Drug interactions
Acetaminophen + Phenytoin
Severity: Minor
Acetaminophen and Phenytoin: minor interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Chronic phenytoin use increases the formation of the toxic acetaminophen metabolite NAPQI. This may raise the risk of liver injury, especially with high doses, overdose or fasting. At usual doses, the risk is small.
What this interaction means in plain words
Acetaminophen and Phenytoin have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised.
Why it happens
Induction of CYP enzymes by phenytoin increases the oxidative conversion of acetaminophen to NAPQI.
What to do
Keep acetaminophen at standard doses and avoid prolonged high-dose use in patients on phenytoin. Monitor liver tests if long-term use is needed.
What to ask your pharmacist
- Is there anything I should notice while taking both?
- Do I need to tell my doctor at the next visit?
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Other interactions of Phenytoin
- Artemether / lumefantrine + Phenytoin Contraindicated
- Bictegravir + Phenytoin Contraindicated
- Cabotegravir + Phenytoin Contraindicated
- Doravirine + Phenytoin Contraindicated
- Elbasvir / grazoprevir + Phenytoin Contraindicated
- Elvitegravir / cobicistat / emtricitabine / tenofovir df + Phenytoin Contraindicated
Frequently asked questions
Can I take Acetaminophen with Phenytoin?
MediHelp rates the interaction as minor. Acetaminophen and Phenytoin have a small, usually unimportant interaction. Most people can take both; the pharmacist may still mention it so that any unexpected effect is recognised. Chronic phenytoin use increases the formation of the toxic acetaminophen metabolite NAPQI. This may raise the risk of liver injury, especially with high doses, overdose or fasting. At usual doses, the risk is small.
How serious is the interaction between Acetaminophen and Phenytoin?
MediHelp rates it minor, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Keep acetaminophen at standard doses and avoid prolonged high-dose use in patients on phenytoin. Monitor liver tests if long-term use is needed.
What other medicines interact with Phenytoin?
MediHelp also lists interactions of Phenytoin with, for example, Artemether / lumefantrine, Bictegravir, Cabotegravir. The full list is on the Phenytoin page.
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