepoxide: (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.
    Amlodipine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Amlodipine; Atorvastatin: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with atorvastatin, a CYP3A substrate, as atorvastatin 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 atorvastatin. A single dose of 10 mg of rosuvastatin was administered alone and after idelalsib150 mg for 12 doses in healthy subjects and no changes in exposure to rosuvastatin were observed. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Amlodipine; Benazepril: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Amlodipine; Olmesartan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Amlodipine; Telmisartan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Amlodipine; Valsartan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Amoxicillin; Clarithromycin; Lansoprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clarithromycin, a CYP3A substrate, as clarithromycin 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 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.
    Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clarithromycin, a CYP3A substrate, as clarithromycin 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.
    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) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with aripiprazole, a CYP3A substrate, as aripiprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. If these drugs must be used together, the manufacturer of aripiprazole recommends that the oral aripiprazole dose be reduced to one-half of the usual dose in patients receiving strong inhibitors of CYP3A4. In adults receiving 300 mg or 400 mg of Abilify Maintena, dose reductions to 200 mg or 300 mg, respectively, are recommended if the CYP3A4 inhibitor is used for more than 14 days. In adults receiving Aristada, the Aristada dose should be reduced to the next lower strength during use of a strong CYP3A4 inhibitor for more than 14 days. For patients receiving 882 mg of Aristada every 6 weeks or 1,064 mg every 2 months, the next lower strength should be 441 mg administered every 4 weeks. No dosage adjustment is necessary in patients taking 441 mg IM of Aristada, if tolerated. Because aripiprazole 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 CYP3A4 and CYP2D6 inhibitor should have their oral aripiprazole dose reduced to one-quarter (25%) of the usual dose with subsequent adjustments based upon clinical response. Adults receiving Abilify Maintena who are PMs and receiving a strong CYP3A4 inhibitor should have a dose reduction to 200 mg/month IM. Patients receiving a combination of a CYP3A4 and CYP2D6 inhibitor for more than 14 days should have their Abilify Maintena dose reduced from 400 mg/month to 200 mg/month or from 300 mg/month to 160 mg/month, respectively. Adults receiving Aristada who are PMs of CYP2D6 and receiving a strong CYP3A4 inhibitor for more than 14 days should have their dose reduced from 662 mg, 882 mg, or 1,064 mg to 441 mg IM; no dose adjustment is needed in patients receiving 441 mg of Aristada, if tolerated. In adults receiving Aristada 662 mg, 882 mg, or 1,064 mg, combined use of a strong CYP2D6 inhibitor and a strong CYP3A4 inhibitor for more than 14 days should be avoided; no dose adjustment is needed in patients taking 441 mg, if tolerated.
    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.
    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; 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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with oxycodone, a CYP3A substrate, as oxycodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Aspirin, ASA; 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.
    Atazanavir: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and atazanavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while atazanavir 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 atazanavir.
    Atazanavir; Cobicistat: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cobicistat, a CYP3A substrate, as cobicistat toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and atazanavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while atazanavir 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 atazanavir.
    Atorvastatin: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with atorvastatin, a CYP3A substrate, as atorvastatin 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 atorvastatin. A single dose of 10 mg of rosuvastatin was administered alone and after idelalsib150 mg for 12 doses in healthy subjects and no changes in exposure to rosuvastatin were observed.
    Atorvastatin; Ezetimibe: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with atorvastatin, a CYP3A substrate, as atorvastatin 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 atorvastatin. A single dose of 10 mg of rosuvastatin was administered alone and after idelalsib150 mg for 12 doses in healthy subjects and no changes in exposure to rosuvastatin were observed.
    Atropine; Hyoscyamine; Phenobarbital; Scopolamine: (Severe) 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.
    Axitinib: (Major) Avoid coadministration of axitinib with idelalisib, due to the risk of increased axitinib-related adverse reactions. The manufacturer of axitinib suggests that reducing the axitinib dose by 50% is acceptable if avoidance is not possible. Subsequent doses can be increased or decreased based on individual safety and tolerability, resuming the original dose of axitinib approximately 3 to 5 half-lives after idelalisib is discontinued. Axitinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. The Cmax and AUC of a sensitive CYP3A substrate (oral midazolam) was increased 2.4-fold and 5.4-fold, respectively, when coadministered with idelalisib. Coadministration with another strong CYP3A4/5 inhibitor, ketoconazole, significantly increased the plasma exposure of axitinib in healthy volunteers.
    Azelastine; Fluticasone: (Moderate) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with fluticasone (a CYP3A substrate) when feasible, as fluticasone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. This interaction may be more likely to occur with inhaled formulations of fluticasone rather than topical or nasal formulations.
    Bedaquiline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bedaquiline, a CYP3A substrate, as bedaquiline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Severe) 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. (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ergotamine, a CYP3A substrate, as ergotamine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Bexarotene: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bexarotene, a CYP3A substrate, as bexarotene toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Boceprevir: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and boceprevir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while boceprevir 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 boceprevir.
    Bortezomib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bortezomib, a CYP3A substrate, as bortezomib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Bosentan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with bosentan, a CYP3A substrate, as bosentan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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 and decreased exposure to idelalisib. 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); monitor for an increase in brigatinib-related adverse reactions and a decrease in the efficacy of idelalisib. After discontinuation of idelalisib, resume the brigatinib dose that was tolerated prior to initiation of idelalisib. Brigatinib is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A inhibitor increased the AUC and Cmax of brigatinib by 101% and 21%, respectively. Idelalisib is also a CYP3A substrate and brigatinib induces CYP3A in vitro. Coadministration with a strong CYP3A4 inducer decreased the geometric mean AUC of idelalisib by 75% and the geometric mean Cmax by 58%; plasma concentrations of idelalisib may decrease when administered with concomitant brigatinib.
