Divalproex (valproate) and Methotrexate interaction
Divalproex (valproate) and Methotrexate: 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
Aspirin, carbapenem antibiotics, estrogen-containing hormonal contraceptives, methotrexate: Monitoring of valproate concentrations is recommended ( 7.1 )
Methotrexate Methotrexate may decrease serum valproate levels and potentially result in increased frequency of seizures or bipolar symptoms.
Prescribers should monitor serum valproate concentrations and clinical response when adding or discontinuing methotrexate and adjust valproate dosage, if necessary.
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.