Leniolisib is an oral kinase inhibitor indicated for the treatment of activated phosphoinositide 3-kinase (PI3K) delta syndrome (APDS) in adults and pediatric patients 12 years and older weighing at least 45 kg. ADPS is a primary immunodeficiency disease caused by mutations in the PIK3CD or PIK3R1 genes that encodes the protein phosphoinositide-3 kinase delta, which is important for the normal development and function of white blood cells. Patients with APDS have low numbers of white blood cells, particularly certain types of B cells and T cells and develop recurrent infections, most often in the sinuses, ears, and respiratory tract. During a clinical trial in adult and pediatric patients 12 years and older, patients treated with leniolisib 70 mg orally twice daily saw a reduction in lymph node size and a 37% improvement in naive B cell counts compared to placebo by day 85. Leniolisib may cause fetal harm; verify pregnancy status in females of reproductive potential prior to starting treatment.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-Advise patients that if a dose is missed by more than 6 hours, wait and take the next dose at the usual time.
-Advise patients if vomiting occurs within 1 hour of taking leniolisib, repeat the dose as soon as possible. If vomiting occurs more than 1 hour after dosing, wait and take the next dose at the usual time.
Oral Solid Formulations
-Administer with or without food.
During clinical trials, headache (24%) and sinusitis (19%) were the most frequently reported adverse reactions in patients receiving leniolisib (n = 21).
Atopic dermatitis, including eczema, was reported in 14% of patients receiving leniolisib during clinical trials (n = 21).
Tachycardia, including sinus tachycardia, diarrhea, fatigue, fever, back pain, neck pain, and alopecia were reported in 10% of patients receiving leniolisib during clinical trials (n = 21).
During clinical trials with leniolisib, 7 of 21 (33%) patients developed an absolute neutrophil count (ANC) between 500 and 1,500 cells/microL. No patients developed an ANC less than 500 cells/microL and there were no reports of infection associated with neutropenia.
Use of leniolisib in patients with moderate to severe hepatic disease is not recommended. The effect of hepatic disease on leniolisib pharmacokinetics has not been studied; however, 60% of leniolisib is metabolized by the liver.
Leniolisib may cause fetal harm if administered during pregnancy based on data from animal studies. Advise patients of reproductive potential of the potential hazard to the fetus and to avoid pregnancy during leniolisib therapy. Embryo-fetal toxicity including malformations were observed in pregnant rats and rabbits after leniolisib doses that were approximately 2 to 6 times higher than the maximum recommended human dose (MRHD).
Counsel patients about the reproductive risk and contraception requirements during leniolisib treatment. Perform pregnancy testing prior to starting treatment in patients of reproductive potential. Advise these patients to use effective contraception during treatment and for 1 week after the last dose. Inform patients who become pregnant while receiving leniolisib of the potential hazard to the fetus.
It is not known whether leniolisib is excreted in human milk or if it has effects on the breast-fed child or on milk production. Because of the potential for serious adverse reactions in the breast-fed child, advise against breast-feeding during treatment and for 1 week after the last dose.
Vaccination with live attenuated vaccines may be less effective if administered during leniolisib treatment.
For the treatment of activated phosphoinositide 3-kinase delta syndrome:
Leniolisib is designated as an orphan drug by the FDA for this indication.
Oral dosage:
Adults weighing 45 kg or more: 70 mg PO twice daily approximately 12 hours apart.
Children and Adolescents 12 to 17 years weighing 45 kg or more: 70 mg PO twice daily approximately 12 hours apart.
Maximum Dosage Limits:
-Adults
weighing 45 kg or more: 140 mg/day PO.
weighing less than 45 kg: Safety and efficacy have not been established.
-Geriatric
weighing 45 kg or more: 140 mg/day PO.
weighing less than 45 kg: Safety and efficacy have not been established.
-Adolescents
weighing 45 kg or more: 140 mg/day PO.
weighing less than 45 kg: Safety and efficacy have not been established.
