CAMZYOS

Cardiac Myosin Inhibitors

Oral Administration

Swallow capsule whole. Do not break, open, or chew the capsules.
May administer without regard to food.
Missed dose: Administer a missed dose as soon as possible and the next scheduled dose at the usual time the following day. Exact timing of dosing during the day is not essential, but do not administer 2 doses on the same day.

Severe

heart failure / Delayed / Incidence not known

Mild

dizziness / Early / 27.0-27.0
syncope / Early / 6.0-6.0

Atrial fibrillation, heart failure, infection

Assess the patient's clinical status and left ventricular ejection fraction (LVEF) prior to and regularly during mavacamten therapy and adjust the mavacamten dose accordingly. Regular LVEF and Valsalva left ventricular outflow tract (LVOT) gradient assessment is required for careful titration to achieve an appropriate target Valsalva LVOT gradient, while maintaining LVEF of 50% or more and avoiding heart failure symptoms. Initiation or up-titration of mavacamten in patients with LVEF less than 55% is not recommended. Interrupt treatment if LVEF is less than 50% or if the patient experiences heart failure symptoms or worsening clinical status while taking mavacamten. Delay dose increases when there is intercurrent illness (e.g., serious infection) or arrhythmia (e.g., atrial fibrillation or other uncontrolled tachyarrhythmia) that may impair systolic function. Consider interruption of mavacamten therapy in patients with intercurrent illness. Mavacamten reduces systolic contraction and can cause heart failure or totally block ventricular function. Patients who experience a serious intercurrent illness or arrhythmia are at greater risk of developing systolic dysfunction and heart failure.

CAMZYOS

Rx

Oral cardiac myosin inhibitor
Used for the treatment of symptomatic New York Heart Association (NYHA) class II to III obstructive hypertrophic cardiomyopathy
Can cause heart failure or totally block ventricular function

For the treatment of symptomatic New York Heart Association (NYHA) class II to III obstructive hypertrophic cardiomyopathy. Oral dosage Adults

5 mg PO once daily, initially. Adjust dose every 4 weeks during initiation phase and every 12 weeks during maintenance phase as needed based on patient clinical status and echocardiographic assessment of patient response. Dose range: 2.5 to 15 mg/day. Interrupt treatment if left ventricular ejection fraction (LVEF) is less than 50% at any time. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions.

