Methotrexate Viatris (Methotrexate)

Methotrexate acts on rapidly dividing cells and immune pathways, making it useful across several disease families.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: limits skin cell proliferation and improves plaque lesions.
• Acute lymphoblastic leukemia: interferes with malignant cell DNA synthesis to achieve remission.
• Non‑Hodgkin lymphoma: induces cytotoxicity in lymphoma cells to control disease spread.
• Ectopic pregnancy: halts trophoblastic growth, allowing non‑surgical resolution.

• Methotrexate inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate and thereby blocking folate‑dependent synthesis of purines and pyrimidines. This disruption impairs DNA, RNA and protein production, leading to reduced proliferation of immune cells and rapidly dividing tumor cells, and providing immunosuppressive and cytotoxic effects.

Methotrexate may cause a range of adverse reactions that vary in frequency and severity.

Common Side Effects

• Nausea or vomiting
• Fatigue or malaise
• Mucositis or mouth ulcers
• Elevated liver enzymes
• Alopecia or hair thinning
• Skin rash or itching

Serious or Rare Side Effects

• Bone marrow suppression leading to pancytopenia
• Severe hepatic toxicity or fibrosis
• Pulmonary fibrosis or interstitial pneumonitis
• Life‑threatening infections
• Acute renal failure
• Anaphylactic or severe hypersensitivity reactions

Before initiating therapy, clinicians should evaluate patient history and monitor laboratory parameters.

• Pregnancy: avoid use unless clearly indicated, as it is teratogenic.
• Liver disease: assess baseline liver function and monitor regularly.
• Renal impairment: adjust dose or avoid if creatinine clearance is markedly reduced.
• Concomitant immunosuppressants: increase risk of infection, require close observation.
• Alcohol consumption: limit intake to reduce hepatic toxicity risk.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Methotrexate interacts with several drug classes, necessitating careful review of concomitant medications.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase methotrexate toxicity.
• Penicillins and sulfonamides: may enhance hematologic toxicity.
• Live vaccines: risk of severe infection due to immunosuppression.
• Alcohol: potentiates hepatic injury.
• Proton‑pump inhibitors: may raise plasma methotrexate levels.

Moderate Interactions (Monitor Closely)

• Azathioprine or cyclosporine: additive immunosuppression.
• Leflunomide: combined hepatotoxic potential.
• Warfarin: may increase anticoagulant effect.
• Phenytoin or carbamazepine: may alter methotrexate clearance.
• Trimethoprim‑sulfamethoxazole: heightened risk of bone‑marrow suppression.