Methadone and Zaleplon interaction
Methadone 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 Methadone (METHADOSE) label · effective 2026-04-27
Managing Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death [see Warnings and Precautions ( 5.2 )].
Reserve concomitant prescribing of benzodiazepines or other CNS depressants in patients in methadone treatment to those for whom alternatives to benzodiazepines or other CNS depressants are inadequate.
Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, and death.
…Concomitant Use of Benzodiazepines or Other CNS Depressants with Methadone Concomitant use of methadone and benzodiazepines and/or other CNS depressants (e.g., alcohol, non-benzodiazepine sedative/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, gabapentinoids [gabapentin or pregabalin], and other opioids), increases the risk…
As a routine part of orientation to methadone treatment, educate patients about the risks of concomitant use of benzodiazepines, sedatives, opioid analgesics, or alcohol.
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.
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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.