Hepatic Impairment

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

Renal Impairment

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

Abacavir; Dolutegravir; Lamivudine: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with mavacamten. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Abemaciclib: (Major) Avoid coadministration of mavacamten with abemaciclib due to decreased exposure to abemaciclib and its active metabolites, which may lead to reduced efficacy. Abemaciclib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with other moderate CYP3A inducers is predicted to decrease the relative potency adjusted unbound AUC of abemaciclib plus its active metabolites (M2, M18, and M20) by 29% to 53%.
Acebutolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of dihydrocodeine as needed. If mavacamten is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Mavacamten is a moderate inducer of CYP3A, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with mavacamten can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Acetaminophen; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If mavacamten is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use can decrease hydrocodone levels.
Acetaminophen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of oxycodone as needed. If mavacamten is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Adagrasib: (Contraindicated) Mavacamten is contraindicated for use with adagrasib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Alfentanil: (Moderate) Consider an increased dose of alfentanil and monitor for evidence of opioid withdrawal if coadministration with mavacamten is necessary. If mavacamten is discontinued, consider reducing the alfentanil dosage and monitor for evidence of respiratory depression. Coadministration of a moderate CYP3A inducer like mavacamten with alfentanil, a CYP3A substrate, may decrease exposure to alfentanil resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to alfentanil. Alfentanil plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Amiodarone: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting amiodarone therapy. Avoid initiation of amiodarone in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable amiodarone therapy. Expect additive negative inotropic effects during concomitant use of mavacamten and amiodarone. If concomitant therapy with amiodarone is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Monitor for decreased efficacy of amiodarone if coadministration with mavacamten is necessary. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions, and may decrease plasma concentrations of amiodarone. Mavacamten is a substrate and moderate inducer of CYP3A and amiodarone is a substrate and moderate inhibitor of CYP3A. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Atorvastatin: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Benazepril: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Celecoxib: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Olmesartan: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Valsartan: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Amobarbital: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Mavacamten is contraindicated for use with clarithromycin due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease efficacy of clarithromycin. Mavacamten is a substrate and moderate inducer of CYP3A and clarithromycin is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. There have been spontaneous or published reports of CYP3A-based interactions of clarithromycin with another CYP3A inducer. (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting omeprazole therapy. Avoid initiation of omeprazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable omeprazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and omeprazole is a weak CYP2C19 inhibitor. Concomitant use of mavacamten 10 mg with omeprazole 20 mg once daily increased overall mavacamten exposure by 48% with no effect on peak exposure in healthy CYP2C19 normal and rapid metabolizers.
Apalutamide: (Contraindicated) Mavacamten is contraindicated for use with apalutamide due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and apalutamide is a strong CYP2C19 and CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use with a strong CYP2C19 or CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Aprepitant, Fosaprepitant: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting aprepitant/fosaprepitant therapy. Avoid initiation of aprepitant/fosaprepitant in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable aprepitant/fosaprepitant therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and aprepitant/fosaprepitant is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Armodafinil: (Contraindicated) Mavacamten is contraindicated for use with armodafinil due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and armodafinil is a moderate CYP2C19 inhibitor.
Aspirin, ASA; Butalbital; Caffeine: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Aspirin, ASA; Carisoprodol: (Moderate) Monitor for an altered clinical response to carisoprodol if coadministration with mavacamten is necessary. Carisoprodol is metabolized by CYP2C19 to form meprobamate; mavacamten is a moderate CYP2C19 inducer. Coadministration could decrease exposure to carisoprodol and increase exposure to meprobamate. The full pharmacological impact of these potential alterations of exposure in terms of either efficacy or safety of carisoprodol is unknown.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Monitor for an altered clinical response to carisoprodol if coadministration with mavacamten is necessary. Carisoprodol is metabolized by CYP2C19 to form meprobamate; mavacamten is a moderate CYP2C19 inducer. Coadministration could decrease exposure to carisoprodol and increase exposure to meprobamate. The full pharmacological impact of these potential alterations of exposure in terms of either efficacy or safety of carisoprodol is unknown. (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Aspirin, ASA; Omeprazole: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting omeprazole therapy. Avoid initiation of omeprazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable omeprazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and omeprazole is a weak CYP2C19 inhibitor. Concomitant use of mavacamten 10 mg with omeprazole 20 mg once daily increased overall mavacamten exposure by 48% with no effect on peak exposure in healthy CYP2C19 normal and rapid metabolizers.
Aspirin, ASA; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of oxycodone as needed. If mavacamten is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Atazanavir: (Contraindicated) Mavacamten is contraindicated for use with atazanavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of atazanavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and atazanavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Atazanavir; Cobicistat: (Contraindicated) Mavacamten is contraindicated for use with atazanavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of atazanavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and atazanavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. (Contraindicated) Mavacamten is contraindicated for use with cobicistat due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of cobicistat leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and cobicistat is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Atenolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Atenolol; Chlorthalidone: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Atogepant: (Major) Avoid use of atogepant and mavacamten when atogepant is used for chronic migraine. Use an atogepant dose of 30 or 60 mg PO once daily for episodic migraine if coadministered with mavacamten. Concurrent use may decrease atogepant exposure and reduce efficacy. Atogepant is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Avacopan: (Major) Avoid concomitant use of avacopan and mavacamten due to the risk of decreased avacopan exposure which may reduce its efficacy. Avacopan is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Avanafil: (Major) Coadministration of avanafil with mavacamten is not recommended by the manufacturer of avanafil due to the potential for decreased avanafil efficacy. Avanafil is a CYP3A substrate and mavacamten is a CYP3A inducer. Although the potential effect of CYP inducers on the pharmacokinetics of avanafil has not been evaluated, plasma concentrations may decrease.
Avapritinib: (Major) Avoid coadministration of avapritinib with mavacamten due to the risk of decreased avapritinib efficacy. Avapritinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer is predicted to decrease the overall exposure and peak of avapritinib by 62% and 55%, respectively.
Avatrombopag: (Major) In patients with chronic immune thrombocytopenia (ITP), increase the starting dose of avatrombopag to 40 mg PO once daily when used concomitantly with mavacamten. In patients starting mavacamten while receiving avatrombopag, monitor platelet counts and adjust the avatrombopag dose as necessary. Dosage adjustments are not required for patients with chronic liver disease. Avatrombopag is a CYP2C9 and CYP3A substrate, and dual moderate or strong inducers such as mavacamten decrease avatrombopag exposure, which may reduce efficacy.
Axitinib: (Major) Avoid coadministration of axitinib with mavacamten if possible due to the risk of decreased efficacy of axitinib. Selection of a concomitant medication with no or minimal CYP3A induction potential is recommended. Axitinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Barbiturates: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Bedaquiline: (Major) Avoid coadministration of mavacamten with bedaquiline due to decreased plasma concentrations of bedaquiline which may reduce its efficacy. Bedaquiline is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased bedaquiline exposure by approximately 20%. The overall exposure and peak of the primary metabolite of bedaquiline (M2) were increased by 70% and 80%, respectively.
Benzhydrocodone; Acetaminophen: (Moderate) Monitor for reduced efficacy of benzhydrocodone and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of benzhydrocodone as needed. If mavacamten is discontinued, consider a dose reduction of benzhydrocodone and frequently monitor for signs of respiratory depression and sedation. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease hydrocodone concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Berotralstat: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting berotralstat therapy. Avoid initiation of berotralstat in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable berotralstat therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and berotralstat is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Beta-adrenergic blockers: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Betaxolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Bexarotene: (Contraindicated) Mavacamten is contraindicated for use with bexarotene due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and bexarotene is a moderate CYP3A inducer.
Bisoprolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Bortezomib: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting bortezomib therapy. Avoid initiation of bortezomib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable bortezomib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and bortezomib is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Bosentan: (Contraindicated) Mavacamten is contraindicated for use with bosentan due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and bosentan is a moderate CYP3A inducer.
Brigatinib: (Major) Avoid coadministration of brigatinib with mavacamten due to decreased plasma exposure to brigatinib which may result in decreased efficacy. If concomitant use is unavoidable, after 7 days of concomitant treatment with mavacamten, increase the dose of brigatinib as tolerated in 30 mg increments to a maximum of twice the original brigatinib dose. After discontinuation of mavacamten, resume the brigatinib dose that was tolerated prior to initiation of mavacamten. Brigatinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease the AUC of brigatinib by approximately 50%.
Brimonidine; Timolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and mavacamten are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A; mavacamten is a moderate inducer of CYP3A.
Buprenorphine: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with mavacamten is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If mavacamten is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A substrate and mavacamten is a CYP3A inducer.
Buprenorphine; Naloxone: (Moderate) Monitor for decreased efficacy of buprenorphine, and potentially the onset of a withdrawal syndrome in patients who have developed physical dependence to buprenorphine, if coadministration with mavacamten is necessary; consider increasing the dose of buprenorphine until stable drug effects are achieved. If mavacamten is discontinued, consider a buprenorphine dose reduction and monitor for signs of respiratory depression. Buprenorphine is a CYP3A substrate and mavacamten is a CYP3A inducer.
Buspirone: (Moderate) Monitor for decreased efficacy of buspirone if mavacamten is added to a patient on a stable dosage of buspirone; a dose increase of buspirone may be needed to maintain anxiolytic activity. Buspirone is a sensitive CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Butabarbital: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Butalbital; Acetaminophen: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Butalbital; Acetaminophen; Caffeine: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Butalbital; Acetaminophen; Caffeine; Codeine: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively. (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Butalbital; Aspirin; Caffeine; Codeine: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively. (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Cabotegravir; Rilpivirine: (Moderate) Coadministration of rilpivirine with mavacamten may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Capmatinib: (Major) Avoid coadministration of capmatinib and mavacamten due to the risk of decreased capmatinib exposure which may reduce its efficacy. Capmatinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased capmatinib exposure by 44%.
Carbamazepine: (Contraindicated) Mavacamten is contraindicated for use with carbamazepine due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure and may decrease carbamazepine concentrations. Mavacamten is a CYP2C19 substrate and substrate and inducer of CYP3A and carbamazepine is a moderate inducer of CYP2C19 and substrate and strong inducer of CYP3A. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Cariprazine: (Major) Coadministration of cariprazine with mavacamten is not recommended as the net effect of CYP3A induction on cariprazine and its metabolites is unclear. Cariprazine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration of cariprazine with CYP3A inducers has not been evaluated.
Carisoprodol: (Moderate) Monitor for an altered clinical response to carisoprodol if coadministration with mavacamten is necessary. Carisoprodol is metabolized by CYP2C19 to form meprobamate; mavacamten is a moderate CYP2C19 inducer. Coadministration could decrease exposure to carisoprodol and increase exposure to meprobamate. The full pharmacological impact of these potential alterations of exposure in terms of either efficacy or safety of carisoprodol is unknown.
Carteolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Carvedilol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Celecoxib; Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of tramadol as needed. If mavacamten is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Cenobamate: (Contraindicated) Mavacamten is contraindicated for use with cenobamate due to risk of heart failure due to systolic dysfunction and risk for reduced mavacamten efficacy. Concomitant use may increase or decrease mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and cenobamate is a moderate CYP2C19 inhibitor and moderate CYP3A inducer.
Ceritinib: (Contraindicated) Mavacamten is contraindicated for use with ceritinib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and ceritinib is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Chloramphenicol: (Contraindicated) Mavacamten is contraindicated for use with chloramphenicol due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and chloramphenicol is a moderate CYP2C19 inhibitor and strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Chlorpheniramine; Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Monitor for reduced efficacy of dihydrocodeine and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of dihydrocodeine as needed. If mavacamten is discontinued, consider a dose reduction of dihydrocodeine and frequently monitor for signs of respiratory depression and sedation. Mavacamten is a moderate inducer of CYP3A, an isoenzyme partially responsible for the metabolism of dihydrocodeine. Concomitant use of dihydrocodeine with mavacamten can decrease dihydrocodeine levels, resulting in less metabolism by CYP2D6 and decreased dihydromorphine concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Chlorpheniramine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If mavacamten is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use can decrease hydrocodone levels.
Cimetidine: (Contraindicated) Mavacamten is contraindicated for use with cimetidine due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and cimetidine is a moderate CYP2C19 inhibitor.
Ciprofloxacin: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting ciprofloxacin therapy. Avoid initiation of ciprofloxacin in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable ciprofloxacin therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and ciprofloxacin is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Clarithromycin: (Contraindicated) Mavacamten is contraindicated for use with clarithromycin due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease efficacy of clarithromycin. Mavacamten is a substrate and moderate inducer of CYP3A and clarithromycin is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. There have been spontaneous or published reports of CYP3A-based interactions of clarithromycin with another CYP3A inducer.
Clozapine: (Moderate) Monitor for loss of clozapine effectiveness if coadministered with mavacamten. Consideration should be given to increasing the clozapine dose if necessary. When mavacamten is discontinued, reduce the clozapine dose based on clinical response. Mavacamten is a moderate inducer of CYP3A, one of the isoenzymes responsible for the metabolism of clozapine.
Cobicistat: (Contraindicated) Mavacamten is contraindicated for use with cobicistat due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of cobicistat leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and cobicistat is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Cobimetinib: (Major) Avoid coadministration of cobimetinib with mavacamten as concurrent use may decrease cobimetinib exposure, which may reduce its efficacy. Cobimetinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer.
Codeine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Guaifenesin: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Phenylephrine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Codeine; Promethazine: (Moderate) Monitor for reduced efficacy of codeine and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of codeine as needed. It is recommended to avoid this combination when codeine is being used for cough. If mavacamten is discontinued, consider a dose reduction of codeine and frequently monitor for signs of respiratory depression and sedation. Codeine is primarily metabolized by CYP2D6 to morphine, and by CYP3A to norcodeine; norcodeine does not have analgesic properties. Mavacamten is a moderate CYP3A inducer. Concomitant use with mavacamten can increase norcodeine levels via increased CYP3A metabolism, resulting in decreased metabolism via CYP2D6 resulting in lower morphine levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Conivaptan: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting conivaptan therapy. Avoid initiation of conivaptan in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable conivaptan therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and conivaptan is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Conjugated Estrogens: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Conjugated Estrogens; Bazedoxifene: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Conjugated Estrogens; Medroxyprogesterone: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Crizotinib: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting crizotinib therapy. Avoid initiation of crizotinib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable crizotinib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and crizotinib is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Cyclosporine: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting cyclosporine therapy. Avoid initiation of cyclosporine in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable cyclosporine therapy. Closely monitor cyclosporine concentrations and adjust the dose of cyclosporine as appropriate if coadministration with mavacamten is necessary. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions, and may decrease cyclosporine exposure resulting in decreased efficacy. Mavacamten is a substrate and moderate inducer of CYP3A and cyclosporine is a substrate and moderate inhibitor of CYP3A; it has a narrow therapeutic index. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Dabrafenib: (Contraindicated) Mavacamten is contraindicated for use with dabrafenib due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and dabrafenib is a moderate CYP3A inducer.
Daclatasvir: (Major) Increase the dose of daclatasvir to 90 mg PO once daily if coadministered with mavacamten due to decreased daclatasvir exposure resulting in potential loss of virologic control. Daclatasvir is a CYP3A substrate; mavacamten is a moderate CYP3A inducer. Coadministration of a moderate CYP3A inducer reduced the daclatasvir AUC by 63%.
Danazol: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting danazol therapy. Avoid initiation of danazol in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable danazol therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and danazol is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Dapsone: (Moderate) Closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia if coadministration with mavacamten is necessary. Dapsone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration may decrease plasma concentrations of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis).
Daridorexant: (Major) Avoid concomitant use of daridorexant and mavacamten. Coadministration may decrease daridorexant exposure which may reduce its efficacy. Daridorexant is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use of another moderate CYP3A inducer decreased daridorexant overall exposure by over 50%.
Darifenacin: (Moderate) Monitor for decreased efficacy of darifenacin if coadministration with mavacamten is necessary; coadministration may result in decreased plasma concentrations of darifenacin. Darifenacin is a CYP3A substrate and mavacamten is a moderate CYP3A inducer; coadministration may result in decreased plasma concentrations of darifenacin.
Darunavir: (Contraindicated) Mavacamten is contraindicated for use with darunavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of darunavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and darunavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Darunavir; Cobicistat: (Contraindicated) Mavacamten is contraindicated for use with cobicistat due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of cobicistat leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and cobicistat is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. (Contraindicated) Mavacamten is contraindicated for use with darunavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of darunavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and darunavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Contraindicated) Mavacamten is contraindicated for use with cobicistat due to risk of hear

t failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of cobicistat leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and cobicistat is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. (Contraindicated) Mavacamten is contraindicated for use with darunavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of darunavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and darunavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Deflazacort: (Major) Avoid concomitant use of deflazacort and mavacamten. Concurrent use may significantly decrease concentrations of 21-desDFZ , the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A substrate; mavacamten is a moderate CYP3A inducer.
Delavirdine: (Contraindicated) Mavacamten is contraindicated for use with delavirdine due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of delavirdine leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a CYP2C19 substrate and substrate and moderate inducer of CYP3A and delavirdine is a moderate CYP2C19 inhibitor and substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. Coadministration of delavirdine with another moderate CYP3A inducer decreased delavirdine exposure by 82%.
Desogestrel; Ethinyl Estradiol: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Dextromethorphan; Quinidine: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and quinidine. If concomitant therapy with quinidine is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Diazepam: (Moderate) Monitor patients for decreased efficacy of diazepam if coadministration with mavacamten is necessary. Concurrent use may decrease diazepam exposure. Diazepam is a CYP2C19 and CYP3A substrate and mavacamten is a CYP2C19 and CYP3A inducer.
Dienogest; Estradiol valerate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Diethylstilbestrol, DES: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Diltiazem: (Major) Avoid coadministration of diltiazem and mavacamten if possible due to decreased plasma concentrations of diltiazem; if unavoidable, monitor blood pressure and heart rate and adjust the diltiazem dose based on clinical response. Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting diltiazem therapy. Avoid initiation of diltiazem in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable diltiazem therapy. Expect additive negative inotropic effects during concomitant use of mavacamten and diltiazem. If concomitant therapy with diltiazem is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten with diltiazem plus a beta-blocker due to association with left ventricular systolic dysfunction and heart failure symptoms. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a substrate and moderate inducer of CYP3A and diltiazem is a substrate and moderate inhibitor of CYP3A. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of mavacamten with diltiazem in CYP2C19 poor metabolizers is predicted to increase mavacamten exposure up to 55%. Coadministration with another moderate CYP3A inducer decreased diltiazem exposure by 69% and decreased exposure to desacetyldiltiazem by 75%.
Disopyramide: (Major) Avoid concomitant use of mavacamten and disopyramide. This medication combination may increase the risk of left ventricular systolic dysfunction and heart failure symptoms. If concomitant therapy with disopyramide is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Dolutegravir: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with mavacamten. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Dolutegravir; Lamivudine: (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with mavacamten. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Dolutegravir; Rilpivirine: (Moderate) Coadministration of rilpivirine with mavacamten may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. (Moderate) Monitor for decreased efficacy of dolutegravir if coadministered with mavacamten. Concurrent use may decrease the plasma concentrations of dolutegravir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Dolutegravir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Doravirine: (Moderate) Concurrent administration of doravirine and mavacamten may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; mavacamten is a moderate CYP3A inducer.
Doravirine; Lamivudine; Tenofovir disoproxil fumarate: (Moderate) Concurrent administration of doravirine and mavacamten may result in decreased doravirine exposure, resulting in potential loss of virologic control. Doravirine is a CYP3A substrate; mavacamten is a moderate CYP3A inducer.
Dorzolamide; Timolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Doxorubicin Liposomal: (Major) Avoid coadministration of doxorubicin with mavacamten due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Inducers of CYP3A may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
Doxorubicin: (Major) Avoid coadministration of doxorubicin with mavacamten due to decreased doxorubicin plasma concentrations. Doxorubicin is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Inducers of CYP3A may decrease the concentration of doxorubicin and compromise the efficacy of chemotherapy.
Dronabinol: (Moderate) Monitor for a decrease in dronabinol efficacy if coadministration with mavacamten is necessary. Coadministration may decrease the exposure of dronabinol. Dronabinol is a CYP2C9 and CYP3A4 substrate; mavacamten is a moderate CYP2C9 and CYP3A inducer.
Dronedarone: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting dronedarone therapy. Avoid initiation of dronedarone in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable dronedarone therapy. Expect additive negative inotropic effects during concomitant use of mavacamten and dronedarone. If concomitant therapy with dronedarone is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and dronedarone is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Drospirenone: (Major) Patients taking both drospirenone and mavacamten should report breakthrough vaginal bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. For patients on hormone replacement treatments (HRT) with drospirenone, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Drospirenone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Drospirenone; Estetrol: (Major) Patients taking both drospirenone and mavacamten should report breakthrough vaginal bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. For patients on hormone replacement treatments (HRT) with drospirenone, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Drospirenone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Drospirenone; Estradiol: (Major) Patients taking both drospirenone and mavacamten should report breakthrough vaginal bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. For patients on hormone replacement treatments (HRT) with drospirenone, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Drospirenone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Drospirenone; Ethinyl Estradiol: (Major) Patients taking both drospirenone and mavacamten should report breakthrough vaginal bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. For patients on hormone replacement treatments (HRT) with drospirenone, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Drospirenone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Drospirenone; Ethinyl Estradiol; Levomefolate: (Major) Patients taking both drospirenone and mavacamten should report breakthrough vaginal bleeding to their prescribers. An alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. For patients on hormone replacement treatments (HRT) with drospirenone, monitor for altered clinical response, such as increased hot flashes, vaginal dryness, changes in withdrawal bleeding, or other signs of decreased hormonal efficacy. Drospirenone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Duvelisib: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting duvelisib therapy. Avoid initiation of duvelisib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable duvelisib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and duvelisib is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Efavirenz: (Contraindicated) Mavacamten is contraindicated for use with efavirenz due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Mavacamten is contraindicated for use with efavirenz due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Contraindicated) Mavacamten is contraindicated for use with efavirenz due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and efavirenz is a moderate CYP3A inducer.
Elacestrant: (Major) Avoid concurrent use of elacestrant and mavacamten due to the risk of decreased elacestrant exposure which may reduce its efficacy. Elacestrant is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced elacestrant overall exposure by 55% to 73%.
Elagolix: (Contraindicated) Mavacamten is contraindicated for use with elagolix due to risk for reduced mavacamten efficacy. There is also risk for increased adverse reactions due to mavacamten. Concomitant use may increase or decrease mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and elagolix is a weak CYP2C19 inhibitor and moderate CYP3A inducer. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall exposure by 48%.
Elagolix; Estradiol; Norethindrone acetate: (Contraindicated) Mavacamten is contraindicated for use with elagolix due to risk for reduced mavacamten efficacy. There is also risk for increased adverse reactions due to mavacamten. Concomitant use may increase or decrease mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and elagolix is a weak CYP2C19 inhibitor and moderate CYP3A inducer. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall exposure by 48%. (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Elbasvir; Grazoprevir: (Major) Coadministration of elbasvir with mavacamten is not recommended due to decreased exposure of elbasvir, resulting in decreased virologic response. Elbasvir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. (Major) Concomitant use of grazoprevir and mavacamten is not recommended due to decreased exposure of grazoprevir, resulting in decreased virologic response. Grazoprevir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Contraindicated) Mavacamten is contraindicated for use with cobicistat due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of cobicistat leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and cobicistat is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. (Moderate) Coadministration of elvitegravir with mavacamten may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Contraindicated) Mavacamten is contraindicated for use with cobicistat due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease the plasma concentrations of cobicistat leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and cobicistat is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. (Moderate) Coadministration of elvitegravir with mavacamten may result in significant decreases in the plasma concentrations of elvitegravir, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Elvitegravir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Coadministration of rilpivirine with mavacamten may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Coadministration of rilpivirine with mavacamten may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Encorafenib: (Major) Avoid coadministration of encorafenib and mavacamten due to decreased encorafenib exposure and potential loss of efficacy. Encorafenib is a CYP3A substrate; mavacamten is a moderate CYP3A inducer. Coadministration with CYP3A inducers has not been studied with encorafenib; however, in clinical trials, steady-state encorafenib exposures were lower than encorafenib exposures after the first dose, suggesting CYP3A auto-induction.
Entrectinib: (Major) Avoid coadministration of entrectinib with mavacamten due to decreased entrectinib exposure and risk of decreased efficacy. Entrectinib is a CYP3A substrate; mavacamten is a moderate CYP3A inducer. Coadministration of a moderate CYP3A inducer is predicted to reduce the entrectinib overall exposure by 56%.
Enzalutamide: (Contraindicated) Mavacamten is contraindicated for use with enzalutamide due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and enzalutamide is a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Erdafitinib: (Major) If coadministration of erdafitinib and mavacamten is necessary at the initiation of erdafitinib therapy, administer the dose of erdafitinib as recommended (8 mg once daily with potential to increase the dose to 9 mg on days 14 to 21 based on phosphate levels and tolerability). If mavacamten must be added to erdafitinib therapy after the initial dose increase period (days 14 to 21), increase the dose of erdafitinib up to 9 mg. If mavacamten is discontinued, continue erdafitinib at the same dose in the absence of drug-related toxicity. Erdafitinib is a CYP2C9 and CYP3A substrate and mavacamten is a moderate CYP2C9 and CYP3A inducer.
Erlotinib: (Major) Avoid coadministration of erlotinib with mavacamten if possible due to the risk of decreased erlotinib efficacy. If concomitant use is unavoidable, increase the dose of erlotinib in 50 mg increments at 2-week intervals as tolerated (maximum dose, 450 mg). Erlotinib is a CYP3A substrate, and mavacamten is a moderate CYP3A inducer.
Erythromycin: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting erythromycin therapy. Avoid initiation of erythromycin in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable erythromycin therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and erythromycin is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Eslicarbazepine: (Contraindicated) Mavacamten is contraindicated for use with eslicarbazepine due to risk for reduced mavacamten efficacy. There is also risk for increased adverse reactions due to mavacamten. Concomitant use may increase or decrease mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and eslicarbazepine is a weak CYP2C19 inhibitor and moderate CYP3A inducer. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall exposure by 48%.
Esmolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Esomeprazole: (Contraindicated) Mavacamten is contraindicated for use with esomeprazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and esomeprazole is a moderate CYP2C19 inhibitor.
