CAMZYOS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CAMZYOS (CAMZYOS).
CAMZYOS (mavacamten) is a selective cardiac myosin inhibitor that reduces myocardial contractility by decreasing the number of active myosin heads and shifting the actin-myosin equilibrium toward a relaxed state. This reduces left ventricular outflow tract obstruction and improves diastolic function in hypertrophic cardiomyopathy.
| Metabolism | Primarily metabolized by CYP2C19 and CYP3A4, with minor contributions from CYP2C9, CYP2D6, and CYP2E1. It is a substrate of P-glycoprotein (P-gp). |
| Excretion | Primarily hepatic metabolism, with ~95% of dose excreted in feces as unchanged drug and metabolites; renal excretion accounts for <3% of the dose. |
| Half-life | Mean terminal elimination half-life is approximately 12–14 days (range 8–17 days) in healthy subjects, supporting once-daily dosing. |
| Protein binding | >99% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution is approximately 2.5 L/kg, indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 40–60% under fed conditions; absorption is enhanced when taken with a high-fat meal. |
| Onset of Action | Peak reduction in left ventricular outflow tract gradient occurs within 2–4 weeks of initiating therapy; hemodynamic effects may be seen as early as 1 week. |
| Duration of Action | Sustained clinical effect over 24 hours with once-daily dosing; pharmacodynamic effects persist for several days after discontinuation due to long half-life. |
2.5 mg orally once daily; may increase to 5 mg once daily after 4 weeks based on tolerability. Maximum recommended dose: 10 mg once daily.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-59 mL/min: 2.5 mg once daily; maximum 5 mg once daily. GFR 15-29 mL/min: 2.5 mg once daily; maximum 2.5 mg once daily. GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: 2.5 mg once daily; maximum 5 mg once daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients under 18 years. No recommended dose. |
| Geriatric use | No specific dose adjustment recommended; monitor for adverse effects due to potential age-related renal impairment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CAMZYOS (CAMZYOS).
| Breastfeeding | It is unknown whether CAMZYOS is excreted in human milk. Animal studies show presence in milk. M/P ratio not available. Breastfeeding is not recommended during treatment and for at least 2 weeks after final dose. |
| Teratogenic Risk | CAMZYOS is contraindicated in pregnancy based on animal studies showing teratogenicity at exposures similar to human therapeutic doses. First trimester: high risk of major congenital malformations including cardiac and skeletal defects. Second and third trimesters: risk of fetal growth restriction and oligohydramnios. No adequate human studies exist. |
■ FDA Black Box Warning
WARNING: HEART FAILURE. CAMZYOS reduces left ventricular ejection fraction (LVEF) and can cause systolic dysfunction and heart failure. Assess LVEF before and during treatment. Do not initiate if LVEF < 55% or if LVEF decreases to < 50% at any time. Interrupt or discontinue if LVEF decreases to < 50%.
| Serious Effects |
["Hypersensitivity to mavacamten or any excipient.","Concurrent use of moderate to strong CYP2C19 inhibitors (e.g., omeprazole, fluconazole, ticlopidine) or strong CYP3A4 inducers (e.g., rifampin, carbamazepine)."]
| Precautions | ["Heart failure and systolic dysfunction: Monitor LVEF via echocardiography every 3 months during dose titration, then periodically.","Risk of atrial fibrillation and stroke: Increased incidence of new-onset atrial fibrillation; manage per standard guidelines.","Drug interactions: Avoid strong CYP2C19 inhibitors and inducers; use with caution with moderate CYP3A4 inhibitors.","Embryo-fetal toxicity: Can cause fetal harm; females of reproductive potential should use effective contraception during treatment and for 4 months after the last dose."] |
| Food/Dietary |
Loading safety data…
| Fetal Monitoring | Monitor pregnancy status prior to initiation and monthly during treatment. Perform pregnancy test at baseline and monthly. If pregnancy occurs, discontinue immediately and refer to fetal medicine for detailed ultrasound and echocardiography. Assess for oligohydramnios and fetal growth restriction. |
| Fertility Effects | In animal studies, CAMZYOS impaired female fertility at exposures below human therapeutic levels. Male fertility effects observed in rats (decreased sperm count and motility). Human data insufficient; advise patients of potential impairment. |
| Grapefruit and grapefruit juice are contraindicated due to CYP3A4 inhibition increasing mavacamten exposure. No other specific food restrictions. |
| Clinical Pearls | CAMZYOS (mavacamten) is a cardiac myosin inhibitor indicated for symptomatic obstructive hypertrophic cardiomyopathy (HCM). Monitor left ventricular ejection fraction (LVEF) via echocardiography at baseline and periodically; dose reduction or interruption required if LVEF <50% or if symptoms of heart failure develop. Do not use with verapamil, diltiazem, or disopyramide due to negative inotropic effects. Concomitant use with moderate-to-strong CYP2C19 inhibitors requires dose adjustment. Assess for drug interactions with CYP2C19 substrates (e.g., omeprazole, clopidogrel). |
| Patient Advice | Take CAMZYOS exactly as prescribed; do not change dose without consulting your doctor. · You will need regular echocardiograms to monitor your heart function. · Report any new or worsening symptoms of heart failure (shortness of breath, fatigue, swelling in ankles/legs) immediately. · Avoid grapefruit and grapefruit juice while taking CAMZYOS. · Inform your healthcare provider of all medications you take, especially heart medications or those used for stomach acid (e.g., omeprazole). · Do not breastfeed while taking CAMZYOS without consulting your doctor. · Store at room temperature, away from moisture and heat. |