    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.
    Brompheniramine; Dextromethorphan; Guaifenesin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Brompheniramine; Guaifenesin; Hydrocodone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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; 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.
    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.
    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%.
    Cabozantinib: (Major) Avoid concomitant use of cabozantinib with idelalisib due to the risk of increased cabozantinib-related toxicities; if coadministration is necessary, reduce the daily cabozantinib capsule (Cometriq) dose by 40 mg (e.g., 140 mg/day to 100 mg/day; 100 mg/day to 60 mg/day) and the cabozantinib tablet (Cabometyx) dose by 20 mg (e.g., 60 mg/day to 40 mg/day; 40 mg/day to 20 mg/day). Resume the prior cabozantinib dose after 2 to 3 days if idelalisib is discontinued. Cabozantinib is primarily metabolized by CYP3A4 and idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor, ketoconazole (400 mg daily for 27 days), increased cabozantinib (single dose) exposure by 38%.
    Caffeine; Ergotamine: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ergotamine, a CYP3A substrate, as ergotamine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Carbamazepine: (Severe) 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.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Ceritinib: (Major) Avoid coadministration of ceritinib with idelalisib due to increased exposure to ceritinib; idelalisib exposure may also increase. If concomitant use is unavoidable, decrease the dose of ceritinib by approximately one-third, rounded to the nearest multiple of the 150 mg capsules; monitor for treatment-related adverse reactions. After idelalisib is discontinued, resume the dose of ceritinib taken prior to initiating idelalisib. Ceritinib is a CYP3A4 substrate and inhibitor. Idelalisib is also a CYP3A4 substrate, as well as a strong CYP3A4 inhibitor. Coadministration with a strong CYP3A4 inhibitor increased the ceritinib AUC by 2.9-fold and the Cmax by 22%. Coadministration with a strong CYP3A inhibitor increased the AUC of idelalisib by 1.8-fold. The strength of inhibition of CYP3A4 by ceritinib is unknown.
    Cevimeline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cevimeline, a CYP3A substrate, as cevimeline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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; 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; Dextromethorphan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Chlorpheniramine; Hydrocodone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cinacalcet, a CYP3A substrate, as cinacalcet toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Cisapride: (Severe) 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.
    Citalopram: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with citalopram, a CYP3A substrate, as citalopram toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Clarithromycin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clarithromycin, a CYP3A substrate, as clarithromycin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Clindamycin: (Moderate) Concomitant use of clindamycin and idelalisib may decrease clindamycin clearance and increase the risk of adverse reactions. Clindamycin is a CYP3A4 substrate; idelalisib is a strong inhibitor of CYP3A4. Caution and close monitoring are advised if these drugs are used together.
    Clobazam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with clobazam, a CYP3A substrate, as clobazam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Clopidogrel: (Moderate) Administer clopidogrel and idelalisib with caution. Clopidogrel requires hepatic biotransformation via 2 cytochrome dependent oxidative steps. The CYP3A4 isoenzyme is involved in 1 of these steps. Idelalisib is a strong inhibitor of CYP3A4 and may decrease the hepatic metabolism of clopidogrel to its active metabolite. Therefore, the therapeutic effectiveness of clopidogrel should be monitored when used concomitantly 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) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cobicistat, a CYP3A substrate, as cobicistat toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cobicistat, a CYP3A substrate, as cobicistat toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cobicistat, a CYP3A substrate, as cobicistat toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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).
    Colchicine: (Major) Due to the risk for serious colchicine toxicity including multi-organ failure and death, avoid coadministration of colchicine and idelalisib in patients with normal renal and hepatic function unless the use of both agents is imperative. Coadministration is contraindicated in patients with renal or hepatic impairment because colchicine accumulation may be greater in these populations. Idelalisib can inhibit colchicine's metabolism via CYP3A4, resulting in increased colchicine exposure. If coadministration in patients with normal renal and hepatic function cannot be avoided, adjust the dose of colchicine by either reducing the daily dose or the dosage frequency, and carefully monitor for colchicine toxicity. Specific dosage adjustment recommendations are available for the Colcrys product for patients who have taken a strong CYP3A4 inhibitor like idelalisib in the past 14 days or require concurrent use: for prophylaxis of gout flares, if the original dose is 0.6 mg twice daily, decrease to 0.3 mg once daily or if the original dose is 0.6 mg once daily, decrease to 0.3 mg once every other day; for treatment of gout flares, give 0.6 mg as a single dose, then 0.3 mg 1 hour later, and do not repeat for at least 3 days; for familial Mediterranean fever, do not exceed a 0.6 mg/day.
    Conivaptan: (Severe) Coadministration of conivaptan with strong CYP3A4 inhibitors like idelalisib is contraindicated. The plasma concentrations of conivaptan may be elevated during concurrent use. Coadministration of conivaptan with ketoconazole, another potent CYP3A4 inhibitor, results in 4- and 11- fold increase in conivaptan Cmax and AUC, respectively; similar pharmacokinetic effects could be seen with the coadministration of conivaptan and idelalisib.
