Tramadol and acetaminophen and Voriconazole interaction

Tramadol and acetaminophen and Voriconazole: 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 Tramadol and acetaminophen (Tramadol Hydrochloride and Acetaminophen) label · effective 2026-01-01

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 tramadol are complex.

Boxed warningby drug classView label on DailyMed
Major

Use of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol hydrochloride and acetaminophen requires careful consideration of the effects on the parent drug, tramadol, and the active metabolite, M1 [see Warnings and Precautions (5.7) , Drug Interactions (7) ] .

Boxed warningby drug classView label on DailyMed
Major

The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors with tramadol are complex.

Boxed warningby drug classView label on DailyMed
Major

Evaluate patients receiving tramadol hydrochloride and acetaminophen and any CYP3A4 inhibitor or inducer at frequent intervals for the risk for serious adverse events including seizures and serotonin syndrome, signs and symptoms that may reflect opioid toxicity and opioid withdrawal when tramadol hydrochloride and acetaminophen is used in conjunction with inhibitors…

Warnings and precautionsby drug classView label on DailyMed
Moderate

Risks of Interactions with Drugs Affecting Cytochrome P450 Isoenzymes The effects of concomitant use or discontinuation of cytochrome P450 3A4 inducers, 3A4 inhibitors, or 2D6 inhibitors on levels of tramadol and M1 from tramadol hydrochloride and acetaminophen are complex.

Warnings and precautionsby drug classView label on DailyMed

From the Voriconazole label · effective 2026-06-02

Moderate

Fentanyl (CYP3A4 Inhibition) Increased Reduction in the dose of fentanyl and other long-acting opiates metabolized by CYP3A4 should be considered when concomitantly administered with voriconazole.

Drug interactionsby drug classView label on DailyMed
Moderate

Extended and frequent monitoring for opiate-associated adverse reactions may be necessary .

Drug interactionsby drug classView label on DailyMed
Moderate

Reduction in the dose of alfentanil and other opiates metabolized by CYP3A4 (e.g., sufentanil) should be considered when concomitantly administered with voriconazole.

Drug interactionsby drug classView label on DailyMed
Moderate

A longer period for monitoring respiratory and other opiate-associated adverse reactions may be necessary.

Drug interactionsby drug classView label on DailyMed
Moderate

Reduction in the dose of oxycodone and other long-acting opiates metabolized by CYP3A4 should be considered when concomitantly administered with voriconazole.

Drug interactionsby 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.