Mavacamten

Confirm absence of pregnancy and use of effective contraception in females of reproductive potential before starting. Initiation or up-titration is not recommended in patients with LVEF below 55%. Regular LVEF and Valsalva left ventricular outflow tract (LVOT) gradient assessment is required for careful titration to achieve an appropriate target Valsalva LVOT gradient while maintaining LVEF at or above 50% and avoiding heart failure symptoms — follow the labelled Initiation, Maintenance and Interruption algorithms (Figures 1-3 of the prescribing information, which were not captured as text in the fetched source). If LVEF falls below 50% while on treatment, interrupt; if interrupted at 2.5 mg, either restart at 2.5 mg or discontinue permanently. Delay dose increases during intercurrent illness (e.g. serious infection) or arrhythmia (e.g. atrial fibrillation or other uncontrolled tachyarrhythmia) that may impair systolic function, and consider interruption. Daily dosing takes weeks to reach steady state, and genetic variation in metabolism and drug interactions can cause large differences in exposure. Missed dose: take as soon as possible and take the next scheduled dose at the usual time the following day; two doses must not be taken on the same day. CYP INTERACTION DOSING: initiate at 5 mg once daily in patients on stable therapy with a weak CYP2C19 inhibitor or a moderate CYP3A4 inhibitor; initiate at 2.5 mg once daily in patients on stable therapy with a moderate CYP2C19 inhibitor or a strong CYP3A4 inhibitor. If a weak to moderate CYP2C19 inhibitor or a moderate to strong CYP3A4 inhibitor is started during treatment, reduce to the next lower daily dose level (15 mg to 10 mg; 10 mg to 5 mg; 5 mg to 2.5 mg), assess clinically and echocardiographically 4 weeks after inhibitor initiation, and do not up-titrate until 12 weeks after inhibitor initiation. Avoid initiating such inhibitors in patients stable on 2.5 mg because no lower once-daily dose is available. For short-term inhibitor use (e.g. 1 week), interrupt mavacamten for the duration and reinitiate at the previous dose immediately on stopping the inhibitor. PAEDIATRIC: safety and effectiveness have not been established in paediatric patients; no paediatric dose is stated. SOURCE: US prescribing information for CAMZYOS (no UK SPC posology was captured in the bundle) — verify against the UK SPC, which may differ.