Hydrocodone and acetaminophen and Isoniazid interaction

Hydrocodone and acetaminophen and Isoniazid: 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 Hydrocodone and acetaminophen (Hydrocodone Bitartrate and Acetaminophen) label · effective 2026-05-13

Major

Cytochrome P450 3A4 Interaction The concomitant use of hydrocodone bitartrate and acetaminophen tablets with all Cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions and may cause potentially fatal respiratory depression.

Boxed warningby drug classView label on DailyMed
Major

Monitor patients receiving hydrocodone bitartrate and acetaminophen tablets and any Cytochrome P450 3A4 inhibitor or inducer for signs of respiratory depression or sedation [see CLINICAL PHARMACOLOGY ; WARNINGS ; PRECAUTIONS, Drug Interactions ].

Boxed warningby drug classView label on DailyMed
Major

The use of hydrocodone bitartrate and acetaminophen tablets is not recommended for patients taking MAOIs or within 14 days of stopping such treatment.

Drug interactionsby drug classView label on DailyMed
Major

Monoamine Oxidase Inhibitor (MAOI) Interaction Inform patients to avoid taking hydrocodone bitartrate and acetaminophen tablets while using any drugs that inhibit monoamine oxidase.

Precautionsby drug classView label on DailyMed
Moderate

Risks of Concomitant Use or Discontinuation of Cytochrome P450 3A4 Inhibitors and Inducers Concomitant use of hydrocodone bitartrate and acetaminophen tablets with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of…

Warningsby drug classView label on DailyMed

From the Isoniazid label · effective 2026-04-27

Moderate

Acetaminophen A report of severe acetaminophen toxicity was reported in a patient receiving isoniazid.

Drug interactionsnames Hydrocodone and acetaminophenView label on DailyMed
Moderate

It is believed that the toxicity may have resulted from a previously unrecognized interaction between isoniazid and acetaminophen and a molecular basis for this interaction has been proposed.

Drug interactionsnames Hydrocodone and acetaminophenView label on DailyMed
Moderate

Studies have demonstrated that pretreatment with isoniazid potentiates acetaminophen hepatotoxicity in rats 1,2 .

Drug interactionsnames Hydrocodone and acetaminophenView label on DailyMed
Minor

Furthermore it has been proposed that isoniazid resulted in induction of P-450IIE1 in the patient's liver which, in turn, resulted in a greater proportion of the ingested acetaminophen being converted to the toxic metabolites.

Drug interactionsnames Hydrocodone 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.