Divalproex (valproate) and Sodium oxybate interaction

Divalproex (valproate) and Sodium oxybate: the Sodium oxybate prescribing label flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Sodium oxybate (Xyrem) label · effective 2025-07-01

Major

Abuse or misuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death [see Warnings and Precautions ( 5.2 )].

Boxed warningby drug classView label on DailyMed
Major

Abuse of illicit GHB, either alone or in combination with other CNS depressants, is associated with CNS adverse reactions, including seizure, respiratory depression, decreases in the level of consciousness, coma, and death.

Warnings and precautionsby drug classView label on DailyMed
Moderate

• Concomitant use with divalproex sodium: An initial reduction in Xyrem dose of at least 20% is recommended ( 2.5 , 7.2 ).

Drug interactionsnames Divalproex (valproate)View label on DailyMed
Moderate

Divalproex Sodium Concomitant use of Xyrem with divalproex sodium results in an increase in systemic exposure to GHB, which was shown to cause a greater impairment on some tests of attention and working memory in a clinical study [see Clinical Pharmacology ( 12.3 )] .

Drug interactionsnames Divalproex (valproate)View label on DailyMed
Moderate

An initial dose reduction of Xyrem is recommended when used concomitantly with divalproex sodium [see Dosage and Administration ( 2.5 )] .

Drug interactionsnames Divalproex (valproate)View label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.