Methofill (Methotrexate)

Methotrexate is employed in the management of inflammatory and malignant diseases by targeting rapidly proliferating cells.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: diminishes skin lesions and plaque formation.
• Acute lymphoblastic leukemia: interferes with leukemic cell replication.
• Non‑Hodgkin lymphoma: impedes growth of malignant lymphocytes.
• Other solid tumors: used as part of combination regimens to enhance cytotoxic effect.

• Methotrexate inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate. This blockade disrupts folate‑dependent synthesis of purines and thymidylate, leading to impaired DNA, RNA and protein synthesis in rapidly dividing cells, which underlies its immunosuppressive and antineoplastic actions.

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

Common Side Effects

• Nausea and vomiting.
• Fatigue or malaise.
• Oral mucosal ulceration.
• Transient elevation of liver enzymes.
• Mild cytopenias (e.g., neutropenia, thrombocytopenia).
• Alopecia (hair thinning).

Serious or Rare Side Effects

• Pulmonary fibrosis or interstitial pneumonitis.
• Severe hepatic toxicity or fibrosis.
• Bone marrow failure leading to pancytopenia.
• Life‑threatening infections due to immunosuppression.
• Acute renal impairment.
• Anaphylactic or severe hypersensitivity reactions.

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

• Pregnancy: contraindicated (Category X); avoid use in pregnant or planning‑to‑conceive women.
• Renal function: assess baseline creatinine; adjust or avoid if severe impairment.
• Liver function: perform regular hepatic enzyme tests; discontinue if significant elevation occurs.
• Hematologic monitoring: obtain baseline and periodic complete blood counts.
• Concomitant NSAIDs: increase risk of toxicity; use only when necessary.
• 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 toxicity.

Major Interactions (Avoid)

• Live vaccines: may cause severe infection.
• Trimethoprim‑sulfamethoxazole: heightened myelosuppression.
• Proton pump inhibitors: may reduce renal clearance.
• Non‑steroidal anti‑inflammatory drugs: increase risk of gastrointestinal and renal toxicity.
• Alcohol: potentiates hepatic injury.

Moderate Interactions (Monitor Closely)

• Penicillins and other β‑lactams: may raise methotrexate plasma levels.
• Sulfonamides: similar effect on clearance.
• Anticonvulsants (e.g., phenytoin): may alter metabolism.
• Folic acid supplements: can diminish efficacy if not timed correctly.
• Cytarabine: additive myelosuppressive effect.