Amitriptyline and Desvenlafaxine interaction
Amitriptyline and Desvenlafaxine: 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.
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).
From the Desvenlafaxine (Pristiq Extended-Release) label · effective 2026-04-28
• Serotonin Syndrome: Increased risk when co-administered with other serotonergic agents, but also when taken alone.
If concomitant use of PRISTIQ with other serotonergic drugs is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms.
Examples selegiline, tranylcypromine, isocarboxazid, phenelzine, linezolid, methylene blue Other Serotonergic Drugs Clinical Impact Concomitant use of PRISTIQ with other serotonergic drugs increases the risk of serotonin syndrome.
Intervention Monitor for symptoms of serotonin syndrome when PRISTIQ is used concomitantly with other drugs that may affect the serotonergic neurotransmitter systems.
If serotonin syndrome occurs, consider discontinuation of PRISTIQ and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2) ].
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.