mavacamten (Rx)

Brand and Other Names:Camzyos
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 2.5mg
  • 5mg
  • 10mg
  • 15mg

Obstructive Hypertrophic Cardiomyopathy

Indicated for symptomatic New York Heart Association class II-III obstructive hypertrophic cardiomyopathy (HCM) to improve exercise capacity and symptoms

Starting dose: 5 mg PO qDay

Allowable subsequent doses with titration are 2.5, 5, 10, or 15 mg qDay

Initiation or up-titration in patients with left ventricular ejection fraction (LVEF) <55% not recommended

Patients may develop heart failure (HF) while taking mavacamten; regular LVEF and Valsalva left ventricular outflow tract (LVOT) gradient assessment required for careful titration to achieve an appropriate target Valsalva LVOT gradient, while maintaining LVEF ≥50% and avoiding HF symptoms

Daily dosing takes weeks to reach steady-state drug levels and therapeutic effects, and genetic variation in metabolism and drug interactions can cause large differences in exposure

When initiating or titrating, first consider LVEF then consider the Valsalva LVOT gradient and patient clinical status to guide appropriate dosing (see algorithm in prescribing information)

Initiation phase dosing (week 4)

  • Valsalva LVOT gradient <20 mmHg: Reduce dose to 2.5 mg/day
  • Valsalva LVOT gradient ≥20 mmHg: Maintain at 5 mg/day

Initiation phase dosing (week 8)

  • Taking 2.5 mg/day
    • Valsalva LVOT gradient <20 mmHg: Withhold drug and resume at Week 12
    • Valsalva LVOT gradient ≥20 mmHg: Maintain at 2.5 mg/day
  • Taking 5 mg/day
    • Valsalva LVOT gradient <20 mmHg: Reduce dose to 2.5 mg/day
    • Valsalva LVOT gradient ≥20 mmHg: Maintain at 5 mg/day

Initiation phase dosing (week 12)

  • Taking 2.5 mg/day
    • Valsalva LVOT gradient <20 mmHg: Restart on 2.5 mg if LVEF ≥50% and recheck clinical status and echocardiogram (ECHO) in 4 weeks
    • Maintain same dose for next 8 weeks, unless LVEF <50%
  • Taking 5 mg/day
    • Refer to maintenance dosing algorithm

Maintenance phase dosing (week 12 and q12wk)

  • LVEF <50%: Interrupt treatment
  • Maintain on same dose and follow-up 12 weeks later
    • LVEF 50-55%, regardless of Valsalva LVOT gradient OR,
    • LVEF ≥55% and Valsalva LVOT gradient <30 mmHg
  • LVEF ≥55% and Valsalva LVOT gradient ≥30 mmHg
    • Up-titration to next higher daily dose level (eg, 2.5 mg to 5 mg; 5 mg to 10 mg; 10 mg to 15 mg)
    • Recheck clinical status and ECHO in 4 weeks and maintain same dose for next 8 weeks unless LVEF <50%
    • Further up-titration allowed after 12 weeks of treatment on same dose level

Treatment interruption if LVEF <50%

  • LVEF <50%
    • Interrupt treatment
    • Recheck ECHO parameters q4wk until LVEF ≥50%
    • Permanently discontinue if LVEF <50% twice on 2.5 mg/day
  • LVEF ≥50%
    • Restart at next lower daily dose; if interrupted at 2.5 mg, restart at 2.5 mg
    • Recheck clinical status and ECHO in 4 weeks and maintain the same dose for the next 8 weeks unless LVEF <50%, THEN
    • Follow maintenance phase dosage
    • Delay dose increases when there is intercurrent illness (eg, serious infection) or arrhythmia (eg, atrial fibrillation, other uncontrolled tachyarrhythmia) that may impair systolic function
    • Consider interruption in patients with intercurrent illness

