Lower dose of sodium oxybate safe, efficacious for narcolepsy with cataplexy
Click Here to Manage Email Alerts
Most participants with narcolepsy with cataplexy who took the sodium oxybate therapy Xyrem at the beginning of a randomized withdrawal study transitioned to lower-sodium oxybate at the same dose or within one titration step.
Those who had not previously taken sodium oxybate achieved an individually optimized lower-sodium oxybate dose after a median of three adjustments. The researchers presented their findings at the American Academy of Neurology annual meeting, which is being held virtually.
“Lower-sodium oxybate (LXB) has 92% less sodium than sodium oxybate and is approved in the United States for the treatment of cataplexy or excessive daytime sleepiness in patients with narcolepsy,” Nancy Foldvary-Schaefer, DO, MS, of the Cleveland Clinic Sleep Disorders Center, said during a presentation. “The efficacy and safety of LXB was established in a double-blind, randomized withdrawal study. The study included an initial 12-week, open label period, during which LXB treatment was initiated with individualized titration and optimization of efficacy and tolerability.”
Foldvary-Schaefer and colleagues included 201 individuals aged 18 to 70 years with narcolepsy and a history of 14 or more cataplexy attacks in a typical timeframe of 2 weeks before receiving narcolepsy treatment. Included participants had taken Xyrem only, Xyrem combined with other anticataplectics, anticataplectics aside from Xyrem or were cataplexy treatment-naive at study entry. Between weeks 3 and 12, those who took SXB only or SXB combined with other anticataplectics completed and adjusted to an optimized dose transition to LXB. Those who took other or no anticataplectics started LXB at 4.5 grams per night and titrated to an optimized dose of 1.5 grams or less per night per week, with a maximum total dose of 9 grams per night. The study culminated in a 2-week stable dose period and a 2-week, double-blind, randomized withdrawal period.
Results showed no adjustments in dose or within one titration step among 91% of participants who took Xyrem at study entry. Foldvary-Schaefer and colleagues reported a median number of adjustments of zero among those who took Xyrem at study entry and three among those who did not take Xyrem at study entry. Among the 41 participants who took Xyrem at study entry, the researchers observed a higher total nightly stable LXB dose and fewer dose adjustments made compared with those not taking it.
“Total nightly doses of LXB had a broad distribution, reflecting individualization of optimal dosing across participants, with peaks at 6, 7.5 and 9 grams per night,” Foldvary-Schaefer said. “The overall treatment-emergent adverse event profile of LXB was consistent with that previously observed for sodium oxybate. During the open-label, individualized titration and optimization period, the group that entered taking sodium oxybate alone had the lowest incidence of adverse events and also had no cases of worsening cataplexy.”