LuciMava (Mavacamten)

About Mavacamten

Mavacamten is used to treat symptomatic obstructive hypertrophic cardiomyopathy (HCM). This medicine helps improve your symptoms and ability to be active. 

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 daily

Allowable subsequent doses with titration are 2.5, 5, 10, or 15 mg daily

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) and subsequent visits

• 2.5 mg/day dosing withheld at Week 8

  • 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%

Maintenance phase dosing (week 12 and q12wk)

• LVEF <50%: Interrupt treatment
• LVEF 50 to <55%: Maintain on same dose and follow-up 12 weeks later

• LVEF ≥55% and Valsalva LVOT gradient <30 mmHg

  • Maintain on same dose During fi¬rst 6-month cycle, check clinical status after 3 months and recheck clinical status and ECHO at 6 months
  • Recheck clinical status and ECHO every 6 months

• 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% occurs 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 same dose for 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-to-moderate CYP2C19 or moderate-to-strong CP3A4 inhibitors

• On stable therapy with weak-to-moderate CYP2C19 inhibitor or a moderate CYP3A4 inhibitor: Initiate at recommended starting dose (5 mg/day)

• On stable therapy with moderate CYP2C19 inhibitor or strong CYP3A4 inhibitor

  • Initiate at 2.5 mg daily
  • Interrupt dosing if Valsalva LVOT gradient <20 mm Hg at Week 4 or Week 8
  • May resume treatment after 4 weeks at 2.5 mg/day if LVEF >=50%
  • If treatment resumed at Week 12, recheck clinical status, Valsalva LVOT gradient, and LVEF in 4 weeks, and maintain current dose for next 8 weeks unless LVEF <50%

• Initiating weak-to-moderate CYP2C19 inhibitor or moderate-to-strong 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)

• Short-term use (eg, 1 week)

  • Weak-to-moderate CYP2C19 inhibitor or moderate-to-strong CYP3A4 inhibitor: Interrupt mavacamten dosing
  • May reinitiate mavacamten at previous dose immediately on discontinuation of concomitant therapy

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