Copiktra

Small Molecule Antineoplastic Phosphatidylinositol-3-Kinase (PI3K) Inhibitors

Emetic Risk
Minimal/Low
Administer prn antiemetics as necessary.

Oral Administration Oral Solid Formulations

Duvelisib may be taken with or without food.
Swallow whole; do not open, break, or chew capsules.
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.[63571]

Severe

neutropenia / Delayed / 30.0-42.0
infection / Delayed / 0-31.0
hyperkalemia / Delayed / 26.0-26.0
nephrotoxicity / Delayed / 24.0-24.0
diarrhea / Early / 23.0-23.0
colitis / Delayed / 23.0-23.0
lymphocytosis / Delayed / 21.0-21.0
thrombocytopenia / Delayed / 10.0-15.0
anemia / Delayed / 11.0-15.0
lymphopenia / Delayed / 9.0-9.0
rash / Early / 9.0-9.0
leukopenia / Delayed / 8.0-8.0
elevated hepatic enzymes / Delayed / 0-8.0
hyponatremia / Delayed / 7.0-7.0
Stevens-Johnson syndrome / Delayed / 0-5.0
Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) / Delayed / 0-5.0
toxic epidermal necrolysis / Delayed / 0-5.0
pneumonitis / Delayed / 5.0-5.0
fatigue / Early / 5.0-5.0
hypophosphatemia / Delayed / 5.0-5.0
hypokalemia / Delayed / 4.0-4.0
hyperamylasemia / Delayed / 4.0-4.0
hypocalcemia / Delayed / 3.0-3.0
abdominal pain / Early / 2.0-2.0
dyspnea / Early / 2.0-2.0
fever / Early / 2.0-2.0
hypoalbuminemia / Delayed / 2.0-2.0
nausea / Early / 0-1.0
vomiting / Early / 1.0-1.0
constipation / Delayed / 0-1.0
anorexia / Delayed / 0-1.0
oral ulceration / Delayed / 1.0-1.0
cough / Delayed / 0-1.0
edema / Delayed / 1.0-1.0
headache / Early / 0-1.0
musculoskeletal pain / Early / 1.0-1.0
arthralgia / Delayed / 0-1.0
erythema multiforme / Delayed / Incidence not known
exfoliative dermatitis / Delayed / Incidence not known

Moderate

erythema / Early / Incidence not known
contact dermatitis / Delayed / Incidence not known

Mild

weight loss / Delayed / 11.0-11.0
maculopapular rash / Early / Incidence not known

Infection

Serious infection including Pneumocystis jirovecii pneumonia (PJP) has been reported with duvelisib therapy; some cases were fatal. Treat infections prior to starting duvelisib. Monitor patients for signs or symptoms of infection. All patients should receive PJP prophylaxis during duvelisib therapy and following therapy until the CD4+ T-cell count is greater than 200 cells/microliter. If PJP is suspected, hold therapy and perform an evaluation; if PJP is confirmed, discontinue therapy. Consider administering prophylactic antiviral agents to prevent cytomegalovirus (CMV) infection or reactivation. Therapy interruption or a dose reduction may be necessary in patients who have a CMV infection or viremia as detected via PCR or an antigen test. Monitor for CMV reactivation at least monthly when duvelisib therapy is resumed.[63571]

Colitis, diarrhea

Diarrhea and colitis have been reported with duvelisib therapy; some cases were fatal. Monitor patients for signs and symptoms of new or worsening diarrhea; monitor patients who develop diarrhea or colitis at least weekly. Start supportive care including antidiarrheal agents and enteric-acting or systemic steroid therapy as necessary based on the severity of the toxicity. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop diarrhea or colitis.[63571]

Pneumonitis

Pneumonitis has been reported with duvelisib therapy; some cases were fatal. Monitor patients for signs and symptoms of new or progressive pulmonary toxicity (e.g., cough, dyspnea, hypoxia, interstitial infiltrates, or a more than 5% decline in oxygen saturation) and evaluate etiology (exclude an infectious etiology). Start systemic steroid therapy in patients who develop grade 2 or higher toxicity. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop noninfectious pneumonitis.[63571]

Copiktra

Rx

Phosphatidylinositol-3-kinase (PI3K) inhibitor
Used in adults with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma
Serious infection, diarrhea/colitis, cutaneous reactions, and pneumonitis have been reported

For the treatment of chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL).
NOTE: Duvelisib has been designated by the FDA as an orphan drug for the treatment of CLL and SLL.
For the treatment of relapsed or refractory CLL and SLL in patients who have received at least 2 prior therapies.
NOTE: On June 30, 2022, the FDA warned about a possible increased risk of death and serious side effects with duvelisib compared with ofatumumab in patients with relapsed or refractory CLL/SLL after a review of 5-year results from a randomized, phase 3 (DUO trial) trial. Pending further review of the data, the FDA recommends that health care providers consider the risks and benefits of continuing duvelisib, discuss the possibility of an increased risk of death and serious adverse events with their patients, and report suspected adverse reactions from duvelisib to the FDA.
Oral dosage Adults

25 mg orally twice daily. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. Therapy interruption, a dose reduction, or discontinuation may be necessary in patients who develop toxicity. All patients should receive Pneumocystis jirovecii (PJP) prophylaxis during and after duvelisib therapy. Consider administering prophylactic antiviral agents to prevent cytomegalovirus infection or reactivation.[63571] At a median follow-up time of 22.4 months, the median progression-free survival time, assessed by an independent review committee (primary endpoint), was significantly improved in patients with CLL/SLL who received duvelisib until disease progression (median duration of therapy, 50 weeks) compared with up to 12 doses of ofatumumab (13.3 months vs. 9.9 months; hazard ratio = 0.52; p less than 0.0001) in a multinational, randomized, phase 3 trial (n = 319; the DUO trial). Patients (median age, 69 years; range, 39 to 90 years) in this trial had received a median of 2 prior therapies.[63691] At a median follow-up of 63 months, the overall survival time was nonsignificantly shorter in patients who received duvelisib compared with ofatumumab (52.3 months vs. 63.3 months; HR = 1.09; 95% CI, 0.79 to 1.51) in the DUO trial. Additionally, treatment with duvelisib was associated with a higher risk of serious side effects including infections, diarrhea, inflammation of the intestine and/or lungs, skin reactions, and elevated liver enzymes.

For the treatment of Non-Hodgkin's lymphoma (NHL)†. For the treatment of relapsed or refractory follicular lymphoma in patients who have received at least 2 prior systemic therapies†.
NOTE: Duvelisib has been designated as an orphan drug by the FDA for the treatment of follicular lymphoma.
NOTE: FDA approval was removed for this indication in December 2021 after initial accelerated approval due to a decision by the manufacturer to voluntarily withdraw the indication. Oral dosage Adults

Dosage not established.

Hepatic Impairment

Baseline Hepatic ImpairmentSpecific guidelines for duvelisib dosage adjustments in patients with baseline hepatic impairment are not available; it appears that no initial dosage adjustments are needed.Treatment-Related ToxicityGrade 2 elevated transaminase levels (increased ALT or AST level greater than 3- to 5-times the upper limit of normal (ULN)): Continue current dosage and monitor liver function tests (LFTs) at least weekly until increased ALT or AST levels return to less than 3-times the ULN.Grade 3 elevated transaminase levels (increased ALT or AST level greater than 5- to 20-times the ULN): Hold therapy and monitor LFTs at least weekly until increased ALT or AST levels return to less than 3-times the ULN. Resume duvelisib at the same dose for the first occurrence or at a reduced dose of 15 mg PO twice daily for a subsequent occurrence.Grade 4 elevated transaminase levels (increased ALT or AST level greater than 20-times the ULN): Discontinue therapy.[63571]