    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 coadministration of crizotinib with idelalisib due to increased crizotinib exposure. Crizotinib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration of a single dose of crizotinib with another strong CYP3A inhibitor increased the AUC of crizotinib by 3.2-fold; the magnitude of effect of CYP3A inhibitors on steady-state crizotinib exposure has not been evaluated.
    Cyclobenzaprine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cyclobenzaprine, a CYP3A substrate, as cyclobenzaprine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Dalfopristin; Quinupristin: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and dalfopristin; quinupristin, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. If the use of both agents is necessary, monitor for signs of idelalisib toxicity and follow recommendations for dose modifications if necessary.
    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.
    Darifenacin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with darifenacin, a CYP3A substrate, as darifenacin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Darunavir: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and darunavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while darunavir 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 darunavir.
    Darunavir; Cobicistat: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with cobicistat, a CYP3A substrate, as cobicistat toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and darunavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while darunavir 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 darunavir.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Severe) 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. (Major) Avoid concurrent administration of idelalisib with dasabuvir; ombitasvir; paritaprevir; ritonavir. Coadministration is expected to result in elevated plasma concentrations idelalisib, ritonavir, dasabuvir, and paritaprevir and increased risk of serious adverse events, such as hepatotoxicity. Idelalisib and ritonavir are both substrates and potent inhibitors of the hepatic isoenzyme CYP3A4; paritaprevir and dasabuvir (minor) are also metabolized by this enzyme. If coadministration is unavoidable, extreme caution and close monitoring are advised.
    Dasatinib: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dasatinib, a CYP3A substrate, as dasatinib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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) Concomitant use of idelalisib, a CYP3A4 substrate, and delavirdine, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while delavirdineis 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 delavirdine.
    Dexamethasone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dexamethasone, a CYP3A substrate, as dexamethasone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dextromethorphan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dextromethorphan; Guaifenesin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dextromethorphan; Guaifenesin; Potassium Guaiacolsulfonate: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dextromethorphan; Promethazine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dextromethorphan; Quinidine: (Severe) 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. (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dextromethorphan, a CYP3A substrate, as dextromethorphan 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: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dihydroergotamine, a CYP3A substrate, as dihydroergotamine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone 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 concomitant use of idelalisib, a strong CYP3A inhibitor, with docetaxel, a CYP3A substrate, as docetaxel toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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.
    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 concomitant use of idelalisib, a strong CYP3A inhibitor, with doxorubicin, a CYP3A substrate, as doxorubicin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Doxorubicin: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with doxorubicin, a CYP3A substrate, as doxorubicin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Dronabinol, THC: (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: (Severe) 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; 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.
    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: (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.
    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: (Severe) 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.
    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.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Severe) 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: (Severe) 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.
    Enalapril; 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.
    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: (Severe) 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.
    Ergotamine: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ergotamine, a CYP3A substrate, as ergotamine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Erlotinib: (Major) Avoid the coadministration of erlotinib with idelalisib due to the risk of increased erlotinib-related adverse reactions. According the manufacturer of erlotinib, if concomitant use is unavoidable and severe reactions occur, reduce the dose of erlotinib by 50 mg decrements. Erlotinib is primarily metabolized by CYP3A4, and to a lesser extent by CYP1A2. Idelalisib is a strong CYP3A4 inhibitor. Idelalisib increased the Cmax and AUC of another CYP3A4 substrate, midazolam, by 2.4-fold and 5.4-fold, respectively. Coadministration of erlotinib with ketoconazole, another strong CYP3A4 inhibitor, increased the erlotinib AUC by 67%; coadministration with idelalisib may also increase erlotinib exposure.
    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.
    Erythromycin; Sulfisoxazole: (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.
    Esomeprazole; Naproxen: (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 Cypionate; 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.
    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.
    Eszopiclone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with eszopiclone, a CYP3A substrate, as eszopiclone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Ethinyl Estradiol; Desogestrel: (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; Ethynodiol Diacetate: (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; Etonogestrel: (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.
    Ethinyl 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.
    Ethinyl Estradiol; Levonorgestrel; Folic Acid; 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.
    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; Norethindrone Acetate; 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.
    Ethinyl 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.
    Ethinyl Estradiol; Norethindrone; 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.
    Ethinyl 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.
    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.
    Etonogestrel: (Minor) Coadministration of etonogestrel and strong CYP3A4 inhibitors such as idelalisib may increase the serum concentration of etonogestrel.
    Etoposide, VP-16: (Major) Monitor for an increased incidence of etoposide-related adverse effects if used concomitantly with idelalisib. Idelalisib is a strong inhibitor of CYP3A4 and etoposide, VP-16 is a CYP3A4 substrate. Coadministration may increase etoposide concentrations.
    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 idelalisib with everolimus (Afinitor; Afinitor Disperz) due to increased plasma concentrations of everolimus. Coadministration of idelalisib with everolimus (Zortress) is not recommended without close monitoring of everolimus whole blood trough concentrations. Everolimus is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor.
    Exemestane: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with exemestane, a CYP3A substrate, as exemestane toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Ezetimibe; Simvastatin: (Severe) 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.
    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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with fentanyl, a CYP3A substrate, as fentanyl toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Flibanserin: (Severe) 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: (Moderate) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with fluticasone (a CYP3A substrate) when feasible, as fluticasone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. This interaction may be more likely to occur with inhaled formulations of fluticasone rather than topical or nasal formulations.
