Bupropion and Selegiline interaction
Bupropion and Selegiline: 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 Selegiline (ZELAPAR) label · effective 2021-06-01
• May cause serotonin syndrome when used with antidepressants (5.2)
Serotonin Syndrome Serotonin syndrome and hyperpyrexia have been reported with the combined treatment of an antidepressant (e.g., selective serotonin reuptake inhibitors-SSRIs, serotonin-norepinephrine reuptake inhibitors-SNRIs, tricyclic antidepressants, tetracyclic antidepressants, triazolopyridine antidepressants) and a non-selective MAOI (e.g., phenelzine,…
In the post-marketing period, fatal and non-fatal cases of serotonin syndrome have been reported in patients treated with antidepressants concomitantly with ZELAPAR [see Contraindications (4) and Drug Interactions ( 7.1 , 7.2 , 7.3 )] .
Because the mechanisms responsible for these reactions are not fully understood, avoid the combination of ZELAPAR with any antidepressant.
…allow concomitant use of any selective serotonin re-uptake inhibitor (e.g., fluoxetine-Prozac, fluvoxamine-Luvox, paroxetine-Paxil, sertraline, venlafaxine-Effexor, or nefazodone-Serzone) or any non-selective serotonin reuptake inhibiting antidepressant drug (except when taken at a low dose and only at night for the purpose of effective sleep) with ZELAPAR.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
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.