-Children
12 years and weighing 45 kg or more: 140 mg/day PO.
12 years and weighing less than 45 kg: Safety and efficacy have not been established.
1 to 11 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Use of leniolisib in patients with moderate to severe hepatic impairment is not recommended. The effect of hepatic impairment on leniolisib pharmacokinetics has not been studied; however, 60% of leniolisib is metabolized by the liver.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with leniolisib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and leniolisib is a BCRP inhibitor.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Acetaminophen; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Adagrasib: (Major) Avoid concomitant use of leniolisib and adagrasib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Alpelisib: (Major) Avoid coadministration of alpelisib with leniolisib due to increased exposure to alpelisib and the risk of alpelisib-related toxicity. If concomitant use is unavoidable, closely monitor for alpelisib-related adverse reactions. Alpelisib is a BCRP substrate and leniolisib is a BCRP inhibitor.
Amlodipine; Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a BCRP and OATP1B1/3 substrate; leniolisib is an inhibitor of BCRP and OATP1B1/3.
Amobarbital: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Avoid concomitant use of leniolisib and clarithromycin due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Apalutamide: (Major) Avoid concomitant use of leniolisib and apalutamide. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and apalutamide is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Aspirin, ASA; Butalbital; Caffeine: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Aspirin, ASA; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Atazanavir: (Major) Avoid concomitant use of leniolisib and atazanavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Atazanavir; Cobicistat: (Major) Avoid concomitant use of leniolisib and atazanavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and atazanavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold. (Major) Avoid concomitant use of leniolisib and cobicistat due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Atogepant: (Major) Limit the dose of atogepant to 10 or 30 mg PO once daily for episodic migraine or 30 mg PO once daily for chronic migraine if coadministered with leniolisib. Concurrent use may increase atogepant exposure and the risk of adverse effects. Atogepant is a substrate of OATP1B1 and OATP1B3 and leniolisib is an OATP inhibitor. Coadministration with an OATP1B1/3 inhibitor resulted in a 2.85-fold increase in atogepant overall exposure and a 2.23-fold increase in atogepant peak concentration.
Atorvastatin: (Moderate) Monitor for an increase in atorvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase atorvastatin exposure. Atorvastatin is a BCRP and OATP1B1/3 substrate; leniolisib is an inhibitor of BCRP and OATP1B1/3.
Bacillus Calmette-Guerin Vaccine, BCG: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Barbiturates: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Bendamustine: (Major) Consider the use of an alternative therapy if leniolisib treatment is needed in patients receiving bendamustine. Concomitant use of leniolisib may increase bendamustine exposure, which may increase the risk of adverse reactions (e.g., myelosuppression, infection, hepatotoxicity). Bendamustine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Bexarotene: (Major) Avoid concomitant use of leniolisib and bexarotene. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and bexarotene is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Bictegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with leniolisib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and leniolisib is a BCRP inhibitor.
Bosentan: (Major) Avoid concomitant use of leniolisib and bosentan. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and bosentan is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Brincidofovir: (Moderate) Postpone the administration of leniolisib for at least three hours after brincidofovir administration and increase monitoring for brincidofovir-related adverse reactions (i.e., elevated hepatic enzymes and bilirubin, diarrhea, other gastrointestinal adverse events) if concomitant use of brincidofovir and leniolisib is necessary. Brincidofovir is an OATP1B1/3 substrate and leniolisib is an OATP1B1/3 inhibitor. In a drug interaction study, the mean AUC and Cmax of brincidofovir increased by 374% and 269%, respectively, when administered with another OATP1B1/3 inhibitor.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with leniolisib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor. Coadministration with another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Butalbital; Acetaminophen: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Butalbital; Acetaminophen; Caffeine: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%. (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Caffeine; Sodium Benzoate: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Carbamazepine: (Major) Avoid concomitant use of leniolisib and carbamazepine. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and carbamazepine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Cenobamate: (Major) Avoid concomitant use of leniolisib and cenobamate. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and cenobamate is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Ceritinib: (Major) Avoid concomitant use of leniolisib and ceritinib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Chikungunya Vaccine, Live: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Chloramphenicol: (Major) Avoid concomitant use of leniolisib and chloramphenicol due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and chloramphenicol is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Clarithromycin: (Major) Avoid concomitant use of leniolisib and clarithromycin due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Clomipramine: (Moderate) Monitor for an increase in clomipramine-related adverse reactions if concomitant use of leniolisib is necessary; a clomipramine dose reduction may be necessary. Concomitant use may increase clomipramine exposure; clomipramine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with leniolisib and monitor for adverse reactions. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is a CYP1A2 substrate and leniolisib is a weak CYP1A2 inhibitor.