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with duvelisib. Coadministration may increase the exposure of dolutegravir. Dolutegravir is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Abemaciclib: (Moderate) Monitor for an increase in abemaciclib-related adverse reactions if coadministration with duvelisib is necessary; consider reducing the dose of abemaciclib in 50-mg decrements if toxicities occur. Discontinue abemaciclib for patients unable to tolerate 50 mg twice daily. Abemaciclib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by approximately 1.6- to 2.4-fold.
Acalabrutinib: (Major) Decrease the acalabrutinib dose to 100 mg PO once daily if coadministered with duvelisib. Coadministration may result in increased acalabrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Acalabrutinib is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. In physiologically based pharmacokinetic (PBPK) simulations, the Cmax and AUC values of acalabrutinib were increased by 2- to almost 3-fold when acalabrutinib was coadministered with moderate CYP3A inhibitors.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with duvelisib may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of duvelisib could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If duvelisib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Duvelisib is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If duvelisib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like duvelisib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If duvelisib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Adagrasib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with adagrasib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; adagrasib is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as adagrasib.
Albuterol; Budesonide: (Major) Avoid coadministration of systemic budesonide with duvelisib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Alfentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If duvelisib is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Alfuzosin: (Moderate) Monitor for evidence of alfuzosin-related adverse effects including hypotension and QT prolongation if coadministered with duvelisib. Increased alfuzosin exposure may occur. Alfuzosin is a CYP3A4 substrate. Duvelisib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased the alfuzosin AUC by 1.3-fold.
Alprazolam: (Major) Avoid coadministration of alprazolam and duvelisib due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with duvelisib, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased alprazolam exposure by 1.6- to 1.98-fold.
Amiodarone: (Moderate) Monitor for increased toxicity of duvelisib and amiodarone during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; amiodarone is also a substrate and moderate inhibitor of CYP3A.
Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Atorvastatin: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Benazepril: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Celecoxib: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Olmesartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Valsartan: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Amobarbital: (Major) Avoid concomitant use of duvelisib with amobarbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When amobarbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with amobarbital. Duvelisib is a CYP3A substrate; amobarbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with clarithromycin. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; clarithromycin is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as clarithromycin.
Apalutamide: (Major) Avoid coadministration of duvelisib with apalutamide. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; apalutamide is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Aprepitant, Fosaprepitant: (Major) Avoid the concomitant use of duvelisib with aprepitant, fosaprepitant due to substantially increased exposure of aprepitant. Fosaprepitant is rapidly converted to aprepitant; therefore, a similar interaction is likely. Increased duvelisib exposure may also occur. Duvelisib is a substrate and moderate inhibitor of CYP3A. Aprepitant is a substrate, and when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor. Coadministration of daily oral aprepitant (230 mg, or 1.8 times the recommended single dose) with another moderate CYP3A4 inhibitor increased the aprepitant AUC 2-fold. When administered as a single oral or single intravenous dose, the inhibitory effect of aprepitant on CYP3A4 is weak and did not result in a clinically significant increase in the AUC of a sensitive substrate.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of duvelisib. Patients receiving both a CYP2D6 inhibitor plus duvelisib may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; duvelisib is a moderate CYP3A inhibitor.
Artemether; Lumefantrine: (Moderate) Monitor for increased toxicity of lumefantrine, including QT prolongation, if coadministered with duvelisib. Coadministration may increase the exposure of lumefantrine. Lumefantrine is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid concomitant use of duvelisib with butalbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When butalbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with butalbital. Duvelisib is a CYP3A substrate; butalbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like duvelisib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If duvelisib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Atazanavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with atazanavir. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; atazanavir is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as atazanavir.
Atazanavir; Cobicistat: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with atazanavir. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; atazanavir is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as atazanavir. (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with cobicistat. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as cobicistat.
Avanafil: (Major) Do not exceed an avanfil dose of 50 mg once every 24 hours during coadministration with duvelisib as avanafil serum conentrations may be increased. Avanafil is a substrate of and primarily metabolized by CYP3A4; duvelisib is a moderate inhibitor of CYP3A4. In drug interaction studies, another moderate CYP3A inhibitor increased avanafil Cmax and AUC equal to approximately 2-fold and 3-fold, respectively, and prolonged the half-life of avanafil to approximately 8 hours.
Avapritinib: (Major) Avoid coadministration of avapritinib with duvelisib due to the risk of increased avapritinib-related adverse reactions. If concurrent use is unavoidable, reduce the starting dose of avapritinib from 300 mg PO once daily to 100 mg PO once daily in patients with gastrointestinal stromal tumor or from 200 mg PO once daily to 50 mg PO once daily in patients with advanced systemic mastocytosis. Avapritinib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration of avapritinib 300 mg PO once daily with a moderate CYP3A4 inhibitor is predicted to increase the AUC of avapritinib by 210% at steady-state.
Berotralstat: (Moderate) Monitor for increased toxicity if duvelisib is coadministered with berotralstat. Coadministration may increase the exposure of duvelisib, increasing the risk of toxicity. Duvelisib is a CYP3A4 substrate; berotralstat is a moderate CYP3A4 inhibitor.
Bexarotene: (Major) Avoid concomitant use of duvelisib with bexarotene. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When bexarotene has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with bexarotene. Duvelisib is a CYP3A substrate; bexarotene is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Bosentan: (Major) Avoid concomitant use of duvelisib with bosentan. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib; the systemic exposure of bosentan may also increase resulting in an increase in treatment-related adverse reactions. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily; a bosentan dose adjustment is not necessary. Administration of bosentan with both duvelisib and a strong or moderate CYP2C9 inhibitor is not recommended. When bosentan has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with bosentan. Duvelisib is a CYP3A substrate and a moderate CYP3A4 inhibitor. Bosentan is a moderate CYP3A inducer and a CYP3A4 and CYP2C9 substrate. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Bosutinib: (Major) Avoid concomitant use of bosutinib and duvelisib as bosutinib plasma exposure may be significantly increased resulting in an increased risk of bosutinib adverse events (e.g., myelosuppression, GI toxicity). Bosutinib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. In a cross-over trial in 18 healthy volunteers, the Cmax and AUC values of bosutinib were increased 1.5-fold and 2-fold, respectively, when bosutinib 500 mg PO was administered with a single dose of a moderate CYP3A4 inhibitor.
Brigatinib: (Major) Avoid coadministration of brigatinib with duvelisib. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib; plasma exposure of brigatinib may also increase resulting in an increase in brigatinib-related adverse reactions. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily; also reduce the dose of brigatinib by approximately 40% without breaking tablets (i.e., from 180 mg to 120 mg; from 120 mg to 90 mg; from 90 mg to 60 mg). When brigatinib has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with brigatinib. If duvelisib is discontinued, resume the brigatinib dose that was tolerated prior to initiation of duvelisib. Duvelisib is a CYP3A substrate and a moderate CYP3A4 inhibitor. Brigatinib is a CYP3A4 substrate and a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase the AUC of brigatinib by approximately 40%.
Bromocriptine: (Major) When bromocriptine is used for diabetes, do not exceed a dose of 1.6 mg once daily during concomitant use of duvelisib. Use this combination with caution in patients receiving bromocriptine for other indications. Concurrent use may increase bromocriptine concentrations. Bromocriptine is extensively metabolized in the liver via CYP3A4; duvelisib is a moderate inhibitor of CYP3A4.
Budesonide: (Major) Avoid coadministration of systemic budesonide with duvelisib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Budesonide; Formoterol: (Major) Avoid coadministration of systemic budesonide with duvelisib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Budesonide; Glycopyrrolate; Formoterol: (Major) Avoid coadministration of systemic budesonide with duvelisib due to increased budesonide exposure; use caution with inhaled budesonide, as systemic exposure may increase. Budesonide is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Buspirone: (Moderate) Monitor for an increase in buspirone-related adverse reactions if coadministration with duvelisib is necessary; the effect may be more pronounced if the patient has been titrated to a stable dose of buspirone and duvelisib is added or removed from therapy. Buspirone is a sensitive CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors increased buspirone exposure by 3.4 to 6-fold and was accompanied by increased buspirone-related adverse reactions.
Butabarbital: (Major) Avoid concomitant use of duvelisib with butabarbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When butabarbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with butabarbital. Duvelisib is a CYP3A substrate; butabarbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Butalbital; Acetaminophen: (Major) Avoid concomitant use of duvelisib with butalbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When butalbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with butalbital. Duvelisib is a CYP3A substrate; butalbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid concomitant use of duvelisib with butalbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When butalbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with butalbital. Duvelisib is a CYP3A substrate; butalbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid concomitant use of duvelisib with butalbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When butalbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with butalbital. Duvelisib is a CYP3A substrate; butalbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid concomitant use of duvelisib with butalbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When butalbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with butalbital. Duvelisib is a CYP3A substrate; butalbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Carbamazepine: (Major) Avoid coadministration of duvelisib with carbamazepine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; carbamazepine is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Cenobamate: (Major) Avoid concomitant use of duvelisib with cenobamate. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When cenobamate has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with cenobamate. Duvelisib is a CYP3A substrate; cenobamate is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Ceritinib: (Major) Reduce the duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ceritinib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ceritinib is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ceritinib.
Chloramphenicol: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with chloramphenicol. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; chloramphenicol is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as chloramphenicol.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with duvelisib may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of duvelisib could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If duvelisib is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Duvelisib is a moderate inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If duvelisib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cilostazol: (Major) Reduce the dose of cilostazol to 50 mg twice daily when coadministered with duvelisib, and monitor for an increase in cilostazol-related adverse reactions. Cilostazol is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the Cmax and AUC of cilostazol (single dose) by 47% and 73%, respectively; the AUC of 4-trans-hydroxycilostazol increased by 141%.
Ciprofloxacin: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with ciprofloxacin. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ciprofloxacin is a moderate CYP3A inhibitor.
Clarithromycin: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with clarithromycin. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; clarithromycin is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as clarithromycin.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with duvelisib and monitor for adverse reactions. If duvelisib is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor.
Cobicistat: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with cobicistat. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as cobicistat.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with duvelisib due to the risk of cobimetinib toxicity. Cobimetinib is a CYP3A substrate and duvelisib is a moderate inhibitor of CYP3A. Simulations showed that predicted steady-state concentrations of cobimetinib at a reduced dose of 20 mg administered concurrently with short-term (less than 14 days) treatment of a moderate CYP3A inhibitor were similar to observed steady-state concentrations of cobimetinib 60 mg alone.
Colchicine: (Major) Avoid concomitant use of colchicine and duvelisib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Conivaptan: (Moderate) Monitor for increased toxicity if duvelisib is coadministered with conivaptan. Coadministration may increase the exposure of duvelisib, increasing the risk of toxicity. Duvelisib is a CYP3A substrate; conivaptan is a moderate CYP3A inhibitor.
Crizotinib: (Moderate) Monitor for increased toxicity of duvelisib and crizotinib during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; crizotinib is also a substrate and moderate inhibitor of CYP3A.
