Methadone and Alprazolam

Desk tier: Serious concern

Mechanism: opioid × benzodiazepine / Z-drug (respiratory depression)

“Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death.”

Methadone HCl tablets, section Boxed Warning (Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants); 5.3. DailyMed label

Why this grade

Methadone HCl tablets label, Boxed Warning (Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants); 5.3

The Methadone HCl tablets label names this interaction in its Boxed Warning: "Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death." Retrieved from DailyMed 2026-09-27.

Open source

FDA boxed / safety communication

FDA boxed warning (2016): opioids plus benzodiazepines or other CNS depressants — profound sedation, respiratory depression, coma, and death.

Open source

PMID 31006110

2019 Clin Pharmacol Ther. 2B6 PM stacks efavirenz. Same isoform as ketamine and methadone.

Open source

Open this pair in the desk

All pairs for Methadone · Alprazolam

Educational reference only. Not FDA-cleared. The Prescribing Information governs.

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