Drug Interactions between sodium oxybate and trimethadione

GENERALLY AVOID: The central nervous system and respiratory depressant effects of sodium oxybate, which is the sodium salt of gamma hydroxybutyrate (GHB), may be potentiated by concomitant use of other agents with CNS depressant effects including anticonvulsants. An increased risk of serious adverse reactions such as respiratory depression, hypotension, profound sedation, syncope, coma, and even death should be considered.

ADJUST DOSE: Animal data suggest a possible pharmacokinetic interaction between sodium oxybate and certain anticonvulsants like valproate, phenytoin, ethosuximide, and trimethadione that can inhibit the enzyme GHB dehydrogenase, which converts GHB to succinic semialdehyde. In humans, coadministration of sodium oxybate (6 gm/day in two equal doses 4 hours apart) with divalproex sodium (1250 mg valproic acid per day) has been associated with a 25% mean increase in systemic exposure to sodium oxybate and a greater impairment on some tests of attention and working memory. Pharmacokinetic data are not available for other anticonvulsants.

MANAGEMENT: Concomitant use of sodium oxybate with other CNS depressants should be avoided whenever possible. Otherwise, close monitoring and/or dosage reductions should be considered. For patients already stabilized on sodium oxybate who are prescribed divalproex sodium, the manufacturer recommends that the nightly dosage of sodium oxybate be reduced initially by at least 20%. Conversely, for patients already taking divalproex sodium, it is recommended that prescribers use a lower starting dosage of sodium oxybate upon initiation of treatment. Further dosage adjustments should be made according to patient response and tolerance. No specific dosage recommendations are available for use with other anticonvulsants. All patients treated with sodium oxybate should be advised not to drive, operate machinery, or engage in hazardous activities requiring mental alertness and motor coordination for at least 6 hours after taking the second nightly dose of sodium oxybate and until they know how the medication affects them.