Cyclosporine: (Moderate) Monitor for increased toxicity of duvelisib and cyclosporine during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; cyclosporine is also a substrate and moderate inhibitor of CYP3A.
Dabrafenib: (Major) Avoid concomitant use of duvelisib with dabrafenib. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When dabrafenib has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with dabrafenib. Duvelisib is a CYP3A substrate; dabrafenib is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Danazol: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with danazol. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; danazol is a moderate CYP3A inhibitor.
Daridorexant: (Major) Limit the daridorexant dose to 25 mg if coadministered with duvelisib. Concomitant use may increase daridorexant exposure and the risk for daridorexant-related adverse effects. Daridorexant is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use of another moderate CYP3A inhibitor increased daridorexant overall exposure 2.4-fold.
Darifenacin: (Moderate) Monitor for increased toxicity of darifenacin if coadministered with duvelisib. Coadministration may increase the exposure of darifenacin. Darifenacin is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Darunavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with darunavir. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; darunavir is a sensitive substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as darunavir.
Darunavir; Cobicistat: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with darunavir. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; darunavir is a sensitive substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as darunavir. (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with cobicistat. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as cobicistat.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with darunavir. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; darunavir is a sensitive substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as darunavir. (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with cobicistat. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as cobicistat.
Dasatinib: (Moderate) Monitor for increased toxicity of dasatinib if coadministered with duvelisib. Coadministration may increase the exposure of dasatinib. Dasatinib is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Deflazacort: (Major) Decrease deflazacort dose to one third of the recommended dosage when coadministered with duvelisib. Concurrent use may significantly increase concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in an increased risk of toxicity. Deflazacort is a CYP3A substrate and duvelisib is a moderate inhibitor of CYP3A.
Delavirdine: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with delavirdine. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; delavirdine is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as delavirdine.
Diltiazem: (Moderate) Monitor for increased toxicity of duvelisib and diltiazem during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; diltiazem is also a substrate and moderate inhibitor of CYP3A.
Disopyramide: (Major) Monitor for increased toxicity of disopyramide if coadministered with duvelisib. Coadministration may increase the exposure of disopyramide. Disopyramide is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor. Cases of life-threatening interactions have been reported for disopyramide when given with other moderate CYP3A4 inhibitors.
Dofetilide: (Major) Monitor for an increase in dofetilide-related adverse effects, including QT prolongation and torsade de pointes (TdP), if coadministered with duvelisib. Coadministration may increase the exposure of dofetilide. Dofetilide is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with duvelisib. Coadministration may increase the exposure of dolutegravir. Dolutegravir is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with duvelisib. Coadministration may increase the exposure of dolutegravir. Dolutegravir is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with duvelisib. Coadministration may increase the exposure of dolutegravir. Dolutegravir is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Doxorubicin Liposomal: (Major) Avoid coadministration of duvelisib with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Duvelisib is a moderate CYP3A4 inhibitor and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
Doxorubicin: (Major) Avoid coadministration of duvelisib with doxorubicin due to increased systemic exposure of doxorubicin resulting in increased treatment-related adverse reactions. Duvelisib is a moderate CYP3A4 inhibitor and doxorubicin is a major substrate of CYP3A4. Concurrent use of CYP3A4 inhibitors with doxorubicin has resulted in clinically significant interactions.
Dronabinol: (Moderate) Monitor for increased toxicity (e.g., feeling high, dizziness, confusion, somnolence) of dronabinol if coadministered with duvelisib. Coadministration may increase the exposure of dronabinol. Dronabinol is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Dronedarone: (Moderate) Monitor for increased toxicity of duvelisib and dronedarone during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; dronedarone is a sensitive substrate and moderate inhibitor of CYP3A.
Efavirenz: (Major) Avoid concomitant use of duvelisib with efavirenz. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When efavirenz has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with efavirenz. Duvelisib is a CYP3A substrate; efavirenz is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of duvelisib with efavirenz. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When efavirenz has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with efavirenz. Duvelisib is a CYP3A substrate; efavirenz is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of duvelisib with efavirenz. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When efavirenz has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with efavirenz. Duvelisib is a CYP3A substrate; efavirenz is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Elacestrant: (Major) Avoid concomitant use of elacestrant and duvelisib due to the risk of increased elacestrant exposure which may increase the risk for adverse effects. Elacestrant is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased elacestrant overall exposure by 2.3-fold.
Elagolix: (Major) Avoid concomitant use of duvelisib with elagolix. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When elagolix has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with elagolix. Duvelisib is a CYP3A substrate; elagolix is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Elagolix; Estradiol; Norethindrone acetate: (Major) Avoid concomitant use of duvelisib with elagolix. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When elagolix has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with elagolix. Duvelisib is a CYP3A substrate; elagolix is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Eletriptan: (Moderate) Monitor for increased toxicity of eletriptan if coadministered with duvelisib. Coadministration may increase the exposure of eletriptan. Eletriptan is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor. In drug interaction studies, coadministration of eletriptan with another moderate CYP3A inhibitor increased the eletriptan AUC by 4-fold.
Elexacaftor; tezacaftor; ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with duvelisib; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); duvelisib is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If duvelisib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold. (Major) Reduce the dosing frequency of elexacaftor; tezacaftor; ivacaftor to every other day in the morning when coadministered with duvelisib; omit the ivacaftor evening dose and administer in the morning every other day alternating with elexacaftor; tezacaftor; ivacaftor (i.e., recommended dose of elexacaftor; tezacaftor; ivacaftor on day 1 in the morning and recommended dose of ivacaftor on day 2 in the morning). Coadministration may increase elexacaftor; tezacaftor; ivacaftor exposure and adverse reactions. Elexacaftor, tezacaftor, and ivacaftor are CYP3A substrates; duvelisib is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure by 2.9-fold. Simulation suggests a moderate inhibitor may increase elexacaftor and tezacaftor exposure by 2.3-fold and 2.1-fold, respectively.
Eliglustat: (Major) In intermediate or poor CYP2D6 metabolizers (IMs or PMs), coadministration of duvelisib with eliglustat is not recommended. In extensive CYP2D6 metabolizers (EMs), coadministration of duvelisib and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. The coadministration of eliglustat with both duvelisib and a moderate or strong CYP2D6 inhibitor is contraindicated in all patients. Eliglustat is a CYP3A and CYP2D6 substrate; duvelisib is a moderate CYP3A inhibitor. Coadministration of eliglustat with CYP3A inhibitors, such as duvelisib, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias); this risk is the highest in CYP2D6 IMs and PMs because a larger portion of the eliglustat dose is metabolized via CYP3A.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with cobicistat. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as cobicistat.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with cobicistat. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; cobicistat is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as cobicistat.
Encorafenib: (Major) Avoid coadministration of encorafenib and duvelisib due to increased encorafenib exposure. If concurrent use cannot be avoided, reduce the encorafenib dose to one-half of the dose used prior to the addition of duvelisib. If duvelisib is discontinued, the original encorafenib dose may be resumed after 3 to 5 elimination half-lives of duvelisib. Encorafenib is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor with a single 50 mg dose of encorafenib (0.1 times the recommended dose) increased the encorafenib AUC and Cmax by 2-fold and 45%, respectively.
Entrectinib: (Major) Avoid coadministration of entrectinib with duvelisib due to increased entrectinib exposure resulting in increased treatment-related adverse effects. If coadministration cannot be avoided in adults and pediatric patients 12 years and older with BSA greater than 1.5 m2, reduce the entrectinib dose to 200 mg PO once daily. If duvelisib is discontinued, resume the original entrectinib dose after 3 to 5 elimination half-lives of duvelisib. Entrectinib is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration of a moderate CYP3A4 inhibitor is predicted to increase the AUC of entrectinib by 3-fold.
Enzalutamide: (Major) Avoid coadministration of duvelisib with enzalutamide. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; enzalutamide is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Eplerenone: (Major) Do not exceed an eplerenone dose of 25 mg PO once daily if given concurrently with duvelisib in a post-myocardial infarction patient with heart failure. In patients with hypertension receiving duvelisib, initiate eplerenone at 25 mg PO once daily; the dose may be increased to a maximum of 25 mg PO twice daily for inadequate blood pressure response. Measure serum creatinine and serum potassium within 3 to 7 days of initiating duvelisib and periodically thereafter. Eplerenone is a CYP3A substrate. Duvelisib is a moderate CYP3A inhibitor. Coadministration with moderate CYP3A inhibitors increased eplerenone exposure by 100% to 190%. Increased eplerenone concentrations may lead to a risk of developing hyperkalemia and hypotension.
Erythromycin: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with erythromycin. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; erythromycin is a moderate CYP3A inhibitor.
Eslicarbazepine: (Major) Avoid concomitant use of duvelisib with eslicarbazepine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When eslicarbazepine has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with eslicarbazepine. Duvelisib is a CYP3A substrate; eslicarbazepine is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Etravirine: (Major) Avoid concomitant use of duvelisib with etravirine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib; etravirine exposure may also increase. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When etravirine has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with etravirine. Duvelisib is a CYP3A substrate and a moderate CYP3A inhibitor. Etravirine is a CYP3A substrate and a moderate CYP3A inducer. Coadministration of duvelisib with etravirine for 12 days decreased duvelisib exposure by 35%.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate and watch for everolimus-related adverse reactions if coadministration with duvelisib is necessary. The dose of everolimus may need to be reduced. Everolimus is a sensitive CYP3A4 substrate and a P-glycoprotein (P-gp) substrate. Duvelisib is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4/P-gp inhibitors increased the AUC of everolimus by 3.5 to 4.4-fold.
Ezetimibe; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with duvelisib is necessary. Coadministration may increase the exposure of simvastatin. Simvastatin is a sensitive substrate of CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor.
Fedratinib: (Moderate) Monitor for increased toxicity if duvelisib is coadministered with fedratinib. Coadministration may increase the exposure of duvelisib, increasing the risk of toxicity. Duvelisib is a CYP3A substrate; fedratinib is a moderate CYP3A inhibitor.
Felodipine: (Moderate) Concurrent use of felodipine and duvelisib should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Concurrent use of another moderate CYP3A4 inhibitor increased felodipine AUC and half-life by approximately 2.5-fold and 2-fold, respectively.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If duvelisib is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or duvelisib; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased overall exposure to finerenone by 248%.
Flibanserin: (Contraindicated) The concomitant use of flibanserin and duvelisib is contraindicated due to increased flibanserin exposure, which can result in severe hypotension and syncope. If initiating flibanserin following use of duvelisib, start flibanserin at least 2 weeks after the last dose of duvelisib. If initiating duvelisib following flibanserin use, start duvelisib at least 2 days after the last dose of flibanserin. Flibanserin is a CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Fluconazole: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with fluconazole. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; fluconazole is a moderate CYP3A inhibitor.
Fluvoxamine: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with fluvoxamine. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; fluvoxamine is a moderate CYP3A inhibitor.
Fosamprenavir: (Moderate) Monitor for an increase in adverse reactions from both drugs if concurrent use of duvelisib and fosamprenavir is necessary. Concomitant use may increase the exposure of both drugs. Duvelisib and fosamprenavir are both CYP3A substrates and moderate CYP3A inhibitors.
Fosphenytoin: (Major) Avoid coadministration of duvelisib with fosphenytoin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; fosphenytoin is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Grapefruit juice: (Major) Advise patients to avoid grapefruit juice while taking duvelisib due to increased duvelisib exposure. Duvelisib is a CYP3A substrate; grapefruit juice is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as grapefruit juice.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If duvelisib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Guanfacine: (Major) Decrease the dose of extended-release guanfacine by 50% if coadministration with duvelisib is necessary; if duvelisib is discontinued, the dose o