Esterified Estrogens: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Esterified Estrogens; Methyltestosterone: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estradiol: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estradiol; Levonorgestrel: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estradiol; Norethindrone: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estradiol; Norgestimate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estradiol; Progesterone: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estrogens affected by CYP3A inducers: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Estropipate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Ethinyl Estradiol; Norelgestromin: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Ethinyl Estradiol; Norethindrone Acetate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Ethinyl Estradiol; Norgestrel: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Ethynodiol Diacetate; Ethinyl Estradiol: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Etonogestrel; Ethinyl Estradiol: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Etravirine: (Contraindicated) Concurrent use of mavacamten and etravirine is contraindicated and may produce unpredictable effects on mavacamten including reduced mavacamten efficacy or an increased risk of mavacamten-related adverse effects such as heart failure due to systolic dysfunction. Etravirine exposure may also be decreased. Mavacamten is a substrate of CYP2C19 and CYP3A and a moderate inducer of CYP2C9, CYP2C19, and CYP3A; etravirine is a CYP2C9, CYP2C19, and CYP3A substrate, a weak CYP2C19 inhibitor, and a moderate CYP3A inducer.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate if coadministration with mavacamten is necessary. The dose of everolimus may need to be increased. Everolimus is a sensitive CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with CYP3A inducers may increase the metabolism of everolimus and decrease everolimus blood concentrations.
Fedratinib: (Contraindicated) Mavacamten is contraindicated for use with fedratinib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease fedratinib exposure which may result in decreased therapeutic response. Mavacamten is a CYP2C19 substrate and substrate and moderate inducer of CYP3A and fedratinib is a CYP3A substrate and moderate CYP2C19 and CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%. Coadministration of fedratinib with another moderate CYP3A inducer decreased the overall exposure of fedratinib by 47%.
Felbamate: (Contraindicated) Mavacamten is contraindicated for use with felbamate due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and felbamate is a moderate CYP2C19 inhibitor.
Fentanyl: (Moderate) Consider an increased dose of fentanyl and monitor for evidence of opioid withdrawal if concurrent use of mavacamten is necessary. If mavacamten is discontinued, consider reducing the fentanyl dosage and monitor for evidence of respiratory depression. Coadministration of a CYP3A inducer like mavacamten with fentanyl, a CYP3A substrate, may decrease exposure to fentanyl resulting in decreased efficacy or onset of withdrawal symptoms in a patient who has developed physical dependence to fentanyl. Fentanyl plasma concentrations will increase once the inducer is stopped, which may increase or prolong the therapeutic and adverse effects, including serious respiratory depression.
Finerenone: (Major) Avoid concurrent use of finerenone and mavacamten due to the risk for decreased finerenone exposure which may reduce its efficacy. Finerenone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased overall exposure to finerenone by 80%.
Flecainide: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and flecainide. If concomitant therapy with flecainide is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Flibanserin: (Major) Avoid concomitant use of flibanserin and mavacamten due to the potential for decreased plasma concentrations of flibanserin. Flibanserin is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased flibanserin exposure by approximately 21%.
Fluconazole: (Contraindicated) Mavacamten is contraindicated for use with fluconazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and fluconazole is a strong CYP2C19 inhibitor and a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Fluoxetine: (Contraindicated) Mavacamten is contraindicated for use with fluoxetine due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and fluoxetine is a strong CYP2C19 inhibitor.
Fluvoxamine: (Contraindicated) Mavacamten is contraindicated for use with fluvoxamine due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and fluvoxamine is a strong CYP2C19 inhibitor and a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Fosamprenavir: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting fosamprenavir therapy. Avoid initiation of fosamprenavir in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable fosamprenavir therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Additionally, monitor for decreased fosamprenavir efficacy as concurrent use may decrease the plasma concentrations of fosamprenavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a CYP3A substrate and moderate CYP3A inducer; fosamprenavir is a CYP3A substrate and moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Fosphenytoin: (Contraindicated) Mavacamten is contraindicated for use with fosphenytoin due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and fosphenytoin is a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Ganaxolone: (Major) Avoid concurrent use of ganaxolone and mavacamten due to the risk of decreased ganaxolone efficacy. If concomitant use is unavoidable, consider increasing ganaxolone dose without exceeding the maximum daily dose. Ganaxolone is a CYP3A4 substrate and mavacamten is a moderate CYP3A4 inducer.
Glasdegib: (Major) Avoid coadministration of glasdegib and mavacamten due to the potential for decreased glasdegib exposure and risk of decreased efficacy. If concurrent use cannot be avoided, increase the glasdegib dosage (i.e., from 100 mg PO daily to 200 mg PO daily or from 50 mg PO daily to 100 mg PO daily). Resume the previous dose of glasdegib after mavacamten has been discontinued for 7 days. Glasdegib is a CYP3A4 substrate; mavacamten is a moderate CYP3A4 inducer. Coadministration with another moderate CYP3A4 inducer was predicted to decrease the glasdegib AUC value by 55%.
Glecaprevir; Pibrentasvir: (Moderate) Caution is advised with coadministration of glecaprevir and mavacamten as decreased plasma concentrations of glecaprevir may occur resulting in the potential loss of efficacy of glecaprevir. Glecaprevir is a substrate of CYP3A and mavacamten is a moderate CYP3A inducer.
Glimepiride: (Moderate) Monitor for a decrease in glimepiride efficacy and worsening glycemic control if coadministration with mavacamten is necessary. Concomitant use may decrease glimepiride exposure. Glimepiride is a CYP2C9 substrate; mavacamten is a moderate CYP2C9 inducer.
Glipizide: (Moderate) Monitor for a decrease in glipizide efficacy and worsening glycemic control if coadministration with mavacamten is necessary. Concomitant use may decrease glipizide exposure. Glipizide is a CYP2C9 substrate; mavacamten is a moderate CYP2C9 inducer.
Glipizide; Metformin: (Moderate) Monitor for a decrease in glipizide efficacy and worsening glycemic control if coadministration with mavacamten is necessary. Concomitant use may decrease glipizide exposure. Glipizide is a CYP2C9 substrate; mavacamten is a moderate CYP2C9 inducer.
Glyburide: (Moderate) Monitor for a decrease in glyburide efficacy and worsening glycemic control if coadministration with mavacamten is necessary. Concomitant use may decrease glyburide exposure. Glyburide is a CYP2C9 substrate; mavacamten is a moderate CYP2C9 inducer.
Glyburide; Metformin: (Moderate) Monitor for a decrease in glyburide efficacy and worsening glycemic control if coadministration with mavacamten is necessary. Concomitant use may decrease glyburide exposure. Glyburide is a CYP2C9 substrate; mavacamten is a moderate CYP2C9 inducer.
Grapefruit juice: (Major) Advise patients to avoid grapefruit and grapefruit juice during mavacamten treatment due to the risk of increased mavacamten exposure and adverse reactions. Mavacamten is a CYP3A substrate and grapefruit juice is a strong CYP3A inhibitor.
Guaifenesin; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If mavacamten is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use can decrease hydrocodone levels.
Guanfacine: (Major) A dose increase of extended-release (ER) guanfacine should be considered if coadministration with mavacamten is necessary. Consider doubling the recommended dose of guanfacine if therapy is added to a patient already taking mavacamten; increase the dose of guanfacine over 1 to 2 weeks if mavacamten therapy is added to a patient already taking guanfacine. Specific recommendations for immediate-release (IR) guanfacine are not available. Guanfacine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Homatropine; Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If mavacamten is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use can decrease hydrocodone levels.
Hydrocodone: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If mavacamten is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use can decrease hydrocodone levels.
Hydrocodone; Ibuprofen: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If mavacamten is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use can decrease hydrocodone levels.
Hydrocodone; Pseudoephedrine: (Moderate) Monitor for reduced efficacy of hydrocodone and signs of opioid withdrawal in patients who have developed physical dependence if coadministration with mavacamten is necessary; consider increasing the dose of hydrocodone as needed. It is recommended to avoid this combination when hydrocodone is being used for cough. If mavacamten is discontinued, consider a dose reduction of hydrocodone and frequently monitor for signs of respiratory depression and sedation. Hydrocodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use can decrease hydrocodone levels.
Ibrexafungerp: (Major) Avoid concurrent administration of ibrexafungerp with mavacamten. Use of these drugs together is expected to significantly decrease ibrexafungerp exposure, which may reduce its efficacy. Ibrexafungerp is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Ibuprofen; Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of oxycodone as needed. If mavacamten is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Idelalisib: (Contraindicated) Mavacamten is contraindicated for use with idelalisib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and idelalisib is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Ifosfamide: (Moderate) Closely monitor for increased ifosfamide-related toxicities (e.g., neurotoxicity, nephrotoxicity) if coadministration with mavacamten is necessary; consider adjusting the dose of ifosfamide as clinically appropriate. Ifosfamide is metabolized to its active alkylating metabolites by CYP3A; mavacamten is a moderate CYP3A inducer. Concomitant use may increase the formation of the neurotoxic/nephrotoxic ifosfamide metabolite, chloroacetaldehyde.
Imatinib: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting imatinib therapy. Avoid initiation of imatinib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable imatinib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and imatinib is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Indinavir: (Contraindicated) Mavacamten is contraindicated for use with indinavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of indinavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and indinavir is a substrate and strong inhibitor of CYP3A. Concomitant use of mavacamten with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. Coadministration with another moderate CYP3A inducer decreased indinavir exposure by up to 46%.
Infigratinib: (Major) Avoid concurrent use of infigratinib and mavacamten. Coadministration may decrease infigratinib exposure resulting in decreased efficacy. Infigratinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Isavuconazonium: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting isavuconazonium therapy. Avoid initiation of isavuconazonium in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable isavuconazonium therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and isavuconazonium is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Isoniazid, INH: (Contraindicated) Mavacamten is contraindicated for use with isoniazid due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and isoniazid is a moderate CYP2C19 inhibitor.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Contraindicated) Mavacamten is contraindicated for use with isoniazid due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and isoniazid is a moderate CYP2C19 inhibitor. (Contraindicated) Mavacamten is contraindicated for use with rifampin due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A and CYP2C19 substrate and rifampin is a strong CYP3A and strong CYP2C19 inducer. Concomitant use of a mavacamten 15 mg single dose with rifampin 600 mg/day is predicted to decrease mavacamten exposure by 87% in CYP2C19 normal metabolizers and by 69% in CYP2C19 poor metabolizers.
Isoniazid, INH; Rifampin: (Contraindicated) Mavacamten is contraindicated for use with isoniazid due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and isoniazid is a moderate CYP2C19 inhibitor. (Contraindicated) Mavacamten is contraindicated for use with rifampin due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A and CYP2C19 substrate and rifampin is a strong CYP3A and strong CYP2C19 inducer. Concomitant use of a mavacamten 15 mg single dose with rifampin 600 mg/day is predicted to decrease mavacamten exposure by 87% in CYP2C19 normal metabolizers and by 69% in CYP2C19 poor metabolizers.
Isradipine: (Moderate) Monitor for decreased efficacy of isradipine if coadministration with mavacamten is necessary. Concomitant use may decrease isradipine exposure. Isradipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Itraconazole: (Contraindicated) Mavacamten is contraindicated for use with itraconazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and itraconazole is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Ketoconazole: (Contraindicated) Mavacamten is contraindicated for use with ketoconazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use of mavacamten 15 mg with ketoconazole 400 mg once daily is predicted to increase mavacamten exposure up to 130%.
Labetalol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Mavacamten is contraindicated for use with clarithromycin due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease efficacy of clarithromycin. Mavacamten is a substrate and moderate inducer of CYP3A and clarithromycin is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. There have been spontaneous or published reports of CYP3A-based interactions of clarithromycin with another CYP3A inducer.
Larotrectinib: (Major) Avoid concurrent use of larotrectinib and mavacamten due to the risk of decreased larotrectinib exposure which may reduce its efficacy. If concomitant use is necessary, double the dose of larotrectinib and monitor response. If mavacamten is discontinued, resume the original larotrectinib dose after 3 to 5 elimination half-lives of mavacamten. Larotrectinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease larotrectinib exposure by 72%.
