mavacamten

Contraindicated in:

Concurrent use of moderate or strong CYP2C19 inhibitors or inducers;
Concurrent use of strong CYP3A4 inhibitors;
Concurrent use of moderate or strong CYP3A4 inducers;
Left ventricular ejection fraction (LVEF) <55%;
OB: Pregnancy.

Use Cautiously in:

Serious infection or arrhythmia (↑ risk of developing systolic dysfunction and HF);
Severe hepatic impairment;
Lactation: Safety not established in breastfeeding;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ↓LVEF, syncope

Neuro: dizziness

Interactions ⬆ ⬇

Drug-drug:

Strong CYP2C19 inhibitors and moderate CYP2C19 inhibitors may significantly ↑ levels and risk of toxicity; concurrent use contraindicated.
Strong CYP3A4 inhibitors, including ketoconazole, may significantly ↑ levels and risk of toxicity; concurrent use contraindicated.
Strong CYP2C19 inducers, including rifampin, and moderate CYP2C19 inducers may significantly ↓ levels and effectiveness; concurrent use contraindicated.
Strong CYP3A4 inducers, including rifampin, and moderate CYP3A4 inducers may significantly ↓ levels and effectiveness; concurrent use contraindicated.
Weak CYP2C19 inhibitors, including omeprazole, may ↑ levels and risk of toxicity; in patients already stabilized on weak CYP2C19 inhibitor therapy, initiate mavacamten at 5 mg once daily. In patients already stabilized on mavacamten therapy, ↓ mavacamten dose by one level when starting weak CYP2C19 inhibitor therapy.
Moderate CYP3A4 inhibitors may ↑ levels and risk of toxicity; in patients already stabilized on moderate CYP3A4 inhibitor therapy, initiate mavacamten at 5 mg once daily. In patients already stabilized on mavacamten therapy, ↓ mavacamten dose by one level when starting moderate CYP3A4 inhibitor therapy.
Use with negative inotropes, including diltiazem (with a beta blocker), disopyramide, ranolazine, or verapamil (with a beta blocker), may ↑ risk of systolic dysfunction and HF; avoid concurrent use.
May ↓ levels and effectiveness of combined hormonal contraceptives; use alternative contraceptive method not affected by CYP450 enzyme induction or add nonhormonal contraceptive method.
May ↓ levels and effectiveness of CYP3A4 substrates, including combined hormonal contraceptives. Use alternative contraceptive method not affected by CYP450 enzyme induction (e.g., intrauterine system) or add nonhormonal contraceptive method (e.g., condom) during concurrent therapy and for 4 mo after last dose of mavacamten.
May ↓ levels and effectiveness of CYP2C9 substrates.
May ↓ levels and effectiveness of CYP2C19 substrates, including omeprazole.

Availability ⬆ ⬇

Capsules: 2.5 mg; 5 mg; 10 mg; 15 mg

Route/Dosage ⬆ ⬇

Initiation Phase

PO (Adults ): 5 mg once daily only if LVEF ≥55%. Wk 4 assessment: If Valsalva left ventricular outflow tract (LVOT) gradient <20 mm Hg, ↓ dose to 2.5 mg once daily. If Valsalva LVOT gradient ≥20 mm Hg, continue 5 mg once daily. Wk 8 assessment: If patient taking 2.5 mg once daily: If Valsalva LVOT gradient <20 mm Hg, interrupt therapy and reassess at Wk 12. If Valsalva LVOT gradient ≥20 mm Hg, continue 2.5 mg once daily. If patient taking 5 mg once daily: If Valsalva LVOT gradient <20 mm Hg, ↓ dose to 2.5 mg once daily. If Valsalva LVOT gradient ≥20 mm Hg, continue 5 mg once daily. Wk 12 assessment: If patient needed to interrupt therapy at Wk 8: If LVEF ≥50%, restart 2.5 mg once daily and continue for the next 12 wk unless LVEF falls <50%. If patient taking 2.5 mg or 5 mg once daily: See Maintenance Phase section below.

Maintenance Phase

PO (Adults ): LVEF <50% at any time: Interrupt treatment and proceed with monitoring (see under Assessment section). LVEF 50–55%, regardless of Valsalva LVOT gradient: Maintain current dose and reassess in 12 wk. LVEF >55% and Valsalva LVOT gradient <30 mm Hg: Maintain current dose and reassess in 12 wk. LVEF ≥55% and Valsalva LVOT gradient ≥30 mm Hg↑ dose to the next higher daily dosage level after being on the same dose for 12 wk (max dose = 15 mg/day).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Acts as a selective, reversible inhibitor of cardiac myosin, thereby modulating the number of myosin heads that cross-bridge to actin during systole or diastole. It helps to produce an energy-sparing, recruitable, super-relaxed state, which reduces dynamic left ventricular outflow tract obstruction and improves cardiac filling pressures.

