Is Dilantin affected by genetics?

Yes — the active ingredient is metabolized by a gene known to vary between individuals.

Relevant genes: CYP2C9, HLA-B

Dilantin is affected by pharmacogenetics through the CYP2C9 and HLA-B genes. Your genotype for these genes can change how your body processes Dilantin, which can affect both how well it works and how well you tolerate it. The strongest evidence level on this page is Strong, based on CPIC or FDA guidelines.

What's in Dilantin

phenytoin affected by CYP2C9, HLA-B

Affected by CYP2C9, HLA-B · CPIC, FDA · Strong evidence

Read the full phenytoin genetics guide →

Phenytoin phenotype recommendations

Published guidance from CPIC and FDA on how phenytoin should be dosed or substituted based on your CYP2C9, HLA-B phenotype.

Phenotype	What it means	Recommendation	Evidence
Normal Metabolizer CYP2C9	Your body processes the drug normally; you can follow the usual dosing with monitoring.	CPIC No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B*15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice. FDA Initiate therapy with recommended starting dose.	Strong
Intermediate Metabolizer CYP2C9	Your body slows the drug slightly, but no dose changes are usually needed.	CPIC No adjustments needed from typical dosing strategies. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice. CPIC For first dose, use typical initial or loading dose. For subsequent doses, use ~25% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice. FDA Consider dose reduction and monitor for CNS toxicity. Avoid phenytoin in CYP2C9*3 carriers if possible. Refer to FDA labeling for specific dosing recommendations.	Moderate
Poor Metabolizer CYP2C9	Your body processes the drug very slowly, so maintenance doses should be cut in half after the first dose.	CPIC + CPIC For first dose, use typical initial or loading dose. For subsequent doses, use ~50% less than typical maintenance dose. Subsequent doses should be adjusted according to therapeutic drug monitoring, response, and side effects. An HLA-B15:02 negative test does not eliminate the risk of phenytoin-induced SJS/TEN, and patients should be carefully monitored according to standard practice. FDA Significantly reduce dose or consider an alternative anticonvulsant. Avoid phenytoin in CYP2C93 carriers. Monitor closely for CNS toxicity and severe cutaneous reactions.	Strong
Indeterminate CYP2C9	The impact of your genotype on response to this drug is unknown.	CPIC + FDA Initiate therapy with recommended starting dose.	—
Not available CYP2C9	The impact of your genotype on response to this drug is unknown.	CPIC + FDA Initiate therapy with recommended starting dose.	—

Sources: CPIC, FDA

The genes behind the guidance

CYP2C9 Cytochrome P450 2C9

CYP2C9 metabolizes warfarin, phenytoin, celecoxib, and some NSAIDs. Variants that reduce its activity are most consequential for warfarin, where even small changes in drug clearance translate into very different doses (and a real bleeding risk if missed).

Poor metabolizers need substantially lower warfarin doses to hit the same INR target.

See all drugs affected by CYP2C9 →

HLA-B Human Leukocyte Antigen B

HLA-B variants don't affect how drugs are metabolized. They affect your immune system's reaction to them. Specific HLA-B alleles are strongly linked to severe skin reactions to drugs like abacavir (HIV), carbamazepine (seizures, bipolar), and allopurinol (gout).

Screening for HLA-B*57:01 before abacavir, and HLA-B*15:02 before carbamazepine in at-risk populations, is now standard of care in much of the world.

See all drugs affected by HLA-B →

Browse the full drug-class: Anticonvulsants.

Related medications

Find out how your genetics affect Dilantin

This page describes the general pharmacogenetics. A Gene2Rx report analyzes your own DNA to tell you which metabolizer group you fall into, across every medication.

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Informational only — not medical advice. Pharmacogenetic guidance describes population-level patterns; your individual response depends on many factors. Never start, stop, or change a medication without talking to your prescribing clinician.