Dosage Modifications

Coadministration with weak CYP2C19 or moderate CP3A4 inhibitors

  • On stable therapy with weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor: Initiate at recommended starting dose (5 mg/day)
  • Initiating weak CYP2C19 inhibitor or moderate CYP3A4 inhibitor
    • Reduce mavacamten dose by 1 dosage level
    • Schedule clinical and ECHO assessment 4 weeks after inhibitor initiation, and do not up-titrate mavacamten until 12 weeks after inhibitor initiation
    • Avoid initiation of concomitant weak CYP2C19 and moderate CYP3A4 inhibitors in patients who are on stable treatment with mavacamten 2.5 mg/day (lower dose unavailable)

Renal impairment

  • Mild-to-moderate (eGFR 30-89 mL/min/1.73 m2): No dosage adjustment required
  • Severe impairment and kidney failure, including patients on dialysis (eGFR <30 mL/min/1.73 m2): Unknown

Hepatic impairment

  • Mild-to-moderate (Child-Pugh A or B): No dosage adjustment required; although AUC increases, no additional dose adjustment required owing to recommended dose titration algorithm and monitoring
  • Severe (Child-Pugh C): Unknown

Dosing Considerations

Daily dosing takes weeks to reach steady-state drug levels and therapeutic effects, and genetic variation in metabolism and drug interactions can cause large differences in exposure

Confirm absence of pregnancy and usage of effective contraception in females of reproductive potential before initiating

Safety and efficacy not established

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Interactions

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            Contraindicated (89)

            • abiraterone

              abiraterone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • amobarbital

              amobarbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • apalutamide

              apalutamide will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              apalutamide will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • armodafinil

              armodafinil will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              armodafinil will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • atazanavir

              atazanavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • belzutifan

              belzutifan will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • bexarotene

              bexarotene will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • bortezomib

              bortezomib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • bosentan

              bosentan will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • butabarbital

              butabarbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • butalbital

              butalbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • cannabidiol

              cannabidiol will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • carbamazepine

              carbamazepine will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              carbamazepine will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • cenobamate

              cenobamate will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              cenobamate will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • chloramphenicol

              chloramphenicol will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              chloramphenicol will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • clarithromycin

              clarithromycin will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • cobicistat

              cobicistat will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • conivaptan

              conivaptan will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • dabrafenib

              dabrafenib will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              dabrafenib will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • darunavir

              darunavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • delavirdine

              delavirdine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • dexlansoprazole

              dexlansoprazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • efavirenz

              efavirenz will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              efavirenz will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • elagolix

              elagolix will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • encorafenib

              encorafenib decreases levels of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • enzalutamide

              enzalutamide will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              enzalutamide will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • eslicarbazepine acetate

              eslicarbazepine acetate will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              eslicarbazepine acetate will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • esomeprazole

              esomeprazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • etravirine

              etravirine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              etravirine will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • fedratinib

              fedratinib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • fexinidazole

              fexinidazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • fluconazole

              fluconazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • fluoxetine

              fluoxetine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • fluvoxamine

              fluvoxamine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              fosphenytoin will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • gemfibrozil

              gemfibrozil will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • grapefruit

              grapefruit will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • idelalisib

              idelalisib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • indinavir

              indinavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • isoniazid

              isoniazid will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • itraconazole

              itraconazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • ivosidenib

              ivosidenib will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • ketoconazole

              ketoconazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              ketoconazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • lansoprazole

              lansoprazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • levoketoconazole

              levoketoconazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • lonafarnib

              lonafarnib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              lonafarnib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • lopinavir

              lopinavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              lopinavir will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

            • loratadine

              loratadine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • lorlatinib

              lorlatinib will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • mifepristone

              mifepristone will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • mitapivat

              mitapivat will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              mitapivat will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • mitotane

              mitotane will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • mobocertinib

              mobocertinib will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • modafinil

              modafinil will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              modafinil will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • nafcillin

              nafcillin will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • nefazodone

              nefazodone will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • nelfinavir

              nelfinavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • nicardipine

              nicardipine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • omeprazole

              omeprazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • pantoprazole

              pantoprazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • pentobarbital

              pentobarbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • pexidartinib

              pexidartinib will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • phenobarbital

              phenobarbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • phenytoin

              phenytoin will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              phenytoin will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • posaconazole

              posaconazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • primidone

              primidone will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • propofol

              propofol will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • rabeprazole

              rabeprazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • rifabutin

              rifabutin will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • rifampin

              rifampin will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated.

