mavacamten: clinical use

Prescribing considerations

• Initiate under a physician experienced in cardiomyopathy management.
• Determine CYP2C19 phenotype because poor metabolisers have substantially higher exposure and greater systolic-dysfunction risk.
• Assess LVEF before initiation; treatment should not begin when LVEF is below 55%.
• Review prescription, non-prescription and herbal products before treatment and whenever therapy changes.
• Obtain a negative pregnancy test and provide contraception counselling where relevant.
• Evidence is insufficient in severe renal or severe hepatic impairment and in people younger than 18 years.

Contraindications and cautions

• Hypersensitivity to mavacamten or an excipient
• Pregnancy
• Women of childbearing potential not using effective contraception
• Strong CYP3A4 inhibitors in CYP2C19 poor metabolisers or when phenotype is undetermined
• Combined strong CYP2C19 and strong CYP3A4 inhibition

Monitoring

• Serial echocardiographic assessment of LVEF, LVOT obstruction and clinical response
• Symptoms suggesting systolic dysfunction or heart failure
• Additional cardiac assessment during serious infection, arrhythmia or other illness that may impair systolic function
• LVEF and clinical response after relevant interacting medicines are started, stopped or changed
• Pregnancy testing where applicable

Clinical pharmacology

Mavacamten is an orally absorbed, highly protein-bound, selective and reversible allosteric cardiac myosin inhibitor. It is metabolised mainly by CYP2C19, with contributions from CYP3A4 and CYP2C9; its terminal half-life is prolonged substantially in CYP2C19 poor metabolisers.

Formulation and product differences

• Available as hard capsules with strength-specific coloured caps and printed strength markings; all have a white body marked “Mava”.
• Capsule shells contain gelatin.
• The capsules are essentially sodium-free and require no special storage conditions.

Capsule

Route: Oral

Strengths: 2.5 mg, 5 mg, 10 mg, 15 mg