Methadone and Tapentadol interaction
Methadone and Tapentadol: 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.
Serotonin Syndrome : Potentially life-threatening condition could result from concomitant serotonergic drug administration.
To further reduce the risk of respiratory depression, consider the following: Patients tolerant to other opioids may be incompletely tolerant to methadone.
From the Tapentadol label · effective 2026-02-26
…SERIOUS AND LIFE-THREATENING RISKS FROM USE OF tapentadol TABLETS Addiction, Abuse, and Misuse Because the use of tapentadol tablets 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…
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.
Reserve concomitant prescribing of tapentadol tablets 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) ] .
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.
Overestimating the tapentadol tablets dosage when converting patients from another opioid product can result in a fatal overdose with the first dose.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
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.