Bupropion and Phenytoin interaction

Bupropion and Phenytoin: 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 Bupropion (BUPROPION HCl ER (XL)) label · effective 2026-02-04

Major

Bupropion hydrochloride extended-release tablets (XL) are contraindicated in patients undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs [see Warnings and Precautions (5.3) and Drug Interactions (7.3)] .

Contraindicationsby drug classView label on DailyMed
Major

Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs (4, 5.3)

Contraindicationsby drug classView label on DailyMed
Moderate

CYP2B6 Inducers: Dose increase may be necessary if coadministered with CYP2B6 inducers (e.g., ritonavir, lopinavir, efavirenz, carbamazepine, phenobarbital, and phenytoin) based on clinical exposure, but should not exceed the maximum recommended dose (7.1).

Drug interactionsnames PhenytoinView label on DailyMed
Moderate

Carbamazepine, Phenobarbital, and Phenytoin: Although not systematically studied, these drugs may induce metabolism of bupropion and may decrease bupropion exposure [see Clinical Pharmacology (12.3)] .

Drug interactionsnames PhenytoinView label on DailyMed
Moderate

…in patients with a seizure disorder or conditions that increase the risk of seizure (e.g., severe head injury, arteriovenous malformation, central nervous system [CNS] tumor or CNS infection, severe stroke, anorexia nervosa or bulimia, or abrupt discontinuation of alcohol, benzodiazepines, barbiturates, and antiepileptic drugs) [see Contraindications (4)] .

Warnings and precautionsby drug classView label on DailyMed

From the Phenytoin label · effective 2024-12-24

Moderate

…Ethosuximide, felbamate, oxcarbazepine, methsuximide, topiramate Azoles Fluconazole, ketoconazole, itraconazole, miconazole, voriconazole Antineoplastic agents Capecitabine, fluorouracil Antidepressants Fluoxetine, fluvoxamine, sertraline Gastric acid reducing agents H 2 antagonists (cimetidine), omeprazole Sulfonamides Sulfamethizole, sulfaphenazole, sulfadiazine,…

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.