Fosphenytoin and Valproic acid interaction

Fosphenytoin and Valproic acid: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.

What the FDA labels say

From the Valproic acid label · effective 2024-05-02

Major

Children under the age of two years are at a considerably increased risk of developing fatal hepatotoxicity, especially those on multiple anticonvulsants, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease.

Boxed warningby drug classView label on DailyMed
Major

In patients over two years of age who are clinically suspected of having a hereditary mitochondrial disease, valproic acid oral solution should only be used after other anticonvulsants have failed.

Boxed warningby drug classView label on DailyMed
Moderate

Patients on multiple anticonvulsants, children, those with congenital metabolic disorders, those with severe seizure disorders accompanied by mental retardation, and those with organic brain disease may be at particular risk.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Hepatic enzyme-inducing drugs (e.g., phenytoin, carbamazepine, phenobarbital, primidone, rifampin) can increase valproate clearance, while enzyme inhibitors (e.g., felbamate) can decrease valproate clearance.

Drug interactionsby drug classView label on DailyMed
Moderate

Therefore increased monitoring of valproate and concomitant drug concentrations and dosage adjustment are indicated whenever enzyme-inducing or inhibiting drugs are introduced or withdrawn (7.1)

Drug interactionsby drug classView label on DailyMed

From the Fosphenytoin (CEREBYX) label · effective 2025-08-28

Moderate

John's wort may vary widely based on preparation. theophylline Drugs that may either increase or decrease phenytoin serum levels Antiepileptic drugs Phenobarbital, valproate sodium, valproic acid 7.2 Drugs Affected by Phenytoin or CEREBYX Table 7 includes commonly occurring drug interactions affected by phenytoin (the active metabolite of CEREBYX).

Drug interactionsnames Valproic acidView label on DailyMed
Moderate

…doxycycline, estrogens, furosemide, oral contraceptives, paroxetine, quinidine, rifampin, sertraline, theophylline, and vitamin D Drugs whose level is decreased by phenytoin Anticoagulants Apixaban, dabigatran, edoxaban, rivaroxaban Antiepileptic drugs The effect of phenytoin on phenobarbital, valproic acid and sodium valproate serum levels is unpredictable.

Drug interactionsnames Valproic acidView 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

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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.