Cobicistat: (Major) Avoid concomitant use of leniolisib and cobicistat due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Dabrafenib: (Major) Avoid concomitant use of leniolisib and dabrafenib. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Darunavir: (Major) Avoid concomitant use of leniolisib and darunavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Darunavir; Cobicistat: (Major) Avoid concomitant use of leniolisib and cobicistat due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold. (Major) Avoid concomitant use of leniolisib and darunavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Avoid concomitant use of leniolisib and cobicistat due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold. (Major) Avoid concomitant use of leniolisib and darunavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and darunavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold. (Moderate) Coadministration of tenofovir alafenamide with leniolisib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and leniolisib is a BCRP inhibitor.
Delavirdine: (Major) Avoid concomitant use of leniolisib and delavirdine due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and delavirdine is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Dolutegravir: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with leniolisib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and leniolisib is a BCRP inhibitor.
Dolutegravir; Lamivudine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with leniolisib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and leniolisib is a BCRP inhibitor.
Dolutegravir; Rilpivirine: (Moderate) Monitor for increased toxicity of dolutegravir if coadministered with leniolisib. Concurrent use may increase the plasma concentrations of dolutegravir. Dolutegravir is a BCRP substrate and leniolisib is a BCRP inhibitor.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Efavirenz: (Major) Avoid concomitant use of leniolisib and efavirenz. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use is predicted to reduce leniolisib overall exposure by 58%.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of leniolisib and efavirenz. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use is predicted to reduce leniolisib overall exposure by 58%. (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of leniolisib and efavirenz. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and efavirenz is a moderate CYP3A inducer. Concomitant use is predicted to reduce leniolisib overall exposure by 58%. (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Elagolix: (Contraindicated) Coadministration of elagolix with leniolisib is contraindicated as concurrent use may increase elagolix exposure and risk for adverse effects. Concomitant use may also decrease leniolisib exposure which may reduce its efficacy. Elagolix is a substrate of OATP1B1 and a moderate CYP3A inducer; leniolisib is an OATP1B1 inhibitor and a CYP3A substrate. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Coadministration of elagolix with leniolisib is contraindicated as concurrent use may increase elagolix exposure and risk for adverse effects. Concomitant use may also decrease leniolisib exposure which may reduce its efficacy. Elagolix is a substrate of OATP1B1 and a moderate CYP3A inducer; leniolisib is an OATP1B1 inhibitor and a CYP3A substrate. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Elbasvir; Grazoprevir: (Contraindicated) Concomitant use of grazoprevir and leniolisib is contraindicated due to the potential for increased grazoprevir exposure. Grazoprevir is a substrate of OATP1B1/3; leniolisib is an inhibitor of OATP1B1/3.
