Bupropion and Flumazenil interaction
Bupropion and Flumazenil: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
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
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)] .
Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs (4, 5.3)
…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)] .
Additional predisposing conditions include diabetes mellitus treated with oral hypoglycemic drugs or insulin, use of anorectic drugs, excessive use of alcohol, use of benzodiazepines, sedatives/hypnotics, or opiates.
From the Flumazenil label · effective 2025-09-23
THESE ARE MOST FREQUENT IN PATIENTS WHO HAVE BEEN ON BENZODIAZEPINES FOR LONG-TERM SEDATION OR IN OVERDOSE CASES WHERE PATIENTS ARE SHOWING SIGNS OF SERIOUS CYCLIC ANTIDEPRESSANT OVERDOSE.
…Flumazenil is contraindicated: in patients with a known hypersensitivity to flumazenil or benzodiazepines. in patients who have been given a benzodiazepine for control of a potentially life-threatening condition (e.g., control of intracranial pressure or status epilepticus). in patients who are showing signs of serious cyclic antidepressant overdose (see WARNINGS ).
Flumazenil is not recommended in cases of serious cyclic antidepressant poisoning, as manifested by motor abnormalities (twitching, rigidity, focal seizure), dysrhythmia (wide QRS, ventricular dysrhythmia, heart block), anticholinergic signs (mydriasis, dry mucosa, hypoperistalsis), and cardiovascular collapse at presentation.
Possible risk factors for seizures include: concurrent major sedative-hypnotic drug withdrawal, recent therapy with repeated doses of parenteral benzodiazepines, myoclonic jerking or seizure activity prior to flumazenil administration in overdose cases, or concurrent cyclic antidepressant poisoning.
In such cases flumazenil should be withheld and the patient should be allowed to remain sedated (with ventilatory and circulatory support as needed) until the signs of antidepressant toxicity have subsided.
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Open in the checkerNot 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.