Drug interactions
Fosphenytoin + Paracetamol
Severity: Moderate
Fosphenytoin and Paracetamol: moderate 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
Fosphenytoin, through its active metabolite phenytoin, induces hepatic enzymes that increase the oxidative metabolism of paracetamol. This can lower paracetamol exposure and raise formation of the hepatotoxic metabolite NAPQI, particularly with high or prolonged paracetamol doses.
What this interaction means in plain words
Fosphenytoin and Paracetamol can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Fosphenytoin belongs to Central Nervous System; Paracetamol belongs to Musculoskeletal.
Why it happens
Phenytoin induces CYP enzymes (such as CYP2E1, CYP1A2, CYP3A4) and glucuronidation, shifting paracetamol toward toxic oxidative metabolism.
What to do
Keep paracetamol at the lowest effective dose and avoid chronic high-dose use in patients on fosphenytoin. Monitor liver function if prolonged use is required.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
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Other interactions of Paracetamol
- Ethanol + Paracetamol Major
- Busulfan + Paracetamol Moderate
- Carbamazepine + Paracetamol Moderate
- Cholestyramine + Paracetamol Moderate
- Felbamate + Paracetamol Moderate
- Imatinib + Paracetamol Moderate
Other interactions of Fosphenytoin
- Dronedarone + Fosphenytoin Contraindicated
- Fosphenytoin + Ledipasvir-sofosbuvir Contraindicated
- Fosphenytoin + Lorlatinib Contraindicated
- Fosphenytoin + Lurasidone Contraindicated
- Fosphenytoin + Ranolazine Contraindicated
- Fosphenytoin + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
Frequently asked questions
Can I take Fosphenytoin with Paracetamol?
MediHelp rates the interaction as moderate. Fosphenytoin and Paracetamol can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Fosphenytoin, through its active metabolite phenytoin, induces hepatic enzymes that increase the oxidative metabolism of paracetamol. This can lower paracetamol exposure and raise formation of the hepatotoxic metabolite NAPQI, particularly with high or prolonged paracetamol doses.
How serious is the interaction between Fosphenytoin and Paracetamol?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Keep paracetamol at the lowest effective dose and avoid chronic high-dose use in patients on fosphenytoin. Monitor liver function if prolonged use is required.
What other medicines interact with Paracetamol?
MediHelp also lists interactions of Paracetamol with, for example, Ethanol, Busulfan, Carbamazepine. The full list is on the Paracetamol page.
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