Eluxadoline: (Major) Reduce the dose of eluxadoline to 75 mg twice daily and monitor for eluxadoline-related adverse effects including decreased mental and physical acuity if coadministered with leniolisib. Coadministration may increase exposure of eluxadoline. Eluxadoline is an OATP1B1 substrate and leniolisib is a an OATP1B1 inhibitor. Coadministration with another OATP1B1 inhibitor increased the exposure of eluxadoline by 4.4-fold.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Avoid concomitant use of leniolisib and cobicistat due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold. (Moderate) Coadministration of tenofovir alafenamide with leniolisib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and leniolisib is a BCRP inhibitor.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Avoid concomitant use of leniolisib and cobicistat due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and cobicistat is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold. (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with leniolisib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and leniolisib is a BCRP inhibitor.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Emtricitabine; Tenofovir alafenamide: (Moderate) Coadministration of tenofovir alafenamide with leniolisib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and leniolisib is a BCRP inhibitor.
Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Encorafenib: (Major) Avoid concomitant use of leniolisib and encorafenib. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and encorafenib is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Enzalutamide: (Major) Avoid concomitant use of leniolisib and enzalutamide. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and enzalutamide is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Ergotamine; Caffeine: (Moderate) Monitor for an increase in caffeine-related adverse reactions, including nervousness, irritability, insomnia, tachycardia, or tremor, if concomitant use of leniolisib is necessary; lower caffeine doses may be necessary. Concomitant use may increase caffeine exposure; caffeine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor.
Eslicarbazepine: (Major) Avoid concomitant use of leniolisib and eslicarbazepine. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and eslicarbazepine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Etravirine: (Major) Avoid concomitant use of leniolisib and etravirine. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and etravirine is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Ezetimibe; Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is an OATP1B1 substrate; leniolisib is an OATP1B1 inhibitor.
Fezolinetant: (Contraindicated) Concomitant use of fezolinetant and leniolisib is contraindicated due to the risk of increased fezolinetant exposure which may increase the risk of fezolinetant-related adverse effects. Fezolinetant is a CYP1A2 substrate; leniolisib is a weak CYP1A2 inhibitor. Concomitant use with another weak CYP1A2 inhibitor increased fezolinetant overall exposure by 100%.
Fluvastatin: (Moderate) Monitor for an increase in fluvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase fluvastatin exposure. Fluvastatin is a substrate of OATP1B3; leniolisib is an inhibitor of OATP1B3.
Fosphenytoin: (Major) Avoid concomitant use of leniolisib and phenytoin/fosphenytoin. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with coadministration of glecaprevir and leniolisib as increased plasma concentrations of glecaprevir may occur resulting in increased risk of glecaprevir-related adverse events. Glecaprevir is a substrate of BCRP and OATP1B1/3; leniolisib is an inhibitor of BCRP and OATP1B1/3. (Moderate) Monitor for an increase in pibrentasvir-related adverse effects if concomitant use of leniolisib is necessary. Concomitant use may increase pibrentasvir exposure. Pibrentasvir is a substrate of BCRP and leniolisib is a BCRP inhibitor.
Glyburide: (Moderate) Monitor for an increase in glyburide-related adverse reactions, such as hypoglycemia, if coadministration with leniolisib is necessary. Concomitant use may increase glyburide exposure. Glyburide is a substrate of OATP1B1/3; leniolisib is an OATP1B1/3 inhibitor.
Glyburide; Metformin: (Moderate) Monitor for an increase in glyburide-related adverse reactions, such as hypoglycemia, if coadministration with leniolisib is necessary. Concomitant use may increase glyburide exposure. Glyburide is a substrate of OATP1B1/3; leniolisib is an OATP1B1/3 inhibitor.
Grapefruit juice: (Major) Avoid concomitant use of leniolisib and grapefruit due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and grapefruit is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Idelalisib: (Major) Avoid concomitant use of leniolisib and idelalisib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Indinavir: (Major) Avoid concomitant use of leniolisib and indinavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and indinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Intranasal Influenza Vaccine: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Avoid concomitant use of leniolisib and rifampin. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use is predicted to reduce leniolisib overall exposure by 78%.
