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Drug overview for INTELENCE (etravirine):
Generic name: ETRAVIRINE (et-ra-VIR-een)
Drug class: Antiviral-HIV (Antiretroviral) Nonnucleoside RT Inhibitor
Therapeutic class: Anti-Infective Agents
Etravirine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nonnucleoside reverse transcriptase inhibitor (NNRTI).
No enhanced Uses information available for this drug.
Generic name: ETRAVIRINE (et-ra-VIR-een)
Drug class: Antiviral-HIV (Antiretroviral) Nonnucleoside RT Inhibitor
Therapeutic class: Anti-Infective Agents
Etravirine, an antiretroviral agent, is a human immunodeficiency virus (HIV) nonnucleoside reverse transcriptase inhibitor (NNRTI).
No enhanced Uses information available for this drug.
DRUG IMAGES
INTELENCE 100 MG TABLET
INTELENCE 200 MG TABLET
The following indications for INTELENCE (etravirine) have been approved by the FDA:
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
Indications:
HIV infection
Professional Synonyms:
Human immunodeficiency virus disease
Human immunodeficiency virus infection
The following dosing information is available for INTELENCE (etravirine):
No enhanced Dosing information available for this drug.
Etravirine is administered orally twice daily following a meal. Etravirine tablets should be swallowed whole with a liquid (e.g., water) and should not be chewed. For patients unable to swallow tablets whole, the dose of etravirine tablets may be placed in 5 mL of water (enough water to cover the tablets) and stirred until a uniform, milky dispersion occurs.
Add 15 mL (1 tablespoon) of liquid; water may be used, but orange juice or milk may improve taste. Do not use carbonated beverages or warm (>40degreesC) water. The dispersion should be consumed immediately; to ensure consumption of the entire dose, the glass should be rinsed several times with water, orange juice, or milk and each rinse swallowed.
Store etravirine tablets at 25degreesC (excursions permitted between 15-30degreesC). Store in the original bottle. Keep the bottle tightly closed in order to protect from moisture. Do not remove the desiccant pouches.
Add 15 mL (1 tablespoon) of liquid; water may be used, but orange juice or milk may improve taste. Do not use carbonated beverages or warm (>40degreesC) water. The dispersion should be consumed immediately; to ensure consumption of the entire dose, the glass should be rinsed several times with water, orange juice, or milk and each rinse swallowed.
Store etravirine tablets at 25degreesC (excursions permitted between 15-30degreesC). Store in the original bottle. Keep the bottle tightly closed in order to protect from moisture. Do not remove the desiccant pouches.
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| INTELENCE 100 MG TABLET | Maintenance | Adults take 2 tablets (200 mg) by oral route 2 times per day after meals |
| INTELENCE 200 MG TABLET | Maintenance | Adults take 1 tablet (200 mg) by oral route 2 times per day after meals |
| DRUG LABEL | DOSING TYPE | DOSING INSTRUCTIONS |
|---|---|---|
| ETRAVIRINE 100 MG TABLET | Maintenance | Adults take 2 tablets (200 mg) by oral route 2 times per day after meals |
| ETRAVIRINE 200 MG TABLET | Maintenance | Adults take 1 tablet (200 mg) by oral route 2 times per day after meals |
The following drug interaction information is available for INTELENCE (etravirine):
There are 6 contraindications.
These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.
| Drug Interaction | Drug Names |
|---|---|
| Delavirdine; Etravirine/Selected Strong CYP3A4 Inducers SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Strong CYP3A4 inducers may induce the metabolism of delavirdine(1) and etravirine(2) by CYP3A4. CLINICAL EFFECTS: Concurrent use of delavirdine(1) or etravirine(2) with strong CYP3A4 inducers may result in sub-therapeutic levels of the non-nucleoside reverse transcriptase inhibitor (NNRTI) and the development of resistance to antiretroviral agents. PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturers of delavirdine(1) and etravirine (2) state that strong CYP3A4 inducers should not be used in combination with delavirdine and etravirine. DISCUSSION: In a study in 8 subjects, administration of various doses of barbiturates, carbamazepine, phenytoin, and phenobarbital with delavirdine (300-400 mg 3 times daily) decreased the minimum concentration (Cmin) of delavirdine by 90%.(1) In a study of 12 subjects, rifabutin (300 mg daily), a moderate CYP3A4 inducer, decreased both the area-under-curve (AUC) and maximum concentration (Cmax) of etravirine by 37%.(2) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, and primidone.(3) |
ASA-BUTALB-CAFFEINE-CODEINE, ASCOMP WITH CODEINE, BRAFTOVI, BUTALB-ACETAMINOPH-CAFF-CODEIN, BUTALBITAL, BUTALBITAL-ACETAMINOPHEN, BUTALBITAL-ACETAMINOPHEN-CAFFE, BUTALBITAL-ASPIRIN-CAFFEINE, CARBAMAZEPINE, CARBAMAZEPINE ER, CARBATROL, CEREBYX, DILANTIN, DILANTIN-125, DONNATAL, EPITOL, EQUETRO, ERLEADA, FIORICET, FIORICET WITH CODEINE, FOSPHENYTOIN SODIUM, LYSODREN, MITOTANE, MYSOLINE, ORKAMBI, PENTOBARBITAL SODIUM, PHENOBARBITAL, PHENOBARBITAL SODIUM, PHENOBARBITAL-BELLADONNA, PHENOBARBITAL-HYOSC-ATROP-SCOP, PHENOHYTRO, PHENYTEK, PHENYTOIN, PHENYTOIN SODIUM, PHENYTOIN SODIUM EXTENDED, PRIMIDONE, SEZABY, TEGRETOL, TEGRETOL XR, TENCON, TIBSOVO, XTANDI |
| Etravirine; Nevirapine/Rifampin; Rifapentine SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Rifampin may induce the metabolism of etravirine(1) and nevirapine by CYP3A4.(2-4) CLINICAL EFFECTS: Concurrent use of rifampin may result in decreased levels and clinical effectiveness of etravirine(1) and nevirapine.(2-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of etravirine states that it should not be used with rifampin or rifapentine.(1) The Australian, UK, and US manufacturers of nevirapine state that rifampin should not be coadministered with nevirapine.(2-4) The Canadian manufacturer of nevirapine states that nevirapine should only be used in combination with rifampin if clearly indicated and with careful monitoring.(5) Rifabutin may be an alternative to rifampin.(2-4) DISCUSSION: In a study in 14 subjects, concurrent nevirapine and rifampin decreased nevirapine area-under-curve (AUC), maximum concentration (Cmax), and minimum concentration (Cmin) of nevirapine by 58%, 50%, and 68%, respectively.(3) There were no significant changes to rifampin Cmax or AUC. (3,4) In a study in 10 HIV-positive tuberculosis patients, concurrent rifampin and nevirapine decreased nevirapine AUC and Cmax by 31% and by 36%, respectively. There was a non-statistically significant decrease in nevirapine Cmin by 21%.(6) |
PRIFTIN, RIFADIN, RIFAMPIN |
| Cobicistat-Elvitegravir/NNRTIs SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Cobicistat inhibits CYP2D6, CYP3A4, BCRP, OATP1B1 and OATP1B3. Elvitegravir induces CYP2C9. Efavirenz may induce the metabolism of cobicistat via CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of cobicistat-elvitegravir with non-nucleoside reverse transcriptase inhibitors (NNRTIs) may result in altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the NNRTI.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The combination product containing cobicistat-elvitegravir-emtricitabine-tenofovir should not be used with non-nucleoside reverse transcriptase inhibitors.(1) DISCUSSION: Concurrent use of cobicistat-elvitegravir with non-nucleoside reverse transcriptase inhibitors may result in altered and/or suboptimal pharmacokinetics of cobicistat, elvitegravir, and/or the NNRTI.(1) |
GENVOYA, STRIBILD |
| Cilostazol (Greater Than 50 mg BID)/Selected Strong & Moderate CYP2C19 Inhibitors SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Strong and moderate inhibitors of CYP2C19 may inhibit the metabolism of cilostazol.(1-4) CLINICAL EFFECTS: Concurrent use of strong or moderate inhibitors of CYP2C19 may result in elevated levels of 3,4-dehydro-cilostazol, a metabolite of cilostazol that is 4-7 times as active as cilostazol.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The dose of cilostazol should be limited to 50 mg twice daily in patients receiving concurrent therapy with strong and moderate inhibitors of CYP2C19.(1) The Australian manufacturer of esomeprazole states concomitant use with cilostazol is contraindicated.(5) DISCUSSION: In a study in 20 subjects examined the effects of omeprazole (40 mg daily) on a single dose of cilostazol (100 mg). Concurrent omeprazole increased the cilostazol maximum concentration (Cmax) and area-under-curve (AUC) by 18% and 26%, respectively. The Cmax and AUC of the 3,4-dehydro-cilostazol metabolite of cilostazol increased 29% and 69%, respectively. The Cmax and AUC of the OPC-13213 metabolite of cilostazol decreased by 22% and 31%, respectively.(4) |
CILOSTAZOL |
| Lonafarnib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of lonafarnib.(1) CLINICAL EFFECTS: Concurrent use of strong and moderate CYP3A4 inducers may decrease the serum levels and effectiveness of lonafarnib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The use of strong or moderate CYP3A4 inducers with lonafarnib is contraindicated. DISCUSSION: With coadministration of a single oral dose of 50 mg lonafarnib (combined with a single oral dose of 100 mg ritonavir) following 600 mg rifampin (a strong CYP3A4 inducer) for 8 days, the area-under-curve (AUC) was reduced by 98% and the maximum concentration (Cmax) was reduced by 92%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, elagolix, etravirine, lesinurad, lorlatinib, modafinil, nafcillin, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, and tovorafenib.(2,3) |
ZOKINVY |
| Etravirine/Tipranavir SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Tipranavir may induce the CYP2C19 and CYP3A4 metabolism of etravirine.(1) CLINICAL EFFECTS: Concurrent use of tipranavir may decrease etravirine levels and result in sub-therapeutic levels of etravirine and the development of resistance to etravirine.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of etravirine states that it should not be coadministered with tipranavir/ritonavir.(1) DISCUSSION: In a study in 19 subjects, concurrent tipranavir/ritonavir (500/200 mg twice daily) decreased etravirine concentration maximum (Cmax), area-under-curve (AUC), and concentration minimum (Cmin) by 71%, 76%, and 82%, respectively. Tipranavir Cmax, AUC, and Cmin increased by 14%, 18%, and 24%, respectively.(1) |
APTIVUS |
There are 90 severe interactions.
These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.
| Drug Interaction | Drug Names |
|---|---|
| Fosamprenavir/Etravirine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The mechanism of this interaction is unclear but may involve P-glycoprotein inhibition by etravirine. Fosamprenavir is a prodrug of amprenavir.(1-2) CLINICAL EFFECTS: Concurrent etravirine and fosamprenavir use with or without low-dose ritonavir may increase amprenavir levels and toxicity.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of etravirine states that coadministration with fosamprenavir (with or without ritonavir) is not recommended.(1) DISCUSSION: In a study in 8 subjects, etravirine increased amprenavir maximum concentration (Cmax), area-under-curve (AUC), and trough concentration (Cmin) by 62%, 69%, and 77%, respectively.(1) |
FOSAMPRENAVIR CALCIUM |
| Selected Protease Inhibitors/Etravirine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Etravirine may induce the metabolism of atazanavir and indinavir.(1) CLINICAL EFFECTS: Concurrent atazanavir or indinavir with etravirine may result in decreased levels and effectiveness of atazanavir and indinavir.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of etravirine states that etravirine should not be co-administered with atazanavir or indinavir without the use of low-dose ritonavir. Co-administration of etravirine with cobicistat-boosted atazanavir is not recommended.(1) DISCUSSION: In a study in 14 subjects, concurrent atazanavir (400 mg daily) increased etravirine maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) by 47%, 50%, and 58%, respectively. Atazanavir Cmax, AUC, and Cmin decreased by 3%, 17%, and 47%, respectively. In a study in 14 subjects, concurrent atazanavir/ritonavir (300/100 mg daily) increased etravirine Cmax, AUC, and Cmin by 30%, 30%, and 26%, respectively. In a study in 13 subjects, atazanavir Cmax, AUC, and Cmin decreased by 3%, 14%, and 38%, respectively.(1) |
ATAZANAVIR SULFATE, EVOTAZ, REYATAZ |
| Rifabutin/Etravirine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Etravirine and rifabutin may induce the metabolism of each other.(1) CLINICAL EFFECTS: Concurrent use may result in decreased levels and effectiveness of both etravirine and rifabutin.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of etravirine recommends a rifabutin dose of 300 mg daily in patients not receiving concurrent therapy with a protease inhibitor.(1) The US manufacturer of etravirine recommends that rifabutin not be administered to patients receiving concurrent etravirine with darunavir/ritonavir, lopinavir/ritonavir, or saquinavir/ritonavir.(1) DISCUSSION: In a study in 12 subjects, concurrent rifabutin (300 mg daily) decreased etravirine maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) by 37%, 37%, and 35%. Rifabutin Cmax, AUC, and Cmin decreased by 10%, 17%, and 24%. The Cmax, AUC, and Cmin of 25-O-desacetylrifabutin decreased by 15%, 17%, and 22%, respectively.(1) |
RIFABUTIN, TALICIA |
| Maraviroc/Etravirine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Etravirine may induce the metabolism of maraviroc by CYP3A4. This effect may be overcome by the concurrent administration of an inhibitor of CYP3A4(1-4) CLINICAL EFFECTS: Concurrent use of etravirine without a strong inhibitor of CYP3A4 may result in decreased levels and effectiveness of maraviroc and the development of resistance. Concurrent use of etravirine with a strong inhibitor of CYP3A4 may result in increased levels of maraviroc and the development of toxicity.(1-4) PREDISPOSING FACTORS: This interaction may be more severe in patients with renal impairment.(3) PATIENT MANAGEMENT: In adults, the recommended dosage of maraviroc in combination with etravirine in the absence of a strong CYP3A4 inhibitor is 600 mg twice daily. The recommended dosage of maraviroc in combination with etravirine and a CYP3A4 inhibitor (except tipranavir/ritonavir) is 150 mg twice daily.(2,3,5) In adults, maraviroc should not be used with a strong CYP3A4 inducer in patients with a creatinine clearance less than 30 ml/min or end-stage renal disease.(3) In children aged 2 years and older weighing at least 10 kg, maraviroc in combination with etravirine is not recommended.(3) No dosage adjustments are recommended for etravirine.(5) DISCUSSION: In a study in 28 healthy subjects, concurrent use of etravirine (200 mg twice daily) with maraviroc (300 mg twice daily) decreased maraviroc area-under-curve (AUC), maximum concentration (Cmax), and minimum concentration (Cmin) by 53%, 60%, and 39%, respectively, when compared to the use of maraviroc (300 mg twice daily) alone.(1-4) There were no significant changes in etravirine pharmacokinetics.(5) The concurrent use of etravirine (200 mg twice daily), darunavir/ritonavir (600/100 mg twice daily), and maraviroc (150 mg twice daily) increased maraviroc AUC, Cmax, and Cmin by 210%, 77%, and 427%, respectively, when compared to the administration of maraviroc (150 mg twice daily) alone.(1-4) There were no significant changes in etravirine pharmacokinetics.(5) |
MARAVIROC, SELZENTRY |
| Deferasirox/Strong UGT Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong inducers of UDP-glucuronosyltransferase (UGT) may induce the metabolism of deferasirox.(1) CLINICAL EFFECTS: Concurrent use of carbamazepine, efavirenz, etravirine, fosphenytoin, phenobarbital, phenytoin, primidone, rifampin, or ritonavir may result in decreased levels and effectiveness of deferasirox.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of strong UGT inducers with deferasirox. If concurrent therapy is warranted, consider increasing the initial dose of deferasirox by 50%. Further dosage adjustments should be made based upon serum ferritin levels and clinical response. Doses above 40 mg/kg are not recommended.(1) DISCUSSION: In a study in healthy subjects, administration of rifampin (600 mg/day for 9 days) decreased the area-under-curve (AUC) of a single dose of deferasirox (30 mg/kg) by 44%.(1) Other strong inducers of UGT, such as carbamazepine, efavirenz, etravirine, fosphenytoin, phenobarbital, phenytoin, primidone, and ritonavir are expected to produce similar results.(1) |
DEFERASIROX, EXJADE, JADENU, JADENU SPRINKLE |
| Clopidogrel/Efavirenz; Etravirine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Clopidogrel is a prodrug and is converted to its active metabolite via a 2 step process. The first conversion step is mediated by CYP2C19, CYP1A2 and CYP2B6, while the second step is mediated by CYP3A4, CYP2B6 and CYP2C19.(1,2) CYP2C19 contributes to both steps and is thought to be the more important enzyme involved in formation of the pharmacologically active metabolite.(1) Efavirenz and etravirine may inhibit the metabolism of clopidogrel to its active form by CYP2C19.(1-4) CLINICAL EFFECTS: Concurrent use of efavirenz or etravirine may result in decreased clopidogrel effectiveness, resulting in increased risk of adverse cardiac events.(1-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of clopidogrel states that concurrent use of inhibitors of CYP2C19, such as efavirenz or etravirine should be avoided.(1) HIV treatment guidelines from the US Department of Health and Human Services and the University of Liverpool HIV Drug Interactions database recommend not to coadminister clopidogrel with efavirenz or etravirine. Consider alternative antiretroviral or antiplatelet therapy.(4,5) The US manufacturer of etravirine recommends alternative to clopidogrel in patients maintained on etravirine.(2) The US manufacturer of clopidogrel states that alternatives to clopidogrel should be considered in patients who are poor metabolizers of CYP2C19.(1) It would be prudent to assume that patients taking strong inhibitors of CYP2C19 are poor metabolizers of this isoenzyme. Moderate CYP2C19 inhibitors, such as efavirenz or etravirine, may also affect this interaction. Consider alternatives to etravirine in patients stabilized on clopidogrel and alternatives to clopidogrel in patients stabilized on etravirine. If concurrent therapy is warranted, consider appropriate testing to assure adequate inhibition of platelet reactivity. DISCUSSION: In a randomized, cross-over study in healthy subjects, ketoconazole (another CYP2C19 inhibitor, 400 mg daily) decreased the maximum concentration (Cmax) of the active metabolite of clopidogrel (300 mg loading dose, followed by 75 mg daily) by 61%. The area-under-curve (AUC) of the active metabolite of clopidogrel was decreased by 22% following the loading dose and by 29% during maintenance dosing. Clopidogrel-induced inhibition of platelet aggregation was decreased by 28% following the loading dose and by 33% during the maintenance dose.(6) In a cross-over study in 72 healthy subjects, simultaneous administration of omeprazole (another CYP2C19 inhibitor, 80 mg daily) and clopidogrel (300 mg loading dose, followed by 75 mg daily) decreased the AUC of the active metabolite of clopidogrel by 46% following the loading dose and by 42% during maintenance dosing. Clopidogrel-induced inhibition of platelet aggregation was decreased by 47% following the loading dose and by 30% during the maintenance dose. In a cross-over study in 72 healthy subjects, administration of omeprazole (another CYP2C19 inhibitor, 80 mg daily) 12 hours after clopidogrel (300 mg loading dose, followed by 75 mg daily) produced similar effects.(1) |
