Phenytoin and CYP2C9
Phenytoin is cleared by CYP2C9 and has a narrow therapeutic index. Reduced-function carriers reach toxic concentrations at standard doses; HLA-B*15:02 separately predicts severe skin reactions.
Why does CYP2C9 matter for Phenytoin?
Phenytoin is cleared by CYP2C9 and has a narrow therapeutic index. Reduced-function carriers reach toxic concentrations at standard doses; HLA-B*15:02 separately predicts severe skin reactions. CYP2C9 clears warfarin (the active S-enantiomer), phenytoin, celecoxib and most other NSAIDs, and several sulfonylureas. The two common decreased-function alleles, *2 and *3, slow clearance enough that carriers need lower warfarin doses and are more prone to bleeding during the first weeks of therapy; together with VKORC1 they explain a large share of the dose variation between patients.
What does CPIC recommend for each CYP2C9 phenotype on Phenytoin?
The guidance below is the CPIC recommendation for prescribers, reproduced for reference. It is written for a clinician who knows the whole picture — never start, stop or change a medicine on the basis of this page.
| Phenotype | CPIC-based guidance |
|---|---|
| Normal Metabolizer | Standard phenytoin dosing. |
| Intermediate Metabolizer | Reduce dose by 25%. Therapeutic drug monitoring recommended. |
| Poor Metabolizer | Reduce dose by 50% or consider alternative anticonvulsant. High risk of toxicity. |
Which CYP2C9 alleles decide the phenotype?
The phenotype is read from the two CYP2C9 star alleles a person carries. The full allele table, with the defining variants and their population frequencies, is on the CYP2C9 gene page.
The *2 (rs1799853) and *3 (rs1057910) variants are on the major consumer chips, so the common CYP2C9 phenotypes are called with good confidence. Rarer alleles such as *5, *6, *8 and *11, which matter most in people of African ancestry, are usually not genotyped.
Other drugs affected by CYP2C9
- Warfarin — Anticoagulant
- Celecoxib — NSAID (COX-2 inhibitor)
- Flurbiprofen/NSAIDs — NSAID
Upload your raw DNA file and see your metaboliser status → · Ask G2: “Does my CYP2C9 genotype affect Phenytoin?”
Genetic associations describe risk across populations, not a diagnosis for any one person. Most variants shift risk modestly and act alongside lifestyle, environment and other genes. Consumer DNA chips do not read every position and can be wrong at any single one. For general education only; talk to a clinician or genetic counsellor before acting on anything here, and never change a prescribed medicine without your prescriber.