    Fluticasone; Salmeterol: (Moderate) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with fluticasone (a CYP3A substrate) when feasible, as fluticasone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. This interaction may be more likely to occur with inhaled formulations of fluticasone rather than topical or nasal formulations.
    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. (Moderate) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with fluticasone (a CYP3A substrate) when feasible, as fluticasone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. This interaction may be more likely to occur with inhaled formulations of fluticasone rather than topical or nasal formulations.
    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. (Moderate) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with fluticasone (a CYP3A substrate) when feasible, as fluticasone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. This interaction may be more likely to occur with inhaled formulations of fluticasone rather than topical or nasal formulations.
    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: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and fosamprenavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while fosamprenavir 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 fosamprenavir.
    Fosphenytoin: (Severe) 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.
    Galantamine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with galantamine, a primary CYP3A substrate, as galantamine toxicity may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Gefitinib: (Major) Monitor for an increased incidence of gefitinib-related adverse effects if gefitinib and idelalisib are used concomitantly. Gefitinib is metabolized significantly by CYP3A4 and idelalisib is a strong CYP3A4 inhibitor; coadministration may decrease the metabolism of gefitinib and increase gefitinib concentrations. Administration of a single 250 mg gefitinib dose with another strong CYP3A4 inhibitor (itraconazole) increased the mean AUC of gefitinib by 80%.
    Glimepiride; Pioglitazone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pioglitazone, a CYP3A substrate, as pioglitazone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Halofantrine: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with halofantrine, a CYP3A substrate, as halofantrine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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; Hydrocodone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Hydrochlorothiazide, HCTZ; 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.
    Hydrocodone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Hydrocodone; Ibuprofen: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Hydrocodone; Phenylephrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Hydrocodone; Potassium Guaiacolsulfonate: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Hydrocodone; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydrocodone, a CYP3A substrate, as hydrocodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Hydroxyprogesterone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with hydroxyprogesterone, a CYP3A substrate, as hydroxyprogesterone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Ibrutinib: (Major) Avoid the 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; idelalisib is a strong CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of other strong CYP3A4 inhibitors, the Cmax and AUC values of ibrutinib were increased significantly.
    Ibuprofen; Oxycodone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with oxycodone, a CYP3A substrate, as oxycodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Ifosfamide: (Major) The concomitant use of ifosfamide, a CYP3A4 substrate, and idelalisib, a strong CYP3A4 inhibitor and substrate, may decrease the metabolism of ifosfamide to its active metabolite, 4-hydroxy-ifosfamide. As a result of this interaction, ifosfamide treatment effectiveness may be reduced.
    Iloperidone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with iloperidone, a CYP3A substrate, as iloperidone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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) Concomitant use of idelalisib, a CYP3A4 substrate, and indinavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while indinavir 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 indinavir.
    Irinotecan Liposomal: (Major) If possible, avoid concomitant use of irinotecan liposomal with idelalisib, a strong CYP3A4 inhibitor, due to increased risk of irinotecan-related toxicity. Discontinue idelalisib at least 1 week prior to initiation of liposomal irinotecan therapy. The metabolism of liposomal irinotecan has not been evaluated; however, coadministration of ketoconazole, a strong CYP3A4 and UGT1A1 inhibitor, with non-liposomal irinotecan HCl resulted in increased exposure to both irinotecan and its active metabolite, SN-38.
    Irinotecan: (Major) Idelalisib is a strong CYP3A4 inhibitor; irinotecan is a CYP3A4 substrate. Exposure to irinotecan and to the active metabolite, SN-38, will increase when the drugs are used together. Do not administer idelalisib concurrently with irinotecan unless there are no therapeutic alternatives; discontinue idelalisib at least 1 week before starting irinotecan. If concomitant use is necessary, monitor for increased irinotecan side effects, including diarrhea, nausea, vomiting, and myelosuppression.
    Isavuconazonium: (Severe) 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: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and isoniazid, INH, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. If the use of both agents is necessary, monitor for signs of idelalisib toxicity and follow recommendations for dose modifications if necessary.
    Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Severe) 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. (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and isoniazid, INH, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. If the use of both agents is necessary, monitor for signs of idelalisib toxicity and follow recommendations for dose modifications if necessary.
    Isoniazid, INH; Rifampin: (Severe) 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. (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and isoniazid, INH, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. If the use of both agents is necessary, monitor for signs of idelalisib toxicity and follow recommendations for dose modifications if necessary.
    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.
    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: (Severe) 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) Avoid concurrent use of idelalisib and ivacaftor. Ivacaftor is a CYP3A substrate, and idelalisib is a strong CYP3A inhibitor. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when idelalisib was given concurrently; hence the manufacturer of idelasib recommends against coadministration of sensitive CYP3A substrates. The manufacturer of ivacaftor recommends administering ivacaftor at the usual recommended dose, but reducing the frequency to twice weekly when used with a strong CYP3A inhibitor, such as idelalisib. Ivacaftor is also a weak inhibitor of CYP3A, and idelalisib is metabolized by CYP3A. Coadministration may increase both idelalisib and ivacaftor exposure leading to increased or prolonged therapeutic effects and adverse events.
    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.