CLOPIDOGREL, CLOPIDOGREL BISULFATE, PLAVIX |
| Citalopram (Greater Than 20 mg)/Select CYP2C19 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Citalopram is primarily metabolized by the CYP2C19 isoenzyme.(1) CLINICAL EFFECTS: Concurrent use of an agent that inhibits CYP2C19 may result in elevated levels of and toxicity from citalopram, including including risks for serotonin syndrome or prolongation of the QTc interval.(1-5) Prolongation of the QT interval may result in life-threatening arrhythmias, including torsades de pointes.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(5) PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, advanced age, poor metabolizer status at CYP2C19, or higher blood concentrations of citalopram.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Predisposing factors for serotonin-related adverse effects include use in the elderly, in patients with hepatic impairment, and in patients receiving multiple agents which increase central serotonin levels.(1,5) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. PATIENT MANAGEMENT: The dose of citalopram should be limited to 20 mg in patients receiving concurrent therapy with an inhibitor of CYP2C19.(1,4) Evaluate the patient for other drugs, diseases and conditions which increase risk for QT prolongation and correct risk factors (e.g. correct hypokalemia, discontinue other QT prolonging drugs) when possible.(1,2) Weigh the specific benefits versus risks for each patient. The US manufacturer recommends ECG monitoring for citalopram patients with congestive heart failure, bradyarrhythmias, taking concomitant QT prolonging medications or receiving concurrent therapy.(4) Citalopram should be discontinued in patients with persistent QTc measurements greater than 500 ms.(2) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: Concurrent use of citalopram (40 mg daily) and cimetidine (400 mg twice daily) for 8 days increased the maximum concentration (Cmax) and area-under-curve (AUC) of citalopram by 39% and 43%, respectively.(1) Inhibitors of CYP2C19 include: abrocitinib, allicin (garlic derivative), berotralstat, cannabidiol (CBD), cenobamate, cimetidine strengths > or = 200 mg, enasidenib, eslicarbazepine, esomeprazole, etravirine, fedratinib, felbamate, fluoxetine, fluvoxamine, givosiran, isoniazid, moclobemide, modafinil, obeticholic acid, omeprazole, piperine, rolapitant, stiripentol, and tecovirimat.(7,8) |
CELEXA, CITALOPRAM HBR |
| Cobimetinib/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of cobimetinib.(1) CLINICAL EFFECTS: Concurrent use of strong or moderate CYP3A4 inducers may decrease the levels and effectiveness of cobimetinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of strong or moderate CYP3A4 inducers in patients receiving therapy with cobimetinib.(1) Consider the use of alternatives with little to no induction potential. DISCUSSION: Based upon simulations, coadministration of cobimetinib with a strong CYP3A4 inducer may decrease cobimetinib exposure by 83%, with a moderate CYP3A4 inducer by 73%, leading to a reduction in efficacy.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, cenobamate, encorafenib, enzalutamide, ivosidenib, lorlatinib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: bosentan, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(1-3) |
COTELLIC |
| Selected Hepatitis C Agents/Efavirenz; Etravirine;Nevirapine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Efavirenz, etravirine, and nevirapine may induce the metabolism of boceprevir,(1,2) telaprevir,(2,3) simeprevir,(4) velpatasvir(5,6) voxilaprevir, glecaprevir(7), and pibrentasvir(7) via CYP3A4. Efavirenz may also decrease absorption of these agents through the P-glycoprotein (P-gp) transporter. CLINICAL EFFECTS: Concurrent use of efavirenz, etravirine, or nevirapine(1,2) may result in decreased levels and effectiveness of boceprevir,(3,4) telaprevir,(4,5) simeprevir,(6) velpatasvir,(6,7) voxilaprevir,(8) glecaprevir,(9) and pibrentasvir(9). PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the concurrent use of boceprevir and efavirenz.(3,4) The concurrent use of efavirenz, etravirine, or nevirapine(1,2) with simeprevir,(6) velpatasvir,(6,7) voxilaprevir,(8) glecaprevir,(9) and pibrentasvir(9) is not recommended. If concurrent therapy is warranted, monitor patients for decreased response to boceprevir,(3,4) telaprevir,(4,5) simeprevir,(6) velpatasvir,(6,7) voxilaprevir,(8) glecaprevir,(9) and pibrentasvir(9). The Swedish manufacturer of telaprevir recommends that the dose of telaprevir be increased to 1125 mg every 8 hours when used concurrently with efavirenz.(10) DISCUSSION: In a study, concurrent efavirenz (600 mg daily for 16 days) decreased the the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of boceprevir (800 mg 3 times daily for 6 days) by 8%, 19%, and 44%, respectively. Efavirenz Cmax and AUC increased by 11% and 20%, respectively.(3,4) In a study in 21 subjects, efavirenz (600 mg daily for 20 days) decreased the Cmax, AUC, and Cmin of telaprevir (750 mg every 8 hours for 10 days) by 9%, 26%, and 47%, respectively. The Cmax, AUC, and Cmin of efavirenz decreased by 16%, 7%, and 2%, respectively.(4,5) In a study in 15 subjects, concurrent telaprevir (1125 mg every 8 hours for 7 days), tenofovir (300 mg daily for 7 days), and efavirenz (600 mg daily for 7 days) decreased telaprevir Cmax, AUC, and Cmin by 14%, 18%, and 25%, respectively. Efavirenz Cmax, AUC, and Cmin decreased by 24%, 18%, and 10%, respectively.(5) In a study in 16 subjects, concurrent telaprevir (1500 mg every 8 hours for 7 days), tenofovir (300 mg daily for 7 days), and efavirenz (600 mg daily for 7 days) decreased telaprevir Cmax, AUC, and Cmin by 3%, 20%, and 48%, respectively. Efavirenz Cmax, AUC, and Cmin decreased by 20%, 15%, and 11%, respectively.(5) In a study in 23 subjects, efavirenz (600 mg daily for 14 days) decreased the Cmax, AUC, and Cmin of simeprevir (150 mg daily for 14 days) by 51%, 71%, and 91%, respectively.(4,6) In a study in 23 subjects, simeprevir (150 mg daily for 14 days) decreased the AUC and Cmin of efavirenz (600 mg daily for 14 days) by 10% and 13%, respectively.(4) In an interaction study, efavirenz 600 mg daily (in combination with emtricitabine-tenofovir DF) decreased velpatasvir Cmax, AUC, and Cmin 47%, 53% and 57% respectively.(7,8) |
EPCLUSA, MAVYRET, SOFOSBUVIR-VELPATASVIR, VOSEVI |
| Bedaquiline/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may induce the metabolism of bedaquiline.(1) CLINICAL EFFECTS: Concurrent or recent use of strong or moderate CYP3A4 inducers may result in decreased levels and effectiveness of bedaquiline.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The concurrent administration of strong or moderate CYP3A4 inducers and bedaquiline should be avoided.(1) DISCUSSION: In a study in healthy subjects, concurrent administration of rifampin (600 mg daily) and bedaquiline (300 mg daily) for 21 days decreased the area-under-curve (AUC) of bedaquiline by 52%.(1) In a study in healthy subjects, pretreatment with efavirenz (600 mg daily for 27 days) decreased the AUC of a single dose of bedaquiline by 20%. There was no effect on bedaquiline Cmax. The AUC and Cmax of the primary metabolite of bedaquiline increased by 70% and 80%, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, and St. John's wort.(1-3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, repotrectinib, sotorasib, telotristat and tovorafenib.(1-3) |
SIRTURO |
| Canagliflozin/UGT Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: UGT inducers may induce the metabolism of canagliflozin, which is glucuronidated by UGT1A9 and UGT2B4.(1) CLINICAL EFFECTS: Concurrent use of an inducer of UGT may result in decreased levels and effectiveness of canagliflozin.(1) PREDISPOSING FACTORS: This interaction may be more severe in patients who have a eGFR of less than 60 ml/min/1.73m2.(1) PATIENT MANAGEMENT: In patients with a eGFR of 60 ml/min/1.73m2 or more who are currently tolerating canagliflozin 100 mg daily and require therapy with an inducer of UGT, the manufacturer of canagliflozin recommends increasing the dose of canagliflozin to 200 mg daily. Patients currently tolerating canagliflozin 200 mg daily and require additional glycemic control may have their dose increased to 300 mg daily.(1) In patients with a eGFR of less than 60 ml/min/1.73m2 who are currently tolerating canagliflozin 100 mg daily and receiving therapy with a UGT inducer, increase the dose of canagliflozin to 200 mg daily. Consider other antihyperglycemic agents in patients who require additional glycemic control.(1) DISCUSSION: Pretreatment with rifampin (600 mg daily for 8 days) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of canagliflozin (300 mg) by 51% and 28%, respectively.(1) Inducers of UGT include: carbamazepine, efavirenz, etravirine, fosphenytoin, lorlatinib, phenobarbital, phenytoin, primidone, rifampin, and ritonavir.(1) |
INVOKAMET, INVOKAMET XR, INVOKANA |
| Dolutegravir/Etravirine; Efavirenz; Nevirapine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Etravirine, efavirenz, and nevirapine may induce the metabolism of dolutegravir via CYP3A4.(1,2) Efavirenz may also induce dolutegravir metabolism via UGT enzymes. CLINICAL EFFECTS: Concurrent use of etravirine, efavirenz, or nevirapine and dolutegravir may result in decreased levels of and clinical effectiveness of dolutegravir.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of dolutegravir states that dolutegravir should not be used with etravirine without atazanavir/ritonavir (ATVr), darunavir/ritonavir (DRVr), or lopinavir/ritonavir (LPVr).(1) The Canadian(3) and UK(4) manufacturers of dolutegravir state that INSTI-naive patients may use etravirine concurrently with dolutegravir at an increased dose of 50 mg twice daily. In pediatric patients, the weight-based once daily dose should be given twice daily. No dose adjustment for dolutegravir is needed when used with etravirine along with concurrent ATVr, DRVr, or LPVr.(1,3-5) When used with efavirenz, the dosage of dolutegravir should be 50 mg twice daily.(1,2) When using the combination abacavir-dolutegravir-lamivudine product, an additional 50 mg dolutegravir table should be taken 12 hours apart from the combination product.(2) Alternative combinations that do not induce metabolic inducers should be considered when possible for INSTI-experience patients with certain INSTI-associated resistance substitutions or clinically suspected INSTI resistance. In pediatric patients, increase the weight-based dose to twice daily. Refer to the current labeling for the specific dosing recommendation.(1) Although the US(1) and Canadian(3) manufacturers of dolutegravir recommend avoiding concurrent use of nevirapine, the US Department of Health and Human Services HIV guidelines recommend standard doses of dolutegravir when administered concurrently with nevirapine.(5) The UK manufacturer of dolutegravir recommends increasing the dose of dolutegravir to 50 mg twice daily when used concurrently with nevirapine.(4) DISCUSSION: In a study in 12 subjects, the administration of efavirenz with dolutegravir (50 mg daily) decreased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of dolutegravir by 39%, 57%, and 75%, respectively.(1) In a study in 16 subjects, the administration of etravirine with dolutegravir (50 mg daily) decreased the Cmax, AUC, and Cmin of dolutegravir by 52%, 71%, and 88%, respectively.(1) In a study in 9 subjects, the administration of etravirine and darunavir/ritonavir (200 mg and 600/100 mg BID) with dolutegravir (50 mg daily) decreased the Cmax, AUC, and Cmin of dolutegravir by 12%, 25%, and 37%, respectively.(1) In a study in 8 subjects, the administration of efavirenz and lopinavir/ritonavir (200 mg and 400/100 mg BID) with dolutegravir (50 mg daily) increased the Cmax, AUC, and Cmin of dolutegravir by 7%, 11%, and 28%, respectively.(1) |
DOVATO, JULUCA, TIVICAY, TIVICAY PD, TRIUMEQ, TRIUMEQ PD |
| Guanfacine/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong or moderate inducers of CYP3A4 may induce the metabolism of guanfacine.(1) CLINICAL EFFECTS: The concurrent administration of a strong or moderate CYP3A4 inducer may result in decreased levels and effectiveness of guanfacine.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Patients maintained on guanfacine may need dosage adjustments if strong or moderate inducers of CYP3A4 are initiated or discontinued. The manufacturer of extended-release guanfacine recommends a starting dose of extended-release guanfacine initiated at up to double the recommended level of the weight based dosing in patients receiving strong or moderate inducers of CYP3A4. If a patient has been maintained on extended-release guanfacine and is started on a strong or moderate CYP3A4 inducer, the dose of extended-release guanfacine should be increased up to double the recommended weight based dose over 1 to 2 weeks. If a patient has been maintained on extended-release guanfacine and a strong or moderate CYP3A4 inducer, and the strong or moderate CYP3A4 inducer is discontinued, the dose of extended-release guanfacine may need to be decreased to the recommended weight based dose over 1 to 2 weeks. Extended-release guanfacine target dose range for attention deficit hyperactivity disorder is 0.05-0.12 mg/kg/day. Doses above 4 mg/day have not been evaluated in children ages 6-12 years and doses above 7 mg/day have not been evaluated in adolescents ages 13-17 years.(1) DISCUSSION: Rifampin (dosage not stated), a strong inducer of CYP3A4, decreased the maximum concentration (Cmax) and area-under-curve (AUC) of guanfacine (dosage not stated) by approximately 50%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, and St. John's wort.(1-3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat, thioridazine, and tovorafenib.(1-3) |
GUANFACINE HCL, GUANFACINE HCL ER, INTUNIV |
| Elbasvir-Grazoprevir/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inducers of CYP3A4 may induce the metabolism of elbasvir and grazoprevir.(1,2) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of elbasvir and grazoprevir.(1,2) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Concurrent use of elbasvir-grazoprevir and a moderate CYP3A4 inducers is not recommended.(1,2) If concurrent use is required, monitor the patient for potential treatment failure and decreased elbasvir and grazoprevir levels. DISCUSSION: In single dose studies, rifampin increased levels of both elbasvir and grazoprevir. In a study in 14 subjects, rifampin (600 mg single IV dose) increased the maximum concentration (Cmax), area-under-curve (AUC), and minimum concentration (Cmin) of a single dose of elbasvir (50 mg) by 41%, 22%, and 31%, respectively. In a study in 14 subjects, rifampin (600 mg single oral dose) increased the Cmax, AUC, and Cmin of a single dose of elbasvir (50 mg) by 29%, 17%, and 21%, respectively. In a study in 12 subjects, rifampin (600 mg single IV dose) increased the Cmax, AUC, and Cmin of a single dose of grazoprevir (200 mg) by 10.94-fold, 10.21-fold, and 1.77-fold, respectively. In a study in 12 subjects, rifampin (600 mg single oral dose) increased the Cmax, AUC, and Cmin of a single dose of grazoprevir (200 mg) by 6.52-fold, 8.35-fold, and 1.61-fold, respectively.(1) However, multiple dose studies with rifampin showed decreased grazoprevir levels. In a study in 12 subjects, rifampin (600 mg orally) decreased the AUC and Cmin of grazoprevir (200 mg daily) by 7% and 90%, respectively. Cmax increased 16%.(1) In a study in 12 subjects, efavirenz (600 mg daily) decreased the Cmax, AUC, and Cmin of elbasvir (50 mg daily) by 45%, 34%, and 59%, respectively.(1) In a study in 12 subjects, efavirenz (600 mg daily) decreased the Cmax, AUC, and Cmin of grazoprevir (200 mg daily) by 87%, 82%, and 69%, respectively.(1) Moderate inducers of CYP3A4 include belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(1-4) |
ZEPATIER |
| Cobicistat-Boosted Darunavir/Efavirenz;Etravirine;Nevirapine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Efavirenz, etravirine, and nevirapine may induce the metabolism of darunavir and cobicistat via CYP3A4.(1,2) CLINICAL EFFECTS: Concurrent use of efavirenz, etravirine, or nevirapine may may result in altered and/or suboptimal pharmacokinetics of cobicistat, resulting in subtherapeutic levels of darunavir.(1,2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Cobicistat boosted darunavir should not be coadministered with efavirenz, etravirine, or nevirapine.(1,2) Note that there is no clinically significant interaction between ritonavir-boosted darunavir and efavirenz, etravirine, or nevirapine, and no dose adjustments are recommended.(2,3) DISCUSSION: Concurrent use of efavirenz, etravirine, or nevirapine with cobicistat boosted darunavir may result in altered and/or suboptimal pharmacokinetics of cobicistat(1,2) In a study of 30 HIV-positive patients, darunavir 800 mg once daily and cobicistat 150 mg once daily administered with etravirine 400 mg once daily resulted in no change to darunavir AUC and Cmax but a 56 % decrease in Cmin. Cobicistat AUC, Cmax, and Cmin decreased 30 %, 14 % and 66 %, respectively.(4) |
DARUNAVIR, PREZCOBIX, PREZISTA, SYMTUZA |