Isoniazid, INH; Rifampin: (Major) Avoid concomitant use of leniolisib and rifampin. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use is predicted to reduce leniolisib overall exposure by 78%.
Itraconazole: (Major) Avoid concomitant use of leniolisib and itraconazole due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Concomitant use increased leniolisib overall exposure by 2-fold.
Ketoconazole: (Major) Avoid concomitant use of leniolisib and ketoconazole due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of leniolisib and clarithromycin due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Letermovir: (Major) Avoid concomitant use of leniolisib and combination letermovir plus cyclosporine due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Additionally, concomitant use may increase letermovir concentrations. Leniolisib is a CYP3A substrate and OATP1B1/3 inhibitor; combination letermovir plus cyclosporine is a strong CYP3A inhibitor and letermovir is a substrate of OATP1B1/3. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Levoketoconazole: (Major) Avoid concomitant use of leniolisib and ketoconazole due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with leniolisib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor. Coadministration with another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with leniolisib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor. Coadministration with another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with leniolisib is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor. Coadministration with another CYP1A2 inhibitor increased lidocaine exposure by 71%.
Live Vaccines: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Lonafarnib: (Major) Avoid concomitant use of leniolisib and lonafarnib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and lonafarnib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lopinavir; Ritonavir: (Major) Avoid concomitant use of leniolisib and ritonavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Lorlatinib: (Major) Avoid concomitant use of leniolisib and lorlatinib. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and lorlatinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of leniolisib and lumacaftor; ivacaftor. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Lumacaftor; Ivacaftor: (Major) Avoid concomitant use of leniolisib and lumacaftor; ivacaftor. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Maraviroc: (Moderate) Monitor for an increase in maraviroc-related adverse reactions if coadministration with leniolisib is necessary. Concomitant use may increase maraviroc exposure. Maraviroc is an OATP1B1 substrate; leniolisib is an OATP1B1 inhibitor.
Mavacamten: (Major) Avoid concomitant use of leniolisib and mavacamten. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Measles/Mumps/Rubella Vaccines, MMR: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Methohexital: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Mexiletine: (Moderate) Monitor for increased toxicity of mexiletine if coadministered with leniolisib. Coadministration may increase serum concentrations of mexiletine. Mexiletine is a CYP1A2 substrate and leniolisib is a weak CYP1A2 inhibitor.
Mifepristone: (Major) Avoid concomitant use of leniolisib and mifepristone due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Mitotane: (Major) Avoid concomitant use of leniolisib and mitotane. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and mitotane is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Momelotinib: (Moderate) Monitor for an increase in momelotinib-related adverse reactions if coadministration with leniolisib is necessary. Concomitant use may increase momelotinib exposure. Momelotinib is an OATP1B1/3 substrate; leniolisib is an OATP1B1/3 inhibitor. Coadministration with another OATP1B1/1B3 inhibitor increased momelotinib exposure by 57%; exposure of its active M21 metabolite increased by 12%.
Nafcillin: (Major) Avoid concomitant use of leniolisib and nafcillin. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and nafcillin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Nefazodone: (Major) Avoid concomitant use of leniolisib and nefazodone due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Nelfinavir: (Major) Avoid concomitant use of leniolisib and nelfinavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and nelfinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Nirmatrelvir; Ritonavir: (Major) Avoid concomitant use of leniolisib and ritonavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Omeprazole; Amoxicillin; Rifabutin: (Major) Avoid concomitant use of leniolisib and rifabutin. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Pazopanib: (Major) Avoid coadministration of pazopanib and leniolisib due to the potential for increased pazopanib exposure. Pazopanib is a BCRP substrate; leniolisib is a BCRP inhibitor. Consider selection of an alternative concomitant medication with no or minimal potential to inhibit BCRP.