              rifampin will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • rifapentine

              rifapentine will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • ritonavir

              ritonavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • rucaparib

              rucaparib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              rucaparib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • saquinavir

              saquinavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • secobarbital

              secobarbital will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • sertraline

              sertraline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • sitaxentan

              sitaxentan will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • sotorasib

              sotorasib will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • St John's Wort

              St John's Wort will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • stiripentol

              stiripentol will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              stiripentol will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • telotristat ethyl

              telotristat ethyl will decrease the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • ticlopidine

              ticlopidine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • tipranavir

              tipranavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • tranylcypromine

              tranylcypromine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • triclabendazole

              triclabendazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            • voriconazole

              voriconazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. Strong CYP3A4 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

              voriconazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Contraindicated. Strong or moderate CYP2C19 inhibitors may increase mavacamten systemic exposure, resulting in heart failure due to systolic dysfunction.

            Serious - Use Alternative (33)

            • atenolol

              atenolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • betaxolol

              betaxolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • bisoprolol

              bisoprolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • celiprolol

              celiprolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • dienogest/estradiol valerate

              mavacamten will decrease the level or effect of dienogest/estradiol valerate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • diltiazem

              diltiazem, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • disopyramide

              disopyramide, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • drospirenone

              mavacamten will decrease the level or effect of drospirenone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • esmolol

              esmolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • ethinylestradiol

              mavacamten will decrease the level or effect of ethinylestradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • etonogestrel

              mavacamten will decrease the level or effect of etonogestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • levonorgestrel intrauterine

              mavacamten will decrease the level or effect of levonorgestrel intrauterine by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • levonorgestrel oral

              mavacamten will decrease the level or effect of levonorgestrel oral by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • levonorgestrel oral/ethinylestradiol/ferrous bisglycinate

              mavacamten will decrease the level or effect of levonorgestrel oral/ethinylestradiol/ferrous bisglycinate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • medroxyprogesterone

              mavacamten will decrease the level or effect of medroxyprogesterone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • megestrol

              mavacamten will decrease the level or effect of megestrol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • metoprolol

              metoprolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • nadolol

              nadolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • nebivolol

              nebivolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • norethindrone

              mavacamten will decrease the level or effect of norethindrone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • norethindrone acetate

              mavacamten will decrease the level or effect of norethindrone acetate by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • norethindrone transdermal

              mavacamten will decrease the level or effect of norethindrone transdermal by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • norgestrel

              mavacamten will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • penbutolol

              penbutolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • progesterone intravaginal gel

              mavacamten will decrease the level or effect of progesterone intravaginal gel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • progesterone micronized

              mavacamten will decrease the level or effect of progesterone micronized by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • propranolol

              propranolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • ranolazine

              ranolazine, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • segesterone/ethinyl estradiol

              mavacamten will decrease the level or effect of segesterone/ethinyl estradiol by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Progestin and ethinyl estradiol are CYP3A4 substrates. Mavacamten may decrease systemic exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or an increase in breakthrough bleeding. Advise patients to use a contraceptive method that is not affected by CYP450 enzyme induction (eg, intrauterine system) or add nonhormonal contraception (eg, condoms) during coadministration and for 4 months after last mavacamten dose.

            • sotalol

              sotalol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • timolol

              timolol, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • verapamil

              verapamil, mavacamten. Either increases effects of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Expect additive negative inotropic effects of mavacamten and other drugs that reduce cardiac contractility.