Lefamulin: (Major) Avoid coadministration of lefamulin with mavacamten unless the benefits outweigh the risks as concurrent use may decrease lefamulin exposure and efficacy. Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting lefamulin therapy. Avoid initiation of lefamulin in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable lefamulin therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and moderate CYP3A inducer and lefamulin is a CYP3A substrate and moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Lemborexant: (Major) Avoid coadministration of lemborexant and mavacamten as concurrent use may decrease lemborexant exposure which may reduce efficacy. Lemborexant is a CYP3A substrate; mavacamten is a moderate CYP3A inducer.
Lenacapavir: (Major) Avoid concurrent use of lenacapavir and mavacamten due to the risk of decreased lenacapavir exposure which may result in loss of therapeutic effect and development of resistance. The exposure of mavacamten may also be increased. Lenacapavir is a CYP3A substrate and moderate CYP3A inhibitor and mavacamten is a CYP3A substrate and moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced lenacapavir overall exposure by 56%. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Leniolisib: (Major) Avoid concomitant use of leniolisib and mavacamten. Concomitant use may decrease leniolisib exposure which may reduce its efficacy. Leniolisib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer reduced leniolisib overall exposure by 58%.
Letermovir: (Major) Mavacamten is contraindicated for use with combination letermovir/cyclosporine due to risk of heart failure due to systolic dysfunction. Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting letermovir therapy without cyclosporine. Avoid initiation of letermovir in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable letermovir therapy without cyclosporine. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and combination letermovir/cyclosporine is a strong CYP3A inhibitor and letermovir is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Levamlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Levobunolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Levoketoconazole: (Contraindicated) Mavacamten is contraindicated for use with ketoconazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and ketoconazole is a strong CYP3A inhibitor. Concomitant use of mavacamten 15 mg with ketoconazole 400 mg once daily is predicted to increase mavacamten exposure up to 130%.
Levonorgestrel; Ethinyl Estradiol: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Levonorgestrel; Ethinyl Estradiol; Ferrous Bisglycinate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Levonorgestrel; Ethinyl Estradiol; Ferrous Fumarate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Lonafarnib: (Contraindicated) Mavacamten is contraindicated for use with lonafarnib due to risk of heart failure due to systolic dysfunction and risk for reduced lonafarnib efficacy. Concomitant use increases mavacamten exposure and may decrease lonafarnib exposure. Mavacamten is a CYP2C19 substrate and substrate and moderate inducer of CYP3A and lonafarnib is a moderate CYP2C19 inhibitor and sensitive substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Lopinavir; Ritonavir: (Contraindicated) Mavacamten is contraindicated for use with ritonavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and ritonavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. (Moderate) Monitor for decreased efficacy of lopinavir if concurrent mavacamten use is necessary. Concurrent use may decrease lopinavir exposure and increase the risk of virologic failure and drug resistance. Lopinavir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Lorlatinib: (Contraindicated) Mavacamten is contraindicated for use with lorlatinib due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure and lorlatinib plasma concentrations, which may reduce its efficacy. Mavacamten is a substrate and moderate inducer of CYP3A and lorlatinib is a substrate and moderate inducer of CYP3A. Administration with another moderate CYP3A inducer decreased lorlatinib exposure by 23%.
Luliconazole: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting topical luliconazole therapy. Avoid initiation of topical luliconazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable topical luliconazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and topical luliconazole is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Lumacaftor; Ivacaftor: (Contraindicated) Mavacamten is contraindicated for use with lumacaftor; ivacaftor due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Lumacaftor; Ivacaftor: (Contraindicated) Mavacamten is contraindicated for use with lumacaftor; ivacaftor due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and lumacaftor; ivacaftor is a strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Lumateperone: (Major) Avoid coadministration of lumateperone and mavacamten as concurrent use may decrease lumateperone exposure which may reduce efficacy. Lumateperone is a CYP3A substrate; mavacamten is a moderate CYP3A inducer. Although data are unavailable for moderate CYP3A inducers, coadministration with a strong CYP3A inducer significantly decreased lumateperone exposure.
Lurasidone: (Moderate) If lurasidone is used with mavacamten, it may be necessary to increase the lurasidone dose after chronic treatment (7 days or more) with mavacamten. Concurrent use may lead to a decrease in efficacy of lurasidone. Mavacamten is a moderate CYP3A inducer; lurasidone is a CYP3A substrate.
Maraviroc: (Major) Increase the adult dose of maraviroc to 600 mg PO twice daily when coadministered with mavacamten without a concomitant strong CYP3A inhibitor. Coadministration of maraviroc and mavacamten is contraindicated in patients with CrCl less than 30 mL/min. For pediatric patients, the concomitant use of maraviroc with mavacamten without also taking a strong CYP3A inhibitor is not recommended. If the adult or pediatric patient's medication regimen also contains a strong CYP3A inhibitor, the CYP3A inhibitor's actions are expected to exceed that of mavacamten; overall, increased maraviroc concentrations are expected (see recommended dose adjustments for use of maraviroc with the strong inhibitor). Maraviroc is a sensitive CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Mefloquine: (Moderate) Use mefloquine with caution if coadministration with mavacamten is necessary as concurrent use may decrease mefloquine exposure and efficacy. Mefloquine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Meperidine: (Moderate) Monitor for reduced efficacy of meperidine and signs of opioid withdrawal if coadministration with mavacamten is necessary. Consider increasing the dose of meperidine as needed. If mavacamten is discontinued, consider a dose reduction of meperidine and frequently monitor for signs of respiratory depression and sedation. Meperidine is a substrate of CYP3A; mavacamten is a moderate CYP3A inducer. Concomitant use can decrease meperidine exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Methadone: (Moderate) Monitor for reduced efficacy of methadone and signs of opioid withdrawal if coadministration with mavacamten is necessary. Consider increasing the dose of methadone as needed. If mavacamten is discontinued, consider a dose reduction of methadone and frequently monitor for signs of respiratory depression and sedation. Methadone is a substrate of CYP3A, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; mavacamten is a moderate CYPC29, CYP2C19, and CYP3A inducer. Concomitant use can decrease methadone exposure resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Methohexital: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Metoprolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Mifepristone: (Contraindicated) Mavacamten is contraindicated for use with mifepristone due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and mifepristone is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Mitapivat: (Major) Avoid coadministration of mitapivat with mavacamten, if possible, due to decreased mitapivat efficacy. Coadministration decreases mitapivat concentrations. If concomitant use is necessary, up-titration of mitapivat may be required. Monitor hemoglobin and titrate the mitapivat dose based on response; do not exceed 100 mg PO twice daily. Mitapivat is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased mitapivat overall exposure by 55% to 60%.
Mitotane: (Contraindicated) Mavacamten is contraindicated for use with mitotane due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and mitotane is a strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Mobocertinib: (Major) Avoid concomitant use of mobocertinib and mavacamten. Coadministration may decrease mobocertinib exposure resulting in decreased efficacy. Mobocertinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Use of a moderate CYP3A inducer is predicted to decrease the overall exposure of mobocertinib and its active metabolites by 58%.
Modafinil: (Contraindicated) Mavacamten is contraindicated for use with modafinil due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and modafinil is a moderate CYP2C19 inhibitor.
Nadolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Nafcillin: (Contraindicated) Mavacamten is contraindicated for use with nafcillin due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and nafcillin is a moderate CYP3A inducer.
Nanoparticle Albumin-Bound Paclitaxel: (Moderate) Monitor for decreased efficacy of nab-paclitaxel if coadministration with mavacamten is necessary due to the risk of decreased plasma concentrations of paclitaxel. Nab-paclitaxel is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Nanoparticle Albumin-Bound Sirolimus: (Moderate) Monitor for reduced sirolimus efficacy if sirolimus is coadministered with mavacamten. Concomitant use may decrease sirolimus exposure. Sirolimus is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Naproxen; Esomeprazole: (Contraindicated) Mavacamten is contraindicated for use with esomeprazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and esomeprazole is a moderate CYP2C19 inhibitor.
Nebivolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Nebivolol; Valsartan: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Nefazodone: (Contraindicated) Mavacamten is contraindicated for use with nefazodone due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and nefazodone is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Nelfinavir: (Contraindicated) Mavacamten is contraindicated for use with nelfinavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of nelfinavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a moderate CYP2C19 inducer and substrate and moderate inducer of CYP3A and nelfinavir is a CYP2C19 substrate and substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Neratinib: (Major) Avoid concomitant use of mavacamten with neratinib due to decreased efficacy of neratinib. Neratinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Simulations using physiologically based pharmacokinetic (PBPK) models suggest that another moderate CYP3A inducer may decrease neratinib exposure by 52%.
Netupitant, Fosnetupitant; Palonosetron: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting netupitant therapy. Avoid initiation of netupitant in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable netupitant therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and netupitant is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Nicardipine: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting nicardipine therapy. Avoid initiation of nicardipine in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable nicardipine therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and nicardipine is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Nilotinib: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting nilotinib therapy. Avoid initiation of nilotinib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable nilotinib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and nilotinib is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Nimodipine: (Moderate) Monitor for decreased efficacy of nimodipine if coadministration with mavacamten is necessary as concomitant use may decrease plasma concentrations of nimodipine. Nimodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Nirmatrelvir; Ritonavir: (Contraindicated) Mavacamten is contraindicated for use with ritonavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and ritonavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. (Moderate) Monitor for a diminished response to nirmatrelvir if concomitant use of mavacamten is necessary. Concomitant use of nirmatrelvir and mavacamten may reduce the therapeutic effect of nirmatrelvir. Nirmatrelvir is a CYP3A substrate and mavacamten is a CYP3A inducer.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with mavacamten as concurrent use may decrease nisoldipine exposure and efficacy. Alternative antihypertensive therapy should be considered. Nisoldipine is a CYP3A substrate and mavacamten is a CYP3A inducer. Coadministration with a strong CYP3A inducer lowered nisoldipine plasma concentrations to undetectable levels.
Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Norethindrone; Ethinyl Estradiol: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Norgestimate; Ethinyl Estradiol: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Olanzapine; Fluoxetine: (Contraindicated) Mavacamten is contraindicated for use with fluoxetine due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and fluoxetine is a strong CYP2C19 inhibitor.
Olaparib: (Major) Avoid coadministration of olaparib with mavacamten due to the risk of decreasing the efficacy of olaparib. Olaparib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer; concomitant use may decrease olaparib exposure. Coadministration with a moderate CYP3A inducer is predicted to decrease the olaparib Cmax by 31% and the AUC by 60%.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Olutasidenib: (Major) Avoid concurrent use of olutasidenib and mavacamten due to the risk of decreased olutasidenib exposure which may reduce its efficacy. Olutasidenib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Omaveloxolone: (Major) Avoid concurrent use of omaveloxolone and mavacamten. Concurrent use may decrease omaveloxolone exposure which may reduce its efficacy. Omaveloxolone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Omeprazole: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting omeprazole therapy. Avoid initiation of omeprazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable omeprazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and omeprazole is a weak CYP2C19 inhibitor. Concomitant use of mavacamten 10 mg with omeprazole 20 mg once daily increased overall mavacamten exposure by 48% with no effect on peak exposure in healthy CYP2C19 normal and rapid metabolizers.
Omeprazole; Amoxicillin; Rifabutin: (Contraindicated) Mavacamten is contraindicated for use with rifabutin due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and rifabutin is a moderate CYP3A inducer. (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting omeprazole therapy. Avoid initiation of omeprazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable omeprazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and omeprazole is a weak CYP2C19 inhibitor. Concomitant use of mavacamten 10 mg with omeprazole 20 mg once daily increased overall mavacamten exposure by 48% with no effect on peak exposure in healthy CYP2C19 normal and rapid metabolizers.
