Drug interactions
Fosphenytoin + Methotrexate
Severity: Moderate
Fosphenytoin 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
Phenytoin, the active metabolite of fosphenytoin, may increase methotrexate toxicity by displacing it from albumin and through its antifolate effects. Methotrexate may also lower phenytoin levels, so seizure control can be compromised. Both drugs can cause hematologic toxicity.
What this interaction means in plain words
Fosphenytoin 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.
Fosphenytoin belongs to Central Nervous System; Methotrexate belongs to Oncology.
Why it happens
Protein-binding displacement and additive antifolate effects of phenytoin, plus a possible reduction in phenytoin absorption or levels with methotrexate.
What to do
Monitor complete blood count and signs of methotrexate toxicity, and check free phenytoin concentrations and seizure control. Adjust the doses accordingly, or consider a non-enzyme-inducing antiseizure drug.
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?
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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
Other interactions of Fosphenytoin
- Dronedarone + Fosphenytoin Contraindicated
- Fosphenytoin + Ledipasvir-sofosbuvir Contraindicated
- Fosphenytoin + Lorlatinib Contraindicated
- Fosphenytoin + Lurasidone Contraindicated
- Fosphenytoin + Ranolazine Contraindicated
- Fosphenytoin + Sofosbuvir-velpatasvir-voxilaprevir Contraindicated
Frequently asked questions
Can I take Fosphenytoin with Methotrexate?
MediHelp rates the interaction as moderate. Fosphenytoin 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. Phenytoin, the active metabolite of fosphenytoin, may increase methotrexate toxicity by displacing it from albumin and through its antifolate effects. Methotrexate may also lower phenytoin levels, so seizure control can be compromised. Both drugs can cause hematologic toxicity.
How serious is the interaction between Fosphenytoin 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: Monitor complete blood count and signs of methotrexate toxicity, and check free phenytoin concentrations and seizure control. Adjust the doses accordingly, or consider a non-enzyme-inducing antiseizure drug.
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.
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