Acetaminophen and codeine and Isoniazid interaction

Acetaminophen and codeine 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 Acetaminophen and codeine (ACETAMINOPHEN AND CODEINE PHOSPHATE) label · effective 2026-01-22

Major

Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with codeine are complex.

Boxed warningby drug classView label on DailyMed
Major

Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with acetaminophen and codeine phosphate tablets requires careful consideration of the effects on the parent drug, codeine, and the active metabolite, morphine ( see WARNINGS and PRECAUTIONS, Drug Interactions ).

Boxed warningby drug classView label on DailyMed
Major

…respiratory depression ( see WARNINGS ). acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment ( see WARNINGS ). concurrent use of monoamine oxidase inhibitors (MAOIs) or use of MAOIs within the last 14 days ( see WARNINGS ). known or suspected gastrointestinal obstruction, including paralytic ileus ( see WARNINGS…

Contraindicationsby drug classView label on DailyMed
Major

Acetaminophen and codeine phosphate tablets should not be used in patients taking MAOIs or within 14 days of stopping such treatment.

Warningsby drug classView label on DailyMed
Moderate

Cytochrome P450 3A4 Interaction The concomitant use of acetaminophen and codeine phosphate tablets with all cytochrome P450 3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir) or discontinuation of a cytochrome P450 3A4 inducer such as rifampin, carbamazepine,…

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 Acetaminophen and codeineView 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 Acetaminophen and codeineView label on DailyMed
Moderate

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

Drug interactionsnames Acetaminophen and codeineView 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 Acetaminophen and codeineView 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.