f extended-release guanfacine may be increased to the recommended level. Monitor patients closely for alpha-adrenergic effects including hypotension, drowsiness, lethargy, and bradycardia. Recommendations for immediate-release guanfacine are not available. Guanfacine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If duvelisib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If duvelisib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If duvelisib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like duvelisib can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If duvelisib is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Ibrutinib: (Major) If ibrutinib is coadministered with duvelisib, reduce the initial ibrutinib dosage to 280 mg/day PO in patients receiving ibrutinib for B-cell malignancy. Resume ibrutinib at the previous dosage if duvelisib is discontinued. No initial ibrutinib dosage adjustment is necessary in patients receiving ibrutinib for chronic graft-versus-host disease. Monitor patients for ibrutinib toxicity (e.g., hematologic toxicity, bleeding, infection); modify the ibrutinib dosage as recommended if toxicity occurs. Ibrutinib is a sensitive CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. When ibrutinib was administered with multiple doses of another moderate CYP3A4 inhibitor, the AUC value of ibrutinib was increased by 3-fold.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like duvelisib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If duvelisib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Idelalisib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with idelalisib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; idelalisib is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as idelalisib.
Ifosfamide: (Moderate) Monitor for a decrease in the efficacy of ifosfamide if coadministration with duvelisib is necessary. Ifosfamide is metabolized by CYP3A4 to its active alkylating metabolites. Duvelisib is a moderate CYP3A4 inhibitor. Coadministration may decrease plasma concentrations of these active metabolites, decreasing the effectiveness of ifosfamide treatment.
Imatinib: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with imatinib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; imatinib is a moderate CYP3A inhibitor.
Indinavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with indinavir. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; indinavir is a sensitive substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as indinavir.
Infigratinib: (Major) Avoid concomitant use of infigratinib and duvelisib. Coadministration may increase infigratinib exposure, increasing the risk of adverse effects. Infigratinib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Isavuconazonium: (Moderate) Monitor for increased toxicity of duvelisib and isavuconazonium during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; isavuconazonium is a sensitive substrate and moderate inhibitor of CYP3A.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid coadministration of duvelisib with rifampin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; rifampin is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with rifampin for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Isoniazid, INH; Rifampin: (Major) Avoid coadministration of duvelisib with rifampin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; rifampin is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with rifampin for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Isradipine: (Moderate) Monitor for an increase in isradipine-related adverse reactions, including hypotension, if coadministration with duvelisib is necessary. Coadministration may increase the exposure of isradipine. Isradipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Itraconazole: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with itraconazole. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; itraconazole is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as itraconazole.
Ivacaftor: (Major) If duvelisib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with duvelisib due to increased plasma concentrations of ivosidenib, which increases the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. Ivosidenib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor is predicted to increase the ivosidenib single-dose AUC to 173% of control based on physiologically-based pharmacokinetic modeling, with no change in Cmax. Multiple doses of the moderate CYP3A4 inhibitor are predicted to increase the ivosidenib steady-state AUC to 152% of control and AUC to 190% of control.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of duvelisib is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Ketoconazole: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ketoconazole. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ketoconazole is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ketoconazole.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with clarithromycin. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; clarithromycin is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as clarithromycin.
Larotrectinib: (Moderate) Monitor for an increase in larotrectinib-related adverse reactions if concomitant use with duvelisib is necessary. Concomitant use may increase larotrectinib exposure. Larotrectinib is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase larotrectinib exposure by 2.7-fold.
Lefamulin: (Moderate) Monitor for increased toxicity if duvelisib is coadministered with oral lefamulin. Coadministration may increase the exposure of both drugs. Both drugs are CYP3A4 substrates and moderate CYP3A4 inhibitors; an interaction is not expected with intravenous lefamulin.
Lemborexant: (Major) Avoid coadministration of lemborexant and duvelisib as concurrent use is expected to significantly increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration of lemborexant with another moderate CYP3A4 inhibitor increased the lemborexant AUC by up to 4.5-fold.
Lenacapavir: (Moderate) Monitor for increased toxicity if duvelisib is coadministered with lenacapavir. Coadministration may increase the exposure of duvelisib, increasing the risk of toxicity. Duvelisib is a CYP3A substrate; lenacapavir is a moderate CYP3A inhibitor.
Letermovir: (Moderate) In patients receiving duvelisib and letermovir WITHOUT concomitant cyclosporine, monitor for an increase in duvelisib-related adverse reactions. In patients who are also receiving treatment with cyclosporine, reduce the dose of duvelisib to 15 mg PO twice daily because the magnitude of this interaction may be amplified. Duvelisib is a CYP3A4 substrate and letermovir is a moderate CYP3A4 inhibitor; however, the combined effect of letermovir and cyclosporine on CYP3A4 substrates may be similar to a strong CYP3A4 inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors.
Levamlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Levoketoconazole: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ketoconazole. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ketoconazole is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ketoconazole.
Lomitapide: (Contraindicated) Concomitant use of duvelisib and lomitapide is contraindicated due to increased lomitapide exposure. If treatment with duvelisib is unavoidable, lomitapide should be stopped during the course of treatment. Lomitapide is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor. Although concomitant use of moderate CYP3A4 inhibitors with lomitapide has not been studied, a significant increase in lomitapide exposure is likely during concurrent use based on the 27-fold increase in exposure observed with coadministration of a strong CYP3A4 inhibitor.
Lonafarnib: (Contraindicated) Coadministration of lonafarnib and duvelisib is contraindicated; concurrent use may increase the exposure of both drugs and the risk of adverse effects. If concomitant use is necessary, reduce the duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity. Lonafarnib is a sensitive CYP3A4 substrate and strong CYP3A4 inhibitor; duvelisib is a CYP3A4 substrate and moderate CYP3A4 inhibitor. Duvelisib exposure is estimated to increase approximately 2-fold if used concomitantly with strong CYP3A4 inhibitors.
Lopinavir; Ritonavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ritonavir. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ritonavir is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ritonavir.
Lorlatinib: (Major) Avoid concomitant use of duvelisib with lorlatinib. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When lorlatinib has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with lorlatinib. Duvelisib is a CYP3A substrate; lorlatinib is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Lovastatin: (Moderate) Monitor for an increase in lovastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with duvelisib is necessary. Coadministration may increase the exposure of lovastatin. Lovastatin is a sensitive substrate of CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of duvelisib with lumacaftor; ivacaftor. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; lumacaftor; ivacaftor is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively. (Major) If duvelisib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Lumacaftor; Ivacaftor: (Major) Avoid coadministration of duvelisib with lumacaftor; ivacaftor. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; lumacaftor; ivacaftor is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Lumateperone: (Major) Reduce the dose of lumateperone to 21 mg once daily if concomitant use of duvelisib is necessary. Concurrent use may increase lumateperone exposure and the risk of adverse effects. Lumateperone is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor increased lumateperone exposure by approximately 2-fold.
Lurasidone: (Major) The recommended starting dose of lurasidone is 20 mg daily (maximum, 80 mg daily) if coadministration with duvelisib is necessary. Reduce the lurasidone dose to half of its original dose level if duvelisib is added to existing lurasidone therapy. Lurasidone is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased lurasidone exposure by 116%.
