Methotrexate Viatris (Methotrexate)

Methotrexate is a folate antagonist used across several disease categories, primarily autoimmune disorders and oncology.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: diminishes skin lesions and plaque formation.
• Certain malignancies (e.g., acute lymphoblastic leukemia, non‑Hodgkin lymphoma): interferes with cancer cell proliferation as part of chemotherapy protocols.

• Methotrexate inhibits dihydrofolate reductase, decreasing tetrahydrofolate production and thereby limiting the synthesis of purine nucleotides and thymidylate. This impairs DNA, RNA, and protein synthesis in rapidly dividing cells, leading to immunosuppression in autoimmune disease and cytotoxicity in malignant cells.

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

Common Side Effects

• Nausea or vomiting: mild to moderate gastrointestinal upset.
• Fatigue: persistent tiredness unrelated to activity level.
• Oral ulceration: painful sores in the mouth or throat.
• Elevated liver enzymes: mild hepatic irritation detected on labs.
• Hair thinning: temporary loss of scalp hair.
• Cytopenias: reduced white blood cells or platelets.

Serious or Rare Side Effects

• Severe liver toxicity: potential for hepatitis or fibrosis.
• Bone marrow suppression: risk of aplastic anemia or severe pancytopenia.
• Pulmonary fibrosis: interstitial lung disease presenting with dyspnea.
• Renal failure: impaired kidney function, especially with high doses.
• Life‑threatening infections: due to immunosuppression.
• Severe skin reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.

Methotrexate requires careful monitoring and specific safety measures before and during therapy.

• Pregnancy contraindication: teratogenic (Category X); avoid use in pregnant or planning patients.
• Renal function: assess creatinine clearance; adjust or avoid if impaired.
• Hepatic monitoring: perform baseline and periodic liver function tests.
• Hematologic surveillance: regular complete blood counts to detect cytopenias.
• Alcohol avoidance: limit intake to reduce hepatic risk.
• Contraception: use effective methods for both sexes during treatment and for a defined period after cessation.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Methotrexate interacts with several drug classes, necessitating vigilance to avoid harmful effects.

Major Interactions (Avoid)

• NSAIDs: increase methotrexate toxicity by reducing renal clearance.
• Penicillins and sulfonamides: may potentiate bone marrow suppression.
• Live vaccines: risk of severe infection due to immunosuppression.
• Alcohol: amplifies hepatic injury risk.
• Other folate antagonists: additive toxicity.

Moderate Interactions (Monitor Closely)

• Warfarin: enhanced anticoagulant effect, monitor INR.
• Proton pump inhibitors: may increase methotrexate serum levels.
• Azathioprine or other immunosuppressants: combined myelosuppression risk.
• Trimethoprim‑sulfamethoxazole: potential for additive hematologic toxicity.