Cyclobenzaprine and Methadone interaction

Cyclobenzaprine 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 Cyclobenzaprine (TONMYA) label · effective 2026-08-14

Major

Based on its structural similarity to TCAs, concomitant use of TONMYA with: MAO inhibitors may be life-threatening [see Contraindications (4) ] , Alcohol, barbiturates, and other CNS depressants may increase the risk of adverse reactions associated with these drugs, Tramadol may increase the seizure risk, Guanethidine or other similar acting drugs may block the…

Drug interactionsby drug classView label on DailyMed
Moderate

CNS Depression and Risk of Operating a Motor Vehicle or Hazardous Machinery TONMYA monotherapy may cause CNS depression and concomitant use of TONMYA with alcohol, barbiturates, or other CNS depressants may increase the risk of CNS depression [see Drug Interactions (7) ].

Warnings and precautionsby drug classView label on DailyMed
Moderate

CNS Depressants: CNS depressant effects of alcohol, barbiturates, and other CNS depressants may be enhanced ( 5.5 , 7 )

Drug interactionsby 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

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

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

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.