Phenelzine and Protriptyline interaction
Phenelzine and Protriptyline: 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
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.
…hydrochloride clomipramine hydrochloride desipramine hydrochloride imipramine hydrochloride doxepin carbamazepine cyclobenzaprine HCl amoxapine maprotiline HCl trimipramine maleate protriptyline HCl mirtazapine Phenelzine sulfate should be used with caution in combination with antihypertensive drugs, including thiazide diuretics and β-blockers, since exaggerated…
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.
From the Protriptyline (Protriptyline Hydrochloride) label · effective 2023-07-25
Anyone considering the use of protriptyline hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need.
When it is desired to substitute protriptyline for a monoamine oxidase inhibitor, a minimum of 14 days should be allowed to elapse after the latter is discontinued.
Tachycardia and postural hypotension may occur more frequently with protriptyline than with other antidepressant drugs.
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).
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.