Omeprazole; Sodium Bicarbonate: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting omeprazole therapy. Avoid initiation of omeprazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable omeprazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and omeprazole is a weak CYP2C19 inhibitor. Concomitant use of mavacamten 10 mg with omeprazole 20 mg once daily increased overall mavacamten exposure by 48% with no effect on peak exposure in healthy CYP2C19 normal and rapid metabolizers.
Oritavancin: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting oritavancin therapy. Avoid initiation of oritavancin in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable oritavancin therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and oritavancin is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Osilodrostat: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting osilodrostat therapy. Avoid initiation of osilodrostat in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable osilodrostat therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and osilodrostat is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Oxcarbazepine: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting oxcarbazepine therapy. Avoid initiation of oxcarbazepine in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable oxcarbazepine therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and oxcarbazepine is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Oxycodone: (Moderate) Monitor for reduced efficacy of oxycodone and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of oxycodone as needed. If mavacamten is discontinued, consider a dose reduction of oxycodone and frequently monitor for signs of respiratory depression and sedation. Oxycodone is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease oxycodone levels; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Paclitaxel: (Moderate) Monitor for decreased efficacy of paclitaxel if coadministration with mavacamten is necessary due to the risk of decreased plasma concentrations of paclitaxel. Paclitaxel is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Pacritinib: (Major) Avoid concurrent use of pacritinib with mavacamten due to the risk of decreased pacritinib exposure which may impair efficacy. Pacritinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Palovarotene: (Major) Avoid concomitant use of palovarotene and mavacamten. Concurrent use may decrease palovarotene exposure which may reduce its efficacy. Palovarotene is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Pemigatinib: (Major) Avoid coadministration of pemigatinib and mavacamten due to the risk of decreased pemigatinib exposure which may reduce its efficacy. Pemigatinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease pemigatinib exposure by more than 50%.
Pentobarbital: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Perampanel: (Major) Start perampanel at a higher initial dose of 4 mg once daily at bedtime if perampanel is added to mavacamten therapy; increase the dose as tolerated in 2 mg increments no more than weekly, based on clinical response. If mavacamten is added or withdrawn from perampanel therapy, closely monitor patient response; a dosage adjustment may be necessary. Perampanel is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Perindopril; Amlodipine: (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Pexidartinib: (Contraindicated) Mavacamten is contraindicated for use with pexidartinib due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and pexidartinib is a moderate CYP3A inducer.
Phenobarbital: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Phenytoin: (Contraindicated) Mavacamten is contraindicated for use with phenytoin due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and phenytoin is a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Pimavanserin: (Major) Avoid coadministration of pimavanserin with mavacamten as concurrent use may decrease pimavanserin exposure which may lead to decreased efficacy. Pimavanserin is a CYP3A substrate; mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer is predicted to decrease the exposure of pimavanserin by approximately 70%.
Pindolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Pioglitazone; Glimepiride: (Moderate) Monitor for a decrease in glimepiride efficacy and worsening glycemic control if coadministration with mavacamten is necessary. Concomitant use may decrease glimepiride exposure. Glimepiride is a CYP2C9 substrate; mavacamten is a moderate CYP2C9 inducer.
Pirtobrutinib: (Major) Avoid concurrent use of pirtobrutinib and mavacamten due to the risk of decreased pirtobrutinib exposure which may reduce its efficacy. The exposure of mavacamten may also be increased. If concomitant use is necessary, dose adjustments of both drugs are needed. If the current pirtobrutinib dosage is 200 mg once daily, increase the dose to 300 mg; if the current dosage is 50 mg or 100 mg once daily, increase the dose by 50 mg. Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting pirtobrutinib therapy. Avoid initiation of pirtobrutinib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable pirtobrutinib therapy. Pirtobrutinib is a CYP3A substrate and weak CYP2C19 inhibitor and mavacamten is a CYP2C19 substrate and moderate CYP3A inducer. Concomitant use with other moderate CYP3A inducers reduced pirtobrutinib overall exposure by 27% and 49%. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Posaconazole: (Contraindicated) Mavacamten is contraindicated for use with posaconazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and posaconazole is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Pralsetinib: (Major) Avoid concurrent use of mavacamten and pralsetinib due to the risk of decreased pralsetinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the current dose of pralsetinib (400 mg to 600 mg; 300 mg to 500 mg; 200 mg to 300 mg) starting on day 7 of coadministration. Pralsetinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the pralsetinib overall exposure by 45%.
Praziquantel: (Moderate) Monitor for reduced response to praziquantel if coadministered with mavacamten. Concomitant use may produce therapeutically ineffective concentrations of praziquantel. In vitro and drug interactions studies suggest that the CYP3A isoenzyme is the major enzyme involved in praziquantel metabolism; mavacamten is a moderate CYP3A inducer.
Pretomanid: (Major) Avoid coadministration of pretomanid with mavacamten as concurrent use may decrease pretomanid exposure which may lead to decreased efficacy. Pretomanid is a CYP3A substrate; mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased pretomanid exposure by 35%.
Primidone: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Procainamide: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and procainamide. If concomitant therapy with procainamide is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Propafenone: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and propafenone. If concomitant therapy with propafenone is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Propranolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Quinidine: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and quinidine. If concomitant therapy with quinidine is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Quizartinib: (Major) Avoid concomitant use of mavacamten with quizartinib due to the risk of decreased quizartinib exposure which may reduce its efficacy. Quizartinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with another moderate CYP3A inducer decreased the quizartinib overall exposure by 90%.
Ranolazine: (Contraindicated) Coadministration of ranolazine with mavacamten is contraindicated due to decreased ranolazine exposure and efficacy. Additionally, concomitant use may increase the risk of left ventricular systolic dysfunction and heart failure symptoms. Ranolazine is a CYP3A substrate; mavacamten is a moderate CYP3A inducer.
Relugolix; Estradiol; Norethindrone acetate: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Ribociclib: (Contraindicated) Mavacamten is contraindicated for use with ribociclib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Ribociclib; Letrozole: (Contraindicated) Mavacamten is contraindicated for use with ribociclib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and ribociclib is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Rifabutin: (Contraindicated) Mavacamten is contraindicated for use with rifabutin due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and rifabutin is a moderate CYP3A inducer.
Rifampin: (Contraindicated) Mavacamten is contraindicated for use with rifampin due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A and CYP2C19 substrate and rifampin is a strong CYP3A and strong CYP2C19 inducer. Concomitant use of a mavacamten 15 mg single dose with rifampin 600 mg/day is predicted to decrease mavacamten exposure by 87% in CYP2C19 normal metabolizers and by 69% in CYP2C19 poor metabolizers.
Rifapentine: (Contraindicated) Mavacamten is contraindicated for use with rifapentine due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and rifapentine is a strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Rilpivirine: (Moderate) Coadministration of rilpivirine with mavacamten may result in decreased plasma concentrations of rilpivirine, leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Rilpivirine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Rimegepant: (Major) Avoid coadministration of rimegepant with mavacamten; concurrent use may significantly decrease rimegepant exposure which may result in loss of efficacy. Rimegepant is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Ripretinib: (Major) Avoid coadministration of ripretinib with mavacamten. If concomitant use is unavoidable, increase the frequency of ripretinib dosing from 150 mg once daily to 150 mg twice daily; monitor for clinical response and tolerability. Resume once daily dosing of ripretinib 14 days after discontinuation of mavacamten. Coadministration is predicted to decrease the exposure of ripretinib and its active metabolite (DP-5439), which may decrease ripretinib anti-tumor activity. Ripretinib and DP-5439 are metabolized by CYP3A and mavacamten is a moderate CYP3A inducer. Drug interaction modeling studies suggest coadministration with a moderate CYP3A inducer may decrease ripretinib exposure by 56%.
Ritlecitinib: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting ritlecitinib therapy. Avoid initiation of ritlecitinib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable ritlecitinib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and ritlecitinib is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%.
Ritonavir: (Contraindicated) Mavacamten is contraindicated for use with ritonavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of ritonavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and ritonavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Rucaparib: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting rucaparib therapy. Avoid initiation of rucaparib in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable rucaparib therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and rucaparib is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Saquinavir: (Contraindicated) Mavacamten is contraindicated for use with saquinavir due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease plasma concentrations of saquinavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a substrate and moderate inducer of CYP3A and saquinavir is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Secobarbital: (Contraindicated) Mavacamten is contraindicated for use with barbiturates due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and barbiturates are a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Segesterone Acetate; Ethinyl Estradiol: (Major) Patients taking both estrogens and mavacamten should report breakthrough vaginal bleeding to their prescribers. If used for contraception, an alternate or additional form of contraception should be considered in patients prescribed mavacamten. Higher-dose hormonal regimens may be indicated where acceptable or applicable. The alternative or additional contraceptive agent may need to be continued for 4 months after discontinuation of mavacamten. Patients taking these hormones for other indications may need to be monitored for reduced clinical effect while on mavacamten, with dose adjustments made based on clinical efficacy. Estrogens are CYP3A substrates and mavacamten is a moderate CYP3A inducer. Concurrent administration may increase estrogen elimination.
Selpercatinib: (Major) Avoid coadministration of selpercatinib and mavacamten due to the risk of decreased selpercatinib exposure which may reduce its efficacy. Selpercatinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with other moderate CYP3A inducers is predicted to decrease selpercatinib exposure by 40% to 70%.
Selumetinib: (Major) Avoid coadministration of selumetinib and mavacamten due to the risk of decreased selumetinib exposure which may reduce its efficacy. Selumetinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with a moderate CYP3A inducer is predicted to decrease selumetinib exposure by 38%.
Sildenafil: (Moderate) Monitor for decreased efficacy of sildenafil if coadministration with mavacamten is necessary as concurrent use may decrease sildenafil exposure. Sildenafil is a sensitive CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Siponimod: (Moderate) Concomitant use of siponimod and mavacamten may decrease siponimod exposure. If the patient is also receiving a drug regimen containing a strong CYP3A inducer or for patients with CYP2C9*1/*3 and *2/*3 genotypes, use of siponimod is not recommended due to a significant decrease in siponimod exposure. Siponimod is a CYP2C9 and CYP3A substrate; mavacamten is a moderate CYP2C9 and CYP3A inducer. Coadministration with a moderate CYP2C9/strong CYP3A dual inducer decreased siponimod exposure by 57%. Across different CYP2C9 genotypes, a moderate CYP3A inducer decreased the exposure of siponimod by up to 52% according to in silico evaluation.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of mavacamten. Concomitant use may decrease sirolimus exposure and efficacy. Sirolimus is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Sofosbuvir; Velpatasvir: (Major) Concomitant use of velpatasvir with mavacamten is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Concomitant use of velpatasvir with mavacamten is not recommended due to the risk of decreased plasma concentrations of velpatasvir, which may result in loss of antiviral efficacy. Velpatasvir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. (Major) Concomitant use of voxilaprevir with mavacamten is not recommended due to the risk of decreased plasma concentrations of voxilaprevir, which may result in loss of antiviral efficacy. Voxilaprevir is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Solifenacin: (Moderate) Monitor for decreased efficacy of solifenacin if coadministration with mavacamten is necessary. Solifenacin is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Sonidegib: (Major) Avoid the concomitant use of sonidegib and mavacamten ; sonidegib exposure may be significantly decreased and its efficacy reduced. Sonidegib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Physiologic-based pharmacokinetics (PBPK) simulations indicate that a moderate CYP3A inducer would decrease the sonidegib AUC by 56% if administered for 14 days and by 69% if the moderate CYP3A inducer is administered for more than 14 days.
