What medications should be avoided in a patient with narcolepsy taking Xywav (calcium, magnesium, potassium, and sodium oxybates)?

Medications That Cannot Be Taken with Xywav

Xywav is absolutely contraindicated with alcohol and sedative hypnotics, and requires extreme caution or dose reduction with any CNS depressant including opioids, benzodiazepines, sedating antidepressants/antipsychotics, sedating anti-epileptic drugs, general anesthetics, and muscle relaxants due to life-threatening risks of respiratory depression, profound sedation, and death. 1

Absolute Contraindications

• Alcohol: Xywav is FDA-contraindicated in combination with alcohol due to compounded CNS depression and respiratory depression risk 1
• Sedative hypnotics: All sedative hypnotic medications are absolutely contraindicated with Xywav 1
• Succinic semialdehyde dehydrogenase deficiency: Xywav is contraindicated in patients with this metabolic disorder 1

Medications Requiring Dose Reduction or Discontinuation

CNS Depressants (High Risk)

• Opioid analgesics: May cause respiratory depression, hypotension, profound sedation, syncope, and death when combined with Xywav; consider interrupting Xywav for short-term opioid use (e.g., post-operative pain) 1
• Benzodiazepines: Significantly increase risk of respiratory depression and profound sedation; dose reduction or discontinuation of one or both agents should be considered 1
• Sedating antidepressants or antipsychotics: Concurrent use increases CNS depression risk and requires dose adjustment 1
• Sedating anti-epileptic drugs: May potentiate CNS depression requiring dose modification 1
• General anesthetics: Require careful coordination and potential Xywav interruption during surgical procedures 1
• Muscle relaxants: Increase risk of respiratory depression and profound sedation 1

Divalproex Sodium (Requires Specific Dose Adjustment)

• When initiating divalproex sodium in patients on stable Xywav: Reduce Xywav dosage by at least 20% with initial concomitant use 1
• When initiating Xywav in patients already on divalproex sodium: Start with a lower Xywav dosage and titrate based on clinical response 1

Critical Safety Monitoring

• Black box warning: Xywav is a Schedule III controlled substance and CNS depressant that may cause clinically significant respiratory depression and obtundation at recommended doses 2, 1
• Timing considerations: If short-term use of an opioid is required (perioperative or post-operative), interruption of Xywav treatment should be considered 1
• Hazardous activities: Patients must avoid operating machinery, automobiles, or airplanes for at least 6 hours after taking Xywav 1

Common Pitfalls to Avoid

• Illicit CNS depressants: Any illicit CNS depressant use (including illicit GHB) dramatically increases risk of seizures, respiratory depression, coma, and death 1
• Underestimating interaction severity: Even "mild" CNS depressants can cause life-threatening respiratory depression when combined with Xywav 1
• Inadequate patient counseling: Patients must be queried about CNS depression-related events at initiation and periodically thereafter 1

REMS Program Requirement

• Xywav is only available through a restricted Risk Evaluation Mitigation Strategy (REMS) program using certified pharmacies due to its abuse potential and serious safety risks 2, 1