Therapeutic effects:

Improves functional capacity and symptoms.

Classifications ⬆ ⬇

Therapeutic Classification: heart failure agents

Pharmacologic Classification: temporary class

Pharmacokinetics ⬆ ⬇

Absorption: 85% absorbed following oral administration.

Distribution: Unknown.

Protein Binding: 97–98%

Metabolism/Excretion: Primarily metabolized in the liver via the CYP2C19 isoenzyme, with some metabolism through CYP3A4 and CYP2C9. 2% of White patients, 4% of Black patients, and 14% of Asian patients have CYP2C19 genotype that results in reduced metabolism of mavacamten (poor metabolizers). Primarily excreted in urine (85%; 3% as unchanged drug) with 7% excreted in feces (1% as unchanged drug).

Half-Life: CYP2C19 normal metabolizers: 6–9 days; CYP2C19 poor metabolizers: 23 days.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1 hr	24 hr

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Advise patient if a dose is missed, take as soon as possible. Exact timing is not essential, but do not take two doses on the same day.
Inform patient to enroll in the CAMZYOS REMS program and comply with ongoing cardiac function monitoring requirements using echocardiogram.
Advise patient to notify health care professional immediately for new or worsening signs of HF (arrhythmia, dyspnea, chest pain, fatigue, palpitations, leg edema).
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise patient to use effective contraception during and for 4 mo after therapy ends. Advise pregnant patient exposed to mavacamten of the pregnancy safety study that monitors outcomes to report to Bristol-Myers Squibb at 1-800-721-5072 orwww.bms.com.

Pronunciation ⬆ ⬇

Code ⬆

NDC Code

48957- PPL Pharma Solutions Riverview LLC
- 48957-0091-
  - 48957-0091-1- 10 kg in 1 CONTAINER (48957-0091-1)

50193- SK biotek Ireland Limited
- 50193-4423-
  - 50193-4423-6- 35 kg in 1 DRUM (50193-4423-6)

63285- Patheon, Inc.
- 63285-874-
  - 63285-874-00- 24845 CAPSULE in 1 DRUM (63285-874-00)

63285- Patheon, Inc.
- 63285-875-
  63285-875-00- 19157 CAPSULE in 1 DRUM (63285-875-00)

63285- Patheon, Inc.
- 63285-876-
  63285-876-00- 22625 CAPSULE in 1 DRUM (63285-876-00)

63285- Patheon, Inc.
- 63285-877-
  63285-877-00- 19934 CAPSULE in 1 DRUM (63285-877-00)

69988- Catalent Micron Technologies, Inc.
- 69988-0060-
  69988-0060-1- 1 BAG in 1 DRUM (69988-0060-1) / 10 POWDER in 1 BAG

70600- Maithri Drugs Private Limited
- 70600-050-
  70600-050-01- 50 kg in 1 DRUM (70600-050-01)

70966- Dasami Lab Private Limited
- 70966-0045-
  70966-0045-1- 1 kg in 1 DRUM (70966-0045-1)

73625- Myokardia, Inc.
- 73625-111- CAMZYOS
  73625-111-11- 30 CAPSULE, GELATIN COATED in 1 BOTTLE, PLASTIC (73625-111-11)

73625- Myokardia, Inc.
- 73625-112- CAMZYOS
  - 73625-112-11- 30 CAPSULE, GELATIN COATED in 1 BOTTLE, PLASTIC (73625-112-11)

73625- Myokardia, Inc.
- 73625-113- CAMZYOS
  - 73625-113-11- 30 CAPSULE, GELATIN COATED in 1 BOTTLE, PLASTIC (73625-113-11)

73625- Myokardia, Inc.
- 73625-114- CAMZYOS
  - 73625-114-11- 30 CAPSULE, GELATIN COATED in 1 BOTTLE, PLASTIC (73625-114-11)

81666- APICHEM Laboratories Private Limited
- 81666-008-
  - 81666-008-01- 65 kg in 1 DRUM (81666-008-01)

81912- Moehs Iberica SL
- 81912-0003-
  81912-0003-0- 3 kg in 1 DRUM (81912-0003-0)

84386- Aurobindo Pharma Limited
- 84386-138-
  84386-138-37- 50 kg in 1 DRUM (84386-138-37)

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Indications ⬇

Contraind./Precautions ⬆ ⬇