Drug interactions
Phenytoin + Warfarin
Severity: Major
Phenytoin and Warfarin: major 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
The interaction is complex: phenytoin induces warfarin metabolism and may lower INR over time, but early on it may transiently raise INR through displacement and competition. Unpredictable INR changes can cause bleeding or thrombosis, and warfarin may also raise phenytoin levels.
What this interaction means in plain words
Phenytoin and Warfarin can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Phenytoin belongs to Central Nervous System; Warfarin belongs to Cardiovascular.
Why it happens
Phenytoin induces CYP2C9 and CYP3A4 while competing for CYP2C9 and displacing protein binding, and warfarin may inhibit phenytoin metabolism.
What to do
Monitor INR frequently when starting, changing or stopping phenytoin, and check phenytoin levels. Adjust warfarin dosing to the target INR.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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Other interactions of Warfarin
- Defibrotide + Warfarin Contraindicated
- Ketorolac + Warfarin Contraindicated
- Abciximab + Warfarin Major
- Acetylsalicylic acid + Warfarin Major
- Adagrasib + Warfarin Major
- Amiodarone + Warfarin Major
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 Phenytoin with Warfarin?
MediHelp rates the interaction as major. Phenytoin and Warfarin can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. The interaction is complex: phenytoin induces warfarin metabolism and may lower INR over time, but early on it may transiently raise INR through displacement and competition. Unpredictable INR changes can cause bleeding or thrombosis, and warfarin may also raise phenytoin levels.
How serious is the interaction between Phenytoin and Warfarin?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor INR frequently when starting, changing or stopping phenytoin, and check phenytoin levels. Adjust warfarin dosing to the target INR.
What other medicines interact with Warfarin?
MediHelp also lists interactions of Warfarin with, for example, Defibrotide, Ketorolac, Abciximab. The full list is on the Warfarin page.
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