Drug-Drug Interactions with Vesicular Monoamine Transporter 2 Inhibitors: Population Estimate of Patients With Tardive Dyskinesia at Risk in Real-World Clinical Practice

Introduction Valbenazine and deutetrabenazine (vesicular monoamine transporter 2 inhibitors) are approved for tardive dyskinesia (TD) treatment in adults. To prevent potential drug-drug interactions (DDIs), valbenazine labeling recommends doses 40 mg/day when taking strong CYP3A4 or CYP2D6 inhibitors and avoidance of strong CYP3A4 inducers and monoamine oxidase inhibitors (MAOIs). Deutetrabenazine labeling recommends doses ≤36-mg/day when taking strong CYP2D6 inhibitors and avoidance of MAOIs. This study estimated proportions of patients with TD at risk of DDIs with valbenazine/deutetrabenazine in real-world practice. Methods Patients aged ≥18 years with TD and ≥1 antipsychotic claim(s) and no valbenazine/ deutetrabenazine claims ≥3 months prior and ≥12 months after diagnosis were identified in the Symphony Health Sciences database (US-based medical, hospital, and pharmacy claims database). Proportions of patients meeting valbenazine/deutetrabenazine concomitant medication labeling restrictions were summarized descriptively. Results 14,264/66,046 patients with TD met inclusion criteria. Proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.2%) and >36 mg/day (21%) versus valbenazine 40 mg/day (4.4%; 22-times difference) and >40 mg/day (28%; 1.3-times difference). Across age groups, underlying conditions (major depressive, mood, and bipolar disorders; schizophrenia), and payer types, proportions of patients at potential risk of DDIs were lower with deutetrabenazine ≤36 mg/day (0.0%– 0.5%) and >36 mg/day (14%– 30%) versus valbenazine 40 mg/day (3%– 5%; 8.0- to >40.0times difference) and >40 mg/day (22%– 35%; 1.2- to >1.5-times difference). Conclusions Estimated proportions of patients with TD at potential risk of DDIs was lower with deutetrabenazine versus valbenazine overall and across age, underlying conditions, and payer types. Funding Teva Branded Pharmaceutical Products R&D, Inc.