Metotrexato A.Forall (Methotrexate)

Methotrexate is a folate antagonist used across several disease families, particularly inflammatory and neoplastic conditions.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: diminishes skin lesions and plaque formation.
• Acute lymphoblastic leukemia: interferes with malignant cell proliferation.
• Osteosarcoma: impedes tumor growth and metastasis.
• Gestational trophoblastic disease: promotes resolution of abnormal trophoblastic tissue.

• Methotrexate inhibits the enzyme dihydrofolate reductase, decreasing tetrahydrofolate levels required for purine and pyrimidine synthesis. This blockade impairs DNA, RNA and protein production, leading to reduced cellular replication in rapidly dividing tissues such as immune cells and malignant tumor cells.

Methotrexate may cause a range of adverse reactions, from mild to severe.

Common Side Effects

• Nausea or vomiting.
• Fatigue or malaise.
• Oral mucosal ulceration.
• Elevated liver enzymes.
• Mild leukopenia or thrombocytopenia.
• Alopecia (hair thinning).

Serious or Rare Side Effects

• Severe hepatic toxicity or fibrosis.
• Pulmonary fibrosis or interstitial pneumonitis.
• Life‑threatening bone marrow suppression.
• Acute renal failure.
• Severe cutaneous reactions (e.g., Stevens‑Johnson syndrome).
• Opportunistic infections due to immunosuppression.

Methotrexate requires careful monitoring and specific safety measures.

• Pregnancy: contraindicated (Category X); avoid use in pregnant or planning patients.
• Liver function: monitor transaminases regularly; adjust or discontinue if significant elevation occurs.
• Hematology: perform complete blood counts before therapy and periodically during treatment.
• Renal function: assess creatinine clearance; dose adjust in impairment.
• Drug interactions: avoid concurrent use with live vaccines or nephrotoxic agents.
• Store below 25°C: keep in original packaging, protect from moisture and direct sunlight.

Methotrexate interacts with several medicines that can alter its efficacy or safety.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase toxicity.
• Penicillins and other β‑lactam antibiotics: may raise methotrexate levels.
• Sulfonamides: potentiate hematologic suppression.
• Live vaccines: risk of severe infection.
• Alcohol: exacerbates hepatic injury.

Moderate Interactions (Monitor Closely)

• Proton pump inhibitors: may affect renal clearance.
• Trimethoprim‑sulfamethoxazole: enhances bone‑marrow suppression.
• Azathioprine or other immunosuppressants: additive cytopenia.
• Warfarin: may increase anticoagulant effect.
• Tetracyclines: potential for reduced methotrexate clearance.