            • vonoprazan

              mavacamten will decrease the level or effect of vonoprazan by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            Monitor Closely (92)

            • amiodarone

              amiodarone will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • amitriptyline

              amitriptyline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • aprepitant

              aprepitant will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

              aprepitant will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • azelastine

              azelastine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • bicalutamide

              bicalutamide will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • brivaracetam

              brivaracetam will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • buprenorphine

              buprenorphine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • buprenorphine buccal

              buprenorphine buccal will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • buprenorphine transdermal

              buprenorphine transdermal will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • ceritinib

              ceritinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • cimetidine

              cimetidine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • citalopram

              citalopram will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • clotrimazole

              clotrimazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • clozapine

              clozapine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

              clozapine will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • crizotinib

              crizotinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • cyclosporine

              cyclosporine will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • desipramine

              desipramine will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • diazepam

              diazepam will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • diltiazem

              diltiazem will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • divalproex sodium

              divalproex sodium will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • doxycycline

              doxycycline will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • dronedarone

              dronedarone will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • drospirenone

              drospirenone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • elagolix

              elagolix will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • entacapone

              entacapone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

              entacapone will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • erythromycin base

              erythromycin base will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • erythromycin ethylsuccinate

              erythromycin ethylsuccinate will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • erythromycin lactobionate

              erythromycin lactobionate will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • erythromycin stearate

              erythromycin stearate will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • ethotoin

              ethotoin will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • fedratinib

              fedratinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • felbamate

              felbamate will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • fenofibrate

              fenofibrate will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • fenofibrate micronized

              fenofibrate micronized will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • fenofibric acid

              fenofibric acid will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • fexinidazole

              fexinidazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • fluconazole

              fluconazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • fluvoxamine

              fluvoxamine will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • fosamprenavir

              fosamprenavir will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

              fosamprenavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • fostamatinib

              fostamatinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • gefitinib

              gefitinib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • haloperidol

              haloperidol will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • ibrexafungerp

              ibrexafungerp will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • iloperidone

              iloperidone will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • imatinib

              imatinib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

              imatinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • imipramine

              imipramine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • indinavir

              indinavir will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • indomethacin

              indomethacin will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • isoniazid

              isoniazid will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • ivacaftor

              ivacaftor will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • lapatinib

              lapatinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • larotrectinib

              larotrectinib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • lefamulin

              lefamulin will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • lenvatinib

              lenvatinib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • letermovir

              letermovir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • letrozole

              letrozole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • losartan

              losartan will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • mephobarbital

              mephobarbital will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • methimazole

              methimazole will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • methoxsalen

              methoxsalen will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • methsuximide

              methsuximide will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • metronidazole

              metronidazole will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • nelfinavir

              nelfinavir will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • netupitant/palonosetron

              netupitant/palonosetron will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • nilutamide

              nilutamide will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • olanzapine

              olanzapine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • orphenadrine

              orphenadrine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • oxcarbazepine

              oxcarbazepine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • paroxetine

              paroxetine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • pentamidine

              pentamidine will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • pimozide

              pimozide will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • pioglitazone

              pioglitazone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • probenecid

              probenecid will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • progesterone micronized

              progesterone micronized will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • quinupristin/dalfopristin

              quinupristin/dalfopristin will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • ribociclib

              ribociclib will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • rosiglitazone

              rosiglitazone will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • saquinavir

              saquinavir will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • schisandra

              schisandra will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • selegiline

              selegiline will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • sertraline

              sertraline will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • sildenafil

              sildenafil will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • tecovirimat

              tecovirimat will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • telmisartan

              telmisartan will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • tetracycline

              tetracycline will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • topiramate

              topiramate will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • torsemide

              torsemide will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • valproic acid

              valproic acid will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • vismodegib

              vismodegib will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            • voxelotor

              voxelotor will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Inititiation of moderate CYP3A4 inhibitors may require decreased mavacamten dose.

            • zafirlukast

              zafirlukast will increase the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Modify Therapy/Monitor Closely. Inititiation of weak CYP2C19 inhibitors may require decreased mavacamten dose.