Pentobarbital: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Pexidartinib: (Major) Avoid concomitant use of leniolisib and pexidartinib. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Phenobarbital: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Phenytoin: (Major) Avoid concomitant use of leniolisib and phenytoin/fosphenytoin. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and phenytoin/fosphenytoin is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Pimozide: (Moderate) Monitor for pimozide-related adverse reactions, including QT prolongation and ventricular arrhythmias, if coadministered with leniolisib. Coadministration may result in elevated pimozide concentrations. Pimozide is metabolized primarily through CYP3A, and to a lesser extent CYP1A2 and CYP2D6; leniolisib is a weak CYP1A2 inhibitor.
Pitavastatin: (Moderate) Monitor for an increase in pitavastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase pitavastatin exposure. Pitavastatin is an OATP1B1 substrate; leniolisib is an OATP1B1 inhibitor.
Posaconazole: (Major) Avoid concomitant use of leniolisib and posaconazole due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Pravastatin: (Moderate) Monitor for an increase in pravastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase pravastatin exposure. Pravastatin is an OATP1B1/3 substrate; leniolisib is an OATP1B1/3 inhibitor.
Primidone: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if concomitant use of leniolisib is necessary. Concomitant use may increase propafenone exposure; propafenone is a CYP1A2 substrate and leniolisib is a weak CYP1A2 inhibitor.
Rasagiline: (Moderate) Monitor for dopaminergic adverse effects during concurrent use of rasagiline and leniolisib. Coadministration may result in increased rasagiline concentrations. A dose reduction of rasagiline may be necessary. Rasagiline is primarily metabolized by CYP1A2; leniolisib is a weak CYP1A2 inhibitor.
Repotrectinib: (Major) Avoid concomitant use of leniolisib and repotrectinib. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and repotrectinib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Resmetirom: (Major) Avoid concomitant use of resmetirom and leniolisib due to the risk for increased resmetirom exposure which may increase the risk for resmetirom-related adverse effects. Resmetirom is an OATP1B1/3 substrate and leniolisib is an OATP1B1/3 inhibitor.
Revefenacin: (Major) Avoid concomitant use of revefenacin and leniolisib. Concomitant use may increase exposure to the active metabolite of revefenacin and the risk for anticholinergic adverse effects. The active metabolite of revefenacin is a substrate of OATP1B1/3; leniolisib is an inhibitor of OATP1B1/3.
Ribociclib: (Major) Avoid concomitant use of leniolisib and ribociclib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Ribociclib; Letrozole: (Major) Avoid concomitant use of leniolisib and ribociclib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Rifabutin: (Major) Avoid concomitant use of leniolisib and rifabutin. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Rifampin: (Major) Avoid concomitant use of leniolisib and rifampin. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and rifampin is a strong CYP3A inducer. Concomitant use is predicted to reduce leniolisib overall exposure by 78%.
Rifapentine: (Major) Avoid concomitant use of leniolisib and rifapentine. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and rifapentine is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Ritonavir: (Major) Avoid concomitant use of leniolisib and ritonavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and ritonavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Rosuvastatin: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with leniolisib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of BCRP and OATP1B1/3; leniolisib is an inhibitor of BCRP and OATP1B1/3.
Rosuvastatin; Ezetimibe: (Moderate) Monitor for an increase in rosuvastatin-related adverse reactions, including myopathy and rhabdomyolysis, during concomitant use with leniolisib. Concurrent use may increase rosuvastatin exposure. Rosuvastatin is a substrate of BCRP and OATP1B1/3; leniolisib is an inhibitor of BCRP and OATP1B1/3.
