Amitriptyline and Rasagiline interaction

Amitriptyline and Rasagiline: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.

Major

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

Major

It should not be given concomitantly with monoamine oxidase inhibitors.

Contraindicationsby drug classView label on DailyMed
Major

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.

Contraindicationsby drug classView label on DailyMed
Minor

Monoamine oxidase inhibitors – see CONTRAINDICATIONS section.

Drug interactionsby drug classView label on DailyMed

From the Rasagiline label · effective 2020-06-30

Major

May cause serotonin syndrome when used with antidepressants ( 5.2 )

Warnings and precautionsby drug classView label on DailyMed
Major

In the postmarketing period, potentially life-threatening serotonin syndrome has been reported in patients treated with antidepressants concomitantly with rasagiline.

Warnings and precautionsby drug classView label on DailyMed
Major

Concomitant use of rasagiline with one of many classes of antidepressants (e.g., SSRIs, SNRIs, triazolopyridine, tricyclic or tetracyclic antidepressants) is not recommended [see Drug Interactions ( 7.5 )].

Warnings and precautionsby drug classView label on DailyMed
Moderate

Although a small number of rasagiline-treated patients were concomitantly exposed to antidepressants (tricyclics n=115; SSRIs n=141), the exposure, both in dose and number of subjects, was not adequate to rule out the possibility of an untoward reaction from combining these agents.

Warnings and precautionsby drug classView label on DailyMed
Moderate

Because of the long half-lives of certain antidepressants (e.g., fluoxetine and its active metabolite), at least five weeks (perhaps longer, especially if fluoxetine has been prescribed chronically and/or at higher doses) should elapse between discontinuation of fluoxetine and initiation of rasagiline [see Drug Interactions ( 7.5 )] .

Warnings and precautionsby drug classView label on DailyMed

Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.

Open in the checker

Not 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.