| Pimavanserin/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong or moderate inducers of CYP3A4 may induce the metabolism of pimavanserin.(1) CLINICAL EFFECTS: Concurrent use of a strong or moderate inducer of CYP3A4 may result in decreased levels and effectiveness of pimavanserin.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of pimavanserin recommends avoiding concomitant use of strong or moderate CYP3A4 inducers.(1) DISCUSSION: Pimavanserin is primarily metabolized by CYP3A4 while other metabolic enzymes CYP2J2, CYP2D6 and FMO play a lesser role.(1) In a study of subjects pretreated with 7 days of rifampin (600 mg daily, a strong CYP3A4 inducer), a single dose of pimavanserin (34 mg) produced an area-under-curve (AUC) and maximum concentration (Cmax) that was 91 % and 71 % lower, respectively, than when pimavanserin is given without rifampin.(1) A physiology-based pharmacokinetic model predicted that efavirenz (a moderate CYP3A4 inducer) would decrease pimavanserin AUC and Cmax by 70 % and 60 %, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(3-4) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, and tovorafenib.(3-4) |
NUPLAZID |
| Venetoclax/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of venetoclax.(1) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of venetoclax.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of venetoclax states that the concurrent use of CYP3A4 inducers should be avoided, and that alternative treatments with less CYP3A4 induction should be considered.(1) DISCUSSION: In a study with 10 healthy subjects, co-administration of rifampin (600 mg daily for 13 days), decreased venetoclax area-under-curve (AUC) by 71% and maximum concentration (Cmax) by 42%.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, telotristat, thioridazine, tipranavir/ritonavir, and tovorafenib.(2-3) |
VENCLEXTA, VENCLEXTA STARTING PACK |
| Neratinib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inducers of CYP3A4 may induce the metabolism of neratinib.(1) CLINICAL EFFECTS: Concurrent use of strong or moderate CYP3A4 inducers may result in decreased effectiveness of neratinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of neratinib with strong or moderate inducers of CYP3A4.(1) If concurrent use is warranted, monitor patients closely for decreased neratinib effectiveness. DISCUSSION: Rifampin, a strong CYP3A4 inducer, decreased maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of neratinib (240 mg) by 76% and 87%, respectively.(1) Strong CYP3A4 inducers include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine and St. John's wort.(1,2) Moderate CYP3A4 inducers include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat, thioridazine, and tovorafenib.(1,2) |
NERLYNX |
| Abemaciclib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Abemaciclib is a substrate of CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of abemaciclib.(1) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of abemaciclib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of abemaciclib states to avoid concurrent administration with moderate CYP3A4 inducers and consider alternative agents.(1) DISCUSSION: Abemaciclib is a substrate of CYP3A4.(1) Concurrent administration of rifampin (600 mg once daily, a strong CYP3A4 inducer) with a single 200 mg dose of abemaciclib decreased the relative potency adjusted unbound area-under-curve (AUC) of abemaciclib and its active metabolites (M2, M18, and M20) by 70% in healthy subjects.(1) Concurrent administration of efavirenz, bosentan, and modafinil (moderate CYP3A4 inducers) are predicted to decrease the relative potency adjusted unbound AUC of abemaciclib and its active metabolites (M2, M18, and M20) by 53%, 41%, and 29%, respectively.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, tipranavir/ritonavir and tovorafenib.(2,3) |
VERZENIO |
| Doravirine/Efavirenz;Etravirine;Nevirapine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Efavirenz, etravirine, and nevirapine may induce the metabolism of doravirine via CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of efavirenz, etravirine, or nevirapine may result in subtherapeutic levels of doravirine.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration of doravirine with efavirenz, etravirine, or nevirapine is not recommended.(1) DISCUSSION: In a study in 17 healthy subjects, coadministration of efavirenz (600 mg daily) with a single dose of doravirine (100 mg) decreased doravirine's area-under-curve (AUC), maximum concentration (Cmax), and 24 hour concentration (C24) by 62%, 35%, and 85%, respectively.(1) |
DELSTRIGO, PIFELTRO |
| Lorlatinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 are expected to increase the metabolism of lorlatinib.(1) CLINICAL EFFECTS: Concurrent or recent use of moderate inducers of CYP3A4 may result in decreased levels and effectiveness of lorlatinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concurrent administration of moderate inducers of CYP3A4 with lorlatinib.(1) If concurrent use of lorlatinib and moderate CYP3A4 inducers cannot be avoided, increase the dose of lorlatinib to 125 mg daily.(1) DISCUSSION: Modafinil (a moderate CYP3A4 inducer) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single 100 mg dose of lorlatinib by 23% and 22%, respectively.(1) Moderate inducers of CYP3A4 include belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, modafinil, nafcillin, pacritinib, pexidartinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(1) |
LORBRENA |
| Brigatinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Brigatinib is a substrate of CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of brigatinib.(1) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of brigatinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of brigatinib states to avoid concurrent administration with moderate CYP3A4 inducers. If concurrent use cannot be avoided, increase the daily dose of brigatinib in 30 mg increments every 7 days, as tolerated, to a maximum of twice the brigatinib dose that was tolerated prior to initiation of the moderate CYP3A4 inducer. After discontinuation of a moderate CYP3A4 inducer, resume the brigatinib dose that was tolerated prior to initiation of the inducer.(1) DISCUSSION: Brigatinib is a substrate of CYP3A4.(1) Concurrent administration of rifampin (600 mg daily, a strong CYP3A4 inducer) with a single 180 mg dose of brigatinib decreased the brigatinib maximum concentration (Cmax) by 60% and area-under-curve (AUC) by 80% compared to brigatinib alone. Moderate CYP3A4 inducers are expected to decrease the AUC of brigatinib by 50%.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat ethyl, thioridazine, tipranavir/ritonavir and tovorafenib.(2-3) |
ALUNBRIG |
| Siponimod/Selected Moderate and Strong CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Drugs that are moderate or strong inducers of CYP3A4 may increase the metabolism of siponimod.(1) Patients with a CYP2C9*1/*3 or *2/*3 genotype who are more dependent on CYP3A4 for the metabolism of siponimod would experience a greater effect of CYP3A4 induction. CLINICAL EFFECTS: Concurrent use of a siponimod with a moderate or strong CYP3A4 inducer in patients with a CYP2C9*1/*3 or *2/*3 genotype may result in decreased levels and effectiveness of siponimod.(1) PREDISPOSING FACTORS: Patients with a CYP2C9*1/*3 or *2/*3 genotype who are more dependent on CYP3A4 for the metabolism of siponimod would experience a greater effect of CYP3A4 induction. Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of siponimod says that the combination of siponimod with a moderate or strong CYP3A4 inducer is not recommended for patients with a CYP2C9*1/*3 or *2/*3 genotype.(1) Agents that are both moderate CYP3A4 inducers and moderate CYP2C9 inducers (e.g., lorlatinib) should be used with caution regardless of the patient's CYP2C9 genotype.(1) DISCUSSION: In a study, efavirenz (a moderate CYP3A4 inducer) decreased the area-under-curve (AUC) of siponimod by up to 52% across CYP2C9 genotypes. Drugs that are moderate or strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, cenobamate, dabrafenib, elagolix, etravirine, fosphenytoin, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pexidartinib, phenobarbital, phenytoin, primidone, rifabutin, rifapentine, St John's Wort, sotorasib, telotristat ethyl, and tovorafenib.(2-3) |
MAYZENT |
| Erdafitinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Erdafitinib is a substrate of CYP2C9 and CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of erdafitinib.(1) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of erdafitinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of erdafitinib states that if a moderate CYP3A4 inducer must be co-administered, increase the erdafitinib dose to 9 mg daily. If a moderate CYP3A4 inducer is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity.(1) DISCUSSION: Carbamazepine (a strong CYP3A4 inducer and weak CYP2C9 inducer) decreased the mean maximum concentration (Cmax) and area-under-curve (AUC) of erdafitinib by 78% and 45%, respectively.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-3) |
BALVERSA |
| Pretomanid/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may induce the metabolism of pretomanid by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and pretomanid may result in decreased levels and clinical effectiveness of pretomanid.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of pretomanid recommends avoiding concurrent use with strong or moderate CYP3A4 inducers during pretomanid therapy.(1) Patients receiving concurrent therapy with strong and moderate CYP3A4 inducers and pretomanid should be observed for decreased levels and clinical effectiveness. DISCUSSION: In a clinical study, concurrent use of pretomanid 200 mg with efavirenz 600 mg for 7 days resulted in decreased mean area-under-curve (AUC) by 35% and maximum concentration (Cmax) by 28%.(1) In a clinical study, concurrent use of pretomanid 200 mg with rifampin 600 mg for 7 days resulted in decreased mean AUC by 66% and Cmax by 53%.(1) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fosphenytoin, ivosidenib, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(1,2) |
PRETOMANID |
| Entrectinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Entrectinib is a substrate of CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of entrectinib.(1) CLINICAL EFFECTS: The concurrent administration of a moderate CYP3A4 inducer may result in decreased levels and effectiveness of entrectinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of entrectinib states that concurrent use with moderate CYP3A4 inducers should be avoided. (1) DISCUSSION: Concomitant administration of rifampin (strong CYP3A4 inducer) with a single 600 mg entrectinib dose decreased entrectinib maximum concentration (Cmax) and area-under-the-curve (AUC) by 56% and 77%.(1) Coadministration with a moderate CYP3A4 inducer is predicted to decrease entrectinib's AUC and Cmax by 56% and 43%.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, and tovorafenib.(2-3) |
ROZLYTREK |
| Fedratinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Fedratinib is a substrate of CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of fedratinib.(1) CLINICAL EFFECTS: The concurrent administration of a moderate CYP3A4 inducer may result in decreased levels and effectiveness of fedratinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of fedratinib states that concurrent use with moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: Coadministration of efavirenz (moderate CYP3A4 inducer: 600 mg once daily) with a single dose of fedratinib (500 mg; 1.25 times the recommended dose) decreased the area-under-curve (AUC) of fedratinib by approximately 47%.(1) Moderate inducers of CYP3A4 include: belzutifan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, modafinil, nafcillin, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(2-3) |
INREBIC |
| Intravenous and Oral Lefamulin/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lefamulin is a substrate of CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of lefamulin.(1) Oral lefamulin tablets may inhibit the metabolism of agents that are also sensitive CYP3A4 substrates.(1-3) CLINICAL EFFECTS: The concurrent administration of a moderate CYP3A4 inducer may result in decreased levels and effectiveness of lefamulin.(1) Coadministration of oral lefamulin with agents that are also sensitive CYP3A4 substrates may result in elevated levels and toxicities of the sensitive CYP3A4 substrate. PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of lefamulin states that concurrent use with moderate CYP3A4 inducers should be avoided.(1) Concomitant use of lefamulin tablets with sensitive CYP3A4 substrates requires close monitoring for adverse effects of these drugs.(1) DISCUSSION: In a study, concurrent administration of rifampin (a strong inducer) with lefamulin injection decreased lefamulin area-under-the-curve (AUC) and maximum concentration (Cmax) by 28% and 8%.(1) In a study, concurrent administration of rifampin (a strong inducer) with oral lefamulin (tablets) decreased lefamulin AUC and Cmax by 72% and 57%.(1) In a study, oral lefamulin tablets administered concomitantly with and at 2 or 4 hours before oral midazolam (a CYP3A4 substrate) increased the area-under-curve (AUC) and maximum concentration (Cmax) of midazolam by 200% and 100%, respectively. No clinically significant effect on midazolam pharmacokinetics was observed when co-administered with lefamulin injection.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mitapivat, modafinil, nafcillin, rifabutin, telotristat, and tovorafenib.(2-3) |
XENLETA |
| Letermovir/P-glycoprotein (P-gp) or UGT Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Letermovir is a substrate of the efflux transporter P-glycoprotein (P-gp) and of UDP-glucuronosyltransferase (UGT) 1A1/3 enzymes. P-gp induction may decrease systemic absorption of letermovir, while UGT1A1/3 induction may increase the metabolism of letermovir.(1) CLINICAL EFFECTS: Concurrent or recent use of P-glycoprotein or UGT1A1/3 inducers may result in decreased levels and loss of effectiveness of letermovir. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of letermovir states that coadministration of P-gp inducers or UGT1A1/3 inducers is not recommended. DISCUSSION: In a study, at 24 hours after the last dose of rifampin (600 mg daily), the AUC of letermovir was decreased by 85 %, compared to letermovir when taken alone.(1) Inducers of P-glycoprotein or of UGT1A1/3 linked to this monograph include: apalutamide, efavirenz, etravirine, fosphenytoin, lorlatinib, phenobarbital, phenytoin, primidone, rifampin, rifapentine, ritonavir, and St. John's wort.(2) |
PREVYMIS |
| Daridorexant/Strong or Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Daridorexant is a substrate of CYP3A4. Strong or moderate inducers of CYP3A4 may induce the metabolism of daridorexant.(1) CLINICAL EFFECTS: The concurrent administration of strong or moderate CYP3A4 inducers may result in decreased levels and effectiveness of daridorexant.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of daridorexant states that concurrent use with strong or moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: Concomitant use of rifampin, a strong CYP3A4 inducer, with daridorexant 50 mg decreased daridorexant area-under-curve (AUC) by more than 50%. Efavirenz 600 mg, a moderate CYP3A4 inducer, decreased daridorexant AUC and maximum concentration (Cmax) by 60% and 40%, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
QUVIVIQ |
| Lumateperone/CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lumateperone is a substrate of CYP3A4. Inducers of CYP3A4 may induce the metabolism of lumateperone.(1) CLINICAL EFFECTS: The concurrent administration of a CYP3A4 inducer may decrease the exposure to lumateperone.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of lumateperone states that concurrent use with CYP3A4 inducers should be avoided.(1) DISCUSSION: Coadministration of lumateperone with rifampin, a strong CYP3A4 inducer, resulted in a 98% reduction in area-under-curve (AUC) and a 90% reduction in concentration maximum (Cmax).(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, repotrectinib, rifabutin, telotristat, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 include: amprenavir, armodafinil, bexarotene, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, eslicarbazepine, garlic, genistein, gingko, ginseng, glycyrrhizin, nevirapine, omaveloxolone, oxcarbazepine, pioglitazone, quercetin, rufinamide, sotorasib, sulfinpyrazone, tecovirimat, terbinafine, ticlopidine, troglitazone, vemurafenib, and vinblastine.(2,3) |
CAPLYTA |
| Avapritinib/Strong or Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong or moderate CYP3A4 inducers may induce the metabolism of avapritinib. CLINICAL EFFECTS: Coadministration of avapritinib with a strong or moderate CYP3A4 inducer decreases avapritinib plasma concentrations, which may decrease efficacy of avapritinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of avapritinib states that concurrent use with strong or moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: Coadministration of avapritinib 400 mg as a single dose with rifampin 600 mg daily, a strong CYP3A4 inducer, decreased avapritinib concentration maximum (Cmax) by 74% and area-under-curve (AUC) by 92%.(1) Coadministration of avapritinib 300 mg once daily with efavirenz 600 mg once daily, a moderate CYP3A4 inducer, is predicted to decrease avapritinib Cmax by 55% and AUC by 62% at steady state.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine and tovorafenib.(2,3) |
AYVAKIT |
| Ibrutinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of ibrutinib.(1) CLINICAL EFFECTS: Concurrent use of moderate CYP3A4 inducers may decrease the levels and effectiveness of ibrutinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of moderate CYP3A4 inducers in patients receiving therapy with ibrutinib.(1) Consider the use of alternative agents with less enzyme induction potential.(1) DISCUSSION: The coadministration of rifampin decreased the maximum concentration (Cmax) and area-under-curve (AUC) of ibrutinib by more than 13-fold and 10-fold.(1) In a pharmacokinetic model, efavirenz (600 mg daily), a moderate CYP3A4 inducer, was predicted to decrease the Cmax and AUC of ibrutinib (560 mg) by 2.4-fold and 2.5-fold, respectively.(2) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(4) |
IMBRUVICA |
| Tazemetostat/Strong or Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong or moderate CYP3A4 inducers may induce the metabolism of tazemetostat.(1) CLINICAL EFFECTS: Coadministration of tazemetostat with a strong or moderate CYP3A4 inducer may decrease tazemetostat plasma concentrations, which may decrease the efficacy of tazemetostat.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of tazemetostat says to avoid coadministration of strong or moderate CYP3A4 inducers with tazemetostat.(1) DISCUSSION: Tazemetostat is a known substrate of CYP3A4. According to the manufacturer, coadministration with a strong or moderate CYP3A4 inducer may decrease tazemetostat plasma concentrations which may decrease the efficacy of tazemetostat. No clinical studies have been conducted.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