Sotalol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and sotalol. If concomitant therapy with sotalol is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved.
Sotorasib: (Contraindicated) Mavacamten is contraindicated for use with sotorasib due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP3A substrate and sotorasib is a moderate CYP3A inducer.
St. John's Wort, Hypericum perforatum: (Contraindicated) Mavacamten is contraindicated for use with St. John's Wort due to risk for reduced mavacamten efficacy. Concomitant use decreases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and St. John's Wort is a moderate CYP2C19 inducer and strong CYP3A inducer. The impact that a CYP3A inducer may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a strong CYP3A inducer is predicted to decrease mavacamten overall exposure by 69% and 87% in poor and normal CYP2C19 metabolizers, respectively.
Stiripentol: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting stiripentol therapy. Avoid initiation of stiripentol in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable stiripentol therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and stiripentol is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if mavacamten must be administered. Monitor for reduced efficacy of sufentanil injection and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of sufentanil injection as needed. If mavacamten is discontinued, consider a dose reduction of sufentanil injection and frequently monitor for signs of respiratory depression and sedation. Sufentanil is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease sufentanil concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate if coadministration with mavacamten is necessary; a tacrolimus dose adjustment may be needed. Concurrent administration may decrease tacrolimus concentrations. Tacrolimus is a sensitive CYP3A substrate with a narrow therapeutic range; mavacamten is a moderate CYP3A inducer.
Tazemetostat: (Major) Avoid coadministration of tazemetostat with mavacamten as concurrent use may decrease tazemetostat exposure, which may reduce its efficacy. Tazemetostat is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Tecovirimat: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting tecovirimat therapy. Avoid initiation of tecovirimat in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable tecovirimat therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and tecovirimat is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Telmisartan: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting telmisartan therapy. Avoid initiation of telmisartan in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable telmisartan therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and telmisartan is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Telmisartan; Amlodipine: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting telmisartan therapy. Avoid initiation of telmisartan in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable telmisartan therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and telmisartan is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%. (Moderate) Closely monitor blood pressure if coadministration of amlodipine with mavacamten is necessary. Amlodipine is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. No information is available on the quantitative effects of CYP3A inducers on amlodipine; however, concomitant use may result in decreased plasma concentrations of amlodipine.
Telmisartan; Hydrochlorothiazide, HCTZ: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting telmisartan therapy. Avoid initiation of telmisartan in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable telmisartan therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and telmisartan is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Ticlopidine: (Contraindicated) Mavacamten is contraindicated for use with ticlopidine due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 substrate and ticlopidine is a strong CYP2C19 inhibitor.
Timolol: (Moderate) Expect additive negative inotropic effects during concomitant use of mavacamten and beta-blockers. If concomitant therapy with beta-blockers is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten and a beta-blocker plus verapamil or diltiazem due to an increased risk of left ventricular systolic dysfunction and heart failure symptoms.
Tipranavir: (Contraindicated) Mavacamten is contraindicated for use with tipranavir due to risk of heart failure due to systolic dysfunction and risk for reduced mavacamten efficacy. Concomitant use may increase or decrease mavacamten exposure and decrease plasma concentrations of tipranavir leading to a reduction of antiretroviral efficacy and the potential development of viral resistance. Mavacamten is a CYP2C19 substrate and substrate and moderate inducer of CYP3A and tipranavir is a moderate CYP2C19 inhibitor and substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Tolbutamide: (Moderate) Monitor for a decrease in tolbutamide efficacy and worsening glycemic control if coadministration with mavacamten is necessary. Concomitant use may decrease tolbutamide exposure. Tolbutamide is a CYP2C9 substrate; mavacamten is a moderate CYP2C9 inducer. Concomitant use of mavacamten once daily in obstructive hypertrophic cardiomyopathy patients is predicted to decrease tolbutamide exposure by 33% to 65%, depending on the dose of mavacamten and CYP2C19 phenotype.
Tramadol: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of tramadol as needed. If mavacamten is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Tramadol; Acetaminophen: (Moderate) Monitor for reduced efficacy of tramadol and signs of opioid withdrawal if coadministration with mavacamten is necessary; consider increasing the dose of tramadol as needed. If mavacamten is discontinued, consider a dose reduction of tramadol and frequently monitor for seizures, serotonin syndrome, and signs of respiratory depression and sedation. Tramadol is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with CYP3A inducers can decrease tramadol concentrations; this may result in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence.
Trandolapril; Verapamil: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting verapamil therapy. Avoid initiation of verapamil in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable verapamil therapy. Expect additive negative inotropic effects during concomitant use of mavacamten and verapamil. If concomitant therapy with verapamil is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten with verapamil plus a beta-blocker due to association with left ventricular systolic dysfunction and heart failure symptoms. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of mavacamten 25 mg with verapamil sustained-release 240 mg increased mavacamten exposure by 15% in CYP2C19 normal and intermediate metabolizers.
Triclabendazole: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting triclabendazole therapy. Avoid initiation of triclabendazole in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable triclabendazole therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and triclabendazole is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Tucatinib: (Contraindicated) Mavacamten is contraindicated for use with tucatinib due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP3A substrate and tucatinib is a strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%.
Ubrogepant: (Major) Increase the initial and second dose of ubrogepant to 100 mg if coadministered with mavacamten as concurrent use may decrease ubrogepant exposure and reduce its efficacy. Ubrogepant is a CYP3A substrate; mavacamten is a moderate CYP3A inducer.
Ulipristal: (Major) Avoid coadministration of ulipristal with mavacamten. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal. Ulipristal is a substrate of CYP3A and mavacamten is a moderate CYP3A inducer.
Valproic Acid, Divalproex Sodium: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting valproic acid therapy. Avoid initiation of valproic acid in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable valproic acid therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and valproic acid is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Venetoclax: (Major) Avoid coadministration of venetoclax with mavacamten as concurrent use may decrease venetoclax exposure and lead to reduced efficacy. Venetoclax is a CYP3A substrate and mavacamten is a moderate CYP3A inducer.
Verapamil: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting verapamil therapy. Avoid initiation of verapamil in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable verapamil therapy. Expect additive negative inotropic effects during concomitant use of mavacamten and verapamil. If concomitant therapy with verapamil is initiated, or if the dose is increased, monitor left ventricular ejection fraction closely until stable doses and clinical response have been achieved. Avoid concomitant use of mavacamten with verapamil plus a beta-blocker due to association with left ventricular systolic dysfunction and heart failure symptoms. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP3A substrate and verapamil is a moderate CYP3A inhibitor. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of mavacamten 25 mg with verapamil sustained-release 240 mg increased mavacamten exposure by 15% in CYP2C19 normal and intermediate metabolizers.
Voclosporin: (Major) Avoid coadministration of voclosporin with mavacamten. Coadministration may decrease voclosporin exposure resulting in decreased efficacy. Voclosporin is a sensitive CYP3A substrate and mavacamten is a moderate CYP3A inducer. Coadministration with moderate CYP3A inducers is predicted to decrease voclosporin exposure by 70%.
Vonoprazan; Amoxicillin: (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting vonoprazan therapy. Avoid initiation of vonoprazan in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable vonoprazan therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and vonoprazan is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Mavacamten is contraindicated for use with clarithromycin due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure and may decrease efficacy of clarithromycin. Mavacamten is a substrate and moderate inducer of CYP3A and clarithromycin is a substrate and strong inhibitor of CYP3A. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. Inducers of CYP3A enzymes decrease plasma concentrations of clarithromycin while increasing those of 14-OH-clarithromycin. Since the microbiological activities of clarithromycin and 14-OH-clarithromycin are different for different bacteria, the intended therapeutic effect could be impaired during concomitant administration of clarithromycin and enzyme inducers. There have been spontaneous or published reports of CYP3A-based interactions of clarithromycin with another CYP3A inducer. (Major) Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting vonoprazan therapy. Avoid initiation of vonoprazan in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable vonoprazan therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a CYP2C19 substrate and vonoprazan is a weak CYP2C19 inhibitor. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Voriconazole: (Contraindicated) Mavacamten is contraindicated for use with voriconazole due to risk of heart failure due to systolic dysfunction. Concomitant use increases mavacamten exposure. Mavacamten is a CYP2C19 and CYP3A substrate and voriconazole is a weak CYP2C19 inhibitor and strong CYP3A inhibitor. Concomitant use with a strong CYP3A inhibitor is predicted to increase mavacamten overall exposure up to 130%. Concomitant use with another weak CYP2C19 inhibitor in CYP2C19 normal and rapid metabolizers increased overall mavacamten exposure by 48%.
Voxelotor: (Major) Avoid coadministration of voxelotor and mavacamten as concurrent use may decrease voxelotor exposure and lead to reduced efficacy. If coadministration is unavoidable, increase voxelotor dosage to 2,000 mg PO once daily in patients 12 years and older. In patients 4 to 11 years old, weight-based dosage adjustments are recommended; consult product labeling for specific recommendations. Reduce the mavacamten dose by 1 level (i.e., 15 to 10 mg, 10 to 5 mg, or 5 to 2.5 mg) in patients receiving mavacamten and starting voxelotor therapy. Avoid initiation of voxelotor in patients who are on stable treatment with mavacamten 2.5 mg per day because a lower dose of mavacamten is not available. Initiate mavacamten at the recommended starting dose of 5 mg PO once daily in patients who are on stable voxelotor therapy. Concomitant use increases mavacamten exposure, which may increase the risk of adverse drug reactions. Mavacamten is a substrate and moderate inducer of CYP3A and voxelotor is a substrate and moderate inhibitor of CYP3A. The impact that a CYP3A inhibitor may have on mavacamten overall exposure varies based on the patient's CYP2C19 metabolizer status. Concomitant use of a moderate CYP3A inhibitor increased mavacamten overall exposure by 15% in CYP2C19 normal and intermediate metabolizers; concomitant use in poor metabolizers is predicted to increase mavacamten exposure by up to 55%. Coadministration of voxelotor with a moderate CYP3A inducer is predicted to decrease voxelotor exposure by up to 24%.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with mavacamten is necessary as concurrent use may decrease the exposure of warfarin leading to reduced efficacy. The active metabolite of warfarin, the S-enantiomer, is a CYP2C9 substrate and mavacamten is a CYP2C9 inducer. The R-enantiomer of warfarin is a CYP3A substrate and mavacamten is a CYP3A inducer. The S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.
Zanubrutinib: (Major) Avoid concurrent use of zanubrutinib and mavacamten due to the risk of decreased zanubrutinib exposure which may reduce its efficacy. If concomitant use is necessary, increase the zanubrutinib dose to 320 mg twice daily and monitor response. Resume the previous dose of zanubrutinib if mavacamten is discontinued. Zanubrutinib is a CYP3A substrate and mavacamten is a moderate CYP3A inducer. Concomitant use with another moderate CYP3A inducer decreased zanubrutinib exposure by 44%.

