Mavacamten Side Effects
Mavacamten carries a serious risk of heart failure due to reduced cardiac contractility, requiring mandatory echocardiographic monitoring through a restricted REMS program, and is absolutely contraindicated in pregnancy due to teratogenic effects. 1, 2
Critical Safety Concerns
Heart Failure Risk (Most Serious)
The most important adverse effect is heart failure from excessive reduction in left ventricular contractility. This occurs when mavacamten reduces the heart's pumping force too much, creating a dangerous situation that can lead to death 2.
Key manifestations to monitor:
- New or worsening shortness of breath
- Leg swelling (peripheral edema)
- Chest pain
- Heart palpitations or racing sensation
- Fatigue
- Rapid weight gain
This risk is heightened when:
- Patients develop serious infections during treatment
- Patients develop irregular heart rhythms (atrial fibrillation)
- Mavacamten is combined with other negative inotropic drugs (disopyramide, ranolazine, verapamil with beta-blockers, diltiazem with beta-blockers) 2
Reduced Left Ventricular Ejection Fraction (LVEF)
Mavacamten must be discontinued immediately if LVEF drops below 50% 1. Clinical trials showed mean LVEF reductions of 3.84% 3, with some patients experiencing more significant decreases requiring dose adjustment or discontinuation 4, 5. This is dose-dependent and more common at higher plasma concentrations 5.
Absolute Contraindication in Pregnancy
Mavacamten is contraindicated in pregnant women due to proven teratogenic effects 1, 2. Animal studies demonstrated:
- Fetal heart malformations (including total situs inversus)
- Skeletal malformations (fused sternebrae)
- Great vessel malformations (dilated pulmonary trunk/aortic arch)
- Post-implantation losses
- Reduced fetal body weight
Mandatory pregnancy prevention:
- Pregnancy testing before initiation
- Effective contraception during treatment and for 4 months after discontinuation
- Hormonal contraceptives may be less effective (mavacamten induces CYP3A4); add barrier methods 2
Common Adverse Events
Cardiovascular
- Atrial fibrillation: Consistently reported across trials 4, 6, 5
- Hypertension: 2.19-fold increased risk versus placebo 7
- Palpitations 8
Other Frequently Reported
Real-world pharmacovigilance data from FAERS identified additional signals 4:
- Dyspnea (shortness of breath)
- Syncope (fainting)
- Peripheral edema (new signal not prominent in trials)
- Urinary tract infections (unexpected new signal)
- Gout (unexpected new signal)
Drug Interactions Increasing Risk
Mavacamten is metabolized by CYP2C19 and CYP3A4. Avoid or dose-reduce with:
- Strong/moderate CYP2C19 inhibitors (increase mavacamten levels)
- Moderate CYP3A4 inhibitors (increase mavacamten levels)
- Other negative inotropes (additive heart failure risk) 2
Mandatory Monitoring Requirements
Due to heart failure risk, mavacamten is only available through the CAMZYOS REMS Program 2:
- Echocardiograms required before first dose and regularly during treatment
- Only enrolled prescribers can prescribe
- Only certified pharmacies can dispense
- Patients must enroll and understand monitoring requirements
Clinical Context
The overall adverse event rate is modestly increased (1.07-fold vs placebo, p=0.008) 7, with most events being mild (80%) to moderate (19%) and often unrelated to the drug (79%) 5. However, the serious adverse event rate is similar to placebo 3, and the specific risks of reduced LVEF and heart failure require vigilant monitoring.
Critical pitfall: Do not assume all patients tolerate mavacamten equally. Those with hepatic or renal impairment, concurrent infections, or on multiple cardiac medications require especially close monitoring 9. The drug's benefits in reducing obstruction and improving symptoms must be balanced against these real risks through individualized echocardiographic surveillance.