TAZVERIK |
| Rimegepant/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of rimegepant by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and rimegepant may result in decreased levels and clinical effectiveness of rimegepant.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of rimegepant recommends avoiding concurrent use with strong or moderate CYP3A4 inducers due to potential decrease in exposure to rimegepant and loss of efficacy.(1) Patients receiving concurrent therapy with strong and moderate CYP3A4 inducers and rimegepant should be observed for decreased clinical effectiveness. DISCUSSION: In a drug interaction study, rifampin, a strong CYP3A4 inducer, decreased the area-under-curve (AUC) and maximum concentration (Cmax) of rimegepant (75 mg) by 80% and 64%, respectively.(1) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fosphenytoin, ivosidenib, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(1,2) |
NURTEC ODT |
| Glasdegib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Glasdegib is a substrate of CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of glasdegib.(1) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of glasdegib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of glasdegib states to avoid concurrent administration with moderate CYP3A4 inducers. If concurrent use cannot be avoided, increase the daily dose of glasdegib as tolerated as follows: - If current dose of glasdegib is 100 mg once daily, increase to 200 mg once daily - If current dose of glasdegib is 50 mg once daily, increase to 100 mg once daily After the moderate CYP3A4 inducer has been discontinued for 7 days, resume the glasdegib dose that was tolerated prior to initiation of the inducer.(1) DISCUSSION: A population-based pharmacokinetic model predicts that efavirenz would decrease glasdegib area-under-curve (AUC) by 55% and maximum concentration (Cmax) by 25%.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, and tovorafenib.(2-3) |
DAURISMO |
| Selumetinib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of selumetinib by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and selumetinib may result in decreased levels and clinical effectiveness of selumetinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of selumetinib recommends avoiding concurrent use with strong or moderate CYP3A4 inducers due to potential decrease in exposure to selumetinib and loss of efficacy.(1) Patients receiving concurrent therapy with strong and moderate CYP3A4 inducers and selumetinib should be observed for decreased clinical effectiveness. DISCUSSION: In a study of 22 healthy subjects, rifampin 600 mg daily (a strong CYP3A4 inducer) decreased selumetinib area-under-curve (AUC) and maximum concentration (Cmax) by 51% and 26%, respectively.(2) Concomitant use of efavirenz, a moderate CYP3A4 inducer, is predicted to decrease selumetinib AUC and Cmax by 38% and 22%, respectively.(1) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fosphenytoin, ivosidenib, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(3) |
KOSELUGO |
| Pemigatinib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of pemigatinib by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and pemigatinib may result in decreased levels and clinical effectiveness of pemigatinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of strong and moderate CYP3A4 inducers with pemigatinib.(1) DISCUSSION: Rifampin, a strong CYP3A4 inducer, decreased pemigatinib maximum concentration (Cmax) by 62% and area-under-curve (AUC) by 85% following a single pemigatinib oral dose of 13.5 mg. Concomitant use of a moderate CYP3A4 inducer is predicted to decrease pemigatinib exposure by more than 50%. Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fosphenytoin, ivosidenib, lesinurad, lorlatinib, mavacamten, lumacaftor, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(3) |
PEMAZYRE |
| Sacituzumab Govitecan/UGT1A1 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inducers of UGT1A1 may increase the metabolism of SN-38, the topoisomerase inhibitor which is the antineoplastic component of sacituzumab govitecan.(1) CLINICAL EFFECTS: Concurrent use of UGT1A1 inducers may result in decreased exposure to sacituzumab govitecan and therapeutic failure.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Avoid the use of UGT1A1 inducers in patients receiving sacituzumab govitecan.(1) DISCUSSION: SN-38, the small molecule moiety of sacituzumab govitecan, is metabolized by UGT1A1, and inducers of UGT1A1 are expected to decrease SN-38 levels and effectiveness.(1) In a clinical trial, patients homozygous for decreased function UGT1A1*28 allele had a 26% incidence of Grade 4 neutropenia, compared to 13% of patients heterozygous for the UGT1A1*28 allele and 11% of patients homozygous for the wild type allele.(1) UGT1A1 inducers linked to this monograph include: carbamazepine, efavirenz, etravirine, fosphenytoin, lorlatinib, phenobarbital, phenytoin, primidone, rifampin, ritonavir. |
TRODELVY |
| Capmatinib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of capmatinib by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and capmatinib may result in decreased exposure to capmatinib and decreased anti-tumor activity.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of strong and moderate CYP3A4 inducers with capmatinib.(1) DISCUSSION: Coadministration with rifampin (a strong CYP3A4 inducer) decreased capmatinib area-under-curve (AUC) by 67% and maximum concentration (Cmax) by 56%. Coadministration with efavirenz (a moderate CYP3A4 inducer) was predicted to decrease capmatinib AUC by 44% and Cmax by 34%.(1) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fosphenytoin, ivosidenib, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(2) |
TABRECTA |
| Selpercatinib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of selpercatinib.(1) CLINICAL EFFECTS: Coadministration of selpercatinib with a strong or moderate CYP3A4 inducer decreases selpercatinib plasma concentrations, which may decrease the efficacy of selpercatinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of selpercatinib states that concurrent use with strong and moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: In a study, multiple doses of rifampin (a strong CYP3A inducer) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of selpercatinib by 87% and 70%, respectively.(1) Coadministration of multiple doses of bosentan or efavirenz (moderate CYP3A inducers) is predicted to decrease the AUC and Cmax of selpercatinib 40-70% and 34-57%, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, repotrectinib, rifabutin, sotorasib, and telotristat ethyl.(2,3) |
RETEVMO |
| Idelalisib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of idelalisib.(1) CLINICAL EFFECTS: Concurrent use of moderate CYP3A4 inducers may decrease the levels and effectiveness of idelalisib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of moderate CYP3A4 inducers in patients receiving therapy with idelalisib.(1) Consider the use of alternative agents with less enzyme induction potential.(1) DISCUSSION: In a study in healthy subjects, rifampin (600 mg daily for 8 days) decreased the concentration maximum (Cmax) and area-under-curve (AUC) of idelalisib (150 mg single dose) by 58% and 75%, respectively.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, cenobamate, dipyrone, efavirenz, etravirine, lesinurad, modafinil, nafcillin, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2) |
ZYDELIG |
| Voclosporin/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of voclosporin.(1) CLINICAL EFFECTS: Concurrent use of strong and moderate CYP3A4 inducers may decrease the serum levels and effectiveness of voclosporin.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The use of strong or moderate CYP3A4 inducers with voclosporin should be avoided.(1) DISCUSSION: Concurrent use of voclosporin with rifampin 600 mg daily for 10 days (strong CYP3A4 inducer) decreased the concentration maximum (Cmax) and area-under-curve (AUC) by 0.32-fold and 0.13-fold, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
LUPKYNIS |
| Crizotinib/Selected Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of crizotinib.(1) CLINICAL EFFECTS: Concurrent use of moderate CYP3A4 inducers may decrease the levels and effectiveness of crizotinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of moderate CYP3A4 inducers in patients receiving therapy with crizotinib.(1) Consider the use of alternative agents with less enzyme induction potential.(1) DISCUSSION: Rifampin (600 mg daily), a strong CYP3A4 inducer, decreased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of crizotinib (250 mg) by 69% and 82%, respectively.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, cenobamate, dabrafenib, elagolix, etravirine, lesinurad, lorlatinib, modafinil, nafcillin, rifabutin, sotorasib, telotristat ethyl, and tovorafenib.(2) |
XALKORI |
| Ibrexafungerp/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of ibrexafungerp by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong or moderate CYP3A4 inducers with ibrexafungerp may result in decreased levels and clinical effectiveness of ibrexafungerp.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of strong and moderate CYP3A4 inducers with ibrexafungerp.(1) DISCUSSION: Ibrexafungerp is a substrate of CYP3A4. The manufacturer of ibrexafungerp states that concurrent use of strong or moderate CYP3A4 inducers are likely to significantly reduce ibrexafungerp exposure, but this interaction has not been studied.(1) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fosphenytoin, ivosidenib, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(2,3) |
BREXAFEMME |
| Ripretinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of ripretinib via this pathway.(1) Ripretinib and the active metabolite DP-5439 contribute to anticancer activity. CYP3A4 is the primary metabolism pathway for both ripretinib and the active metabolite DP-5439.(1) CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may alter the clinical effectiveness of ripretinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of ripretinib with moderate CYP3A4 inducers.(1) When possible, select alternative agents in place of the moderate CYP3A4 inducer. If the moderate CYP3A4 inducer cannot be avoided, increase the dose of ripretinib from 150 mg once daily to 150 mg twice daily during concurrent therapy. Monitor patients receiving concurrent therapy for reduced efficacy.(1) If the moderate CYP3A4 inducer is discontinued, reduce the dose of ripretinib back to 150 mg once daily 14 days after discontinuation of the moderate CYP3A4 inducer.(1) If a dose of ripretinib is missed (in patients taking twice daily dosing): -If less than 4 hours have passed since missed dose, patient should take the dose as soon as possible and then take the next dose at the regularly scheduled time. -If more than 4 hours have passed since missed dose, patient should skip the missed dose and then take the next dose at the regularly scheduled time.(1) DISCUSSION: The primary metabolism pathway for ripretinib and DP-5439 is via CYP3A4.(1) In an interaction study of rifampin (a strong CYP3A inducer) and ripretinib, concurrent use decreased ripretinib concentration maximum (Cmax) by 18% and area-under-curve (AUC) by 61%, as well as decreased the active metabolite DP-5439 AUC by 57% and increased Cmax by 37%.(1) In a pharmacokinetic model of efavirenz (a moderate CYP3A inducer), concurrent use was predicted to decrease ripretinib Cmax by 24% and decrease AUC by 56%.(1) In an interaction study of itraconazole (a strong CYP3A4 inhibitor) and ripretinib, concurrent use increased ripretinib Cmax by 36% and AUC by 99%. Concurrent use increased the AUC of DP-5439 by 99% with no change in Cmax.(1) Moderate CYP3A4 inducers linked to this monograph are: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
QINLOCK |
| Finerenone/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of finerenone by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong or moderate CYP3A4 inducers with finerenone may result in decreased levels and clinical effectiveness of finerenone.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of strong or moderate CYP3A4 inducers with finerenone.(1) DISCUSSION: Finerenone is a substrate of CYP3A4. Concurrent use of efavirenz (a moderate CYP3A4 inducer) and rifampicin (a strong CYP3A4 inducer) decreased finerenone area-under-curve (AUC) by 80% and 90%, respectively.(1) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fosphenytoin, ivosidenib, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(2,3) |
KERENDIA |
| Atogepant/CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong, moderate, and weak CYP3A4 inducers may increase the metabolism of atogepant by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong, moderate, or weak CYP3A4 inducers with atogepant may result in decreased levels and clinical effectiveness of atogepant.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of atogepant recommends that patients on concomitant strong, moderate, or weak CYP3A4 inducers receive atogepant 30 mg or 60 mg once daily for prevention of episodic migraines and avoid use of atogepant for prevention of chronic migraines.(1) Patients receiving concurrent therapy with CYP3A4 inducers and atogepant should be observed for decreased clinical effectiveness. DISCUSSION: In a study of healthy subjects, rifampin, a strong CYP3A4 inducer, decreased the area-under-curve (AUC) and maximum concentration (Cmax) of atogepant by 60% and 30%, respectively. Topiramate, a weak CYP3A4 inducer, decreased atogepant AUC and Cmax by 25% and 24%, respectively.(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine and tovorafenib. Weak CYP3A4 inducers linked to this monograph include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, eslicarbazepine, floxacillin, garlic, genistein, ginseng, glycyrrhizin, methylprednisolone, mobocertinib, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(1,2) |
QULIPTA |
| Avacopan/Strong or Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Avacopan is a substrate of CYP3A4. Strong or moderate inducers of CYP3A4 may induce the metabolism of avacopan.(1) CLINICAL EFFECTS: The concurrent administration of strong or moderate CYP3A4 inducers may result in decreased levels and effectiveness of avacopan.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of avacopan states that concurrent use with strong or moderate CYP3A4 inducers should be avoided.(1) The Australian manufacturer of avacopan states that patients anticipated to require long-term administration of a CYP3A4 inducer should not be treated with avacopan. If short term co-administration cannot be avoided in a patient already on avacopan, closely monitor for reoccurrence of disease activity.(4) DISCUSSION: Co-administration of rifampin 600 mg once daily for 11 days, a strong CYP3A4 inducer, decreased the avacopan concentration maximum (Cmax) by 79% and area-under-curve (AUC) by 93%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: belzutifan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, modafinil, nafcillin, rifabutin, sotorasib, telotristat ethyl, thioridazine and tovorafenib.(2-3) |
TAVNEOS |
| Duvelisib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may accelerate the metabolism of duvelisib.(1) CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may alter the clinical effectiveness of duvelisib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of duvelisib with moderate CYP3A4 inducers.(1) When possible, select alternative agents in place of the moderate CYP3A4 inducer. If the moderate CYP3A4 inducer cannot be avoided, increase the dose of duvelisib on day 12 of concurrent therapy as follows: - If the initial dose of duvelisib is 25 mg twice daily, increase the duvelisib dose to 40 mg twice daily. - If the initial dose of duvelisib is 15 mg twice daily, increase the duvelisib dose to 25 mg twice daily. Monitor patients receiving concurrent therapy for reduced efficacy.(1) If the moderate CYP3A4 inducer is discontinued, reduce the dose of duvelisib back to the initial dose 14 days after discontinuation of the moderate CYP3A4 inducer.(1) DISCUSSION: The primary metabolism pathway for duvelisib is CYP3A4.(1) In an interaction study, etravirine (a moderate CYP3A inducer) 200 mg twice daily decreased the maximum concentration (Cmax) and area-under-curve (AUC) of single dose duvelisib 25 mg by 16% and 35%, respectively.(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, modafinil, nafcillin, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-4) |
COPIKTRA |
| Mitapivat/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may increase the metabolism of mitapivat.(1) CLINICAL EFFECTS: Concurrent use of a moderate CYP3A4 inducer may result in decreased levels and effectiveness of mitapivat.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Consider alternative therapies that are not moderate CYP3A4 inducers in patients who are on mitapivat. If concurrent use is necessary, monitor hemoglobin closely and titrate mitapivat dose, not to exceed a maximum dose of 100 mg twice daily.(1) DISCUSSION: Mitapivat is a CYP3A4 substrate. In a pharmacokinetic study with 5 or 20 mg twice daily of mitapivat, efavirenz decreased area-under-curve (AUC) and concentration maximum (Cmax) by 60% and 30%, respectively. After mitapivat doses of 50 mg twice daily, efavirenz decreased AUC and Cmax by 55% and 24%, respectively.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, modafinil, nafcillin, pacritinib, pexidartinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
PYRUKYND |
| Ganaxolone/Strong or Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Ganaxolone is a substrate of CYP3A4. Strong or moderate inducers of CYP3A4 may induce the metabolism of ganaxolone.(1) CLINICAL EFFECTS: The concurrent administration of strong or moderate CYP3A4 inducers may result in decreased levels and effectiveness of ganaxolone.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of ganaxolone states that concurrent use with strong or moderate CYP3A4 inducers should be avoided. If concurrent use is unavoidable, consider increasing the dose of ganaxolone. Do not exceed the recommended maximum daily dose.(1) In patients who are stable on ganaxolone and are initiated on anticonvulsants that are CYP3A4 inducers, consider increasing the dose of ganaxolone. Do not exceed the recommended maximum daily dose.(1) DISCUSSION: Co-administration of rifampin, a strong CYP3A4 inducer, decreased the ganaxolone concentration maximum (Cmax) by 57% and area-under-curve (AUC) by 68%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-3) |
ZTALMY |