Mavacamten Oral Cap: 2.5mg, 5mg, 10mg, 15mg

Adults

15 mg/day PO.

Geriatric

15 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Safety and efficacy have not been established.

Neonates

Safety and efficacy have not been established.

Mavacamten is an allosteric and reversible inhibitor selective for cardiac myosin. Mavacamten modulates the number of myosin heads that can enter "on actin" (power-generating) states, thus reducing the probability of force-producing (systolic) and residual (diastolic) cross-bridge formation. Excess myosin actin cross-bridge formation and dysregulation of the super-relaxed state are mechanistic hallmarks of hypertrophic cardiomyopathy (HCM). Mavacamten shifts the overall myosin population towards an energy-sparing, recruitable, super-relaxed state. In HCM patients, myosin inhibition with mavacamten reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures.

Mavacamten is administered orally. The plasma protein binding of mavacamten is about 98%. Mavacamten exposure increases generally dose proportionally after multiple once-daily doses of 1 to 15 mg. Mavacamten is extensively metabolized, primarily through CYP2C19 (74%), CYP3A4 (18%), and CYP2C9 (8%). After a single radiolabeled mavacamten dose, 7% of the dose was recovered in the feces (1% unchanged) and 85% was recovered in the urine (3% unchanged). Mavacamten has a variable half-life that depends on CYP2C19 metabolic status. At steady-state, the peak-to-trough plasma concentration ratio with once daily dosing is approximately 1.5.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4
Mavacamten is a CYP2C9, CYP2C19, and CYP3A4 substrate and a CYP2B6, CYP2C8, CYP2C9, CYP2C19, and CYP3A4 inducer.

Oral Route

Mavacamten has an estimated oral bioavailability of at least 85% and time to maximum concentration (Tmax) of 1 hour. There were no clinically significant differences in mavacamten pharmacokinetics observed after its administration with a high fat meal; Tmax was increased by 4 hours.

Pregnancy

Mavacamten may cause fetal harm when administered during pregnancy based on animal data. There are no human data on the use of mavacamten during pregnancy to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise females of reproductive potential about the potential risk to the fetus with maternal exposure to mavacamten during pregnancy. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to mavacamten; information about the registry can be obtained at www.bms.com or by telephone at 1-800-721-5072. In animal embryofetal development studies, mavacamten-related decreases in mean fetal body weight, reductions in fetal ossification of bones, and increases in post-implantation loss (early and/or late resorptions) were observed in rats and increases in visceral and skeletal malformations were observed in both rabbits and rats at dose exposures similar to that achieved at the maximum recommended human dose (MRHD).

Mavacamten may be associated with reproductive risk based on animal studies. Confirm absence of pregnancy with pregnancy testing in females of reproductive potential prior to mavacamten treatment. Discuss contraception requirements with the patient. Advise patients to use effective contraception during mavacamten treatment and for 4 months after the last dose. Mavacamten may reduce the effectiveness of combined hormonal contraceptives. Advise patients using combined hormonal contraceptives to use an alternative contraceptive method that is not affected by CYP450 enzyme induction or to add nonhormonal contraception.