            Minor (0)

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              Adverse Effects

              >10%

              Dizziness (27%)

              1-10%

              Syncope (6%)

              Reduced LVEF (6%)

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              Warnings

              Black Box Warnings

              Risk of heart failure (HF)

              • Reduces left ventricular ejection fraction (LVEF) and can cause HF owing to systolic dysfunction
              • ECG assessments of LVEF required before and during treatment
              • Initiation in patients with LVEF <55% not recommended
              • Interrupt dosing if LVEF <50% at any visit or if patient experiences HF symptoms or worsening clinical status
              • Coadministration with certain CYP450 inhibitors or discontinuation of certain CYP450 inducers may increase HF risk due to systolic dysfunction
              • Available only through restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called Camzyos REMS Program; information available at www.camzyosrems.com or by telephone at 1-833-628-7367
              • Contraindicated with following
                • Moderate-to-strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
                • Moderate-to-strong CYP2C19 or CYP3A4 inducers

              Contraindications

              Coadministration with moderate-to-strong CYP2C19 inhibitors or strong CYP3A4 inhibitors

              Coadministration with moderate-to-strong CYP2C19 or CYP3A4 inducers

              Cautions

              Only available through restricted REMS program requiring certification of prescribers and pharmacies, and enrollment of patients

              Based on animal studies, may cause fetal toxicity when administered to pregnant females; confirm absence of pregnancy in females of reproductive potential before initiating and instruct patient on use of effective contraception

              Heart failure

              • Reduces systolic contraction and can cause HF or totally block ventricular function
              • Patients who experience a serious intercurrent illness (eg, serious infection) or arrhythmia (eg, atrial fibrillation, other uncontrolled tachyarrhythmia) are at greater risk of developing systolic dysfunction and HF
              • Patients should report any signs or symptoms of heart failure immediately to their healthcare provider
              • Assess clinical status and LVEF before and regularly during treatment and adjust dose accordingly
              • Promptly evaluate new or worsening arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema, or elevations in N-terminal pro-B-type natriuretic peptide (NT-proBNP) as these may be signs and symptoms of HF
              • Asymptomatic LVEF reduction, intercurrent illnesses, and arrhythmias require additional dosing considerations
              • Initiation with LVEF <55% is not recommended

              Drug interaction overview

              • Primarily metabolized by CYP2C19 and CYP3A4
              • Coadministration with drugs that interact with these enzymes may lead to life-threatening drug interactions (eg, heart failure) or loss of effectiveness
              • Advise patients of potential drug interactions, including OTC medications (eg, omeprazole, esomeprazole, or cimetidine)
              • Moderate-to-strong CYP2C19 or strong CYP3A4 inhibitors
                • Contraindicated
                • Coadministration with moderate-to-strong CYP2C19 inhibitors or strong CYP3A4 inhibitors increases mavacamten systemic exposure, which may increase risk of HF due to systolic dysfunction
              • Moderate-to-strong CYP2C19 or CYP3A4 inducers
                • Contraindicated
                • Coadministration with moderate-to-strong CYP2C19 or CYP3A4 inducers decreases mavacamten systemic exposure, which may reduce efficacy
                • May increase risk of adverse effects
              • Hormonal contraceptives
                • Use alternant contraceptive (eg, intrauterine system) not affected by CYP450 induction or add nonhormonal contraception during treatment and for 4 months after last dose
                • Progestin and ethinyl estradiol are CYP3A4 substrates
                • Mavacamten may decrease exposures of ethinyl estradiol and progestin, which may lead to contraceptive failure or increased breakthrough bleeding
              • Weak CYP2C19 or moderate CYP3A4 inhibitors
                • On stable therapy with weak CYP2C19 or moderate CYP3A4 inhibitor: Initiate at recommended 5 mg/day dose
                • Intend to initiate weak CYP2C19 or moderate CYP3A4 inhibitor: Reduce mavacamten dose by 1 level
                • On stable treatment with mavacamten 2.5 mg/day: Avoid initiating weak CYP2C19 or moderate CYP3A4 inhibitor (no lower mavacamten dose available)
              • Drugs that reduce cardiac contractility
                • Avoid coadministration
                • Coadministration with disopyramide in combination with verapamil or diltiazem has been associated with left ventricular systolic dysfunction and HF symptoms in patients with obstructive HCM
                • Avoid concomitant use in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations were excluded from the clinical study
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              Pregnancy & Lactation

