Diazoxide choline extended-release (DCCR) use in Prader-Willi syndrome: patient selection, dosing, and management.

Abstract

Prader-Willi syndrome (PWS) is a rare genetic disorder marked by metabolic, endocrine, and behavioral challenges, with hyperphagia as a central feature contributing to significant health risks. Diazoxide choline extended-release (DCCR; VYKAT™ XR) is a once-daily adenosine triphosphate (ATP)-sensitive potassium channel activator recently approved for the treatment of hyperphagia in individuals with genetically confirmed PWS aged 4 years and older. As this novel therapy enters clinical practice, clinicians require practical guidance on appropriate use. This manuscript provides actionable recommendations for patient selection, baseline assessments, and strategies for optimizing comorbid conditions prior to initiation. Structured, weight-based dosing and titration protocols are outlined, along with recommendations for monitoring glycemia and edema and managing common adverse events (AEs), including hyperglycemia, peripheral edema, and rash. Special considerations are discussed for patients with diabetes, cardiopulmonary risk factors, and those on concomitant medications with potential drug-drug interactions. The guidance is informed by data from the phase 3 DESTINY-PWS program, long-term extension studies, and real-world clinical experience. Emphasis is placed on early identification and management of AEs and the importance of a multidisciplinary approach to care. These recommendations aim to support clinicians in safely and effectively incorporating DCCR into the management of PWS, improving outcomes for affected individuals. Ongoing research and real-world evidence will continue to refine best practices and address remaining gaps in knowledge.