Calcium, magnesium, potassium, and sodium oxybates oral solution for cataplexy or excessive daytime sleepiness associated with narcolepsy

ABSTRACT

Introduction

Lower-sodium oxybate (LXB) is a novel formulation that is approved by the US Food and Drug Administration (FDA) to treat cataplexy and excessive daytime sleepiness (EDS) in adult patients and children ≥7 years with narcolepsy. LXB contains 92% less sodium than sodium oxybate (SXB), which adds 550–1640 mg of sodium/day at usual doses of 3–9 g/day. The FDA has declared LXB to be clinically superior to SXB due to greater safety by reducing the chronic sodium load. Narcolepsy patients have high comorbidities for hypertension and cardiovascular disease conditions, which can be adversely affected by high sodium intake.

Areas covered

This drug review discusses narcolepsy, current and upcoming pharmacotherapy, and LXB chemistry, pharmacodynamics, pharmacokinetics, and metabolism. Published results from LXB’s phase 1 studies, a phase 3 study, and two post-marketing studies are reviewed. Databases searched included PubMed, Google Scholar, Lexi-Comp, Scopus, Science, and Ovid.

Expert opinion

LXB is efficacious in treating daytime sleepiness and cataplexy in adults and children ≥7 years with narcolepsy. Using LXB instead of SXB formulations may benefit narcolepsy patients with cardiovascular comorbidities and hypertension, but long-term studies are needed to prove it.

KEYWORDS:

• Narcolepsy
• cataplexy
• pharmacotherapy
• narcolepsy market
• lower-sodium oxybate
• drug review

Article highlights

• Calcium, magnesium, potassium, and sodium oxybates, also called lower sodium oxybate, has 92% less sodium than sodium oxybate. The FDA has declared LXB to be clinically superior to SXB due to greater safety by reducing the chronic sodium load.

• LXB was FDA-approved in 2020 to treat cataplexy or EDS in patients ≥7 years with narcolepsy. In adult narcolepsy, LXB is effective at doses of 4.5–9 g/night. LXB may be monotherapy or add-on therapy to other wake-promoting drugs/stimulants/anticataplectic agents. Transitioning from SXB to LXB is easy with gram for gram substitution.

• Safety and efficacy of LXB in patients with narcolepsy has been demonstrated in phase 3 trials with fewer weekly cataplexy attacks, lower ESS scores, greater percentages with improvement in narcolepsy symptoms, and better QoL measurements.

• As shown in SXB studies, efficacy of oxybate preparations is dependent on dose and duration of therapy. The safety and tolerability profile of LXB is consistent with the known safety profile of SXB. The most common adverse events are headache, nausea, and decreased appetite.

• LXB is a controlled substance that is available only through a risk evaluation and mitigation strategy (REMS) program in the United States and in Europe.

Declaration of interest

V. C. Abad reports being a consultant and lecturer for Medscape Web/MD video/tutorials on narcolepsy. The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.