Managing mavacamten drug interactions in obstructive hypertrophic cardiomyopathy: the role of a clinical pharmacist in a multidisciplinary team
E K Lozo, F Loncaric, D Milicic, B Skoric, I Planinc, M CikesAbstract
Introduction
Patients with obstructive hypertrophic cardiomyopathy (oHCM) often present with multiple comorbidities requiring complex medication management. Mavacamten, increasingly prescribed in this patient population, is primarily metabolised by CYP2C19 and CYP3A4, which increases the risk of clinically significant drug–drug interactions (DDIs). As members of the multidisciplinary oHCM team, clinical pharmacists can support risk management throughout treatment initiation and dose adjustment.
Purpose
To evaluate the contribution of a clinical pharmacist in identifying, preventing, and managing potential DDIs with mavacamten in routine clinical practice, integrating pharmacogenetic findings and a comprehensive medication review.
Methods
From July 2024 to September 2025, a prospective observational review was conducted in 23 oHCM patients approved for treatment with mavacamten (mean age 57.4 years; 61% female). Medication regimens were assessed prior to mavacamten initiation and after 12 weeks of therapy. All patients underwent CYP2C19 and CYP3A4 pharmacogenetic testing prior to mavacamten initiation (Figure 1). Comprehensive medication reconciliation was conducted, and DDIs were evaluated using a validated DDI database. Pharmacist interventions included drug substitution, dose adjustment, enhanced monitoring, or delayed initiation of mavacamten. The primary endpoint was the change in the number and severity of DDIs.
Results
Before mavacamten initiation, 30 clinically significant interactions were identified among 155 prescribed medications (19.4%): 22 were categorised as level C (monitor therapy), 7 as level D (consider therapy modification), and 1 as level X (avoid combination). Targeted interventions based on pharmacogenetics and concomitant therapy included proton pump inhibitor substitution (n=2), beta-blocker adjustment according to CYP2D6 phenotype (n=1), verapamil/disopyramide dose modification (n=4), tacrolimus dose titration (n=1), delayed initiation after clarithromycin treatment (n=1), and reduced mavacamten starting dose with fluoxetine (n=1). After 12 weeks of therapy, all C-level interactions persisted, D-level interactions decreased from seven to three, and the single X-level interaction was eliminated. Total DDIs decreased from 30 to 25 (–16.7%), with complete elimination of the highest-risk category (Figure 2). No DDI-related adverse events occurred.
Conclusion
This single-centre experience confirms previously reported clinically significant DDIs among oHCM patients initiating mavacamten therapy, particularly with drug combinations such as antiarrhythmics (1) and macrolide antibiotics (2). Structured pharmacist assessment should be considered a key component of safe mavacamten implementation, highlighting the clinical pharmacist as an important member of the multidisciplinary team and improving the quality of care in oHCM.For image description, please refer to the figure legend and surrounding text.For image description, please refer to the figure legend and surrounding text.