Cyclobenzaprine and Oxycodone interaction

Cyclobenzaprine and Oxycodone: 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 Oxycodone (Oxycodone Hydrochloride) label · effective 2026-04-16

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 Oxycodone Hydrochloride Oral Solution and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see Warnings and Precautions (5.4) , 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

Advise both patients and caregivers about the risks of respiratory depression and sedation when Oxycodone Hydrochloride Oral Solution is used with benzodiazepines or other CNS depressants (including alcohol and illicit drugs).

Warnings and precautionsby drug classView label on DailyMed
Major

Screen patients for risk of substance use disorders, including opioid abuse and misuse, and warn them of the risk for overdose and death associated with the use of additional CNS depressants including alcohol and illicit drugs [see Drug Interactions (7) ].

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.