Amitriptyline and Divalproex (valproate) interaction
Amitriptyline and Divalproex (valproate): both prescribing labels describe an interaction that usually calls for monitoring, a dose change, or spacing the doses.
Usually manageable with monitoring or a dose change. Tell your pharmacist you take both.
What the FDA labels say
From the Divalproex (valproate) (Depakote ER) label · effective 2026-03-31
Dosage adjustment of amitriptyline/nortriptyline, propofol, warfarin, and zidovudine may be necessary if used concomitantly with Depakote ER ( 7.2 )
Drugs for which a potentially important valproate interaction has been observed Amitriptyline/Nortriptyline Administration of a single oral 50 mg dose of amitriptyline to 15 normal volunteers (10 males and 5 females) who received valproate (500 mg BID) resulted in a 21% decrease in plasma clearance of amitriptyline and a 34% decrease in the net clearance of nortriptyline.
Rare postmarketing reports of concurrent use of valproate and amitriptyline resulting in an increased amitriptyline level have been received.
Concurrent use of valproate and amitriptyline has rarely been associated with toxicity.
Monitoring of amitriptyline levels should be considered for patients taking valproate concomitantly with amitriptyline.
From the Amitriptyline (Amitriptyline Hydrochloride) label · effective 2025-11-25
Guanethidine or similarly acting compounds; thyroid medication; alcohol, barbiturates and other CNS depressants; and disulfiram – see WARNINGS section.
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.