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

Abstract: Background: Valbenazine and deutetrabenazine (vesicular monoamine transporter 2 inhibitors) are approved in the US for treatment of adults with tardive dyskinesia (TD). Valbenazine labeling recommends dose adjustment to the lowest available dose (40 mg/day) when taking strong CYP3A4 or CYP2D6 inhibitors and avoidance of strong CYP3A4 inducers and monoamine oxidase inhibitors (MAOIs) because of potential drug–drug interactions (DDIs). Deutetrabenazine labeling recommends dose adjustment to ≤36 mg/day when taking strong CYP2D6 inhibitors and avoidance of MAOIs. This study was designed to estimate the proportion of patients with TD at risk of DDIs with valbenazine/deutetrabenazine use in real-world practice. Methods: Patients aged ≥18 years with TD and ≥1 antipsychotic claim(s) and no valbenazine/deutetrabenazine claims within ≥3 months prior and ≥12 months after diagnosis were identified in the Symphony Health Sciences database (a US-based medical, hospital, and pharmacy claims database). Proportions of patients meeting valbenazine/deutetrabenazine concomitant medication labeling restrictions were summarized descriptively. Results: Among 66,046 patients with TD, 14,264 met the inclusion criteria and were included in this analysis. Proportions of patients at risk of DDIs (largely driven by strong CYP2D6 inhibitor use [20.8% of patients]) were lower with deutetrabenazine ≤36 mg/day (0.2%) versus valbenazine 40 mg/day (4.4%; 22-times difference), and lower with deutetrabenazine >36 mg/day (21%) versus valbenazine >40 mg/day (27%; 1.3-times difference). Similar results were observed when patients with ≥1 valbenazine/deutetrabenazine claim following TD diagnosis were included. Conclusions: Using this real-world data, the proprotion of patients with TD at risk of DDIs was substantially lower with deutetrabenazine than with valbenazine.Short Description: Valbenazine and deutetrabenazine product labeling both recommend dose adjustment for and/or avoidance of certain concomitant medications because of potential drug–drug interactions (DDIs). The proportion of patients with tardive dyskinesia (TD) at risk of DDIs with deutetrabenazine ≤36 mg/day and >36 mg/day was lower than valbenazine 40 mg/day and >40 mg/day, respectively. These results suggest that prescribing deutetrabenazine results in a lower risk of DDIs for a larger proportion of patients with TD.Name of Sponsoring Organization(s): Teva Branded Pharmaceutical Products R&D, Inc.