| Vonoprazan/Strong or Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Vonoprazan is a substrate of CYP3A4. Strong or moderate inducers of CYP3A4 may increase the metabolism of vonoprazan.(1) CLINICAL EFFECTS: The concurrent administration of strong or moderate CYP3A4 inducers may result in decreased levels and effectiveness of vonoprazan.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of vonoprazan states that concurrent use with strong or moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: Strong CYP3A4 inducers like rifampin are predicted to decrease the area-under-curve (AUC) of vonoprazan by 80%, and moderate CYP3A4 inducers like efavirenz are predicted to decrease vonoprazan AUC by 50%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-3) |
VOQUEZNA, VOQUEZNA DUAL PAK |
| Vonoprazan-Clarithromycin-Amoxicillin/Strong or Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Vonoprazan and clarithromycin are substrates of CYP3A4. Strong or moderate inducers of CYP3A4 may increase the metabolism of vonoprazan and clarithromycin.(1) CLINICAL EFFECTS: The concurrent administration of strong or moderate CYP3A4 inducers may result in decreased levels and effectiveness of vonoprazan and clarithromycin.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of vonoprazan states that concurrent use with strong or moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: Vonoprazan and clarithromycin are CYP3A4 substrates. Strong CYP3A4 inducers like rifampin are predicted to decrease the area-under-curve (AUC) of vonoprazan by 80%, and moderate CYP3A4 inducers like efavirenz are predicted to decrease vonoprazan AUC by 50%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, enzalutamide, fosphenytoin, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: belzutifan, cenobamate, dipyrone, etravirine, lesinurad, modafinil, nafcillin, telotristat ethyl, and tovorafenib.(2-3) |
VOQUEZNA TRIPLE PAK |
| Betibeglogene Autotemcel/Anti-Retrovirals; Hydroxyurea SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Betibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. Hydroxyurea may interfere with hematopoietic stem cell (HSC) mobilization of CD34+ cells.(1) CLINICAL EFFECTS: Use of hydroxyurea before mobilization may result in unsuccessful stem cell mobilization. Use of antiretrovirals before mobilization and apheresis may interfere with the production of betibeglogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals and hydroxyurea for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications and hydroxyurea may interfere with the manufacturing of betibeglogene autotemcel therapy.(1) |
ZYNTEGLO |
| Elivaldogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Elivaldogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of elivaldogene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of elivaldogene autotemcel therapy.(1) |
SKYSONA |
| Olutasidenib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may increase the metabolism of olutasidenib by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and olutasidenib may result in decreased levels and clinical effectiveness of olutasidenib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of strong and moderate CYP3A4 inducers with olutasidenib.(1) DISCUSSION: Coadministration of multiple doses of rifampin (a strong CYP3A4 inducer) decreased olutasidenib area-under-curve (AUC) and maximum concentration (Cmax) by 80% and 43%, respectively.(1) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, belzutifan, bosentan, carbamazepine, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, encorafenib, enzalutamide, etravirine, fosphenytoin, ivosidenib, lesinurad, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, rifampin, rifapentine, St. John's wort, sotorasib, telotristat, thioridazine, and tovorafenib.(2) |
REZLIDHIA |
| Lenacapavir/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may accelerate the metabolism of lenacapavir.(1-3) CLINICAL EFFECTS: Concurrent use of moderate CYP3A4 inducers may decrease the levels and effectiveness of lenacapavir.(1-3) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of lenacapavir states that concurrent use of moderate CYP3A4 inducers is not recommended.(1-3) DISCUSSION: In a study, efavirenz 600 mg once daily (inducer of CYP3A4 [moderate] and P-glycoprotein) decreased the maximum concentration (Cmax) and area-under-curve (AUC) of lenacapavir by 36% and 56%, respectively.(1) Moderate CYP3A4 inducers linked to this monograph include: barbiturates, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, modafinil, nafcillin, nevirapine, oxcarbazepine, phenobarbital, primidone, rifabutin, sotorasib, telotristat ethyl, thioridazine, tipranavir-ritonavir, and tovorafenib.(4,5) |
SUNLENCA |
| Cariprazine/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Cariprazine and its major active metabolite DDCAR are metabolized by CYP3A4. Strong and moderate inducers of CYP3A4 may accelerate the metabolism of cariprazine.(1-4) CLINICAL EFFECTS: Concurrent use of a strong or moderate inducer of CYP3A4 may result in decreased levels and effectiveness of cariprazine.(1-4) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of cariprazine does not recommend concurrent use of strong CYP3A4 inducers.(1) The Australian, Canadian, and UK manufacturers of cariprazine state that concurrent use of strong and moderate CYP3A4 inducers is contraindicated.(2-4) DISCUSSION: Cariprazine and its active metabolites are primarily metabolized by CYP3A4. Coadministration with CYP3A4 inducers has not been studied and the net effect is unclear. Due to the long half life of the active metabolites, it takes several weeks for cariprazine to reach steady state after dosage changes.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(5-6) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(5-6) |
VRAYLAR |
| Elacestrant/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Elacestrant is metabolized by CYP3A4. Strong and moderate inducers of CYP3A4 may increase the metabolism of elacestrant.(1) CLINICAL EFFECTS: Concurrent use of a strong or moderate inducer of CYP3A4 may result in decreased levels and effectiveness of elacestrant.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of elacestrant with strong or moderate CYP3A4 inducers.(1) DISCUSSION: Coadministration of 200 mg dose of elacestrant with rifampin (a strong CYP3A inducer) decreased the maximum concentration (Cmax) and area-under-curve (AUC) of elacestrant by 73% and 86%, respectively.(1) Efavirenz is predicted to decrease the Cmax and AUC of elacestrant by 44 to 63% and 55% to 73%, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(2,3) |
ORSERDU |
| Pirtobrutinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Pirtobrutinib is metabolized by CYP3A4. Moderate inducers of CYP3A4 may increase the metabolism of pirtobrutinib.(1) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of pirtobrutinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of pirtobrutinib with moderate CYP3A4 inducers.(1) If concomitant use of moderate CYP3A4 inducers is unavoidable, and the current dose of pirtobrutinib is 200 mg daily, increase the dose to 300 mg daily. If the current pirtobrutinib dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg.(1) DISCUSSION: Efavirenz and bosentan (moderate CYP3A inducers) are predicted to decrease the area-under-curve (AUC) of pirtobrutinib by 49% and 27%, respectively.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, and thioridazine.(2,3) |
JAYPIRCA |
| Omaveloxolone/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Omaveloxolone is metabolized by CYP3A4. Strong and moderate inducers of CYP3A4 may increase the metabolism of omaveloxolone.(1) CLINICAL EFFECTS: Concurrent use of a strong or moderate inducer of CYP3A4 may result in decreased levels and effectiveness of omaveloxolone.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of omaveloxolone with strong or moderate CYP3A4 inducers.(1) DISCUSSION: Omaveloxolone is a substrate of CYP3A4. The effect of concomitant use with strong CYP3A4 inducers is unknown. Concurrent administration of a single dose of efavirenz (moderate CYP3A4 inducer) with omaveloxolone decreased the maximum concentration (Cmax) and area-under-the-curve (AUC) of omaveloxolone by 38% and 48%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(2,3) |
SKYCLARYS |
| Leniolisib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Leniolisib is metabolized by CYP3A4. Strong and moderate inducers of CYP3A4 may increase the metabolism of leniolisib.(1) CLINICAL EFFECTS: Concurrent use of a strong or moderate inducer of CYP3A4 may result in decreased levels and effectiveness of leniolisib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of leniolisib with strong or moderate CYP3A4 inducers.(1) DISCUSSION: PBPK model-based simulations predicted a maximum decrease of 78% and 58% in leniolisib area-under-curve (AUC) with rifampin (strong CYP3A4 inducer) and efavirenz (moderate CYP3A4 inducer), respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(2,3) |
JOENJA |
| Zanubrutinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Zanubrutinib is a substrate of CYP3A4. Moderate inducers of CYP3A4 may induce the metabolism of zanubrutinib.(1) CLINICAL EFFECTS: The concurrent administration of moderate CYP3A4 inducers may result in decreased levels and effectiveness of zanubrutinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of zanubrutinib states that concurrent use with moderate CYP3A4 inducers should be avoided. If concurrent use cannot be avoided, increase zanubrutinib dosage to 320 mg twice daily.(1) DISCUSSION: Co-administration of multiple doses of efavirenz, a moderate CYP3A4 inducer, is predicted to decrease zanubrutinib Cmax by 58% and AUC by 60%.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-3) |
BRUKINSA |
| Axitinib/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of axitinib.(1) CLINICAL EFFECTS: Concurrent use of strong or moderate CYP3A4 inducers may decrease the levels and effectiveness of axitinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of strong or moderate CYP3A4 inducers in patients receiving therapy with axitinib.(1) Consider the use of alternatives with little to no induction potential.(1) DISCUSSION: Rifampin (600 mg daily for 9 days), a strong CYP3A4 inducer, decreased the maximum concentration (Cmax) and area-under-curve (AUC) of axitinib to less than half and less than 25% of levels seen without concurrent rifampin.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, dexamethasone, encorafenib, enzalutamide, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifabutin, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat ethyl, thioridazine and tovorafenib.(1-3) |
INLYTA |
| Palovarotene/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Palovarotene is extensively metabolized by CYP3A4. Strong and moderate inducers of CYP3A4 may increase the metabolism of palovarotene.(1) CLINICAL EFFECTS: Concurrent use of a strong or moderate inducer of CYP3A4 may result in decreased levels and effectiveness of palovarotene.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of palovarotene with strong and moderate CYP3A4 inducers.(1) DISCUSSION: In a clinical trial, rifampin, a strong CYP3A4 inducer, decreased the maximum concentration (Cmax) and area-under-curve (AUC) of palovarotene by 81% and 89%, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2) |
SOHONOS |
| Erlotinib/CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inducers of CYP3A4 may induce the metabolism of erlotinib.(1) CLINICAL EFFECTS: Concurrent or recent use of a CYP3A4 inducer may result in decreased levels and effectiveness of erlotinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of CYP3A4 inducers in patients receiving therapy with erlotinib. Consider the use of alternative agents with less enzyme induction potential.(1) Consider increasing the dosage of erlotinib by 50 mg increments as tolerated at two week intervals (to a maximum of 450 mg) while closely monitoring the patient. The highest dosage studied with concurrent rifampin is 450 mg. If the dosage of erlotinib is increased, it will need to be decreased when the inducer is discontinued.(1) DISCUSSION: Pretreatment and concurrent therapy with rifampin increased erlotinib clearance by 3-fold and decreased the erlotinib area-under-curve (AUC) by 66% to 80%. This is equivalent to a dose of about 30 mg to 50 mg in NSCLC.(1) In a study, pretreatment with rifampin for 11 days decreased the AUC of a single 450 mg dose of erlotinib to 57.6% of the AUC observed with a single 150 mg dose of erlotinib.(1) In a case report, coadministration of phenytoin (180mg daily) and erlotinib (150mg daily) increased the phenytoin concentration from 8.2mcg/ml to 24.2mcg/ml and decreased the erlotinib concentration 12-fold (from 1.77mcg/ml to 0.15mcg/ml) and increased the erlotinib clearance by 10-fold (from 3.53 L/h to 41.7 L/h).(2) In a study, concurrent use of sorafenib (400 mg twice daily) and erlotinib (150 mg daily) decreased the concentration minimum (Cmin), concentration maximum (Cmax), and AUC of erlotinib.(3) In an animal study, concurrent use of dexamethasone and erlotinib decreased the AUC of erlotinib by 0.6-fold.(4) Strong inducers of CYP3A4 include: barbiturates, encorafenib, enzalutamide, fosphenytoin, ivosidenib, mitotane, phenobarbital, phenytoin, primidone, rifampin, and rifapentine.(5,6) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat, thioridazine, and tovorafenib.(5,6) Weak inducers of CYP3A4 include: amprenavir, armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dicloxacillin, echinacea, eslicarbazepine, flucloxacillin, garlic, genistein, ginkgo, ginseng, glycyrrhizin, mobocertinib, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(5,6) |
ERLOTINIB HCL, TARCEVA |
| Olaparib/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of olaparib.(1) CLINICAL EFFECTS: Concurrent use of strong or moderate CYP3A4 inducers may decrease the levels and effectiveness of olaparib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of strong or moderate CYP3A4 inducers in patients receiving therapy with olaparib.(1) Consider the use of alternatives with little to no induction potential. DISCUSSION: In a drug interaction trial, olaparib area-under-curve (AUC) and maximum concentration (Cmax) decreased 87% and 71% respectively when olaparib was administered with rifampin. Based upon simulated models, a moderate CYP3A4 inducer is predicted to decrease olaparib AUC by 50-60% and Cmax by 20-30%.(1-3) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(4-5) |
LYNPARZA |
| Palbociclib/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of palbociclib.(1) CLINICAL EFFECTS: Concurrent use of strong or moderate CYP3A4 inducers may decrease the levels and effectiveness of palbociclib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of strong or moderate CYP3A4 inducers in patients receiving therapy with palbociclib.(1) Consider the use of alternatives with little to no induction potential. DISCUSSION: In a study in 14 healthy subjects, rifampin (600 mg daily) decreased the maximum concentration (Cmax) and area-under-curve (AUC) of a single dose of palbociclib by 70% and 85%, respectively.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-3) |
IBRANCE |
| Sonidegib/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of sonidegib.(1) CLINICAL EFFECTS: Concurrent use of strong or moderate CYP3A4 inducers may decrease the levels and effectiveness of sonidegib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of strong or moderate CYP3A4 inducers in patients receiving therapy with sonidegib.(1) Consider the use of alternatives with little to no induction potential. DISCUSSION: In an interaction study, 16 healthy subjects received a single dose of sonidegib 800mg alone or 5 days after receiving rifampin 600 mg daily for 14 days. Mean sonidegib area-under-curve (AUC) was decreased by 75% and maximum concentration (Cmax) decreased 54% when taken with rifampin. Based upon population based pharmacokinetic (PBPK) simulations, a moderate CYP3A4 inducer such as efavirenz given for 14 days is predicted to decrease sonidegib AUC 56% in cancer patients taking sonidegib 200 mg daily. Coadministration with a moderate CYP3A4 inducer for 4 months is predicted to decrease sonidegib exposure (AUC) by 69%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-3) |
ODOMZO |
| Quizartinib/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents that induce the CYP3A4 isoenzyme may induce the metabolism of quizartinib.(1) CLINICAL EFFECTS: Concurrent use of strong or moderate CYP3A4 inducers may decrease the levels and effectiveness of quizartinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of strong or moderate CYP3A4 inducers in patients receiving therapy with quizartinib.(1) DISCUSSION: The area-under-curve (AUC) of quizartinib decreased by 90% and maximum concentration (Cmax) by 45% following concomitant use of a single 53 mg dose of quizartinib with efavirenz (a moderate CYP3A inducer). The AUC of active metabolite AC886 decreased by 96% and the Cmax by 68%. The effect of concomitant use with a strong CYP3A inducer may result in even greater effect on quizartinib pharmacokinetics based on mechanistic understanding of the drugs involved. Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: bosentan, cenobamate, dabrafenib, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, and tovorafenib.(2-3) |
VANFLYTA |
| Pralsetinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of pralsetinib.(1) CLINICAL EFFECTS: Concurrent use of a moderate CYP3A4 inducer may result in a loss of pralsetinib efficacy.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of pralsetinib with moderate CYP3A4 inducers.(1) If coadministration with a moderate CYP3A4 inducer cannot be avoided, increase the dose of pralsetinib on day 7 of coadministration with pralsetinib as follows: -If the current dose is 400 mg once daily, increase the dose to 600 mg daily. -If the current dose is 300 mg once daily, increase the dose to 500 mg daily. -If the current dose is 200 mg once daily, increase the dose to 300 mg daily. After discontinuation of a moderate CYP3A4 inducer for at least 14 days, resume the previous pralsetinib dose prior to initiating the moderate CYP3A4 inducer.(1) Monitor patients receiving concurrent therapy for reduced efficacy. DISCUSSION: Coadministration of efavirenz 600 mg once daily is expected to decrease pralsetinib concentration maximum (Cmax) by 18% and area-under-curve (AUC) by 45%.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-3) |
GAVRETO |
