Is it safe to take Mavacamten (myosin inhibitor) with sertraline (Selective Serotonin Reuptake Inhibitor, SSRI)?

Mavacamten and Sertraline: Potential Drug Interaction Concerns

Concomitant use of mavacamten and sertraline should be approached with caution due to potential drug interactions through the cytochrome P450 pathway, requiring close monitoring of left ventricular ejection fraction (LVEF) and dose adjustments as needed. 1

Pharmacokinetic Considerations

• Mavacamten is extensively metabolized by hepatic cytochromes, primarily CYP2C19 1, 2
• Sertraline may interact with drugs metabolized by CYP2D6 3
• The interaction potential exists because both medications utilize cytochrome P450 pathways

Safety Monitoring Requirements

For Mavacamten

• Mavacamten requires strict monitoring under a Risk Evaluation and Mitigation Strategy (REMS) program 4
• Regular echocardiographic assessment of LVEF is mandatory, as 4.6% of patients develop LVEF <50% 4
• Dose titration is guided by echocardiographic parameters to optimize efficacy while minimizing risk 2

For Sertraline

• Sertraline has potential for drug-drug interactions, particularly with medications metabolized by CYP2D6 3
• Side effects include dizziness, insomnia, fatigue, somnolence, and headache 3

Management Approach

1. Initial Assessment:

   • Evaluate baseline LVEF before starting combination therapy
   • Consider CYP2C19 metabolizer status if available, as this affects mavacamten exposure 2

2. Dosing Strategy:

   • Start with lower doses of both medications
   • Consider starting mavacamten at 2.5 mg (lower than standard 5 mg starting dose) 5
   • Increase doses slowly with careful monitoring 3

3. Monitoring Protocol:

   • Follow mavacamten REMS program requirements for LVEF monitoring 4
   • Monitor for symptoms of heart failure or decreased LVEF
   • Schedule more frequent echocardiographic assessments during initial combination therapy
   • Watch for signs of serotonin syndrome, especially in the first 24-48 hours after dosage changes 3

4. Dose Adjustments:

   • If LVEF decreases to <50%, temporarily interrupt mavacamten 4
   • Consider dose reduction of either medication if adverse effects occur
   • Titrate mavacamten based on echocardiographic parameters 2

Special Considerations

• Mavacamten is indicated for symptomatic obstructive hypertrophic cardiomyopathy (HCM) 3
• Sertraline may actually be beneficial in some cardiovascular conditions, including idiopathic orthostatic hypotension 3
• The combination may be particularly challenging in patients who are poor CYP2C19 metabolizers 2

Potential Alternatives

If the combination proves problematic:

• For HCM: Consider beta-blockers, calcium channel blockers, or disopyramide as alternatives to mavacamten 3
• For depression/anxiety: Consider alternative SSRIs with potentially fewer drug interactions, such as citalopram/escitalopram which may have less effect on CYP450 isoenzymes 3

While concomitant use is possible with careful monitoring, the interaction potential through cytochrome P450 pathways necessitates vigilance and possibly more frequent assessment of cardiac function than would be required with either medication alone.