Phenytoin and Topiramate interaction

Phenytoin and Topiramate: both prescribing labels describe an interaction that usually calls for monitoring, a dose change, or spacing the doses.

Moderate

Usually manageable with monitoring or a dose change. Tell your pharmacist you take both.

What the FDA labels say

From the Phenytoin label · effective 2024-12-24

Moderate

…Affect Phenytoin Concentrations Interacting Agent Examples Drugs that may increase phenytoin serum levels Antiepileptic drugs Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline…

Drug interactionsnames TopiramateView label on DailyMed
Moderate

Carbamazepine, felbamate, lamotrigine, topiramate, oxcarbazepine, lacosamide Antilipidemic agents Atorvastatin, fluvastatin, simvastatin Antiplatelets Ticagrelor Antiviral agents Efavirenz, lopinavir/ritonavir, indinavir, nelfinavir, ritonavir, saquinavir Fosamprenavir: phenytoin when given with fosamprenavir alone may decrease the concentration of amprenavir,…

Drug interactionsnames TopiramateView label on DailyMed
Moderate

Limited evidence suggests that HLA-B*1502 may be a risk factor for the development of SJS/TEN in patients of Asian ancestry taking other antiepileptic drugs associated with SJS/TEN, including phenytoin.

Warnings and precautionsby drug classView label on DailyMed
Moderate

…defects), and abnormalities characteristic of fetal hydantoin syndrome, including dysmorphic skull and facial features, nail and digit hypoplasia, growth abnormalities (including microcephaly), and cognitive deficits, have been reported among children born to epileptic women who took phenytoin alone or in combination with other antiepileptic drugs during pregnancy.

Warnings and precautionsby drug classView label on DailyMed

From the Topiramate (Trokendi XR) label · effective 2026-03-20

Moderate

Antiepileptic Drugs Concomitant administration of phenytoin or carbamazepine with topiramate resulted in a clinically significant decrease in plasma concentrations of topiramate when compared to topiramate given alone.

Drug interactionsnames PhenytoinView label on DailyMed
Moderate

Because of the potential of topiramate to cause CNS depression, as well as other cognitive and/or neuropsychiatric adverse reactions, TROKENDI XR should be used with extreme caution if used in combination with alcohol and other CNS depressants [see Contraindications (4) and Warnings and Precautions (5.7) ].

Drug interactionsby drug classView label on DailyMed

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Not medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.