| Zuranolone/CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Inducers of CYP3A4 may induce the metabolism of zuranolone.(1) CLINICAL EFFECTS: Concurrent use of a CYP3A4 inducer may result in a loss of zuranolone efficacy.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid the concurrent use of zuranolone with CYP3A4 inducers.(1) DISCUSSION: Coadministration of zuranolone with rifampin decreased the maximum concentration (Cmax) by 0.31-fold and area-under-curve (AUC) by 0.15-fold.(1) Strong CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib. Weak CYP3A4 inducers linked to this monograph include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, eslicarbazepine, flucloxacillin, garlic, genistein, ginseng, glycyrrhizin, methylprednisolone, mobocertinib, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3) |
ZURZUVAE |
| Fruquintinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of fruquintinib.(1) CLINICAL EFFECTS: Concurrent or recent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of fruquintinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: If possible, avoid concurrent use of moderate inducers of CYP3A4 with fruquintinib. If concurrent use cannot be avoided, continue to administer fruquintinib at the recommended dosage.(1) DISCUSSION: Concomitant use with efavirenz (moderate CYP3A4 inducer) is predicted to decrease the fruquintinib maximum concentration (Cmax) by 4% and the area-under-curve (AUC) by 32%.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
FRUZAQLA |
| Capivasertib/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong and moderate inducers of CYP3A4 may increase the metabolism of capivasertib.(1) CLINICAL EFFECTS: Concurrent use of a strong or moderate inducer of CYP3A4 may result in decreased levels and effectiveness of capivasertib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Avoid concomitant use of capivasertib with strong and moderate CYP3A4 inducers.(1) DISCUSSION: Rifampin (strong CYP3A4 inducer) is predicted to decrease capivasertib area-under-curve (AUC) by 70% and maximum concentration (Cmax) by 60%.(1) Efavirenz (moderate CYP3A4 inducer) is predicted to decrease capivasertib AUC by 60% and Cmax by 50%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, and tovorafenib.(2,3) |
TRUQAP |
| Repotrectinib/Strong or Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong or moderate CYP3A4 inducers may induce the metabolism of repotrectinib.(1) CLINICAL EFFECTS: Coadministration of repotrectinib with a strong or moderate CYP3A4 inducer decreases repotrectinib plasma concentrations, which may decrease efficacy of repotrectinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of repotrectinib states that concurrent use with strong or moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: Coadministration of repotrectinib with rifampin, a strong CYP3A4 and P-glycoprotein inducer, decreased concentration maximum (Cmax) by 79% and area-under-curve (AUC) by 92%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, encorafenib, etravirine, lesinurad, modafinil, nafcillin, pacritinib, pexidartinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
AUGTYRO |
| Nirogacestat/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong or moderate CYP3A4 inducers may induce the metabolism of nirogacestat.(1) CLINICAL EFFECTS: Coadministration of nirogacestat with a strong or moderate CYP3A4 inducer decreases nirogacestat plasma concentrations, which may decrease efficacy of nirogacestat.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of nirogacestat states that concurrent use with strong or moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: In a PKPB model, coadministration of rifampin, a strong CYP3A4 inducer, following multiple doses of nirogacestat (150 mg BID) is predicted to decrease the area-under-curve (AUC) of nirogacestat by 85%.(1) In a PKPB model, coadministration of efavirenz, a moderate CYP3A4 inducer, following multiple doses of nirogacestat (150 mg BID) is predicted to decrease the AUC of nirogacestat by 67%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(2,3) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, modafinil, nafcillin, pacritinib, pexidartinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
OGSIVEO |
| Lovotibeglogene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lovotibeglogene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of lovotibeglogene autotemcel.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization and until all cycles of apheresis are completed.(1) There are some long-acting antiretroviral medications that may require a longer duration of discontinuation for elimination of the medication. If a patient is taking anti-retrovirals for HIV prophylaxis, confirm a negative test for HIV before beginning mobilization and apheresis of CD34+ cells.(1) DISCUSSION: Antiretroviral medications may interfere with the manufacturing of lovotibeglogene autotemcel therapy.(1) |
LYFGENIA |
| Lemborexant/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Lemborexant is a substrate of CYP3A4. Strong or moderate inducers of CYP3A4 may induce the metabolism of lemborexant.(1) CLINICAL EFFECTS: The concurrent administration of strong or moderate CYP3A4 inducers may result in decreased levels and effectiveness of lemborexant.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of lemborexant states that concurrent use with strong or moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: A pharmacokinetic model predicted that co-administration of rifampin, a strong CYP3A4 inducer, would decrease the AUC of lemborexant by 90%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
DAYVIGO |
| Praziquantel/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of praziquantel.(1,2) CLINICAL EFFECTS: Concurrent or recent use of a moderate inducer of CYP3A4 may decrease the levels and effectiveness of praziquantel.(1,2) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of praziquantel recommends avoiding concomitant administration with moderate CYP3A4 inducers due to the risk of a clinically significant decrease in praziquantel plasma concentration which may lead to reduced therapeutic effect of praziquantel.(2) In patients receiving a clinically significant CYP3A4 inducer drug who need immediate treatment for schistosomiasis, alternative agents for schistosomiasis should be considered, where possible. If praziquantel treatment is necessary immediately, increase monitoring for reduced anthelmintic efficacy associated with praziquantel, when used in combination with a moderate CYP3A4 inducer.(2) In patients receiving a clinically significant CYP3A4 inducer drug whose treatment could be delayed, discontinue the CYP3A4 inducer drug at least 2 to 4 weeks before administration of praziquantel and, where possible, consider starting alternative medications that are not CYP3A4 inducers. The CYP3A4 inducer drug can be restarted 1 day after completion of praziquantel treatment, if needed.(2) DISCUSSION: In a crossover study, 20 healthy subjects ingested a single 40 mg/kg oral dose of praziquantel following pre-treatment with oral efavirenz (400 mg daily for 13 days). Oral efavirenz reduced the mean praziquantel area-under-curve (AUC) by 77% and maximum concentration (Cmax) by 79%, when coadministered with praziquantel compared to praziquantel given alone.(2) Moderate CYP3A4 inducers include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(3-4) |
BILTRICIDE, PRAZIQUANTEL |
| Atidarsagene Autotemcel/Anti-Retrovirals SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Atidarsagene autotemcel is prepared from apheresed cells that are transduced with a replication defective, self-inactivating lentiviral vector. Antiretrovirals may interfere with the manufacturing of apheresed cells. CLINICAL EFFECTS: Use of antiretrovirals before mobilization and apheresis may interfere with the production of atidarsagene autotemcel. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discontinue antiretrovirals for at least one month prior to mobilization (or the expected duration of time needed for elimination of the medication) until all cycles of apheresis are completed. If a patient requires antiretrovirals for HIV prophylaxis, then confirm a negative HIV test before beginning mobilization and apheresis of CD34+ cells. DISCUSSION: Antiretroviral medications may interfere with the manufacturing of atidarsagene autotemcel therapy.(1) |
LENMELDY |
| Lazertinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of lazertinib via this pathway.(1) CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may reduce the clinical effectiveness of lazertinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of lazertinib states that concurrent use of moderate CYP3A4 inducers should be avoided. Consider an alternative concomitant medication with no potential to induce CYP3A4.(1) DISCUSSION: In a pharmacokinetic modelling study, concomitant use of efavirenz (moderate CYP3A4 inducer) is predicted to decrease lazertinib steady state concentration maximum (Cmax) and area-under-curve (AUC) by at least 32% and 44%, respectively.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
LAZCLUZE |
| Revumenib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate CYP3A4 inducers may induce the metabolism of revumenib by CYP3A4 and increase formation of the M1 metabolite which contributes to revumenib's effects on the QTc interval.(1) CLINICAL EFFECTS: Concurrent use of moderate CYP3A4 inducers may result in decreased levels and effectiveness of revumenib and increased risk of QT prolongation due to increased exposure to revumenib's M1 metabolite. The risk of potentially life-threatening arrhythmias including torsades de pointes may be increased.(1) PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, or advanced age.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of revumenib states that concomitant use of moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: Revumenib is primarily metabolized by CYP3A4. Concomitant use of a moderate CYP3A4 inducer may decrease revumenib concentrations and increase M1 systemic exposure, resulting in decreased revumenib efficacy or increased risk of QT prolongation.(1) In clinical trials, QTc interval prolongation was reported as an adverse event in 29% of 135 patients treated with the recommended dosage of revumenib; 12% of patients had Grade 3 QTc prolongation. Revumenib increased the QTc interval in a concentration-dependent manner. At the mean steady-state Cmax using the highest approved recommended dosage of revumenib without CYP3A4 inhibitors, QTc increase was predicted to be 27 msec (upper bound of 90% confidence interval = 30 msec). At the steady-state Cmax using the highest approved recommended dosage of revumenib with CYP3A4 inhibitors, QTc increase was predicted to be 19 msec (upper bound of 90% confidence interval = 22 msec).(1) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, and tovorafenib.(3) |
REVUFORJ |
| Acoramidis/UGT and Selected CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: UGT and selected CYP3A4 inducers may induce the metabolism of acoramidis, which is glucuronidated by UGT1A9, UGT1A1, and UGT2B7.(1) CLINICAL EFFECTS: Concurrent use of UGT and selected CYP3A4 inducers may result in decreased levels and effectiveness of acoramidis.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The manufacturer of acoramidis states to avoid concomitant use of acoramidis with UGT inducers and strong CYP3A inducers.(1) DISCUSSION: UGT and selected CYP3A4 inducers linked to this monograph include: carbamazepine, efavirenz, etravirine, fosphenytoin, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and ritonavir. |
ATTRUBY |
| Vanzacaftor-Tezacaftor-Deutivacaftor/Moderate CYP3A4 Inducer SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of vanzacaftor, tezacaftor, and deutivacaftor.(1) CLINICAL EFFECTS: Concurrent or recent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of vanzacaftor, tezacaftor, and deutivacaftor.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Concurrent use of moderate CYP3A4 inducers in patients maintained on vanzacaftor- tezacaftor-deutivacaftor is not recommended.(1) DISCUSSION: Concurrent administration with efavirenz (a moderate inducer of CYP3A4) is predicted to decrease vanzacaftor and deutivacaftor area-under-curve (AUC) by 69% and 73%, respectively, and maximum concentration (Cmax) by 65% and 56%, respectively.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
ALYFTREK |
| Bictegravir/Efavirenz; Etravirine SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Efavirenz and etravirine may induce the metabolism of bictegravir via CYP3A4 and UGT1A1.(1-3) Efavirenz and etravirine are moderate CYP3A4 and UGT1A1 inducers.(2) CLINICAL EFFECTS: The concurrent use of bictegravir and efavirenz or etravirine may lead to decreased levels of bictegravir, which may result in the loss of therapeutic effect and development of resistance to bictegravir.(1-4) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The HIV guidelines state that bictegravir and efavirenz or etravirine should not be coadministered.(3) DISCUSSION: In a single dose study, rifampin (a strong CYP3A4 and UGT1A1 inducer) decreased the maximum concentration (Cmax) and area-under-curve (AUC) levels of bictegravir by 28% and 75%, respectively.(1) |
BIKTARVY |
| Suzetrigine/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of suzetrigine.(1) CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may reduce the clinical effectiveness of suzetrigine.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of suzetrigine states that concurrent use of moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: Concomitant administration of efavirenz (moderate CYP3A inducer) with suzetrigine is predicted to decrease suzetrigine and active metabolite M6-SUZ area-under-curve (AUC) by 63% and 60%, respectively, while suzetrigine maximum concentration (Cmax) is predicted to decrease by 29% and M6-SUZ Cmax is predicted to increase by 1.3-fold, respectively.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
JOURNAVX |
| Ranolazine/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of ranolazine.(1,2) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of ranolazine.(1,2) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of ranolazine states that the concurrent use of CYP3A4 inducers such as rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, and St. John's wort is contraindicated. Concurrent use of moderate CYP3A4 inducers should be avoided.(1) The UK manufacturer of ranolazine states that ranolazine should not be used in patients receiving CYP3A4 inducers.(2) DISCUSSION: Concurrent rifampin (600 mg daily), strong inducer of CYP3A4, decreased ranolazine plasma concentrations by 95%.(1,2) The effects of a moderate CYP3A4 inducer on ranolazine concentrations has not been studied. Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mitapivat, modafinil, nafcillin, pexidartinib, repotrectinib, sotorasib, telotristat, and tovorafenib.(1-4) |
ASPRUZYO SPRINKLE, RANOLAZINE ER |
| Atrasentan/Moderate CYP3A4 Inducers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of atrasentan.(1) CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may reduce the clinical effectiveness of atrasentan.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of atrasentan states that concurrent use of moderate CYP3A4 inducers should be avoided.(1) DISCUSSION: In a study, atrasentan trough concentration (Ctrough) decreased by 90% following coadministration of a single dose of 10 mg of atrasentan with rifampin (strong CYP3A4 inducer).(1) The effects of a moderate CYP3A4 inducer on atrasentan concentrations has not been studied. Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
VANRAFIA |
| Mavacamten/Moderate CYP2C19 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Moderate CYP2C19 inhibitors may decrease the metabolism of mavacamten.(1-3) CLINICAL EFFECTS: Concurrent use of a moderate CYP2C19 inhibitor increases plasma exposure of mavacamten which may increase the incidence and severity of adverse reactions of mavacamten.(1-3) PREDISPOSING FACTORS: CYP2C19 rapid and ultrarapid metabolizers may experience an increased incidence or severity of adverse effects.(1-3) PATIENT MANAGEMENT: The US manufacturer of mavacamten recommends initiating mavacamten at the recommended starting dosage of 2.5 mg orally once daily in patients who are on stable therapy with a moderate CYP2C19 inhibitor. Reduce dose by one level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients who are on mavacamten treatment and intend to initiate a moderate CYP2C19 inhibitor. Schedule clinical and echocardiographic assessment 4 weeks after inhibitor initiation, and do not up-titrate mavacamten until 12 weeks after inhibitor initiation.(1) Avoid initiation of concomitant moderate CYP2C19 inhibitors in patients who are on stable treatment with 2.5 mg of mavacamten because a lower dose is not available.(1) For short-term use (e.g. 1 week), interrupt mavacamten therapy for the duration of the moderate CYP2C19 inhibitor. After therapy with the moderate CYP2C19 inhibitor is discontinued, mavacamten may be reinitiated at the previous dose immediately upon discontinuation.(1) The Canadian manufacturer of mavacamten states concomitant use with moderate CYP2C19 inhibitors is contraindicated.(2) The UK manufacturer of mavacamten states concomitant use with moderate CYP2C19 inhibitors is dependent on CYP2C19 phenotype. Labeling recommends: -In patients who are CYP2C19 poor metabolizers, moderate CYP2C19 inhibitors may be used concurrently without dose adjustment of mavacamten. Monitor left ventricular ejection fraction (LVEF) in 4 weeks then resume usual monitoring schedule. -In patient who are CYP2C19 intermediate, normal, rapid, or ultrarapid metabolizers: Moderate CYP2C19 inhibitors may be used concurrently without dose adjustment of mavacamten starting dose of 5 mg daily. If starting a moderate CYP2C19 inhibitor, reduce mavacamten dose by one dose level or discontinue 2.5 mg. Monitor LVEF in 4 weeks then resume usual monitoring schedule. -If CYP2C19 phenotype is unknown, consider a mavacamten starting dose of 2.5 mg daily. If starting a moderate CYP2C19 inhibitor, reduce mavacamten dose from 5 mg to 2.5 mg or discontinue mavacamten if on 2.5 mg. Monitor LVEF in 4 weeks then resume usual monitoring schedule.(3) DISCUSSION: Concomitant use of mavacamten (15 mg) with omeprazole (20 mg), a weak CYP2C19 inhibitor, once daily increased mavacamten area-under-curve (AUC) by 48% with no effect on maximum concentration (Cmax) in healthy CYP2C19 normal metabolizers and rapid metabolizers.(1) Moderate CYP2C19 inhibitors linked to this monograph include: abrocitinib, cannabidiol, efavirenz, esomeprazole, etravirine, moclobemide, omeprazole, stiripentol, triclabendazole.(4,5) |
CAMZYOS |
There are 16 moderate interactions.
The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.