Rotavirus Vaccine: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Saquinavir: (Major) Avoid concomitant use of leniolisib and saquinavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and saquinavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Secobarbital: (Major) Avoid concomitant use of leniolisib and barbiturates. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and barbiturates are strong CYP3A inducers. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Simvastatin: (Moderate) Monitor for an increase in simvastatin-related adverse reactions, including myopathy and rhabdomyolysis, if coadministration with leniolisib is necessary. Concomitant use may increase simvastatin exposure. Simvastatin is an OATP1B1 substrate; leniolisib is an OATP1B1 inhibitor.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Smallpox Vaccine, Vaccinia Vaccine: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Sodium Phenylbutyrate; Taurursodiol: (Moderate) Avoid coadministration of sodium phenylbutyrate; taurursodiol and leniolisib. Concomitant use may increase plasma concentrations of sodium phenylbutyrate; taurursodiol. Sodium phenylbutyrate; taurursodiol is an OATP1B3 substrate and leniolisib is an OATP1B3 inhibitor.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid concomitant use of voxilaprevir and leniolisib. Concomitant use may increase voxilaprevir exposure and the risk of voxilaprevir-related adverse reactions. Voxilaprevir is a substrate of OATP1B1/3; leniolisib is an OATP1B1/3 inhibitor.
Sotorasib: (Major) Avoid concomitant use of leniolisib and sotorasib. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and sotorasib is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
St. John's Wort, Hypericum perforatum: (Major) Avoid concomitant use of leniolisib and St. John's wort. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and St. John's wort is a strong CYP3A inducer. Concomitant use with another strong CYP3A inducer reduced leniolisib overall exposure by 78%.
Talazoparib: (Moderate) Monitor for an increase in talazoparib-related adverse reactions if concomitant use of leniolisib is necessary. Concomitant use may increase talazoparib exposure. Talazoparib is a BCRP substrate and leniolisib is a BCRP inhibitor.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with leniolisib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and leniolisib is a BCRP inhibitor.
Tenofovir Alafenamide: (Moderate) Coadministration of tenofovir alafenamide with leniolisib may result in increased plasma concentrations of tenofovir leading to an increase in tenofovir-related adverse effects. Tenofovir alafenamide is a BCRP substrate and leniolisib is a BCRP inhibitor.
Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of tenofovir disoproxil fumarate with leniolisib may result in increased plasma concentrations of tenofovir, leading to an increase in tenofovir-related adverse effects. Tenofovir disoproxil fumarate is a BCRP substrate and leniolisib is a BCRP inhibitor.
Theophylline, Aminophylline: (Moderate) Monitor theophylline concentrations and watch for an increase in theophylline-related adverse reactions if coadministration with leniolisib is necessary; a theophylline dose reduction may be necessary. Theophylline is a CYP1A2 substrate with a narrow therapeutic index and leniolisib is a CYP1A2 inhibitor.
Tipranavir: (Major) Avoid concomitant use of leniolisib and tipranavir due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and tipranavir is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Tizanidine: (Major) Avoid concomitant use of tizanidine and leniolisib as increased tizanidine exposure may occur. If use together is necessary, initiate tizanidine at 2 mg and increase by 2 to 4 mg/day based on clinical response. Discontinue tizanidine if hypotension, bradycardia, or excessive drowsiness occurs. Tizanidine is a CYP1A2 substrate and leniolisib is a weak CYP1A2 inhibitor.
Topotecan: (Major) Avoid coadministration of leniolisib with oral topotecan due to increased topotecan exposure; leniolisib may be administered with intravenous topotecan. Coadministration increases the risk of topotecan-related adverse reactions. Oral topotecan is a BCRP substrate and leniolisib is a BCRP inhibitor.
Tucatinib: (Major) Avoid concomitant use of leniolisib and tucatinib due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Typhoid Vaccine: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with leniolisib. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a BCRP substrate and leniolisib is a BCRP inhibitor.
Varicella-Zoster Virus Vaccine, Live: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Avoid concomitant use of leniolisib and clarithromycin due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and clarithromycin is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Voriconazole: (Major) Avoid concomitant use of leniolisib and voriconazole due to the risk for increased leniolisib exposure which may increase the risk for adverse effects. Leniolisib is a CYP3A substrate and voriconazole is a strong CYP3A inhibitor. Concomitant use with another strong CYP3A inhibitor increased leniolisib overall exposure by 2-fold.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with leniolisib is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. The R-enantiomer of warfarin is a CYP1A2 substrate and leniolisib is a CYP1A2 inhibitor. 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.
