Methotrexat Accord (Methotrexate)

Methotrexate is employed in autoimmune and oncologic conditions that involve rapid cell proliferation or immune‑mediated inflammation.

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

• Methotrexate inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate. This blockade reduces the synthesis of purine nucleotides and thymidylate, leading to impaired DNA, RNA, and protein synthesis. The resulting antiproliferative effect targets rapidly dividing cells in malignant tissues and modulates immune cell activity, contributing to its therapeutic actions in cancer and autoimmune disorders.

Methotrexate may cause a range of adverse reactions, from mild to severe, depending on dose, route, and patient factors.

Common Side Effects

• Nausea and vomiting.
• Mucositis or mouth sores.
• Fatigue and lethargy.
• Transient liver enzyme elevation.
• Mild bone marrow suppression (e.g., reduced white blood cells).
• Alopecia (hair thinning or loss).

Serious or Rare Side Effects

• Severe hepatotoxicity or fibrosis.
• Persistent or severe myelosuppression leading to infection.
• Pulmonary toxicity, including interstitial pneumonitis.
• Renal impairment or failure.
• Life‑threatening hypersensitivity reactions.
• Development of secondary malignancies.

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

• Baseline assessment: obtain liver function tests, renal function, and complete blood count prior to initiation.
• Monitoring: conduct regular laboratory evaluations to detect hepatotoxicity or myelosuppression.
• Pregnancy avoidance: contraindicated in pregnancy (Category X); ensure effective contraception for both sexes.
• Drug interactions: avoid concomitant use with nephrotoxic or hepatotoxic agents without supervision.
• Patient education: advise on signs of infection, bleeding, or severe mucosal ulceration.
• Store at ambient temperature: keep below 25°C in the original container, protect from moisture and direct sunlight.

Methotrexate interacts with several drug classes that can alter its efficacy or toxicity.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase risk of renal toxicity.
• Proton pump inhibitors: may elevate methotrexate plasma levels.
• Trimethoprim‑sulfamethoxazole: potentiate myelosuppression.

Moderate Interactions (Monitor Closely)

• Penicillins and other antibiotics: may affect renal clearance.
• Phenytoin and other enzyme inducers: reduce methotrexate effectiveness.
• Vitamin supplements containing folic acid: can diminish therapeutic activity, requiring dose adjustment.