Topiramate and Zaleplon interaction
Topiramate and Zaleplon: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Zaleplon label · effective 2025-10-08
The use of zaleplon with other sedative-hypnotics at bedtime or the middle of the night is not recommended (see ).
Post-marketing reports have shown that complex sleep behaviors may occur with zaleplon alone at recommended dosages, with or without the concomitant use of alcohol or other central nervous system (CNS) depressants.
Coadministration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression.
Dosage adjustments of zaleplon and of other concomitant CNS depressants may be necessary when zaleplon is administered with such agents because of the potentially additive effects.
The risk of next-day psychomotor impairment, including impaired driving, is increased if zaleplon is taken with less than a full night of sleep remaining (7 to 8 hours); if a higher than the recommended dose is taken; if coadministered with other CNS depressants or alcohol; or if coadministered with other drugs that increase the blood levels of zaleplon.
From the Topiramate (Trokendi XR) label · effective 2026-03-20
Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, TROKENDI XR should be used with extreme caution if used in combination with alcohol and other CNS depressants [see Contraindications (4) and Warnings and Precautions (5.7) ].
CNS Depressants Concomitant administration of topiramate with other CNS depressant drugs or alcohol has not been evaluated in clinical studies.
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Open in the checkerNot 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.