Yellow Fever Vaccine, Live: (Moderate) Patients receiving leniolisib may have a diminished response to live vaccines. Counsel patients receiving leniolisib about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Zavegepant: (Major) Avoid concomitant use of zavegepant and leniolisib. Concomitant use may increase zavegepant exposure and the risk for zavegepant-related adverse effects. Zavegepant is an OATP1B3 substrate and leniolisib is an OATP1B3 inhibitor. Concomitant use with another OATP1B3 inhibitor increased zavegepant overall exposure by 2.3-fold.
Leniolisib inhibits phosphoinositide 3-kinase delta (PI3K-delta) by blocking the active binding site of PI3K-delta. Gain-of-function variants in the gene encoding the p110-delta catalytic subunit or loss of function variants in the gene encoding the p85-alpha regulatory subunit each cause hyperactivity of PI3K-delta. Leniolisib inhibits the signaling pathways that lead to increased production of PIP3, hyperactivity of the downstream mTOR/AKT pathway, and to the dysregulation of B and T cells.
Leniolisib is administered orally. It is highly protein bound (94.5%) with an estimated volume of distribution of 28.5 L in patients with activated phosphoinositide 3-kinase delta syndrome (APDS). Leniolisib is 60% metabolized by the liver; CYP3A4 is the most predominant enzyme involved (94.5%) in the primary oxidative metabolism while other enzymes (3.5% CYP3A5, 0.7% CYP1A2, and 0.4% CYP2D6) are minor contributors. Intestinal secretion by BCRP and extrahepatic CYP1A1 cannot be excluded as excretion routes. It exhibits a bi-exponential systemic decay in plasma concentration over time, indicating a distribution delay towards peripheral tissues. The apparent terminal elimination half-life is approximately 10 hours. After a single 70 mg oral dose, the mean recovery of total 14C-radioactivity was 92.5% (67% and 25.5% recovered via feces and urine, respectively) 168 hours post dose. Unchanged leniolisib (6.32%) was the predominant drug-related material recovered in urine.
Treatment with leniolisib 70 mg twice daily at steady state is estimated to produce time-averaged reduction of pAkt-positive B cells by approximately 80%.
Affected cytochrome P450 isoenzymes and drug transporters: CYP3A4, CYP1A2, BCRP, OATP1B1, and OATP1B3.
Leniolisib is a substrate of CYP3A4. In vitro, leniolisib is a time dependent inhibitor of CYP1A2 as well as an inhibitor of BCRP, OATP1B1, and OATP1B3.
-Route-Specific Pharmacokinetics
Oral Route
Leniolisib AUC and Cmax increased dose proportionally within the studied range of oral doses (20 to 140 mg twice daily and single doses of 10 to 400 mg). During twice daily dosing approximately 12 hours apart, leniolisib accumulates approximately 1.4-fold (range of 1 to 2.2) in achieving steady-state, consistent with an effective half-life of approximately 7 hours. Steady state concentrations are expected to be reached 2 to 3 days after treatment. The median Tmax occurred at about 1 hour post dose independent of dose and was not altered after multiple oral doses. Administration of leniolisib with food is unlikely to have a clinically meaningful effect on systemic exposure.
-Special Populations
Hepatic Impairment
The effect of hepatic impairment on leniolisib pharmacokinetics has not been studied; however, 60% of leniolisib is metabolized by the liver.
Pediatrics
Leniolisib systemic exposures are comparable between pediatric patients (12 to 17 years) and adults (18 years and older). After a single 70 mg oral dose, the median Tmax was reached approximately 3 hours (range 1 to 5 hours) post dose in patients 12 to 17 years. The difference in the median Tmax between pediatric patients and adults is not clinically relevant.