Divalproex (valproate) and Nortriptyline interaction
Divalproex (valproate) and Nortriptyline: the Divalproex (valproate) prescribing label 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.
Consideration should be given to lowering the dose of amitriptyline/nortriptyline in the presence of valproate.
In contrast, drugs that are inhibitors of cytochrome P450 isozymes, e.g., antidepressants, may be expected to have little effect on valproate clearance because cytochrome P450 microsomal mediated oxidation is a relatively minor secondary metabolic pathway compared to glucuronidation and beta-oxidation.
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.