Methotrexate Amdipharm Limited (Methotrexate Sodium)

Methotrexate is a folate antagonist used across multiple disease families, particularly inflammatory and malignant disorders.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: diminishes skin plaque formation and severity.
• Acute lymphoblastic leukemia: interferes with leukemic cell proliferation.
• Non‑Hodgkin lymphoma: impedes malignant lymphocyte growth.
• Gestational trophoblastic disease: promotes resolution of abnormal trophoblastic tissue.
• Osteosarcoma: limits tumor cell replication.

• 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, accounting for its immunosuppressive and antineoplastic actions.

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

Common Side Effects

• Nausea and vomiting.
• Fatigue or malaise.
• Oral ulcerations or mouth sores.
• Transient elevation of liver enzymes.
• Decreased white blood cell count.
• Mild hair thinning.

Serious or Rare Side Effects

• Severe hepatic toxicity or fibrosis.
• Pulmonary fibrosis or interstitial pneumonitis.
• Profound bone marrow suppression leading to pancytopenia.
• Acute renal failure.
• Life‑threatening skin reactions such as Stevens‑Johnson syndrome.
• Opportunistic infections due to immunosuppression.

Patients should be monitored closely for safety concerns before and during therapy.

• Liver monitoring: perform baseline and periodic liver function tests.
• Hematologic monitoring: check complete blood counts regularly.
• Pregnancy avoidance: contraindicated in pregnancy; effective contraception required.
• Renal function: adjust dose or avoid in significant renal impairment.
• Concomitant drugs: review use of other folate antagonists or nephrotoxic agents.
• Store at room temperature: keep in the original container, protect from moisture and direct sunlight.

Methotrexate interacts with several drug classes; awareness helps prevent toxicity.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase methotrexate plasma levels.
• Sulfonamide antibiotics (e.g., trimethoprim‑sulfamethoxazole): potentiate bone‑marrow suppression.
• Live vaccines: risk of severe infection due to immunosuppression.
• Other folate antagonists (e.g., pemetrexed): additive toxicity.
• High‑dose penicillins: may reduce renal clearance.

Moderate Interactions (Monitor Closely)

• Azathioprine: combined immunosuppression may heighten infection risk.
• Allopurinol: can increase methotrexate toxicity.
• Warfarin: may enhance anticoagulant effect.
• Oral contraceptives: reduced efficacy reported.
• ACE inhibitors or ARBs: monitor renal function and methotrexate levels.