    Ixabepilone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ixabepilone, a CYP3A substrate, as ixabepilone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Ketoconazole: (Severe) Concomitant use of idelalisib, a CYP3A4 substrate, and ketoconazole, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. In healthy subjects, ketoconazole 400 mg administered daily for 4 days increased the geometric mean AUC of idelalisib by 1.8-fold. No changes to the geometric mean Cmax were observed. Additionally, idelalisib is a strong CYP3A inhibitor while ketoconazole 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 ketoconazole.
    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; Naproxen: (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.
    Lapatinib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with lapatinib, a CYP3A substrate, as lapatinib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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.
    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.
    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.
    Loperamide: (Major) The plasma concentration of loperamide, a CYP3A4 substrate, may be increased when administered concurrently with idelalisib, a potent CYP3A4 inhibitor. If these drugs are used together, 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).
    Loperamide; Simethicone: (Major) The plasma concentration of loperamide, a CYP3A4 substrate, may be increased when administered concurrently with idelalisib, a potent CYP3A4 inhibitor. If these drugs are used together, 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).
    Lopinavir; Ritonavir: (Severe) 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. (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and lopinavir; ritonavir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while lopinavir and ritonavir are CYP3A substrates. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Avoid concomitant use of idelalisib and lopinavir; ritonavir.
    Loratadine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with loratadine, a CYP3A substrate, as loratadine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Loratadine; Pseudoephedrine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with loratadine, a CYP3A substrate, as loratadine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Lovastatin: (Severe) 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.
    Lovastatin; Niacin: (Severe) 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 concurrent use of idelalisib and ivacaftor. Ivacaftor is a CYP3A substrate, and idelalisib is a strong CYP3A inhibitor. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when idelalisib was given concurrently; hence the manufacturer of idelasib recommends against coadministration of sensitive CYP3A substrates. The manufacturer of ivacaftor recommends administering ivacaftor at the usual recommended dose, but reducing the frequency to twice weekly when used with a strong CYP3A inhibitor, such as idelalisib. Ivacaftor is also a weak inhibitor of CYP3A, and idelalisib is metabolized by CYP3A. Coadministration may increase both idelalisib and ivacaftor exposure leading to increased or prolonged therapeutic effects and adverse events. (Major) Do not use idelalisib with lumacaftor; ivacaftor because idelalisib exposure may be significantly reduced and efficacy compromised. Lumacaftor is a strong CYP3A inducer, and idelalisab is CYP3A substrate. In addition, because idelalisib is a strong CYP3A inhibitor, coadministration would alter the metabolism of ivacaftor and potentially require a dosage adjustment.
    Lumacaftor; Ivacaftor: (Major) Do not use idelalisib with lumacaftor; ivacaftor because idelalisib exposure may be significantly reduced and efficacy compromised. Lumacaftor is a strong CYP3A inducer, and idelalisab is CYP3A substrate. In addition, because idelalisib is a strong CYP3A inhibitor, coadministration would alter the metabolism of ivacaftor and potentially require a dosage adjustment.
    Lurasidone: (Severe) 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.
    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, and 50 mg PO twice daily for children weighing 10 to 19 kg.
    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.
    Mestranol; 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.
    Metformin; Pioglitazone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pioglitazone, a CYP3A substrate, as pioglitazone 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: (Severe) 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 as significantly increased exposure of midostaurin and its active metabolites may occur resulting in increased toxicity. Consider an alternative agent to replace idelalisib. If coadministration cannot be avoided, monitor patients for signs and symptoms of midostaurin toxicity (e.g., gastrointestinal toxicity, hematologic toxicity, bleeding, and infection), particularly during the first week of midostaurin therapy for systemic mastocytosis/mast cell leukemia and the first week of each cycle of midostaurin therapy for acute myeloid leukemia. Midostaurin is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. The AUC values of midostaurin and its metabolites CGP62221 and CGP52421 increased by 10.4-fold, 3.5-fold, and 1.2-fold, respectively, when midostaurin was administered with another strong CYP3A4 inhibitor in a drug interaction study. The Cmin (trough) levels of midostaurin and its metabolites CGP62221 and CGP52421 on day 28 increased by 2.1-fold, 1.2-fold, and 1.3-fold, respectively, when midostaurin was administered with another strong CYP3A4 inhibitor compared with day 21 Cmin levels with midostaurin alone in another drug interaction study.
    Mifepristone, RU-486: (Major) Avoid coadministration of mifepristone and idelalisib because it may lead to an increase in the serum concentration of either drug. Idelalisib is a potent CYP3A4 inhibitor and can inhibit the metabolism of mifepristone. In addition, mifepristone, RU-486 inhibits CYP3A4 in vitro and can inhibit the metabolism of drugs that are CYP3A4 substrates, such as idelalisib. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. When mifepristone is used in the treatment of Cushing's syndrome, coadministration with strong CYP3A inhibitors should be done only when necessary, and in such cases the dose of mifepristone should be limited to 600 mg per day. In a patient already receiving idelalisib, initiate mifepristone at a dose of 300 mg and titrate to a maximum of 600 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 mifepristone 900 mg or 1200 mg, reduce the mifepristone dose to 600 mg.
    Mirabegron: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with mirabegron, a CYP3A substrate, as mirabegron toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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.
    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.
    Montelukast: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with montelukast, a CYP3A substrate, as montelukast toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Nateglinide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with nateglinide, a CYP3A substrate, as nateglinide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Nefazodone: (Severe) 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: (Severe) 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 481%; concomitant use with other strong inhibitors of CYP3A4 may also increase neratinib concentrations.
