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HOW Dare You Give Warfarin with Dilantin?

Updated: May 23


Managing patients with seizure disorders who are also on anticoagulants like warfarin can be challenging due to potential drug interactions. Dilantin (phenytoin) is a commonly used anticonvulsant but poses significant interaction risks with warfarin. Switching to Keppra (levetiracetam) is often recommended to mitigate these risks. This blog will provide a comprehensive guide on why and how to make this transition safely.

Why Switch from Dilantin to Keppra for Patients on Warfarin?

Drug Interactions:

  1. Phenytoin and Warfarin:

  • Increased Bleeding Risk: Phenytoin can alter warfarin metabolism, resulting in unpredictable anticoagulant effects that can either increase the risk of bleeding or reduce warfarin's efficacy, leading to potential thromboembolic events.

  • CYP450 Enzyme Interaction: Phenytoin is a potent inducer of the cytochrome P450 (CYP450) enzymes, which significantly affects warfarin metabolism, leading to fluctuating INR levels.

  1. Levetiracetam and Warfarin:

  • Minimal Interaction: Keppra (levetiracetam) does not significantly interact with the CYP450 enzymes and has minimal effects on warfarin metabolism. This makes it a safer option for patients requiring anticoagulation therapy.

Detailed Teaching on Keppra (Levetiracetam)

Mechanism of Action:

Levetiracetam is an anticonvulsant medication that stabilizes neuronal activity by binding to the synaptic vesicle protein SV2A. This modulation helps prevent seizures.


For adult patients, the typical starting dose of Keppra for seizure management is:

  • Keppra 500 mg orally twice a day.


  • Keppra can be taken with or without food.

  • It should be taken at the same times each day to maintain consistent blood levels.

Key Teaching Points for Patients:

  1. Medication Adherence:

  • Take Keppra exactly as prescribed.

  • Do not skip doses or abruptly stop taking the medication, as this can precipitate seizures.

  1. Side Effects:

  • Common side effects include drowsiness, dizziness, and fatigue.

  • Rare but serious side effects can include mood changes, depression, and suicidal thoughts. Patients should report any significant mood changes to their healthcare provider immediately.

  1. Monitoring:

  • Routine blood tests are generally not required for Keppra, making it more convenient for patients compared to Dilantin.

  • However, patients should still be monitored for seizure control and any potential side effects.

  1. Drug Interactions:

  • Keppra has fewer drug interactions compared to phenytoin, making it a safer choice for patients on multiple medications, including warfarin.

Practical Transition Plan:

  1. Discontinuing Dilantin:

  • Gradually taper off Dilantin under the supervision of a healthcare provider to prevent withdrawal seizures.

  • Typically, the dose of Dilantin is reduced gradually over several days to weeks.

  1. Initiating Keppra:

  • Start Keppra at a dose of 500 mg twice a day.

  • This dose can be adjusted based on patient response and tolerance, but the usual effective dose range is 500-1500 mg twice daily.

  1. Monitoring During Transition:

  • Closely monitor the patient for seizure control and any adverse effects during the transition period.

  • Check INR levels more frequently initially to ensure warfarin remains within the therapeutic range as phenytoin is tapered off.


Switching from Dilantin to Keppra in patients on warfarin is a strategic move to minimize drug interactions and enhance patient safety. Keppra’s favorable interaction profile, coupled with its efficacy in seizure control, makes it an excellent alternative. Proper education and careful monitoring during the transition are essential to ensure patient safety and optimal therapeutic outcomes.


  1. Dilantin (Phenytoin) Prescribing Information. Accessed on [19/5/2024].

  2. Guidelines for the Management of Epilepsy. American Epilepsy Society. Accessed on [19/5/2024].

  3. Warfarin Therapy and Management. American Heart Association. [Accessed on [19/5/2024].

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