Phenytoin

Phenytoin/Fosphenytoin & CYP2C9

Click below to learn more about the use of CYP2C9 genetics in the prescribing of phenytoin and fosphenytoin.

Phenytoin and fosphenytoin are metabolized by the liver to inactive metabolites. The protein in the liver responsible for the majority of this metabolism is the cytochrome p450 enzyme CYP2C9 (pronounced "sip two see nine").

Across populations, CYP2C9 protein alleles can have different genetic variants that impact their ability to metabolize NSAIDs and other medications. The different alleles can produce three different metabolism phenotypes: normal, intermediate, and poor metabolizers. Of these, the intermediate and poor metabolizer phenotypes have been shown to have higher drug levels and increased risk of adverse effects.

The Clinical Pharmacogenetics Implementation Consortium (CPIC) is a group that evaluates the evidence for the use of pharmacogenetics and then develops clinical practice guidelines. For phenytoin and fosphenytoin, extensive guideline information can be found at: https://cpicpgx.org/guidelines/guideline-for-phenytoin-and-cyp2c9-and-hla-b/, a reference maintained by CPIC.

Here is video that reviews the CPIC guideline for phenytoin/fosphenytoin: https://www.youtube.com/watch?v=cqTEmwVH2eI

At UCHealth the use of pharmacogenetics when prescribing phenytoin or fosphenytoin will occur in patients who meet the following conditions:

1) Provided a blood or saliva sample to the Colorado Center for Personalized Medicine (CCPM) biobank laboratory and this sample has undergone genotyping.
2) Have consented for return of their results.
3) Are prescribed phenytoin or fosphenytoin.

This process takes a minimum of 4-6 weeks but may take several years. Therefore, results will not be available at initial presentation if a patient has not previously enrolled in the biobank.

If you are a provider AND your patient is a CYP2C9 intermediate or poor metabolizer, an inline medication warning will appear if you attempt to prescribe or refill phenytoin or fosphenytoin in UCHealth's EHR. If the inline medication warning is visible, links to resources will be listed for your reference. There is patient education text available for UCHealth providers to use in discharge paperwork or the after visit summary (AVS).

Click here for dosing tips.

Phenytoin Tip Sheets

Webpage updated as of: 4/17/2023

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15-0461 PI: Casey Greene, PhD: Director, CCPM; Professor and Chair, Department of Biomedical Informatics

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Phenytoin/Fosphenytoin & CYP2C9

Click below to learn more about the use of CYP2C9 genetics in the prescribing of phenytoin and fosphenytoin.

Colorado Center for Personalized Medicine

Phenytoin/Fosphenytoin & CYP2C9

Click below to learn more about the use of CYP2C9 genetics in the prescribing of phenytoin and fosphenytoin.

Phenytoin & Fosphenytoin Metabolism and Pharmacogenetics

Clinical Evidence

Clinical Implementation

Further Questions

Colorado Center for Personalized Medicine