Meperidine and Methadone interaction

Meperidine and Methadone: 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 Meperidine (DEMEROL) label · effective 2026-07-20

Major

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF DEMEROL Addiction, Abuse, and Misuse Because the use of DEMEROL Injection exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of…

Boxed warningby drug classView label on DailyMed
Major

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants 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.

Boxed warningby drug classView label on DailyMed
Major

Reserve concomitant prescribing of DEMEROL Injection and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.3) , Drug Interactions (7) ] .

Boxed warningby drug classView label on DailyMed
Major

• 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.

Boxed warningby drug classView label on DailyMed
Major

Overestimating the DEMEROL Injection dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.

Warnings and precautionsby drug classView label on DailyMed

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

To further reduce the risk of respiratory depression, consider the following: Patients tolerant to other opioids may be incompletely tolerant to methadone.

Warnings and precautionsby 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.