Metotrexate Ebewe (Methotrexate Disodium)

Methotrexate is used across autoimmune and oncologic disease pathways to inhibit abnormal cell proliferation.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: diminishes skin lesions and plaque formation.
• Acute lymphoblastic leukemia: eradicates rapidly dividing leukemic blasts.
• Non‑Hodgkin lymphoma: impedes lymphoma cell growth.
• 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 production. The resulting inhibition of cell division particularly affects rapidly proliferating immune cells and malignant cells, providing its immunosuppressive and antineoplastic effects.

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

Common Side Effects

• Nausea and vomiting: gastrointestinal upset occurring shortly after administration.
• Stomatitis: inflammation and ulceration of the oral mucosa.
• Fatigue: generalized tiredness and reduced energy.
• Elevated liver enzymes: mild hepatic enzyme rise detectable on labs.
• Mild cytopenias: slight reductions in white blood cells or platelets.

Serious or Rare Side Effects

• Severe hepatotoxicity: potential liver injury requiring monitoring.
• Pulmonary fibrosis: interstitial lung disease presenting with cough and dyspnea.
• Myelosuppression: profound bone‑marrow suppression leading to infection risk.
• Renal toxicity: impaired kidney function, especially with high doses.
• Severe mucositis: extensive oral and gastrointestinal ulceration.
• Anaphylaxis: rare hypersensitivity reaction requiring immediate medical attention.

Methotrexate requires careful monitoring and patient education to minimize risks.

• Pregnancy: contraindicated (Category X); teratogenic effects can be fatal to the fetus.
• Renal function: assess creatinine clearance before each dose; adjust or avoid if impaired.
• Hepatic function: perform baseline and periodic liver function tests; avoid in severe liver disease.
• Hematologic monitoring: regular complete blood counts to detect myelosuppression.
• Concomitant NSAIDs: use with caution as they may increase toxicity.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

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

Major Interactions (Avoid)

• Live vaccines: may cause severe infection due to immunosuppression.
• NSAIDs (e.g., ibuprofen, naproxen): increase risk of renal toxicity and gastrointestinal ulceration.
• Penicillins (e.g., ampicillin): potentiate myelosuppression.

Moderate Interactions (Monitor Closely)

• Sulfonamides and trimethoprim: may enhance hematologic toxicity.
• Proton pump inhibitors: can raise methotrexate plasma levels.
• Azathioprine or other immunosuppressants: additive bone‑marrow suppression.
• Vitamin supplements containing folic acid: may reduce therapeutic effect; dosing should be coordinated with prescriber.