    Netupitant; 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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with nevirapine, a CYP3A substrate, as nevirapine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Niacin; Simvastatin: (Severe) 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: (Major) Avoid coadministration of nifedipine with idelalisib and consider alternative therapy if possible. If coadministration is necessary, monitor the patient closely for desired cardiovascular effects on heart rate, blood pressure, or chest pain. The FDA-approved labeling for some nifedipine products contraindicates coadministration with strong CYP3A4 inducers, while other manufacturers classify the recommendation as a warning. Nifedipine is a CYP3A4 substrate, and idelalisib is a strong CYP3A4 inducer. Coadministration of nifedipine with another strong CYP3A4 inducer reduced the AUC and Cmax of nifedipine by approximately 70%.
    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.
    Nintedanib: (Moderate) Idelalisib is a potent inhibitor of CYP3A4 and nintedanib is a minor CYP3A4 substrate. Coadministration may increase the concentration and clinical effect of nintedanib. If concomitant use of idelalisib and nintedanib is necessary, closely monitor for increased nintedanib side effects including gastrointestinal toxicity, elevated liver enzymes, and hypertension. A dose reduction, interruption of therapy, or discontinuation of therapy may be necessary.
    Nisoldipine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with nisoldipine, a CYP3A substrate, as nisoldipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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 and consider alternative agents with less CYP3A4 inhibition due to increased olaparib exposure. If concomitant use is unavoidable, reduce the dose of olaparib tablets to 100 mg twice daily; reduce the dose of olaparib capsules to 150 mg twice daily. Olaparib is a CYP3A4/5 substrate and idelalisib is a strong CYP3A4 inhibitor.
    Ombitasvir; Paritaprevir; Ritonavir: (Severe) 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. (Major) Avoid concurrent administration of idelalisib with dasabuvir; ombitasvir; paritaprevir; ritonavir. Coadministration is expected to result in elevated plasma concentrations idelalisib, ritonavir, dasabuvir, and paritaprevir and increased risk of serious adverse events, such as hepatotoxicity. Idelalisib and ritonavir are both substrates and potent inhibitors of the hepatic isoenzyme CYP3A4; paritaprevir and dasabuvir (minor) are also metabolized by this enzyme. If coadministration is unavoidable, extreme caution and close monitoring are advised.
    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; 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.
    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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with oxycodone, a CYP3A substrate, as oxycodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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.
    Paliperidone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with paliperidone, a CYP3A substrate, as paliperidone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Pantoprazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pantoprazole, a CYP3A substrate, as pantoprazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with amlodipine, a CYP3A substrate, as amlodipine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Phenobarbital: (Severe) 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: (Severe) 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 17 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.
    Pimozide: (Severe) 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.
    Pioglitazone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with pioglitazone, a CYP3A substrate, as pioglitazone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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: (Severe) 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.
    Propafenone: (Severe) 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: (Severe) 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.
    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: (Severe) 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 concomitant use of idelalisib, a strong CYP3A inhibitor, with regorafenib, a CYP3A substrate, as regorafenib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Ribociclib: (Major) Avoid coadministration of ribociclib with idelalisib, as the systemic exposure of ribociclib may be increased resulting in an increase in ribociclib-related adverse reactions (e.g., neutropenia, QT prolongation); consider an alternative treatment with less potential for CYP3A inhibition. If concomitant use is unavoidable, reduce the dose of ribociclib to 400 mg once daily; if idelalisib is discontinued, the original dose of ribociclib may be resumed after at least 5 half-lives of idelalisib. Ribociclib is extensively metabolized by CYP3A4 and idelalisib is a strong CYP3A4 inhibitor.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with idelalisib, as the systemic exposure of ribociclib may be increased resulting in an increase in ribociclib-related adverse reactions (e.g., neutropenia, QT prolongation); consider an alternative treatment with less potential for CYP3A inhibition. If concomitant use is unavoidable, reduce the dose of ribociclib to 400 mg once daily; if idelalisib is discontinued, the original dose of ribociclib may be resumed after at least 5 half-lives of idelalisib. Ribociclib is extensively metabolized by CYP3A4 and idelalisib is a strong CYP3A4 inhibitor.
    Rifabutin: (Severe) 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: (Severe) 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.
    Rilpivirine: (Severe) 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.
    Ritonavir: (Severe) 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) Modify the ruxolitinib dosage when coadministered with idelalisib. Subsequent ruxolitinib dose modifications should be made with frequent monitoring of safety and efficacy. Increased ruxolitinib exposure is possible if coadministered with idelalisib. Ruxolitinib is a CYP3A4 substrate; idelalisib is a strong CYP3A4 inhibitor. Coadministration with another strong CYP3A4 inhibitor increased the ruxolitinib Cmax and AUC by 33% and 91%, respectively. Ruxolitinib dosage adjustments when coadministered with a strong CYP3A4 inhibitor are as follows: In patients with myelofibrosis (MF) and platelet counts greater than or equal to 100 x 10^9/L, initiate ruxolitinib at 10 mg PO twice daily; if platelet counts are greater than 50 x 10^9/L and less than 100 x 10^9/L, initiate ruxolitinib at 5 mg PO once daily. In patients with polycythemia vera (PV), stabilized on ruxolitinib doses greater than or equal to 10 mg PO twice daily, decrease the ruxolitinib dose by 50% rounded to the nearest available tablet strength; for PV patients stabilized on ruxolitinib 5 mg PO twice daily, decrease ruxolitinib to 5 mg PO once daily; avoid coadministration in PV patients stabilized on ruxolitinib 5 mg PO once daily or interrupt ruxolitinib therapy for the duration of idelalisib use.
