Evidence of Accidental Dosing Errors with Immediate-Release Sodium Oxybate: Data from the US Food and Drug Administration Adverse Event Reporting System.

Introduction: Sodium oxybate has been approved by the US Food and Drug Administration (FDA) to treat narcolepsy for 20 years; however, the only available products have been immediate-release (IR) formulations given twice nightly-once at bedtime and a second dose 2.5-4 h later-creating inherent risks with dosing administration errors.

Objectives: Evidence and risks associated with accidental ingestion of the second IR oxybate dose < 2.5 h after the first dose were examined.

Methods: The FDA Adverse Event Reporting System database was searched for "inappropriate schedule of product administration" with IR sodium oxybate or calcium/magnesium/potassium/sodium oxybates; reports classified as serious and with IR oxybate as the suspect product were further analyzed.

Results: Of 541 reports meeting the search criteria, 178 were classified as serious: accidental early administration of the second dose resulting in adverse events (AEs; n = 41); "near miss" (no harm reported following early dosing; n = 9); intentionally taking second dose early (n = 25); other inappropriate use (late dosing/not taking daily; n = 102); and one duplicate report. Of the 41 reports of taking the second dose too early resulting in AEs, 22% (9/41) used emergency services and 27% (11/41) resulted in hospitalizations. AEs reported with accidentally taking the second dose too early included CNS depression, bradycardia, respiratory depression, dizziness, seizure, confusion, delirium, difficulty awakening, drowsiness, falls, nausea, vomiting, and enuresis.

Conclusions: Patients, caregivers, clinicians, and Poison Control Centers should be aware of the risk of accidentally dosing twice-nightly IR oxybates earlier than 2.5 h after the first dose and the subsequent harm that may occur with early dosing.