Ketamine and Oxycodone and acetaminophen interaction

Ketamine and Oxycodone and acetaminophen: 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 Ketamine (Ketalar) label · effective 2026-03-27

Major

Benzodiazepines, Opioid Analgesics, or other CNS Depressants : Concomitant use may result in profound sedation, respiratory depression, coma, or death.

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Moderate

Benzodiazepines, Opioid Analgesics, or Other CNS Depressants Concomitant use of ketamine with opioid analgesics, benzodiazepines, or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Drug Interactions ( 7.3 )] .

Warnings and precautionsby drug classView label on DailyMed
Moderate

Closely monitor neurological status and respiratory parameters, including respiratory rate and pulse oximetry, when KETALR and opioid analgesics, benzodiazepines, or other CNS depressants are co-administered.

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Moderate

Concomitant use of opioid analgesics may prolong recovery time.

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Moderate

Benzodiazepines, Opioid Analgesics, Or Other CNS Depressants Concomitant use of ketamine with opioid analgesics, benzodiazepines, or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions ( 5.9 )] .

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From the Oxycodone and acetaminophen (OXYCODONE HYDROCHLORIDE) label · effective 2025-06-05

Major

…LIFE-THREATENING RESPIRATORY DEPRESSION; ACCIDENTAL INGESTION; NEONATAL OPIOID WITHDRAWAL SYNDROME; CYTOCHROME P450 3A4 INTERACTION; and RISKS FROM CONCOMITANT USE WITH BENZODIAZEPINES OR OTHER CNS DEPRESSANTS Addiction, Abuse, and Misuse Oxycodone hydrochloride tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to…

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 [see Warnings and Precautions ( 5.5), Drug Interactions ( 7)] .

Boxed warningby drug classView label on DailyMed
Major

Reserve concomitant prescribing of oxycodone hydrochloride tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate.

Boxed warningby drug classView label on DailyMed
Major

Advise both patients and caregivers about the risks of respiratory depression and sedation when oxycodone hydrochloride tablets are 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), Patient Counseling Information ( 17)] .

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.