| Drug Interaction | Drug Names |
|---|---|
| Clarithromycin/NNRTIs SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Efavirenz, etravirine, and nevirapine may induce the metabolism of clarithromycin via CYP3A4. Clarithromycin may inhibit the metabolism of etravirine by CYP3A4. Also, delavirdine may inhibit the metabolism of clarithromycin by CYP3A4. CLINICAL EFFECTS: Concurrent use of clarithromycin with efavirenz, etravirine, or nevirapine may alter blood levels of clarithromycin and its active metabolite, 14-OH-clarithromycin, resulting in decreased effectiveness and/or toxicity. Concurrent use of clarithromycin may increase etravirine levels. Concurrent use of clarithromycin with delavirdine may increase the levels and toxicities of clarithromycin. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturers of efavirenz,(1,2) etravirine,(3) and nevirapine(4) state that concurrent use with clarithromycin is not recommended and that alternative antibiotic agents, such as azithromycin, should be considered. If concurrent therapy is warranted, monitor patients closely for efficacy and adverse effects. No dosage adjustment of efavirenz(2) or the combination of efavirenz/emtricitabine/tenofovir(3) is recommended. The US manufacturer of delavirdine recommends that the dose of clarithromycin be reduced by 50% in patients with a CrCl of 30 ml/min to 60 ml/min. For patients with a CrCl of less than 30 ml/min, the dose of clarithromycin should be reduced by 75%. No adjustment is necessary in patients with normal renal function.(5) DISCUSSION: In a study in 11 subjects, concurrent efavirenz (400 mg) and clarithromycin (500 mg twice daily) decreased the maximum concentration (Cmax), AUC, and minimum concentration (Cmin) by 26%, 39%, and 53%, respectively. The Cmax, AUC, and Cmin of 14-OH-clarithromycin increased by 49%, 34%, and 26%, respectively. The Cmax of efavirenz increased by 11%. In uninfected subjects, 46% developed a rash during concurrent therapy.(1,2) In a study in 15 subjects, concurrent clarithromycin (500 mg twice daily) increased the Cmax, AUC, and Cmin of etravirine (dosage not stated) by 46%, 42%, and 46%, respectively. The Cmax, AUC, and Cmin of clarithromycin decreased by 34%, 39%, and 53%, respectively. The Cmax, AUC, and Cmin of 14-OH-clarithromycin increased by 33%, 21%, and 5%, respectively.(3) In a study in 15 subjects, concurrent nevirapine (200 mg daily for 14 days, then 200 mg twice daily for 14 days) and clarithromycin (500 mg twice daily) decreased the Cmax, AUC, and Cmin of clarithromycin by 23%, 31%, and 56%, respectively. The Cmax and AUC of 14-OH-clarithromycin increased by 47% and 42 %, respectively.(4) Although 14-OH-clarithromycin is an active metabolite, it has reduced activity against Mycobacterium avium-intracellulare complex.(4) In a study in 6 subjects, concurrent delavirdine (300 mg 3 times daily) with clarithromycin (500 mg 3 times daily) increased the area-under-curve (AUC) of clarithromycin by 100%. There was no effect on delavirdine levels.(5) |
CLARITHROMYCIN, CLARITHROMYCIN ER, LANSOPRAZOL-AMOXICIL-CLARITHRO, OMECLAMOX-PAK |
| Citalopram (Less than or Equal To 20 mg)/Selected CYP2C19 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Citalopram is primarily metabolized by the CYP2C19 isoenzyme.(1) CLINICAL EFFECTS: Concurrent use of an agent that inhibits CYP2C19 may result in elevated levels of and toxicity from citalopram, including including risks for serotonin syndrome or prolongation of the QTc interval.(1-5) Prolongation of the QT interval may result in life-threatening arrhythmias, including torsades de pointes.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(5) PREDISPOSING FACTORS: The risk of QT prolongation or torsades de pointes may be increased in patients with cardiovascular disease (e.g. heart failure, myocardial infarction, history of torsades de pointes, congenital long QT syndrome), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female gender, advanced age, poor metabolizer status at CYP2C19, or higher blood concentrations of citalopram.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Predisposing factors for serotonin-related adverse effects include use in the elderly, in patients with hepatic impairment, and in patients receiving multiple agents which increase central serotonin levels.(1,5) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. PATIENT MANAGEMENT: The dose of citalopram should be limited to 20 mg in patients receiving concurrent therapy with an inhibitor of CYP2C19.(1,4) Evaluate the patient for other drugs, diseases and conditions which increase risk for QT prolongation and correct risk factors (e.g. correct hypokalemia, hypocalcemia, hypomagnesemia, discontinue other QT prolonging drugs) when possible.(1,2) Weigh the specific benefits versus risks for each patient. The US manufacturer recommends ECG monitoring for citalopram patients with congestive heart failure, bradyarrhythmias, taking concomitant QT prolonging medications or receiving concurrent therapy.(4) Citalopram should be discontinued in patients with persistent QTc measurements greater than 500 ms.(2) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: Concurrent use of citalopram (40 mg daily) and cimetidine (400 mg twice daily) for 8 days increased the maximum concentration (Cmax) and area-under-curve (AUC) of citalopram by 39% and 43%, respectively.(1) Inhibitors of CYP2C19 include: abrocitinib, allicin (garlic derivative), berotralstat, cannabidiol (CBD), cenobamate, cimetidine strengths > or = 200 mg, enasidenib, eslicarbazepine, esomeprazole, etravirine, fedratinib, felbamate, fluoxetine, fluvoxamine, givosiran, isoniazid, moclobemide, modafinil, obeticholic acid, omeprazole, piperine, rolapitant, stiripentol, and tecovirimat.(7,8) |
CELEXA, CITALOPRAM HBR |
| Escitalopram (Greater Than 15 mg)/Selected CYP2C19 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: At lower systemic concentrations, escitalopram is primarily metabolized by CYP2C19; at higher concentrations is also metabolized by CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of an agent which significantly inhibits CYP2C19, or which inhibits both CYP2C19 and CYP3A4 may result in elevated concentrations and toxicity from escitalopram, including risks for serotonin syndrome or prolongation of the QTc interval.(1,5) Prolongation of the QT interval may result in life-threatening arrhythmias, including torsades de pointes.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(3) PREDISPOSING FACTORS: The risk of QT prolongation may be increased in patients with congenital long QT syndrome, cardiovascular disease (e.g. heart failure, myocardial infarction), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female sex, advanced age, poor metabolizer status at CYP2C19, concurrent use of more than one agent known to cause QT prolongation, or with higher blood concentrations of escitalopram.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Predisposing factors for serotonin-related adverse effects include use in the elderly, in patients with hepatic impairment, and in patients receiving multiple agents which increase central serotonin levels.(1,3) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. PATIENT MANAGEMENT: Evaluate patient for other drugs, diseases and conditions which may further increase risk for QT prolongation and correct risk factors (e.g. correct hypokalemia, discontinue other QT prolonging drugs) when possible.(2,3) It would be prudent to limit the escitalopram dose to 10 mg daily in patients with QT prolonging risk factors who also receive concurrent therapy with selected CYP2C19 inhibitors.(5) Weigh the specific benefits versus risks for each patient. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: A thorough QT study evaluating escitalopram 10 mg or 30 mg once daily was conducted; a change of 10 msec for upper bound of the 95% confidence level is the threshold for regulatory concern. In this study, changes to the upper bound of the 95% confidence interval were 6.4 msec and 12.6 msec for the 10 mg and supratherapeutic 30 mg dose respectively. The Cmax for 30 mg was 1.7-fold higher than the Cmax for the maximum recommended escitalopram dose of 20 mg. Systemic exposure at the 30 mg dose was similar to expected steady state concentrations in 2C19 poor metabolizers following a 20 mg escitalopram dose.(1) In an interaction study, 30 mg of omeprazole, an irreversible inhibitor of CYP2C19 was administered daily for 6 days. On day 5 a single dose of escitalopram 20 mg was also administered; the area-under-curve (AUC) of escitalopram was increased by 50%. Manufacturer prescribing information recommends a maximum citalopram dose of 20mg daily in patients receiving CYP2C19 inhibitors.(1) Inhibitors of CYP2C19 include: abrocitinib, allicin (garlic derivative), berotralstat, cannabidiol (CBD), cenobamate, cimetidine strengths > or = 200 mg, enasidenib, eslicarbazepine, esomeprazole, etravirine, fedratinib, felbamate, fluoxetine, fluvoxamine, givosiran, isoniazid, moclobemide, modafinil, obeticholic acid, omeprazole, piperine, rolapitant, stiripentol, tecovirimat, and tipranavir.(4) |
ESCITALOPRAM OXALATE, LEXAPRO |
| Exemestane/Selected Moderate-Weak CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: CYP3A4 inducers may induce the metabolism of exemestane.(1) CLINICAL EFFECTS: Concurrent use of a CYP3A4 inducer may result in decreased levels and effectiveness of exemestane.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of exemestane recommends that patients receiving concurrent therapy with a strong CYP3A4 inducer receive 50 mg of exemestane daily after a meal.(1) It may be prudent to consider a dosage increase for patients receiving weaker CYP3A4 inducers. DISCUSSION: In a study in 10 healthy postmenopausal subjects, pretreatment with rifampin (a strong CYP3A4 inducer, 600 mg daily for 14 days) decreased the area-under-curve (AUC) and maximum concentration (Cmax) of a single dose of exemestane (25 mg) by 54% and 41%, respectively.(1) Strong inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 80% or more and include: carbamazepine, enzalutamide, mitotane, phenobarbital, phenytoin, rifabutin, rifampin, and St. John's wort.(1-3) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, elafibranor, enasidenib, eslicarbazepine, floxacillin, garlic, gingko, ginseng, glycyrrhizin, lorlatinib, meropenem-vaborbactam, methylprednisolone, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, quercetin, relugolix, rufinamide, sarilumab, sulfinpyrazone, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3) |
AROMASIN, EXEMESTANE |
| Perampanel/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong and moderate CYP3A4 inducers may induce the metabolism of perampanel by CYP3A4.(1) CLINICAL EFFECTS: The concurrent use of strong and moderate CYP3A4 inducers and perampanel may result in decreased levels and clinical effectiveness of perampanel.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Patients receiving concurrent therapy with strong and moderate CYP3A4 inducers and perampanel should be observed for decreased anticonvulsant levels and clinical effectiveness. The manufacturer of perampanel recommends a starting dose of 4 mg once daily at bedtime in patients receiving concurrent therapy with CYP3A4 inducers. Dose increases are recommended by 2 mg increments once daily based on clinical response and tolerability, no more frequently than at weekly intervals. The highest studied dose with concurrent enzyme-inducing antiepileptic drugs was 12 mg once daily.(1) The dose of the anticonvulsant may need to be adjusted if a strong or moderate CYP3A4 inducer is added to or removed from therapy.(1) DISCUSSION: In a study in healthy subjects, carbamazepine 300 mg BID decreased the maximum concentration (Cmax) and area-under-curve (AUC) of a single 2 mg tablet dose of perampanel by 26% and 67%, respectively. The half-life (t1/2) of perampanel was shortened from 56.8 hours to 25 hours. In clinical studies examining partial-onset and primary generalized tonic-clonic seizures, a population pharmacokinetic analysis showed that perampanel AUC was reduced by 64% in patients on carbamazepine compared to the AUC in patients not on enzyme-inducing antiepileptic drugs.(1) In a study in partial-onset and primary generalized tonic-clonic seizures, a population pharmacokinetic analysis showed that perampanel AUC was reduced by 48% in patients on oxcarbazepine compared to patients not on enzyme-inducing antiepileptic drugs.(1) In a study in partial-onset and primary generalized tonic-clonic seizures, a population pharmacokinetic analysis showed that perampanel AUC was reduced by 43% in patients on phenytoin compared to patients not on enzyme-inducing antiepileptic drugs.(1) In a study in partial-onset and primary generalized tonic-clonic seizures in clinical trials (40 patients co-administered phenobarbital and 9 patients co-administered primidone), no significant effect on perampanel AUC was found. A modest effect of phenobarbital and primidone on perampanel concentrations cannot be excluded.(1) In a study in 76 patients, concentration-to-dose (CD) ratio of perampanel was assessed with and without concurrent antiepileptic agents. In patients only on perampanel the mean CD ratio was 3963 ng/mL/mg/kg (range: 1793-13,299) compared to the mean CD ratio in patients using enzyme-inducing AEDs [1760 (range: 892-3090), 2256 (range: 700-4703), and 1120 (range: 473-1853) ng/mL/mg/kg in patients taking phenytoin, phenobarbital, and carbamazepine, respectively], and carbamazepine had a significantly greater reduction in the CD ratio compared with phenytoin or phenobarbital (P < 0.001).(3) Strong and moderate CYP3A4 inducers linked to this monograph include: apalutamide, barbiturates, bosentan, carbamazepine, cenobamate, dabrafenib, efavirenz, elagolix, encorafenib, enzalutamide, eslicarbazepine, etravirine, fosphenytoin, ivosidenib, lorlatinib, lumacaftor, mavacamten, mitapivat, mitotane, modafinil, nafcillin, oxcarbazepine, pacritinib, pexidartinib, phenobarbital, phenytoin, primidone, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(1,2) |
FYCOMPA |
| Escitalopram (Less Than or Equal To 15 mg)/Selected CYP2C19 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: At lower systemic concentrations, escitalopram is primarily metabolized by CYP2C19; at higher concentrations is also metabolized by CYP3A4.(1) CLINICAL EFFECTS: Concurrent use of an agent which significantly inhibits CYP2C19, or which inhibits both CYP2C19 and CYP3A4 may result in elevated concentrations and toxicity from escitalopram, including risks for serotonin syndrome or prolongation of the QTc interval.(1,5) Prolongation of the QT interval may result in life-threatening arrhythmias, including torsades de pointes.(2) Symptoms of serotonin syndrome may include tremor, agitation, diaphoresis, hyperreflexia, clonus, tachycardia, hyperthermia, and muscle rigidity.(3) PREDISPOSING FACTORS: The risk of QT prolongation may be increased in patients with congenital long QT syndrome, cardiovascular disease (e.g. heart failure, myocardial infarction), hypokalemia, hypomagnesemia, hypocalcemia, bradycardia, female sex, advanced age, poor metabolizer status at CYP2C19, concurrent use of more than one agent known to cause QT prolongation, or with higher blood concentrations of escitalopram.(2) Concurrent use of more than one drug known to cause QT prolongation or higher systemic concentrations of either QT prolonging drug are additional risk factors for torsades de pointes. Factors which may increase systemic drug concentrations include rapid infusion of an intravenous dose or impaired metabolism or elimination of the drug (e.g. coadministration with an agent which inhibits its metabolism or elimination, genetic impairment in drug metabolism or elimination, and/or renal/hepatic dysfunction).(2) Predisposing factors for serotonin-related adverse effects include use in the elderly, in patients with hepatic impairment, and in patients receiving multiple agents which increase central serotonin levels.(1,3) If concurrent therapy is warranted, consider obtaining serum calcium, magnesium, and potassium levels and monitoring ECG at baseline and at regular intervals. Correct any electrolyte abnormalities. Instruct patients to report any irregular heartbeat, dizziness, or fainting. PATIENT MANAGEMENT: Evaluate patient for other drugs, diseases and conditions which may further increase risk for QT prolongation and correct risk factors (e.g. correct hypokalemia, discontinue other QT prolonging drugs) when possible.(2,3) It would be prudent to limit the escitalopram dose to 10 mg daily in patients with QT prolonging risk factors who also receive concurrent therapy with selected CYP2C19 inhibitors.(5) Weigh the specific benefits versus risks for each patient. If concurrent therapy is warranted, patients should be monitored for signs and symptoms of serotonin syndrome. Instruct patients to report muscle twitching, tremors, shivering and stiffness, fever, heavy sweating, heart palpitations, restlessness, confusion, agitation, trouble with coordination, or severe diarrhea. DISCUSSION: A thorough QT study evaluating escitalopram 10 mg or 30 mg once daily was conducted; a change of 10 msec for upper bound of the 95% confidence level is the threshold for regulatory concern. In this study, changes to the upper bound of the 95% confidence interval were 6.4 msec and 12.6 msec for the 10 mg and supratherapeutic 30 mg dose respectively. The Cmax for 30 mg was 1.7-fold higher than the Cmax for the maximum recommended escitalopram dose of 20 mg. Systemic exposure at the 30 mg dose was similar to expected steady state concentrations in 2C19 poor metabolizers following a 20 mg escitalopram dose.(1) In an interaction study, 30 mg of omeprazole, an irreversible inhibitor of CYP2C19 was administered daily for 6 days. On day 5 a single dose of escitalopram 20 mg was also administered; the area-under-curve (AUC) of escitalopram was increased by 50%. Manufacturer prescribing information recommends a maximum citalopram dose of 20mg daily in patients receiving CYP2C19 inhibitors.(1) Inhibitors of CYP2C19 include: abrocitinib, allicin (garlic derivative), berotralstat, cannabidiol (CBD), cenobamate, cimetidine strengths > or = 200 mg, enasidenib, eslicarbazepine, esomeprazole, etravirine, fedratinib, felbamate, fluoxetine, fluvoxamine, givosiran, isoniazid, moclobemide, modafinil, obeticholic acid, omeprazole, piperine, rolapitant, stiripentol, tecovirimat, and tipranavir.(4) |
ESCITALOPRAM OXALATE, LEXAPRO |
| Oxcarbazepine/Selected UGT and Strong CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Oxcarbazepine is metabolized by CYP3A4 to the active metabolite, eslicarbazepine, which is conjugated by UDP-glucuronosyltransferase (UGT) enzymes. Strong CYP3A4 inducers and UGT inducers decrease exposure to eslicarbazepine.(3) CLINICAL EFFECTS: Concurrent use of oxcarbazepine with UGT inducers and strong CYP3A4 inducers may lead to decreased levels and effectiveness of oxcarbazepine, e.g loss of seizure control.(3) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: For patients stabilized on UGT or strong CYP3A4 inducers, the US manufacturer of extended release oxcarbazepine recommends initiating extended release oxcarbazepine at 900 mg once daily in adults and 12-15 mg/kg once daily (not to exceed 900 mg per day in the first week) in pediatric patients.(3) If a strong CYP3A4 inducer or UGT inducer is added in a patient stabilized on oxcarbazepine, the dose of oxcarbazepine may need to be increased. Onset of induction is gradual and may not be maximal for days or weeks. If a strong CYP3A4 inducer or UGT inducer is discontinued in a patient stabilized on oxcarbazepine, the concentration of oxcarbazepine will increase over 1 to 4 weeks. Monitor serum levels and adjust dosages as needed. DISCUSSION: In interaction studies, phenytoin doses of 250 mg to 500 mg daily decreased the concentration of oxcarbazepine's active metabolite (eslicarbazepine) by approximately 30%.(3) Similarly, phenobarbital doses of 100 mg to 150 mg daily decreased the mean concentration of eslicarbazepine by 25%.(3) UGT and strong CYP3A inducers linked to this monograph include: apalutamide, carbamazepine, efavirenz, encorafenib, enzalutamide, etravirine, ivosidenib, lorlatinib, lumacaftor, mitotane, rifampin, rifapentine, and St. John's wort.(1-2) |
OXCARBAZEPINE, OXCARBAZEPINE ER, OXTELLAR XR, TRILEPTAL |
| Cilostazol (Less Than or Equal To 50 mg BID)/Selected Strong & Moderate CYP2C19 Inhibitors SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong and moderate inhibitors of CYP2C19 may inhibit the metabolism of cilostazol.(1-4) CLINICAL EFFECTS: Concurrent use of strong or moderate inhibitors of CYP2C19 may result in elevated levels of 3,4-dehydro-cilostazol, a metabolite of cilostazol that is 4-7 times as active as cilostazol.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The dose of cilostazol should be limited to 50 mg twice daily in patients receiving concurrent therapy with strong and moderate inhibitors of CYP2C19.(1) The Australian manufacturer of esomeprazole states concomitant use with cilostazol is contraindicated.(5) DISCUSSION: In a study in 20 subjects examined the effects of omeprazole (40 mg daily) on a single dose of cilostazol (100 mg). Concurrent omeprazole increased the cilostazol maximum concentration (Cmax) and area-under-curve (AUC) by 18% and 26%, respectively. The Cmax and AUC of the 3,4-dehydro-cilostazol metabolite of cilostazol increased 29% and 69%, respectively. The Cmax and AUC of the OPC-13213 metabolite of cilostazol decreased by 22% and 31%, respectively.(4) |
CILOSTAZOL |
