Methotrexat Accord (Methotrexate)

Methotrexate is used across autoimmune and oncologic disease families where folate pathway inhibition is required.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: diminishes skin plaque formation and severity.
• Acute lymphoblastic leukemia: eradicates rapidly dividing leukemic cells.
• Non‑Hodgkin lymphoma: contributes to remission by inhibiting tumor cell replication.
• 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, impairing DNA, RNA and protein synthesis. The resulting effect is cytotoxic to rapidly dividing cells and immunosuppression through reduced lymphocyte proliferation.

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

Common Side Effects

• Nausea and vomiting
• Mucositis or oral ulceration
• Fatigue or malaise
• Alopecia (hair loss)
• Elevated liver enzymes
• Mild skin rash

Serious or Rare Side Effects

• Bone marrow suppression leading to pancytopenia
• Pulmonary toxicity (interstitial pneumonitis)
• Severe hepatotoxicity or fibrosis
• Acute renal failure
• Life‑threatening infection
• Secondary malignancies (e.g., leukemia)

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

• Pregnancy: contraindicated (Category X); teratogenic risk is high.
• Renal function: assess baseline and monitor regularly; dose adjust if impairment occurs.
• Hepatic function: check liver enzymes before initiation and periodically thereafter.
• Hematologic monitoring: perform complete blood counts to detect marrow suppression.
• Infection risk: avoid live vaccines and monitor for signs of infection.
• Elderly patients: consider dose reduction and close observation.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze.

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

Major Interactions (Avoid)

• NSAIDs (e.g., ibuprofen): increase methotrexate toxicity.
• Penicillins and other β‑lactam antibiotics: may raise serum levels.
• Sulfonamide antibiotics: additive bone‑marrow suppression.
• Live vaccines: heightened risk of severe infection.
• Alcohol: exacerbates hepatotoxicity.

Moderate Interactions (Monitor Closely)

• Proton pump inhibitors: may affect renal clearance.
• Azathioprine or other immunosuppressants: additive myelosuppression.
• Warfarin: potential for enhanced anticoagulant effect.
• Phenytoin: may reduce methotrexate efficacy.
• Trimethoprim‑sulfamethoxazole: increased risk of hematologic toxicity.