Investigators affiliated with Avadel Pharmaceuticals plc, a company that has tentative Food and Drug Administration (FDA) approval for a once-nightly sodium oxybate for adults with narcolepsy, published a paper with real-world data describing the risk of accidental dosing errors with immediate-release twice-nightly oxybate. The paper was published in Drugs — Real World Outcomes.
Oxybates are currently available as a twice-nightly formulation, which requires patients with narcolepsy to take a first dose at bedtime and the second dose 2.5 to 4 hours later. The investigators conducted an analysis using post-marketing safety surveillance data from the FDA Adverse Event Reporting System (FAERS) to identify reports of suspected dosing errors.
Out of 541 reports where the second dose of an immediate-release twice-nightly oxybate may not have been taken as prescribed, 177 were submitted as serious reports and subsequently analyzed, including:
- Accidental early administration of the second dose resulting in adverse events (AEs; n=41)
- “Near miss” with no harm reported following early dosing (n=9)
- Intentionally taking second dose early (n=25)
- Other inappropriate use, such as late dosing or not taking daily (n=102)
- Among 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 central nervous system depression, bradycardia, respiratory depression, dizziness, seizure, confusion, delirium, difficulty awakening, drowsiness, falls, nausea, vomiting, and enuresis
- 20% of accidental early administration cases took their two doses at or almost at the exact same time; 39% consumed their second dose of immediate-release sodium oxybate oral solution less than 1 hour after the first dose; 61% took the second dose between 1 and 2.5 hours after the first dose
- There was a greater frequency of reported harm to patients in the group who took their second dose 1 hour or less after their first dose
Currently, there is no information pertaining to the risk of accidentally consuming the second dose less than 2.5 hours after the first dose or related potential patient harm in the labeling for the marketed immediate-release twice-nightly oxybate products.
“Post-marketing adverse event reports are recognized to represent just the ‘tip of the iceberg’ as reporting is voluntary for patients and clinicians and likely underestimates incidence,” says Jennifer Gudeman, PharmD, senior vice president, medical and clinical affairs of Avadel, in a release. “This analysis identified and described serious reports due to patients accidentally consuming their second, middle-of-the-night immediate-release sodium oxybate dose less than 2.5 hours after the first dose. Nearly one-fourth of these cases resulted in emergency medical services or emergency department visits, and another 27% resulted in hospitalization.
“The medical and patient community should be aware of this risk with immediate-release oxybates, as it is not currently described in the labeling. An extended-release once-nightly sodium oxybate product that eliminates a second, middle-of-the-night dose, could potentially mitigate these risks.”