Bupropion and Phenelzine interaction
Bupropion and Phenelzine: 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
The use of MAOIs (intended to treat psychiatric disorders) concomitantly with bupropion hydrochloride extended-release tablets (XL) or within 14 days of discontinuing treatment with bupropion hydrochloride extended-release tablets (XL) is contraindicated.
There is an increased risk of hypertensive reactions when bupropion hydrochloride extended-release tablets (XL) are used concomitantly with MAOIs.
The use of bupropion hydrochloride extended-release tablets (XL) within 14 days of discontinuing treatment with an MAOI is also contraindicated.
Starting bupropion hydrochloride extended-release tablets (XL) in a patient treated with reversible MAOIs such as linezolid or intravenous methylene blue is contraindicated [see Dosage and Administration (2.8), Warnings and Precautions (5.4), and Drug Interactions (7.6)] .
Monoamine Oxidase Inhibitors (MAOIs): Do not use MAOIs intended to treat psychiatric disorders with bupropion hydrochloride extended-release tablets (XL) or within 14 days of stopping treatment with bupropion hydrochloride extended-release tablets (XL).
From the Phenelzine (phenelzine sulfate) label · effective 2026-05-21
The concurrent administration of an MAO inhibitor and bupropion hydrochloride (Wellbutrin®) is contraindicated.
At least 14 days should elapse between discontinuation of an MAO inhibitor and initiation of treatment with bupropion hydrochloride.
Anyone considering the use of phenelzine sulfate or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
At least 14 days should elapse between the discontinuation of phenelzine sulfate and the institution of another antidepressant or buspirone HCl, or the discontinuation of another MAO inhibitor and the institution of phenelzine sulfate.
Concomitant Use with Dibenzazepine Derivative Drugs If the decision is made to administer phenelzine sulfate concurrently with other antidepressant drugs, or within less than 10 days after discontinuation of antidepressant therapy, the patient should be cautioned by the physician regarding the possibility of adverse drug interaction.
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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.