Lurbinectedin: (Major) Avoid coadministration of lurbinectedin and duvelisib due to the risk of increased lurbinectedin exposure which may increase the incidence of lurbinectedin-related adverse reactions. If concomitant use is unavoidable, consider reducing the dose of lurbinectedin if clinically indicated. Lurbinectedin is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Maraviroc: (Moderate) Monitor for increased toxicity of maraviroc if coadministered with duvelisib. Coadministration may increase the exposure of maraviroc. Maraviroc is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Mavacamten: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting duvelisib therapy. Avoid initiation of duvelisib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable duvelisib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Methohexital: (Major) Avoid concomitant use of duvelisib with methohexital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When methohexital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with methohexital. Duvelisib is a CYP3A substrate; methohexital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Midazolam: (Moderate) Consider reducing the dose of midazolam and monitor for signs of toxicity during coadministration with duvelisib. Coadministration may increase the exposure of midazolam. Duvelisib is a moderate CYP3A inhibitor and midazolam is a sensitive CYP3A substrate. In drug interaction studies, coadministration of duvelisib and midazolam increased the AUC of oral midazolam by approximately 4-fold.
Mifepristone: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with chronic mifepristone therapy. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; mifepristone is a substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as mifepristone. The clinical significance of this interaction with the short-term use of mifepristone for termination of pregnancy is unknown.
Mitapivat: (Moderate) Do not exceed mitapivat 20 mg PO twice daily during coadministration with duvelisib and monitor hemoglobin and for adverse reactions from mitapivat. Coadministration increases mitapivat concentrations. Mitapivat is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased mitapivat overall exposure by 2.6-fold.
Mitotane: (Major) Avoid coadministration of duvelisib with mitotane. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; mitotane is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and duvelisib; reduce the dose of mobocertinib by approximately 50% and monitor the QT interval more frequently if use is necessary. Concomitant use may increase mobocertinib exposure and the risk for adverse reactions. Mobocertinib is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Use of a moderate CYP3A inhibitor is predicted to increase the overall exposure of mobocertinib and its active metabolites by 100% to 200%.
Nafcillin: (Major) Avoid concomitant use of duvelisib with nafcillin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When nafcillin has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with nafcillin. Duvelisib is a CYP3A substrate; nafcillin is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Naldemedine: (Moderate) Monitor for potential naldemedine-related adverse reactions if coadministered with duvelisib. The plasma concentrations of naldemedine may be increased during concurrent use. Naldemedine is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor.
Naloxegol: (Major) Avoid concomitant administration of naloxegol and duvelisib due to the potential for increased naloxegol exposure. If coadministration cannot be avoided, decrease the naloxegol dosage to 12.5 mg once daily and monitor for adverse reactions including opioid withdrawal symptoms such as hyperhidrosis, chills, diarrhea, abdominal pain, anxiety, irritability, and yawning. Naloxegol is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased naloxegol exposure by approximately 3.4-fold.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration of nab-paclitaxel with duvelisib is necessary due to the risk of increased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. In vitro, coadministration with both strong and moderate CYP3A4 inhibitors increased paclitaxel exposure; however, the concentrations used exceeded those found in vivo following normal therapeutic doses. The pharmacokinetics of paclitaxel may also be altered in vivo as a result of interactions with CYP3A4 inhibitors.
Nanoparticle Albumin-Bound Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of duvelisib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Nefazodone: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with nefazodone. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; nefazodone is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as nefazodone.
Nelfinavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with nelfinavir. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; nelfinavir is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as nelfinavir.
Neratinib: (Major) Avoid concomitant use of duvelisib with neratinib due to an increased risk of neratinib-related toxicity. Neratinib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibition on neratinib concentrations has not been studied; however, coadministration with a strong CYP3A4 inhibitor increased neratinib exposure by 481%. Because of the significant impact on neratinib exposure from strong CYP3A4 inhibition, the potential impact on neratinib safety from concomitant use with moderate CYP3A4 inhibitors should be considered as they may also significantly increase neratinib exposure.
Netupitant, Fosnetupitant; Palonosetron: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with netupitant. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; netupitant is a moderate CYP3A inhibitor.
Niacin; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with duvelisib is necessary. Coadministration may increase the exposure of simvastatin. Simvastatin is a sensitive substrate of CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor.
Nilotinib: (Moderate) Monitor for increased toxicity of duvelisib if coadministered with nilotinib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; nilotinib is a moderate CYP3A inhibitor.
Nimodipine: (Moderate) Monitor blood pressure and reduce the dose of nimodipine as clinically appropriate if coadministration with duvelisib is necessary. Nimodipine is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Nirmatrelvir; Ritonavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ritonavir. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ritonavir is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ritonavir.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with duvelisib due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a sensitive CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Olaparib: (Major) Avoid coadministration of olaparib with duvelisib due to the risk of increased olaparib-related adverse reactions. If concomitant use is unavoidable, reduce the dose of olaparib to 150 mg twice daily; the original dose may be resumed 3 to 5 elimination half-lives after duvelisib is discontinued. Olaparib is a CYP3A substrate and duvelisib is a moderate CYP3A4 inhibitor; concomitant use may increase olaparib exposure. Coadministration with a moderate CYP3A inhibitor is predicted to increase the olaparib Cmax by 14% and the AUC by 121%.
Oliceridine: (Moderate) Monitor patients closely for respiratory depression and sedation at frequent intervals and base subsequent doses on the patient's severity of pain and response to treatment if concomitant administration of oliceridine and duvelisib is necessary; less frequent dosing of oliceridine may be required. Concomitant use of oliceridine and duvelisib may increase the plasma concentration of oliceridine, resulting in increased or prolonged opioid effects. If duvelisib is discontinued, consider increasing the oliceridine dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oliceridine is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Omaveloxolone: (Major) Avoid concomitant use of omaveloxolone and duvelisib. If concomitant use is necessary, decrease omaveloxolone dose to 100 mg once daily; additional dosage reductions may be necessary. Concomitant use may increase omaveloxolone exposure and the risk for omaveloxolone-related adverse effects. Omaveloxolone is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased omaveloxolone overall exposure by 1.25-fold.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concomitant use of duvelisib with rifabutin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib; rifabutin exposure may also be increased. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. Monitor for rifabutin-related adverse reactions. When rifabutin has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with rifabutin. Duvelisib is a CYP3A substrate and a moderate CYP3A4 inhibitor. Rifabutin is a CYP3A4 substrate and a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a moderate inhibitor like duvelisib can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If duvelisib is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Paclitaxel: (Moderate) Monitor for an increase in paclitaxel-related adverse reactions if coadministration with duvelisib is necessary. Coadministration may increase the exposure of paclitaxel. Paclitaxel is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Pacritinib: (Major) Avoid concurrent use of pacritinib with duvelisib due to the risk of increased pacritinib exposure which increases the risk of adverse reactions. Pacritinib is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Palovarotene: (Major) Avoid concomitant use of palovarotene and duvelisib due to the risk for increased palovarotene exposure which may increase the risk for adverse effects. If concomitant use is necessary, decrease the palovarotene dose by half. Palovarotene is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased palovarotene overall exposure by 2.5-fold.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and duvelisib due to the risk of increased pemigatinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of pemigatinib to 9 mg PO once daily if original dose was 13.5 mg per day and to 4.5 mg PO once daily if original dose was 9 mg per day. If duvelisib is discontinued, resume the original pemigatinib dose after 3 elimination half-lives of duvelisib. Pemigatinib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase pemigatinib exposure by approximately 50% to 80%.
