Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (44)
- 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.
- capivasertib
mavacamten will decrease the level or effect of capivasertib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease capivasertib exposure, which may reduce efficacy.
- 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.
- elacestrant
mavacamten will decrease the level or effect of elacestrant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- 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.
- fruquintinib
mavacamten will decrease the level or effect of fruquintinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration with moderate CYP3A4 inducers is unavoidable, continue to administer fruquintinib at recommended dosage.
- lenacapavir
mavacamten will decrease the level or effect of lenacapavir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of lenacapavir with moderate CYP3A4 inducers.
- leniolisib
mavacamten will decrease the level or effect of leniolisib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- 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.
- olutasidenib
mavacamten will decrease the level or effect of olutasidenib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Strong or moderate CYP3A inducers decrease olutasidenib (a CYP3A4 substrate) plasma concentrations and efficacy.
- omaveloxolone
mavacamten will decrease the level or effect of omaveloxolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- palovarotene
mavacamten will decrease the level or effect of palovarotene by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- 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.
- pirtobrutinib
mavacamten will decrease the level or effect of pirtobrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. If coadministration unavoidable, increase pirtobrutinib dose to 300 mg qDay (if dose is 200 mg qDay) or increase pirtobrutinib dose by 50 mg (if current pirtobrutinib dose is 50 mg or 100 mg qDay).
- 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.
- quizartinib
mavacamten will decrease the level or effect of quizartinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- 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.
- repotrectinib
mavacamten will decrease the level or effect of repotrectinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.
- 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.
- zanubrutinib
mavacamten will decrease the level or effect of zanubrutinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of zanubrutinib (a CYP3A4 substrate) with moderate CYP3A4 inhibitors. If unavoidable, increase zanubrutinib dose to 320 mg PO BID. After discontinuing the CYP3A4 inhibitor, resume previous dose of zanubrutinib.
Monitor Closely (95)
- 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.
- 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.
- 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. - fosaprepitant
fosaprepitant 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.
fosaprepitant 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.
- lenacapavir
lenacapavir will increase the level or effect of mavacamten by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
- 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.
- norgestrel
mavacamten will decrease the level or effect of norgestrel by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Moderate CYP3A4 inducers may decrease progestin concentration; consider use of additional barrier methods
- 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.
- sparsentan
sparsentan will decrease the level or effect of mavacamten by affecting hepatic enzyme CYP2C19 metabolism. Use Caution/Monitor. Sparsentan (a CYP2C19 inducer) decreases exposure of CYP2C19 substrates and reduces efficacy related to these substrates.
- 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)
Adverse Effects
>10%
Dizziness (27%)
1-10%
Syncope (6%)
Reduced LVEF (6%)
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
CYP450 inhbitors and inducers
- Coadministration with certain CYP450 inhibitors or discontinuation of certain CYP450 inducers may increase HF risk due to systolic dysfunction
-
Contraindicated with following
- Moderate-to-strong CYP2C19 inhibitors or strong CYP3A4 inhibitors
- Moderate-to-strong CYP2C19 or CYP3A4 inducers
REMS
- 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
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; avoid concomitant use of mavacamten in patients on disopyramide, ranolazine, verapamil with a beta blocker, or diltiazem with a beta blocker as these medications and combinations increase risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited
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 increase risk of left ventricular systolic dysfunction and heart failure symptoms and clinical experience is limited
- If concomitant therapy with negative inotrope initiated, or if dose of negative inotrope increased, monitor LVEF closely until stable doses and clinical response achieved
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.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)
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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Formulary
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