    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.
    Selegiline: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with selegiline, a CYP3A substrate, as selegiline toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    Sibutramine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with sibutramine, a CYP3A substrate. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Strong CYP3A4 inhibitors may moderately increase sibutramine Cmax and AUC, which might increase the risk for sibutramine-related side effects.
    Sildenafil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with sildenafil, a CYP3A substrate, as sildenafil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Silodosin: (Severe) 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.
    Simeprevir: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with simeprevir, a CYP3A substrate, as simeprevir toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Simvastatin: (Severe) 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.
    Simvastatin; Sitagliptin: (Severe) 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.
    Sirolimus: (Major) Avoid the use of sirolimus with potent CYP3A4 inhibitors, such as idelalisib. Idelalisib may affect absorption and elimination of sirolimus leading to increased blood concentrations. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. Sirolimus is extensively metabolized by CYP3A4 in the gut and liver and undergoes counter-transport from enterocytes of the small intestine into the gut lumen by the P-glycoprotein drug efflux pump. Sirolimus is potentially recycled between enterocytes and the gut lumen to allow continued metabolism by CYP3A4.
    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.
    St. John's Wort, Hypericum perforatum: (Severe) 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.
    Streptogramins: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and dalfopristin; quinupristin, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. If the use of both agents is necessary, monitor for signs of idelalisib toxicity and follow recommendations for dose modifications if necessary.
    Sufentanil: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with sufentanil, a CYP3A substrate, as sufentanil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Sunitinib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with sunitinib, a CYP3A substrate, as sunitinib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Suvorexant: (Major) Suvorexant is primarily metabolized by CYP3A, and the manufacturer recommends against concurrent use of suvorexant with strong CYP3A inhibitors. Idelalisib is a strong CYP3A4 inhibitor, and suvorexant plasma concentrations may increase during concurrent use of these drugs.
    Tacrolimus: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tacrolimus, a CYP3A substrate, as tacrolimus toxicities may be significantly increased. 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.
    Tamoxifen: (Major) Idelalisib is a strong CYP3A4 inhibitor; tamoxifen is metabolized by CYP3A4, CYP2D6, and to a lesser extent, CYP2C9 and CYP2C19, to other potent active metabolites including endoxifen, which are then inactivated by sulfotransferase 1A1 (SULT1A1). Idelalisib may inhibit the CYP3A4 metabolism of tamoxifen to these metabolites, which have up to 33 times more affinity for the estrogen receptor than tamoxifen. Concomitant use of idelalisib and tamoxifen may result in decreased concentrations of the active metabolites of tamoxifen, which can compromise efficacy. If it is not possible to avoid concomitant use, monitor patients for changes in the therapeutic efficacy of tamoxifen.
    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.
    Telaprevir: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and telaprevir, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while telaprevir 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 telaprevir.
    Telithromycin: (Major) Concomitant use of idelalisib, a CYP3A4 substrate, and telithromycin, a strong CYP3A4 inhibitor, may increase the exposure of idelalisib. Additionally, idelalisib is a strong CYP3A inhibitor while telithromycin 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 telithromycin.
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and idelalisib is necessary, as the systemic exposure of idelalisib may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of idelalisib. Idelalisib is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Temsirolimus: (Major) Avoid coadministration of temsirolimus with idelalisib due to the risk of an increase in temsirolimus-related adverse events. If concomitant use cannot be avoided, consider a temsirolimus dose reduction to 12.5 mg per week. If idelalisib is discontinued, allow a washout period of approximately 1 week before the temsirolimus dose is increased to the dose used before initiation of idelalisib. Temsirolimus is a CYP3A4 substrate and idelalisib is a strong inhibitor of CYP3A4. Coadministration of temsirolimus with ketoconazole, a strong CYP3A4 inhibitor, had no significant effect on the AUC or Cmax of temsirolimus, but increased the AUC and Cmax of the active metabolite sirolimus by 3.1-fold and 2.2-fold, respectively. Idelalisib increased the Cmax and AUC of oral midazolam, another CYP3A4 substrate, by 2.4-fold and 5.4-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.
    Testosterone: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with testosterone, a CYP3A substrate, as testosterone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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.
    Tolterodine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tolterodine, a CYP3A substrate, as tolterodine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Tolvaptan: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with tolvaptan, a CYP3A substrate, as tolvaptan toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Trabectedin: (Major) Avoid the concomitant use of trabectedin with idelalisib due to significantly increased trabectedin exposure. If short-term idelalisib (less than 14 days) cannot be avoided, begin administration 1 week after the trabectedin infusion and discontinue it the day prior to the next trabectedin infusion. Trabectedin is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Coadministration with ketoconazole (200 mg twice daily for 7.5 days), another strong CYP3A inhibitor, increased the systemic exposure of a single dose of trabectedin (0.58 mg/m2 IV) by 66% and the Cmax by 22% 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.
    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 concomitant use of idelalisib, a strong CYP3A inhibitor, with trazodone, a CYP3A substrate, as trazodone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Triazolam: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with triazolam, a CYP3A substrate, as triazolam toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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.
