Antiseizure

Phenytoin and fosphenytoin

Two genes doing two different jobs on one prescription: one decides how much drug there is, the other decides whether it is safe to start at all.

What this drug connects to

The genes involved

CYP2C9

Drug-Induced Stevens–Johnson Syndrome and Toxic Epidermal Necrolysis →

Phenytoin has a narrow therapeutic index and large variability in blood level between people, partly because CYP2C9 clears it and CYP2C9 activity varies. Separately, HLA-B*15:02 is associated with an increased risk of Stevens–Johnson syndrome and toxic epidermal necrolysis on phenytoin — the same allele that carries that risk with carbamazepine. CPIC issued combined guidance in 2021 covering both genes: one governs how much drug there is, the other governs whether it is safe to start at all. Fosphenytoin is a prodrug the body converts into phenytoin, so both genes apply to it in exactly the same way and the guideline names the two together.

CPIC Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing (Clin Pharmacol Ther 2021, PMID 32779747).

Whose work this rests on

Every guideline above was written by people. Named here because they are contributors to this page in the same sense anybody else on this site is.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for CYP2C9 and HLA-B Genotypes and Phenytoin Dosing: 2020 Update

Karnes JH, Rettie AE, Somogyi AA, Huddart R, Fohner AE, Formea CM, Ta Michael Lee M, Llerena A, Whirl-Carrillo M, Klein TE, Phillips EJ, Mintzer S

and 3 more — show all

Gaedigk A, Caudle KE, Callaghan JT

Clinical pharmacology and therapeutics · 2021 · PMID 32779747

Variants MyGeneLog™ reports for these genes

These are the positions in your own file that carry the genes above. Not every gene in a guideline is one we report — where that is the case the gene appears above without a variant here, and the note says so.

X-17654 levels

CYP2C9 · rs1934969

Appendicular lean mass

CYP2C9 · rs28371678

Deoxyuridine 5'-triphosphate nucleotidohydrolase, mitochondrial protein levels (SomaScan ID:25464-1)

CYP2C9 · rs80159642

Dehydroepiandrosterone sulphate levels

CYP2C9 · rs2185570

Omega-3 Fatty Acids to Polyunsaturated Fatty Acids percentage

CYP2C9 · rs9332238

Urine X-24354 levels in chronic kidney disease

CYP2C9 · rs111667734

Omega-3 fatty acid levels

CYP2C9 · rs55891451

X-11787 levels

CYP2C9 · rs9332172

Warfarin maintenance dose

CYP2C9 · rs4918798

X-11787 levels

CYP2C9 · rs1934963

X-21849 levels

CYP2C9 · rs9332217

Questions about Phenytoin and fosphenytoin

What are phenytoin and fosphenytoin?

Phenytoin and fosphenytoin are antiseizure medicines. Two genes act on them for two different reasons: CYP2C9 governs how much drug is in the blood, and HLA-B*15:02 governs whether it’s safe to start at all.

Does the CYP2C9 variant affect my phenytoin dose?

Yes. CYP2C9 clears phenytoin, and its activity varies between people, contributing to phenytoin’s narrow therapeutic index and large between-person variability in blood level.

Does HLA-B*15:02 affect phenytoin the same way it affects carbamazepine?

Yes — it’s the same allele. HLA-B*15:02 is associated with an increased risk of Stevens-Johnson syndrome and toxic epidermal necrolysis on phenytoin, just as it is with carbamazepine.

Does fosphenytoin carry the same CYP2C9 and HLA-B*15:02 considerations as phenytoin?

Yes. Fosphenytoin is a prodrug the body converts into phenytoin, so both genes apply to it in exactly the same way, which is why CPIC’s 2021 guidance names the two drugs together.

Quoting this page

Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.

Phenytoin and fosphenytoin. MyGeneLog™. https://www.mygenelog.com/drugs/phenytoin

This page is educational and contains no dosing information. Where a clinical guideline covers one of these gene-drug pairs it is written for prescribers and works through validated algorithms alongside clinical monitoring. Nothing here is a reason to start, stop, or change a medication — that conversation belongs with the clinician or pharmacist managing your treatment.