Amitriptyline and Phenelzine interaction
Amitriptyline 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 Amitriptyline (Amitriptyline Hydrochloride) label · effective 2025-11-25
Anyone considering the use of amitriptyline hydrochloride tablets or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
It should not be given concomitantly with monoamine oxidase inhibitors.
When it is desired to replace a monoamine oxidase inhibitor with amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued.
The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide).
Monoamine oxidase inhibitors – see CONTRAINDICATIONS section.
From the Phenelzine (phenelzine sulfate) label · effective 2026-05-21
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.
Phenelzine sulfate should not be used in combination with dextromethorphan or with CNS depressants such as alcohol and certain narcotics.
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.
A List of Dibenzazepine Derivative Drugs by Generic Name Follows: nortriptyline hydrochloride amitriptyline hydrochloride perphenazine and amitriptyline hydrochloride clomipramine hydrochloride desipramine hydrochloride imipramine hydrochloride doxepin carbamazepine cyclobenzaprine HCl amoxapine maprotiline HCl trimipramine maleate protriptyline HCl mirtazapine…
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.