Drug interactions
Leflunomide + Methotrexate
Severity: Major
Leflunomide and Methotrexate: major 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
Combining these drugs increases the risk of hepatotoxicity and bone marrow suppression, including pancytopenia. Both are hepatotoxic, and leflunomide's long-lived active metabolite prolongs the exposure.
What this interaction means in plain words
Leflunomide and Methotrexate can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for.
Leflunomide belongs to Musculoskeletal; Methotrexate belongs to Oncology.
Why it happens
Additive hepatotoxic and myelosuppressive effects; a pharmacokinetic contribution is not well established.
What to do
Monitor ALT, AST, albumin and complete blood counts at baseline and regularly (monthly initially); reduce dose or stop one drug if abnormalities develop.
What to ask your pharmacist
- Does the benefit of taking both outweigh the risk in my case?
- Do I need any blood test, ECG or other check while on both?
- What early warning signs should I watch for, and what should I do if they appear?
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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 Leflunomide
- Bcg vaccine live + Leflunomide Contraindicated
- Influenza virus vaccine quadrivalent intranasal + Leflunomide Contraindicated
- Leflunomide + Measles mumps and rubella vaccine live Contraindicated
- Leflunomide + Measles mumps rubella and varicella vaccine live Contraindicated
- Leflunomide + Measles vaccine Contraindicated
- Leflunomide + Smallpox vaccine live Contraindicated
Frequently asked questions
Can I take Leflunomide with Methotrexate?
MediHelp rates the interaction as major. Leflunomide and Methotrexate can interact in a way that may be serious. Using them together is sometimes necessary, but it needs a deliberate decision by the prescriber, a plan for monitoring, and clear advice on the warning signs to watch for. Combining these drugs increases the risk of hepatotoxicity and bone marrow suppression, including pancytopenia. Both are hepatotoxic, and leflunomide's long-lived active metabolite prolongs the exposure.
How serious is the interaction between Leflunomide and Methotrexate?
MediHelp rates it major, on a four-level scale (minor, moderate, major, contraindicated) based on published labels and references. What to do, in brief: Monitor ALT, AST, albumin and complete blood counts at baseline and regularly (monthly initially); reduce dose or stop one drug if abnormalities develop.
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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