Pentobarbital: (Major) Avoid concomitant use of duvelisib with pentobarbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When pentobarbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with pentobarbital. Duvelisib is a CYP3A substrate; pentobarbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Perindopril; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Pexidartinib: (Major) Avoid concomitant use of pexidartinib and duvelisib due to the risk of increased pexidartinib exposure and decreased duvelisib exposure. If concomitant use is necessary, the dose of both drugs will need to be adjusted. Dose adjustments for pexidartinib are as follows: 500 mg/day or 375 mg/day of pexidartinib, reduce to 125 mg twice daily; 250 mg/day of pexidartinib, reduce to 125 mg once daily. For duvelisib, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. Pexidartinib is a CYP3A substrate and moderate CYP3A inducer; duvelisib is a CYP3A substrate and moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased pexidartinib overall exposure by 67%. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Phenobarbital: (Major) Avoid coadministration of duvelisib with phenobarbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; phenobarbital is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid coadministration of duvelisib with phenobarbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; phenobarbital is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Phenytoin: (Major) Avoid coadministration of duvelisib with phenytoin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; phenytoin is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Posaconazole: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with posaconazole. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; posaconazole is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as posaconazole.
Pralsetinib: (Major) Avoid concomitant use of duvelisib with pralsetinib due to the risk of increased pralsetinib exposure which may increase the risk of adverse reactions. If concomitant use is necessary, reduce the daily dose of pralsetinib by 100 mg. Pralsetinib is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A inhibitor is predicted to increase the overall exposure of pralsetinib by 71%.
Primidone: (Major) Avoid coadministration of duvelisib with primidone. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; primidone is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Probenecid; Colchicine: (Major) Avoid concomitant use of colchicine and duvelisib due to the risk for increased colchicine exposure which may increase the risk for adverse effects. If concomitant use is necessary, consider a colchicine dosage reduction. Specific dosage reduction recommendations are available for colchicine tablets for some indications; it is unclear if these dosage recommendations are appropriate for other products or indications. For colchicine tablets being used for gout prophylaxis, reduce a dose of 0.6 mg twice daily to 0.3 mg twice daily or 0.6 mg once daily; reduce a dose of 0.6 mg once daily to 0.3 mg once daily. For colchicine tablets being used for gout treatment, reduce the dose from 1.2 mg followed by 0.6 mg to 1.2 mg without an additional dose. For colchicine tablets being used for Familial Mediterranean Fever, the maximum daily dose is 1.2 mg. Colchicine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with other moderate CYP3A inhibitors increased colchicine overall exposure by 1.4- to 1.9-fold.
Propafenone: (Moderate) Monitor for increased toxicity of propafenone if coadministered with duvelisib. Coadministration may increase the exposure of propafenone. Propafenone is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor.
Quetiapine: (Moderate) Monitor for increased toxicity of quetiapine if coadministered with duvelisib. Coadministration may increase the exposure of quetiapine. Quetiapine is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Quinine: (Moderate) Monitor for increased toxicity of duvelisib and quinine during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; quinine is also a substrate and moderate inhibitor of CYP3A.
Ranolazine: (Major) Limit the dose of ranolazine to 500 mg twice daily if coadministration with duvelisib is necessary. Coadministration may increase the exposure of ranolazine. Ranolazine is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased plasma levels of ranolazine by 100%.
Ribociclib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ribociclib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ribociclib is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ribociclib.
Ribociclib; Letrozole: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ribociclib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ribociclib is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ribociclib.
Rifabutin: (Major) Avoid concomitant use of duvelisib with rifabutin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib; rifabutin exposure may also be increased. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. Monitor for rifabutin-related adverse reactions. When rifabutin has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with rifabutin. Duvelisib is a CYP3A substrate and a moderate CYP3A4 inhibitor. Rifabutin is a CYP3A4 substrate and a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Rifampin: (Major) Avoid coadministration of duvelisib with rifampin. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; rifampin is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with rifampin for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Rifapentine: (Major) Avoid coadministration of duvelisib with rifapentine. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; rifapentine is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for seven days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Rimegepant: (Major) Avoid a second dose of rimegepant within 48 hours if coadministered with duvelisib; concurrent use may increase rimegepant exposure. Rimegepant is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Ritlecitinib: (Moderate) Monitor for increased toxicity if duvelisib is coadministered with ritlecitinib. Coadministration may increase the exposure of duvelisib, increasing the risk of toxicity. Duvelisib is a CYP3A substrate; ritlecitinib is a moderate CYP3A inhibitor.
Ritonavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with ritonavir. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; ritonavir is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as ritonavir.
Saquinavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with saquinavir. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; saquinavir is a sensitive substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as saquinavir.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Secobarbital: (Major) Avoid concomitant use of duvelisib with secobarbital. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When secobarbital has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with secobarbital. Duvelisib is a CYP3A substrate; secobarbital is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Segesterone Acetate; Ethinyl Estradiol: (Minor) Coadministration of segesterone and moderate CYP3A4 inhibitors such as duvelisib may increase the serum concentration of segesterone.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and duvelisib due to the risk of increased selpercatinib exposure which may increase the risk of adverse reactions, including QT prolongation. If coadministration is unavoidable, reduce the dose of selpercatinib to 80 mg PO twice daily if original dose was 120 mg twice daily, and to 120 mg PO twice daily if original dose was 160 mg twice daily. Monitor ECGs for QT prolongation more frequently. If duvelisib is discontinued, resume the original selpercatinib dose after 3 to 5 elimination half-lives of duvelisib. Selpercatinib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with other moderate CYP3A4 inhibitors is predicted to increase selpercatinib exposure by 60% to 99%.
Selumetinib: (Major) Avoid coadministration of selumetinib and duvelisib due to the risk of increased selumetinib exposure which may increase the risk of adverse reactions. If coadministration is unavoidable, reduce the dose of selumetinib to 20 mg/m2 PO twice daily if original dose was 25 mg/m2 twice daily and 15 mg/m2 PO twice daily if original dose was 20 mg/m2 twice daily. If duvelisib is discontinued, resume the original selumetinib dose after 3 elimination half-lives of duvelisib. Selumetinib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP3A4 inhibitor is predicted to increase selumetinib exposure by 41%.
Sildenafil: (Moderate) Monitor for an increase in sildenafil-related adverse reactions if coadministration with duvelisib is necessary; a dose reduction of sildenafil may be necessary when prescribed for erectile dysfunction. Sildenafil is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor.
Silodosin: (Moderate) Monitor for silodosin-related adverse reactions if coadministration with duvelisib is necessary. Coadministration may increase the exposure of silodosin. Silodosin is a substrate of CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor. The effect of moderate CYP3A4 inhibitors has not been evaluated; however, plasma concentrations of silodosin may increase based on its interaction with strong CYP3A4 inhibitors.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with duvelisib is necessary. Coadministration may increase the exposure of simvastatin. Simvastatin is a sensitive substrate of CYP3A4 and duvelisib is a moderate CYP3A4 inhibitor.
Siponimod: (Moderate) Concomitant use of siponimod and duvelisib may increase siponimod exposure. If the patient is also receiving a drug regimen containing a moderate CYP2C9 inhibitor, use of siponimod is not recommended due to a significant increase in siponimod exposure. Siponimod is a CYP2C9 and CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration with a moderate CYP2C9/CYP3A4 dual inhibitor led to a 2-fold increase in the exposure of siponimod.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of duvelisib. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sirolimus overall exposure 1.6-fold.
Sonidegib: (Major) Avoid coadministration of sonidegib with duvelisib due to increased plasma concentrations of sonidegib, with may result in increased adverse reactions including musculoskeletal toxicity. Sonidegib is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Physiologic-based pharmacokinetic (PBPK) simulations indicate a moderate 3A4 inhibitor would increase the sonidegib AUC by 1.8-fold if administered for 14 days and by 2.8-fold if the moderate CYP3A inhibitor is administered with sonidegib for more than 14 days.
Sotorasib: (Major) Avoid concomitant use of duvelisib with sotorasib. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. If concomitant use is necessary, increase the dose of duvelisib on day 12 of coadministration from 25 mg PO twice daily to 40 mg PO twice daily; or from 15 mg PO twice daily to 25 mg PO twice daily. When sotorasib has been discontinued for at least 14 days, resume duvelisib at the dose taken prior to initiating treatment with sotorasib. Duvelisib is a CYP3A substrate; sotorasib is a moderate CYP3A inducer. Coadministration of duvelisib with another moderate CYP3A inducer for 12 days decreased duvelisib exposure by 35%.
