Oxycodone and acetaminophen and Rifampin interaction

Oxycodone and acetaminophen and Rifampin: 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 Oxycodone and acetaminophen (OXYCODONE HYDROCHLORIDE) label · effective 2025-06-05

Major

Examples: Rifampin, carbamazepine, phenytoin Benzodiazepines and Other Central Nervous System (CNS) Depressants Clinical Impact: Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, can increases the risk of hypotension, respiratory depression, profound sedation, coma, and death.

Drug interactionsnames RifampinView label on DailyMed
Major

In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in oxycodone plasma concentration.

Boxed warningby drug classView label on DailyMed
Moderate

Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in oxycodone hydrochloride tablets-treated patients may increase oxycodone plasma concentrations and prolong opioid adverse reactions.

Warnings and precautionsby drug classView label on DailyMed
Moderate

When using Oxycodone Hydrochloride Tablets with CYP3A4 inhibitors or discontinuing CYP3A4 inducers in oxycodone hydrochloride tablets-treated patients, monitor patients closely at frequent intervals and consider dosage reduction of oxycodone hydrochloride tablets until stable drugs effects are achieved [see Drug Interactions ( 7)].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Concomitant use of oxycodone hydrochloride tablets with CYP3A4 inducers or discontinuation of an CYP3A4 inhibitor could decrease oxycodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to oxycodone.

Warnings and precautionsby drug classView label on DailyMed

From the Rifampin (Rifadin IV) label · effective 2026-05-27

Moderate

Decrease AUC by 56% Narcotic Analgesics Oxycodone Decrease AUC by 86% Morphine Decrease exposure Progestin Antagonist Mifepristone Prevention or Management: Refer to the posttreatment assessment in the mifepristone prescribing information to verify that treatment has been successful.

Drug interactionsnames Oxycodone and acetaminophenView 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.