Methadone and Zolpidem interaction
Methadone and Zolpidem: 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 Zolpidem (zolpidem tartrate) label · effective 2025-11-19
The use of Zolpidem Tartrate with other sedative-hypnotics (including other zolpidem products) at bedtime or the middle of the night is not recommended.
Opioids: Concomitant use may increase risk of respiratory depression ( 5.7 , 7.1 )
Opioids The concomitant use of Zolpidem Tartrate with opioids may increase the risk of respiratory depression.
CNS-Depressant Effects: Impaired alertness and motor coordination, including risk of morning impairment.
Risk increases with dose and use with other CNS depressants and alcohol.
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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.