Phenobarbital and Phenytoin interaction

Phenobarbital and Phenytoin: 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 Phenobarbital (SEZABY) label · effective 2025-12-23

Moderate

Additionally, consider alternatives to structurally similar drugs such as carboxamides (e.g., carbamazepine) and hydantoins (e.g., phenytoin) in these same patients.

Warnings and precautionsnames PhenytoinView label on DailyMed

From the Phenytoin label · effective 2024-12-24

Moderate

John’s wort may vary widely based on preparation. , sucralfate, theophylline Drugs that may either increase or decrease phenytoin serum levels Antiepileptic drugs Phenobarbital, valproate sodium Valproate sodium and valproic acid are similar medications.

Drug interactionsnames PhenobarbitalView 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 PhenobarbitalView 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

Additionally, consider alternatives to structurally similar drugs such as carboxamides (e.g., carbamazepine), barbiturates, succinimides, and oxazolidinediones (e.g., trimethadione) in these same patients.

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

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

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.