              Pregnancy

              Based on animal data, may cause fetal harm when administered to pregnant females

              Human data are not available on use during pregnancy to evaluate for drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes

              Confirm absence of pregnancy in females of reproductive potential prior to initiation and use of effective contraception

              Animal 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) observed in rats and increases in visceral and skeletal malformations observed in both rabbits and rats at dose exposures like that achieved at maximum recommended human dose (MRHD)

              Contraception

              • Advise females of reproductive potential to use effective contraception during treatment and for 4 months after last dose
              • Mavacamten may reduce effectiveness of combination hormonal contraceptives; advise using an alternant contraceptive method or add nonhormonal contraception

              Clinical considerations

              • Underlying maternal condition during pregnancy poses risk to mother and fetus
              • Obstructive HCM in pregnancy associated with increased risk for preterm birth
              • Advise pregnant females about potential risk to fetus with maternal exposure to mavacamten during pregnancy

              Lactation

              Unknown if present in human or animal milk, effects on breastfed infants, and effects on milk production

              Consider developmental and health benefits of breastfeeding along with the mother’s clinical need for mavacamten and any potential adverse effects on the breastfed child from the drug or from the underlying maternal condition

              Pregnancy Categories

              A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

              B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

              C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

              D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

              X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

              NA: Information not available.

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              Pharmacology

              Mechanism of Action

              Selective allosteric inhibitor of cardiac myosin

              Modulates number of myosin heads that can enter “on actin” (power-generating) states, thus reduces 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 HCM

              Mavacamten shifts overall myosin population towards an energy-sparing, recruitable, super-relaxed state

              In patients with HCM, myosin inhibition with mavacamten reduces dynamic left ventricular outflow tract (LVOT) obstruction and improves cardiac filling pressures

              Absorption

              Bioavailability: 85%

              Peak plasma concentration: 1 hr

              Effect of food

              • No clinically significant difference after high fat meal
              • Peak plasma time increased by 4 hr

              Distribution

              Protein bound: 97-98%

              Metabolism

              Extensively metabolized, primarily through CYP2C19 (74%), CYP3A4 (18%), and CYP2C9 (8%)

              Elimination

              Excretion: 7% feces (1% unchanged); 85% urine (3% unchanged)

              Half-life

              • Variable terminal half-life that depends on CYP2C19 metabolic status
              • Normal metabolizers: 6-9 days
              • Poor metabolizers: 23 days

              Pharmacogenomics

              AUC increased by 241% and peak plasma concentration increased by 47% in CYP2C19 poor metabolizers (PMs) compared with normal metabolizers (NMs) following a single 15-mg dose

              NMs carry 2 normal function alleles (eg, *1/*1)

              PMs carry 2 no function alleles (eg, *2/*2, *2/*3, *3/*3)

              Prevalence of CYP2C19 poor metabolizers differs depending on ancestry; ~2% of individuals of European ancestry and 4% of individuals of African ancestry are PMs; prevalence of PMs is higher in Asian populations (eg, ~13% of East Asians)

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              Administration

              Oral Administration

              May take with or without food

              Swallow capsules whole; do not break, open, or chew

              Missed dose

              • If dose missed, take as soon as possible, and then take the next scheduled dose at the usual time the following day
              • Exact timing of dosing during the day is not essential, but do not take 2 doses on the same day

              Storage

              Store at 20-25ºC (68-77ºF); excursions permitted to 15-30ºC (59-86ºF)

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              Images

              No images available for this drug.
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              Patient Handout

              A Patient Handout is not currently available for this monograph.
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              Formulary

              FormularyPatient Discounts

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              Tier Description
              1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
              2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
              3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
              4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
              NC NOT COVERED – Drugs that are not covered by the plan.
              Code Definition
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              Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.