Sparsentan: (Moderate) Monitor for an increase in sparsentan-related adverse effects if concomitant use with duvelisib is necessary. Concomitant use may increase sparsentan exposure. Sparsentan is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Concomitant use with another moderate CYP3A inhibitor increased sparsentan overall exposure by 70%.
St. John's Wort, Hypericum perforatum: (Major) Avoid coadministration of duvelisib with St. John's Wort. Coadministration may decrease the exposure of duvelisib, which may reduce the efficacy of duvelisib. Duvelisib is a CYP3A substrate; St. John's Wort is a strong CYP3A inducer. In drug interaction studies, coadministration of duvelisib with another strong CYP3A inducer for 7 days decreased duvelisib Cmax and AUC by 66% and 82%, respectively.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if duvelisib must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of duvelisib is necessary. If duvelisib is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a moderate CYP3A4 inhibitor like duvelisib can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If duvelisib is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate and watch for tacrolimus-related adverse reactions if coadministration with duvelisib is necessary. The dose of tacrolimus may need to be reduced. Tacrolimus is a sensitive CYP3A substrate with a narrow therapeutic range. Duvelisib is a moderate CYP3A inhibitor.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with duvelisib as concurrent use may increase tazemetostat exposure and the frequency and severity of adverse reactions. If concomitant use is unavoidable, decrease current tazemetostat daily dosage by 50% (e.g., decrease 800 mg PO twice daily to 400 mg PO twice daily; 600 mg PO twice daily to 400 mg PO for first dose and 200 mg PO for second dose; 400 mg PO twice daily to 200 mg PO twice daily). If duvelisib is discontinued, wait at least 3 half-lives of duvelisib before increasing the dose of tazemetostat to the previous tolerated dose. Tazemetostat is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration of another moderate CYP3A4 inhibitor increased tazemetostat exposure by 3.1-fold.
Telmisartan; Amlodipine: (Moderate) Monitor for symptoms of hypotension and edema if coadministration of amlodipine with duvelisib is necessary; adjust the dose of amlodipine as clinically appropriate. Amlodipine is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with a moderate CYP3A4 inhibitor in elderly hypertensive patients increased systemic exposure to amlodipine by 60%. However, coadministration with another moderate CYP3A4 inhibitor in healthy volunteers did not significantly change amlodipine exposure.
Tezacaftor; Ivacaftor: (Major) Adjust the tezacaftor; ivacaftor dosing schedule when coadministered with duvelisib; coadministration may increase tezacaftor; ivacaftor exposure and adverse reactions. When combined, dose 1 tezacaftor; ivacaftor combination tablet every other day in the morning and 1 ivacaftor tablet every other day in the morning on alternate days (i.e., tezacaftor/ivacaftor tablet on Day 1 and ivacaftor tablet on Day 2). The evening dose of ivacaftor should not be taken. Both tezacaftor and ivacaftor are CYP3A substrates (ivacaftor is a sensitive substrate); duvelisib is a moderate CYP3A inhibitor. Coadministration of a moderate CYP3A inhibitor increased ivacaftor exposure 3-fold. Simulation suggests a moderate inhibitor may increase tezacaftor exposure 2-fold. (Major) If duvelisib and ivacaftor are taken together, administer ivacaftor at the usual recommended dose but reduce the frequency to once daily. Coadministration is not recommended in patients younger than 6 months. Ivacaftor is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. Coadministration with another moderate CYP3A inhibitor increased ivacaftor exposure by 3-fold.
Ticagrelor: (Moderate) Monitor for increased bleeding if ticagrelor is coadministered with duvelisib. Coadministration may increase the exposure of ticagrelor. Ticagrelor is a sensitive substrate of CYP3A; duvelisib is a moderate inhibitor of CYP3A.
Tipranavir: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity of both drugs when coadministered with tipranavir. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; tipranavir is a sensitive substrate and strong inhibitor of CYP3A. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as tipranavir.
Tolvaptan: (Major) Avoid coadministration of duvelisib when tolvaptan is administered for hyponatremia. In patients with autosomal dominant polycystic kidney disease (ADPKD), reduce tolvaptan dosage if administered with duvelisib. In ADPKD patients receiving tolvaptan 90 mg every morning and 30 mg every evening, reduce the dose to 45 mg every morning and 15 mg every evening; for those receiving tolvaptan 60 mg every morning and 30 mg every evening, reduce the dose to 30 mg every morning and 15 mg every evening; for those receiving tolvaptan 45 mg every morning and 15 mg every evening, reduce the dose to 15 mg every morning and 15 mg every evening. Consider additional dosage reduction if the reduced dose is not tolerated. Tolvaptan is a sensitive CYP3A substrate; duvelisib is a moderate CYP3A inhibitor. Coadministration of another moderate CYP3A inhibitor increased the tolvaptan AUC by 200%.
Trandolapril; Verapamil: (Moderate) Monitor for increased toxicity of duvelisib and verapamil during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; verapamil is also a substrate and moderate inhibitor of CYP3A.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with duvelisib and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and duvelisib is a moderate CYP3A inhibitor.
Tucatinib: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with tucatinib. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; tucatinib is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as tucatinib.
Ubrogepant: (Major) Limit the initial dose of ubrogepant to 50 mg and avoid a second dose within 24 hours if coadministered with duvelisib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor resulted in a 3.5-fold increase in the exposure of ubrogepant.
Vardenafil: (Major) Do not use vardenafil orally disintegrating tablets with duvelisib due to increased vardenafil exposure; do not exceed a single dose of 5 mg per 24-hour period of vardenafil oral tablets. Vardenafil is primarily metabolized by CYP3A4/5; duvelisib is a moderate CYP3A4 inhibitor. Coadministration with another moderate CYP3A4 inhibitor increased the AUC of vardenafil by 4-fold.
Venetoclax: (Major) Reduce the dose of venetoclax by at least 50% and monitor for venetoclax toxicity (e.g., hematologic toxicity, GI toxicity, and tumor lysis syndrome) if coadministered with duvelisib due to the potential for increased venetoclax exposure. Resume the original venetoclax dose 2 to 3 days after discontinuation of duvelisib. Venetoclax is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor.
Verapamil: (Moderate) Monitor for increased toxicity of duvelisib and verapamil during coadministration. Coadministration may increase the exposure of both drugs. Duvelisib is a substrate and moderate inhibitor of CYP3A; verapamil is also a substrate and moderate inhibitor of CYP3A.
Vinblastine: (Moderate) Monitor for an earlier onset and/or increased severity of vinblastine-related adverse reactions, including myelosuppression, constipation, and peripheral neuropathy, if coadministration with duvelisib is necessary. Vinblastine is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Enhanced vinblastine toxicity was reported with coadministration of another moderate CYP3A4 inhibitor.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with duvelisib is necessary. Vinorelbine is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor.
Voclosporin: (Major) Reduce the voclosporin dosage to 15.8 mg PO in the morning and 7.9 mg PO in the evening if coadministered with duvelisib. Concomitant use may increase voclosporin exposure and the risk of voclosporin-related adv erse effects such as nephrotoxicity, hypertension, and QT prolongation. Voclosporin is a sensitive CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. Coadministration with moderate CYP3A4 inhibitors is predicted to increase voclosporin exposure by 3-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with clarithromycin. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; clarithromycin is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as clarithromycin.
Voriconazole: (Major) Reduce duvelisib dose to 15 mg PO twice daily and monitor for increased toxicity when coadministered with voriconazole. Coadministration may increase the exposure of duvelisib. Duvelisib is a CYP3A substrate; voriconazole is a strong CYP3A inhibitor. The increase in exposure to duvelisib is estimated to be approximately 2-fold when used concomitantly with strong CYP3A inhibitors such as voriconazole.
Voxelotor: (Moderate) Monitor for increased toxicity if duvelisib is coadministered with voxelotor. Coadministration may increase the exposure of duvelisib, increasing the risk of toxicity. Duvelisib is a CYP3A substrate; voxelotor is a moderate CYP3A inhibitor.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with duvelisib is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Duvelisib is a moderate CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zanubrutinib: (Major) Decrease the zanubrutinib dose to 80 mg PO twice daily if coadministered with duvelisib. Coadministration may result in increased zanubrutinib exposure and toxicity (e.g., infection, bleeding, and atrial arrhythmias). Further decrease the zanubrutinib dose as recommended if adverse reactions occur. After discontinuation of duvelisib, resume the previous dose of zanubrutinib. Zanubrutinib is a CYP3A4 substrate; duvelisib is a moderate CYP3A4 inhibitor. The AUC of zanubrutinib is predicted to increase by 157% to 317% when coadministered with other moderate CYP3A4 inhibitors.
Zolpidem: (Moderate) Monitor for an increase in zolpidem-related adverse reactions, including excess sedation, if coadministration with duvelisib is necessary. A dose reduction of zolpidem may be necessary. Zolpidem is a CYP3A4 substrate and duvelisib is a moderate CYP3A4 inhibitor. There is evidence of an increase in pharmacodynamic effects and systemic exposure of zolpidem during coadministration with some potent inhibitors of CYP3A4.

