Drug interactions
Divalproex + Methotrexate
Severity: Moderate
Divalproex and Methotrexate: moderate interaction.
Last updated
For healthcare professionals — reference only. This page is a brief summary, not medical advice and not a substitute for official labeling or clinical judgement. Always verify before prescribing or dispensing.
Summary
Methotrexate has been reported to lower valproate concentrations, which may lead to loss of seizure or mood control. The mechanism is unclear, and the effect has mostly been seen in case reports.
What this interaction means in plain words
Divalproex and Methotrexate can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken.
Why it happens
Mechanism is not established; increased valproate clearance has been suggested.
What to do
Check valproate concentrations and clinical response when methotrexate is started or stopped, and adjust the valproate dose accordingly. Watch for breakthrough seizures or mood symptoms.
What to ask your pharmacist
- Should I take them at different times of day?
- Does the dose of either medicine need to change?
- Is there anything I should avoid, such as alcohol or certain foods, while on both?
Pro+ members
Unlock the full page
Create an account and start a Pro+ trial to unlock the full management advice for Divalproex and Methotrexate, the additional notes, the evidence detail and the whole-prescription interaction checker.
- Full clinical management advice
- Additional notes
- Evidence detail
- Interaction checker for a whole prescription
Try Pro+ free for 7 days on the web. No card needed.
Other interactions of Methotrexate
- Acitretin + Methotrexate Contraindicated
- Adenovirus types 4 and 7 live + Methotrexate Contraindicated
- Influenza virus vaccine quadrivalent intranasal + Methotrexate Contraindicated
- Ketorolac + Methotrexate Contraindicated
- Measles mumps and rubella vaccine live + Methotrexate Contraindicated
- Measles mumps and rubella vaccine + Methotrexate Contraindicated
Frequently asked questions
Can I take Divalproex with Methotrexate?
MediHelp rates the interaction as moderate. Divalproex and Methotrexate can affect each other. The combination is often manageable, but it may need a change of dose, a change of timing, or extra checks while both are taken. Methotrexate has been reported to lower valproate concentrations, which may lead to loss of seizure or mood control. The mechanism is unclear, and the effect has mostly been seen in case reports.
How serious is the interaction between Divalproex and Methotrexate?
MediHelp rates it moderate, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Check valproate concentrations and clinical response when methotrexate is started or stopped, and adjust the valproate dose accordingly. Watch for breakthrough seizures or mood symptoms.
What other medicines interact with Methotrexate?
MediHelp also lists interactions of Methotrexate with, for example, Acitretin, Adenovirus types 4 and 7 live, Influenza virus vaccine quadrivalent intranasal. The full list is on the Methotrexate page.
Full monographs, dosing and an interaction checker in the MediHelp app
Open the complete reference, check multi-drug interactions and use dosing tools in the MediHelp app.
