Is it safe to take Mavacamten (mavacamten) with Sertraline (sertraline), a selective serotonin reuptake inhibitor (SSRI)?

Safety of Taking Mavacamten with Sertraline

Based on current evidence, taking mavacamten with sertraline poses potential risks due to drug interactions, and caution is warranted when using these medications together.

Understanding the Medications

Mavacamten

• First-in-class cardiac myosin inhibitor approved for symptomatic obstructive hypertrophic cardiomyopathy (HCM)
• Primarily metabolized through CYP2C19 pathway 1
• Requires careful monitoring of left ventricular ejection fraction (LVEF) due to risk of systolic dysfunction 2

Sertraline

• Selective serotonin reuptake inhibitor (SSRI) used for depression and anxiety disorders
• Generally considered weight-neutral with long-term use 3
• Metabolized through multiple CYP pathways

Potential Drug Interaction Concerns

Serotonergic Drug Interactions

• Ozanimod guidelines specifically list sertraline among serotonergic drugs that may cause serious adverse reactions when combined with medications that have MAO inhibition properties 3
• While mavacamten is not explicitly listed as having MAO inhibition properties, caution is warranted with any new cardiac medication

Cardiovascular Considerations

• Mavacamten can reduce LVEF, with approximately 4.6% of patients developing LVEF <50% in real-world data 2
• SSRIs like sertraline have been associated with QT prolongation in some patients 3
• The combination could potentially compound cardiovascular risks

Monitoring Recommendations

If both medications must be used concurrently:

1. Cardiac Monitoring:

   • More frequent echocardiographic assessment of LVEF
   • Monitor for signs of heart failure (shortness of breath, edema, fatigue)
   • Watch for symptoms of bradycardia or arrhythmias

2. Dose Adjustments:

   • Consider starting with lower doses of both medications
   • Follow mavacamten's echocardiography-guided dose titration protocol strictly 1
   • Adjust sertraline dose cautiously, watching for side effects

3. Watch for Adverse Effects:

   • Monitor for serotonin syndrome symptoms (confusion, agitation, tremors, hyperreflexia, autonomic hyperactivity) 3
   • Be alert for signs of behavioral activation/agitation, especially early in treatment or with dose increases 3

Alternative Considerations

If the risk seems too high:

• Consider alternative antidepressants with potentially fewer drug interactions
• Bupropion might be an alternative for depression with less potential for cardiovascular side effects 3
• For HCM, ensure mavacamten is the most appropriate option before combining with sertraline

Conclusion

While there is no absolute contraindication documented specifically between mavacamten and sertraline, the potential for drug interactions affecting cardiovascular function warrants caution. Consult with both a cardiologist and psychiatrist before combining these medications, and ensure close monitoring if they must be used together.