| Ubrogepant/Moderate and Weak CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate or weak CYP3A4 inducers may induce the metabolism of ubrogepant.(1) CLINICAL EFFECTS: Concurrent use of a moderate or weak CYP3A4 inducer may result in decreased levels and effectiveness of ubrogepant.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer recommends a dosage adjustment of ubrogepant when coadministered with moderate or weak CYP3A4 inducers. Initial dose of ubrogepant should be 100 mg. If a second dose is needed, the dose of ubrogepant should be 100 mg.(1) DISCUSSION: Coadministration of ubrogepant with rifampin, a strong CYP3A4 inducer, resulted in an 80% reduction in ubrogepant exposure. No dedicated drug interaction studies were conducted to assess concomitant use with moderate or weak CYP3A4 inducers. Dose adjustment for concomitant use of ubrogepant with moderate or weak CYP3A4 inducers is recommended based on a conservative prediction of 50% reduction in exposure of ubrogepant.(1) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pexidartinib, rifabutin, telotristat, thioridazine, and tovorafenib.(2,3) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, dexamethasone, dicloxacillin, echinacea, elafibranor, enasidenib, eslicarbazepine, floxacillin, garlic, genistein, ginseng, glycyrrhizin, meropenem-vaborbactam, methylprednisolone, nevirapine, omaveloxolone, oritavancin, oxcarbazepine, pioglitazone, pitolisant, relugolix, repotrectinib, rufinamide, sarilumab, sulfinpyrazone,suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vemurafenib, vinblastine, and zanubrutinib.(2,3) |
UBRELVY |
| Rolapitant/Moderate CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Rolapitant is metabolized primarily by CYP3A4. Moderate inducers of CYP3A4 may increase the metabolism and clearance of rolapitant via CYP3A4.(1) CLINICAL EFFECTS: Concurrent use with moderate inducers of CYP3A4 may result in significantly decreased levels and effectiveness of rolapitant.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The UK manufacturer of rolapitant states that rolapitant is not recommended in patients already taking moderate CYP3A4 inducers.(1) If concomitant use is warranted, monitor the patient for decreased antiemetic efficacy. When possible and clinically appropriate, consider use of an alternative antiemetic or alternatives to the moderate CYP3A4 inducer. DISCUSSION: The effect of moderate CYP3A4 inducers on rolapitant has not been studied. The UK manufacturer of rolapitant does not recommend the concurrent use of rolapitant with moderate CYP3A4 inducers. Rifampin (600 mg daily for 14 days), a strong CYP3A4 inducer, decreased the Cmax and AUC of a single dose of rolapitant (180 mg on Day 7) by 30% and 85%, respectively. The half-life of rolapitant decreased from 176 hours to 41 hours.(3) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
VARUBI |
| Artesunate/Strong UGT Inducers; Nevirapine SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Strong inducers of UDP-glucuronosyltransferase (UGT) and nevirapine may increase the metabolism of dihydroartemisinin (DHA, the active metabolite of artesunate).(1) CLINICAL EFFECTS: Concurrent use of carbamazepine, efavirenz, etravirine, fosphenytoin, nevirapine, phenobarbital, phenytoin, primidone, rifampin, or ritonavir may result in decreased levels and effectiveness of DHA.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If coadministration of strong UGT inducers or nevirapine with artesunate is necessary, monitor for possible reduced antimalarial efficacy.(1) DISCUSSION: In a study, nevirapine decreased the maximum concentration (Cmax) and area-under-curve (AUC) of DHA by 59% and 68%, respectively.(1) In a study of healthy volunteers, ritonavir (100 mg twice daily for 7 days) decreased the Cmax and AUC of DHA by 27% and 38%, respectively.(1,2) A study of healthy subjects who were coadministered lopinavir-ritonavir 400 mg-100 mg twice daily for 14 days) and artesunate-mefloquine found that artesunate Cmax and AUC decreased by 37% and 45%, respectively, compared to artesunate-mefloquine alone.(3) Agents linked to this monograph include: carbamazepine, efavirenz, etravirine, fosphenytoin, nevirapine, phenobarbital, phenytoin, primidone, rifampin, and ritonavir. |
ARTESUNATE |
| Tacrolimus/Moderate and Weak CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate or weak CYP3A4 inducers may accelerate the metabolism of tacrolimus.(1) CLINICAL EFFECTS: Concurrent use of a moderate or weak CYP3A4 inducer may result in decreased levels and effectiveness of tacrolimus.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of tacrolimus recommends monitoring tacrolimus whole blood trough concentrations and adjusting tacrolimus dose if needed. Monitor clinical response closely.(1) DISCUSSION: A 13-year-old cystic fibrosis patient with a history of liver transplant on stable doses of tacrolimus underwent 2 separate courses of nafcillin therapy (a moderate CYP3A4 inducer). During the 1st course of nafcillin, his tacrolimus levels started to fall 3 days after starting nafcillin, became undetectable at day 8, and recovered to therapeutic levels without a change in tacrolimus dose 5 days after discontinuation of nafcillin. During the 2nd course of nafcillin, tacrolimus level became undetectable 4 days after starting nafcillin and recovered 3 days after stopping nafcillin.(2) Moderate inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 50-80% and include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, modafinil, nafcillin, repotrectinib, telotristat, and tovorafenib.(3,4) Weak inducers of CYP3A4 would be expected to decrease the AUC of a sensitive 3A4 substrate by 20-50% and include: armodafinil, bexarotene, brigatinib, brivaracetam, clobazam, danshen, darolutamide, dexamethasone, dicloxacillin, echinacea, elafibranor, enasidenib, eslicarbazepine, floxacillin, garlic, genistein, ginseng, glycyrrhizin, meropenem-vaborbactam, nevirapine, oritavancin, omaveloxolone, oxcarbazepine, pioglitazone, relugolix, rufinamide, sulfinpyrazone, suzetrigine, tazemetostat, tecovirimat, terbinafine, ticlopidine, topiramate, troglitazone, vinblastine, and zanubrutinib.(3,4) |
ASTAGRAF XL, ENVARSUS XR, PROGRAF, TACROLIMUS, TACROLIMUS XL |
| Larotrectinib/Moderate CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may increase the metabolism of larotrectinib.(1) CLINICAL EFFECTS: Concurrent use of a moderate inducer of CYP3A4 may result in decreased levels and effectiveness of larotrectinib.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The manufacturer of larotrectinib states that the concurrent use of moderate CYP3A4 inducers requires a dose modification. Double the dose of larotrectinib when coadministered with moderate CYP3A4 inducers. After the moderate CYP3A4 inducer has been discontinued for 3 to 5 elimination half-lives, resume the larotrectinib dose at the dose taken prior to initiating the CYP3A4 inducer.(1) DISCUSSION: In a study, efavirenz (a moderate CYP3A4 inducer) was predicted to decrease area-under-curve (AUC) and maximum concentration (Cmax) by 72% and 60%, respectively, compared to larotrectinib administered alone.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(3-4) |
VITRAKVI |
| Sildenafil (PAH)/Strong and Moderate CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Sildenafil is metabolized by CYP3A4. Strong and moderate inducers of CYP3A4 may increase the metabolism of sildenafil.(1) CLINICAL EFFECTS: Concurrent use of a strong or moderate inducer of CYP3A4 may result in substantially decreased levels and effectiveness of sildenafil.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: Concomitant use of sildenafil with strong or moderate CYP3A4 inducers should be monitored closely. An increased dosage of sildenafil may be needed. Reduce sildenafil dose to 20 mg three times daily when discontinuing treatment with strong and moderate CYP3A4 inducers.(1) DISCUSSION: Population pharmacokinetic analysis of data from patients in clinical trials found that sildenafil clearance increased about 3-fold when coadministered with mild CYP3A4 inducers.(1) A randomized, double-blind, placebo-controlled, parallel-group study of 55 healthy volunteers found that 10 days of bosentan (125 mg twice daily), a moderate CYP3A4 inducer, decreased the maximum concentration (Cmax) and area-under-curve (AUC) of sildenafil by 55.4% and 62.6%, respectively. Sildenafil increased bosentan Cmax and AUC by 42% and 49.8%, respectively. The combination was well tolerated without serious adverse events.(2) In a study of 15 HIV-negative subjects, etravirine (800 mg twice daily for 14 days), a moderate CYP3A4 inducer, decreased the Cmax and AUC of sildenafil by 45% and 57%, respectively.(3) The authors of a review article on drug interactions in pulmonary arterial hypertension therapy state that phenytoin and rifampin (strong CYP3A4 inducers) are not recommended with sildenafil due to an expected near-complete clearance of sildenafil.(4) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort.(5,6) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat, thioridazine, and tovorafenib.(5,6) |
REVATIO, SILDENAFIL CITRATE |
| Crinecerfont/Moderate CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Moderate inducers of CYP3A4 may induce the metabolism of crinecerfont.(1) CLINICAL EFFECTS: Concurrent or recent use of moderate CYP3A4 inducers may reduce the clinical effectiveness of crinecerfont.(1) PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. PATIENT MANAGEMENT: The US manufacturer of crinecerfont states that concurrent use of moderate CYP3A4 inducers requires a dose adjustment of crinecerfont. Increase the evening dose of crinecerfont by 2-fold. Do not increase the morning dose. In adults, increase the dosage of crinecerfont to 100 mg in the morning and 200 mg in the evening. In pediatric patients 4 years and older weighing: - 10 kg to <20 kg: increase the crinecerfont dosage to 25 mg in the morning and 50 mg in the evening, - 20 kg to <55 kg: increase the crinecerfont dosage to 50 mg in the morning and 100 mg in the evening, - >=55 kg: increase the crinecerfont dosage to 100 mg in the morning and 200 mg in the evening.(1) DISCUSSION: In a study, concomitant use of rifampin (strong CYP3A4 inducer) decreased crinecerfont maximum concentration (Cmax) by 23% and area-under-curve (AUC) by 62%.(1) Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2,3) |
CRENESSITY |
| Apixaban; Rivaroxaban/Strong & Moderate CYP3A4 Inducers SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Apixaban and rivaroxaban are both substrates of CYP3A4 and P-glycoprotein (P-gp). Apixaban is about 20% metabolized and rivaroxaban is about 18% metabolized, mainly by CYP3A4.(1-8) Strong and moderate CYP3A4 inducers may induce the metabolism of apixaban and rivaroxaban by CYP3A4. CLINICAL EFFECTS: Concurrent or recent use of a CYP3A4 inducer may result in decreased levels and effectiveness of apixaban(1-4) or rivaroxaban,(5-8) especially in the setting of concurrent therapy with an agent that induces P-gp. PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks. Drug-associated risk factors include concurrent use of P-gp inducers. PATIENT MANAGEMENT: The US, Australian, Canadian, and UK manufacturers of apixaban provide recommendations regarding concurrent use with strong inducers of both CYP3A4 and P-gp, but do not provide guidance for concurrent use with agents that induce CYP3A4 alone.(1) The US manufacturer of rivaroxaban provides recommendations regarding concurrent use with strong inducers of both CYP3A4 and P-gp, but does not provide guidance for concurrent use with agents that induce CYP3A4 alone.(5) The Australian manufacturer of rivaroxaban states that concurrent use of strong CYP3A4 inducers should be approached with caution.(6) The Canadian and UK labels for rivaroxaban state that concurrent use of strong CYP3A4 inducers should be avoided.(7-8) When considering concurrent therapy with a strong or moderate CYP3A4 inducer with either apixaban or rivaroxaban, evaluate the patient's other concurrent therapy for CYP3A4 and P-gp effects. In patients who are taking strong CYP3A4 inducers and are also on concurrent P-gp inducers, consider the manufacturer recommendations for use with dual CYP3A4 and P-gp inducers. The US manufacturers of apixaban and rivaroxaban both state to avoid the concurrent use of agents that are combined P-gp and strong CYP3A4 inducers in patients receiving apixaban or rivaroxaban.(1-8) In patients who are taking moderate CYP3A4 inducers and are also on concurrent P-gp inducers, It may be prudent to consider alternative therapy or monitor the patient closely. DISCUSSION: The concurrent use of apixaban or rivaroxaban with strong CYP3A4 inducers that are not also P-gp inducers has not been studied. Apixaban and rivaroxaban are metabolized primarily by CYP3A4. Strong CYP3A4 inducers may decrease the levels and effectiveness of apixaban and rivaroxaban. The US manufacturer of apixaban states that apixaban dose reduction is recommended when apixaban exposure increases by more than 50%, while efficacy is maintained when exposure is 25% lower. Therefore, no dose adjustment of apixaban is recommended for drug interactions that affect apixaban exposure by 75% to 150%.(9) An article evaluating the clinical significance of efflux transporters like P-gp and BCRP in apixaban exposure analyzed pharmacokinetic data from drug-drug interaction studies and concluded that all apixaban interactions can be explained by inhibition of intestinal CYP3A4. The authors explain that apixaban is a highly permeable and soluble compound, so its ability to undergo passive diffusion renders the role of membrane transporters irrelevant, as evidenced by a lack of change in apixaban absorption rate in the presence of drugs known to inhibit P-gp and BCRP.(10) Strong CYP3A4 inducers linked to this monograph include: encorafenib, ivosidenib, lumacaftor, and mitotane.(11,12) Moderate CYP3A4 inducers linked to this monograph include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, elagolix, etravirine, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(11,12) |
ELIQUIS, RIVAROXABAN, XARELTO |
The following contraindication information is available for INTELENCE (etravirine):
Drug contraindication overview.
None.
None.
There are 1 contraindications.
Absolute contraindication.
| Contraindication List |
|---|
| Lactation |
There are 0 severe contraindications.
There are 0 moderate contraindications.
The following adverse reaction information is available for INTELENCE (etravirine):
Adverse reaction overview.
The most common adverse effects (>=2%) of moderate to severe intensity occurring at a higher rate than placebo in adults are rash and peripheral neuropathy. The most common adverse effects (>=2%) of pediatric patients are rash and diarrhea.
The most common adverse effects (>=2%) of moderate to severe intensity occurring at a higher rate than placebo in adults are rash and peripheral neuropathy. The most common adverse effects (>=2%) of pediatric patients are rash and diarrhea.
There are 28 severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
| None. |
Increased alanine transaminase Increased aspartate transaminase |
| Rare/Very Rare |
|---|
|
Acute myocardial infarction Angina Angioedema Atrial fibrillation Bloody vomit Bronchospastic pulmonary disease Diabetes mellitus DRESS syndrome Drug-induced hepatitis Dyspnea Erythema multiforme Graves' disease Guillain-barre syndrome Hemolytic anemia Hemorrhagic stroke Hepatic failure Hepatomegaly Hypersensitivity drug reaction Pancreatitis Polymyositis Renal failure Rhabdomyolysis Seizure disorder Steatosis of liver Stevens-johnson syndrome Toxic epidermal necrolysis |
There are 36 less severe adverse reactions.
| More Frequent | Less Frequent |
|---|---|
|
Diarrhea Peripheral neuropathy Skin rash |
Hypertriglyceridemia |
| Rare/Very Rare |
|---|
|
Abdominal distension Acute cognitive impairment Anorexia Blurred vision Constipation Disturbance of attention Dream disorder Drowsy Dry skin Eosinophilia Flatulence Gastritis Gastroesophageal reflux disease Gynecomastia Hyperhidrosis Hypersomnia Hypoesthesia Lipodystrophy associated with human immunodeficiency virus infection Memory impairment Mixed hyperlipidemia Myopathy Nervousness Night sweats Nightmares Sleep disorder Stomatitis Symptoms of anxiety Syncope Tremor Vertigo Vomiting Xerostomia |
The following precautions are available for INTELENCE (etravirine):
Safety and efficacy of etravirine have not been established in pediatric patients younger than 2 years of age. Five HIV-infected subjects from 1 year to less than 2 years of age were enrolled in the TMC125-C234/IMPAACT P1090 study. Etravirine exposure in these pediatric subjects was lower than that reported in HIV-infected adults.
Safety, efficacy, and pharmacokinetics of etravirine have been evaluated in antiretroviral-experienced pediatric patients 2 years to less than 18 years of age weighing at least 10 kg. Adverse effects reported in pediatric patients in a clinical study after 24 weeks of etravirine therapy were similar to those reported in adults (e.g., rash, diarrhea), although rash was reported more frequently in pediatric patients than in adults. Postmarketing cases of Stevens-Johnson syndrome have been reported in pediatric patients treated with etravirine.
Contraindicated
Severe Precaution
Management or Monitoring Precaution
Safety, efficacy, and pharmacokinetics of etravirine have been evaluated in antiretroviral-experienced pediatric patients 2 years to less than 18 years of age weighing at least 10 kg. Adverse effects reported in pediatric patients in a clinical study after 24 weeks of etravirine therapy were similar to those reported in adults (e.g., rash, diarrhea), although rash was reported more frequently in pediatric patients than in adults. Postmarketing cases of Stevens-Johnson syndrome have been reported in pediatric patients treated with etravirine.
Contraindicated
| None |
Severe Precaution
| None |
Management or Monitoring Precaution
| None |
The Antiretroviral Pregnancy Registry (APR) monitors pregnancy outcomes in women exposed to etravirine during pregnancy. Clinicians are encouraged to register patients in the APR by calling 800-258-4263 or visiting https://www.apregistry.com/.
Etravirine has been evaluated in a limited number of women during pregnancy. In animal studies, etravirine was not associated with adverse developmental effects at exposures equivalent to those at the maximum recommended human dose. Based on prospective reports from the APR of 116 live births following exposure to etravirine-containing antiretroviral regimens during pregnancy, the number of birth defects in live births for etravirine was 1 out of 66 with first trimester exposure and 0 out of 38 with second/third trimester exposure.
Etravirine has been evaluated in a limited number of women during pregnancy. In animal studies, etravirine was not associated with adverse developmental effects at exposures equivalent to those at the maximum recommended human dose. Based on prospective reports from the APR of 116 live births following exposure to etravirine-containing antiretroviral regimens during pregnancy, the number of birth defects in live births for etravirine was 1 out of 66 with first trimester exposure and 0 out of 38 with second/third trimester exposure.
Based on limited data, etravirine has been shown to be present in human breast milk. There are no data on the effects on the breastfed infant or the effects of etravirine on milk production. The HHS perinatal HIV transmission guideline provides updated recommendations on infant feeding.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
The guideline states that patients with HIV should receive evidence-based, patient-centered counseling to support shared decision making about infant feeding. During counseling, patients should be informed that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates the risk of postnatal HIV transmission to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces the risk of breastfeeding HIV transmission to <1%, but does not completely eliminate the risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.
Insufficient experience in patients 65 years of age and older to determine whether they respond differently than younger adults. Population pharmacokinetic analysis in HIV-infected subjects showed that etravirine pharmacokinetics are not considerably different within the age range (18-77 years) evaluated.
The following prioritized warning is available for INTELENCE (etravirine):
No warning message for this drug.
No warning message for this drug.
The following icd codes are available for INTELENCE (etravirine)'s list of indications:
| HIV infection | |
| B20 | Human immunodeficiency virus [HIv] disease |
| B97.35 | Human immunodeficiency virus, type 2 [HIV 2] as the cause of diseases classified elsewhere |
| O98.7 | Human immunodeficiency virus [HIv] disease complicating pregnancy, childbirth and the puerperium |
| O98.71 | Human immunodeficiency virus [HIv] disease complicating pregnancy |
| O98.711 | Human immunodeficiency virus [HIv] disease complicating pregnancy, first trimester |
| O98.712 | Human immunodeficiency virus [HIv] disease complicating pregnancy, second trimester |
| O98.713 | Human immunodeficiency virus [HIv] disease complicating pregnancy, third trimester |
| O98.719 | Human immunodeficiency virus [HIv] disease complicating pregnancy, unspecified trimester |
| O98.72 | Human immunodeficiency virus [HIv] disease complicating childbirth |
| O98.73 | Human immunodeficiency virus [HIv] disease complicating the puerperium |
| Z21 | Asymptomatic human immunodeficiency virus [HIv] infection status |
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