    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) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with vardenafil, a CYP3A substrate, as vardenafil toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Vemurafenib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with vemurafenib, a CYP3A substrate, as vemurafenib toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Venetoclax: (Major) Avoid the concomitant use of venetoclax and idelalisib; venetoclax is a CYP3A4 substrate and idelalisib is a strong CYP3A4 inhibitor. The concomitant use of these agents together is contraindicated during the initial and dose titration phase of venetoclax. If concomitant use of these drugs is required when the patient is on a steady venetoclax dose (after the titration phase), reduce the venetoclax dosage by at least 75% (maximum dose of 100 mg/day). If idelalisib is discontinued, wait 2 to 3 days and then resume the recommended venetoclax dosage (or prior dosage if less). Monitor patients for signs and symptoms of venetoclax toxicity such as hematologic toxicity, GI toxicity, and tumor lysis syndrome. In a drug interaction study, the venetoclax Cmax and AUC values were increased by 2.3-fold and 6.4-fold, respectively, when a strong CYP3A4 inhibitor was co-administered in NHL patients.
    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: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with vinblastine, a CYP3A substrate, as vinblastine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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: (Major) Use caution and monitor patients for an earlier onset and/or an increased severity of adverse effects, including neurotoxicity and myelosuppression, if idelalisib is used concomitantly with vinorelbine. Idelalisib is a CYP3A4 inhibitor and vinorelbine is a CYP3A4 substrate; coadministration may cause the metabolism of vinorelbine to be decreased.
    Voriconazole: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with voriconazole, a CYP3A substrate, as voriconazole toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Warfarin: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with warfarin, a CYP3A substrate, as warfarin toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib. In addition, the use of warfarin in patients with blood dyscrasias is contraindicated. Therefore, to minimize the bleeding risk, warfarin should be used cautiously in patients receiving antineoplastic agents that cause myelosuppression or blood dyscrasias. In addition, effects of antineoplastic agents on protein synthesis as well as protein binding may lead to transient changes in a patient's INR while receiving warfarin. The INR may increase and/or decrease throughout the chemotherapy cycle leading to supra- or sub-therapeutic values; monitor warfarin therapy closely.
    Yohimbine: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with yohimbine, a CYP3A substrate, as yohimbine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Zileuton: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with zileuton, a CYP3A substrate, as zileuton toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Ziprasidone: (Severe) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ziprasidone, a CYP3A substrate, as ziprasidone toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    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: (Major) Avoid concurrent use of idelalisib, a strong CYP3A inhibitor, with CYP3A substrates such as zolpidem if possible. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when co-administered with idelalisib. If concurrent use cannot be avoided, closely monitor zolpidem tolerability and safety, and consider using a lower dose of zolpidem to minimize the potential for adverse CNS effects. CYP3A4 is the primary isoenzyme responsible for zolpidem metabolism, and there is evidence of an increase in pharmacodynamic effects and systemic exposure of zolpidem during co-administration with some potent inhibitors of CYP3A4.
    Zonisamide: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with zonisamide, a CYP3A substrate, as zonisamide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.

    PREGNANCY AND LACTATION

    Pregnancy

    Idelalisib is designated as pregnancy category D according to the manufacturer. Fetal harm may occur if idelalisib is administered during pregnancy, based on findings in animal studies. Females of childbearing potential should avoid becoming pregnant during therapy. Women who become pregnant while receiving idelalisib should be apprised of the potential reproductive risk. 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).

    Advise female patients not to breast-feed while taking idelalisib. Breast-feeding should be discontinued while taking the drug because of the potential for serious adverse reactions in nursing infants from idelalisib. It is not known if idelalisib is excreted into human milk.

    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 greater than 84% 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 stead state is 23 liters. The systemic clearance at steady state is 14.9 L/hr, 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; 49% of the radioactivity in the urine and 44% in the feces was owing to the inactive metabolite, GS-563117.
     
    Idelalisib is metabolized by aldehyde oxidase and cytochrome P 450 (CYP) 3A to its major metabolite which is inactive, GS-563117; additionally, it undergoes minor metabolism by UGT1A4.
     
    Affected cytochrome P450 isoenzymes and drug transporters:  CYP3A4, CYP2B6, CYP2C8, CYP2C9, CYP2C19
    Idelalisib is a strong inhibitor of the CYP3A4 isoenzyme. It is also a weak substrate of UGT1A4. In vitro, idelalisib is a substrate for aldehyde oxidase, CYP3A, P-glycoprotein (P-gp), BCRP, and UGT1A4; it inhibits CYP2C8, CYP2C19, CYP3A, and UGT1A1. GS-563117 inhibits CYP2C8, CYP2C9, CYP2C19, CYP3A, and UGT1A1 in vitro and is an in vitro substrate of P-gp and BCRP. Additionally, both idelalisib and GS-563117 inhibit P-gp, OATP1B1, and OATP1B3 invitro. Avoid coadministration of idelalisib with strong CYP3A inducers and CYP3A substrates. If idelalisib is administered with a CYP3A inhibitor, monitor for signs of idelalisib toxicity.

    Oral Route

    The median Tmax of idelalisib is 1.5 hours. Administration of a single dose of idelalisib with a high-fat meal increased the AUC 1.4-fold relative to fasting conditions; however, it may be administered without regard to food. Idelalisib exposure increases in a less than dose-proportional manner at doses of 50—350 mg by mouth twice daily.