Methadone and Trazodone interaction

Methadone and Trazodone: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

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

Major

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 )].

Boxed warningby drug classView label on DailyMed
Major

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.

Boxed warningby drug classView label on DailyMed
Major

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

Boxed warningby drug classView label on DailyMed
Major

Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration.

Warnings and precautionsby drug classView label on DailyMed
Major

Serotonin Syndrome with Concomitant Use of Serotonergic Drugs Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of METHADOSE with serotonergic drugs.

Warnings and precautionsby drug classView label on DailyMed

From the Trazodone (RALDESY TM) label · effective 2026-09-01

Moderate

CNS Depressants: RALDESY may enhance effects of alcohol, barbiturates, or other CNS depressants ( 7 ).

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Moderate

Central Nervous System (CNS) Depressants Clinical Impact: RALDESY may enhance the response CNS depressants.

Drug interactionsby drug classView label on DailyMed
Moderate

Intervention: Patients should be counseled that RALDESY may enhance the response to alcohol, barbiturates, and other CNS depressants.

Drug interactionsby drug classView label on DailyMed

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Not 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.