Copiktra/Duvelisib Oral Cap: 15mg, 25mg

Adults

50 mg/day PO.

Geriatric

50 mg/day PO.

Adolescents

Safety and efficacy not established.

Children

Safety and efficacy not established.

Infants

Safety and efficacy not established.

Duvelisib is an inhibitor of phosphatidylinositol 3-kinase (PI3K); it works primarily to inhibit PI3K-delta and PI3K-gamma isoforms expressed in normal and malignant B-cells. In cell lines derived from malignant B-cells and in primary CLL tumor cells, it induced growth inhibition in cells and reduced cell viability. Additionally, duvelisib inhibits several cell signaling pathways, including B-cell receptor signaling and the CXCR12-mediated chemotaxis of malignant B-cells. It also inhibits CXCR12-induced T-cell migration and macrophage colony-stimulating factor and IL-4 driven M2 polarization of macrophages.[63571]

Duvelisib is administered orally. It is greater than 98% bound to plasma proteins. The mean blood-to-plasma ratio is 0.5. The geometric mean apparent volume of distribution at steady state is 28.5 L (coefficient of variance (CV), 62%), the geometric mean terminal elimination half-life is 4.7 hours (CV, 57%), and the geometric mean apparent clearance at steady state is 4.2 L/hour (CV, 56%). Following a single radiolabeled dose of duvelisib 25 mg PO, 79% of the dose was excreted in the feces and 14% in the urine; 11% and less than 1% of the dose was recovered as unchanged duvelisib in the feces and urine, respectively. Duvelisib is primarily metabolized by CYP3A4.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, P-gp, BCRPDuvelisib is a substrate of CYP3A4. Avoid the concomitant use of duvelisib with strong CYP3A4 inducers. If duvelisib is administered with a strong or moderate CYP3A inhibitor, monitor for signs of duvelisib toxicity; reduced the dosage when coadministered with a strong CYP3A4 inhibitor. Additionally, duvelisib is a moderate CYP3A4 inhibitor and may increase the exposure of CYP3A4 substrates; monitor for signs of toxicity if duvelisib is coadministered with a sensitive CYP3A4 substrate. Duvelisib is a substrate of the P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) transporters in vitro.[63571]

Oral Route

The absolute bioavailability of duvelisib was 42% after a single, 25-mg dose administered in healthy volunteers; the median Tmax of duvelisib was 1 to 2 hours. The exposure of duvelisib increased in a dose-proportional manner at doses of 8 to 75 mg PO twice daily (0.3- to 3-time the recommended dose). The steady-state geometric mean Cmax and AUC values were 1.5 mcg/mL (CV, 64%) and 7.9 mcg X hour/mL (CV, 77%), respectively, following duvelisib 25 mg twice daily.
Effect of food: Administration of a single dose of duvelisib with a high-fat meal decreased the Cmax by 37% and decreased the AUC by 6% relative to fasting conditions; therefore, it may be administered without regard to food.[63571]

Pregnancy

Duvelisib may cause fetal harm if administered during pregnancy based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant during and after duvelisib therapy. If a woman becomes pregnant while taking this drug, she should be apprised of the potential hazard to the fetus. Duvelisib caused embryo-fetal toxicity including embryo-fetal death, decreased fetal weight, and structural abnormalities/malformations in rats and rabbits following maternal doses that were 10- and 39-times the recommended human duvelisib dosage.[63571]

It is not known if duvelisib or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or milk production. Due to the risk of serious adverse reactions in nursing infants, women should discontinue breast-feeding during duvelisib therapy and for 1 month after the last dose.[63571]