Phenelzine and Selegiline interaction
Phenelzine 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 Phenelzine (phenelzine sulfate) label · effective 2026-05-21
Phenelzine sulfate should not be administered together with or in rapid succession to other MAO inhibitors because HYPERTENSIVE CRISES and convulsive seizures, fever, marked sweating, excitation, delirium, tremor, coma, and circulatory collapse may occur.
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.
From the Selegiline (ZELAPAR) label · effective 2021-06-01
• Concomitant use of other drugs in the monoamine oxidase inhibitor (MAOI) class or other drugs that are potent inhibitors of monoamine oxidase, including linezolid), because of an increased risk for hypertensive crisis [see Warnings and Precautions (5.1)].
• 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.
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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.