Fluoxetine and Phenelzine interaction
Fluoxetine 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 Fluoxetine (Prozac) label · effective 2026-01-08
Serotonin Syndrome and MAOIs: Do not use MAOIs intended to treat psychiatric disorders with PROZAC or within 5 weeks of stopping treatment with PROZAC.
Do not use PROZAC within 14 days of stopping an MAOI intended to treat psychiatric disorders.
Monoamine Oxidase Inhibitors (MAOIs) The use of MAOIs intended to treat psychiatric disorders with PROZAC or within 5 weeks of stopping treatment with PROZAC is contraindicated because of an increased risk of serotonin syndrome.
The use of PROZAC within 14 days of stopping an MAOI intended to treat psychiatric disorders is also contraindicated [see Dosage and Administration ( 2.9 ) and Warnings and Precautions ( 5.2 )] .
Starting PROZAC in a patient who is being treated with MAOIs such as linezolid or intravenous methylene blue is also contraindicated because of an increased risk of serotonin syndrome [see Dosage and Administration ( 2.10 ) and Warnings and Precautions ( 5.2 )] .
From the Phenelzine (phenelzine sulfate) label · effective 2026-05-21
There have been reports of serious reactions (including hyperthermia, rigidity, myoclonic movements and death) when serotoninergic drugs (e.g., dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxine) have been combined with an MAO inhibitor.
At least 14 days should elapse between the discontinuation of an MAO inhibitor and the start of a serotonin re-uptake inhibitor or vice-versa, with the exception of fluoxetine.
Allow at least five weeks between discontinuation of fluoxetine and initiation of phenelzine sulfate and at least 14 days between discontinuation of phenelzine sulfate and initiation of fluoxetine, or other serotoninergic agents.
Drug Interactions In patients receiving nonselective monoamine oxidase (MAO) inhibitors in combination with serotoninergic agents (e.g., dexfenfluramine, fluoxetine, fluvoxamine, paroxetine, sertraline, citalopram, venlafaxine) there have been reports of serious, sometimes fatal, reactions.
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.
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.