Metex (Methotrexate)

Methotrexate is used in several disease categories, primarily targeting immune‑mediated and proliferative disorders.

• Rheumatoid arthritis: reduces joint inflammation, pain, and stiffness while slowing structural damage and preserving function.
• Psoriasis: decreases skin plaque formation and scaling by limiting keratinocyte proliferation and inflammatory signaling.
• Acute lymphoblastic leukemia: interferes with malignant cell DNA synthesis, leading to reduced replication and remission induction.
• Gestational trophoblastic disease: promotes resolution of abnormal trophoblastic tissue, decreasing hCG levels and preventing disease progression.
• Juvenile idiopathic arthritis: alleviates joint swelling and improves mobility in pediatric patients.

• Methotrexate acts as a folate antagonist by competitively inhibiting the enzyme dihydrofolate reductase. This inhibition blocks the conversion of dihydrofolate to tetrahydrofolate, reducing the synthesis of purine nucleotides and thymidylate required for DNA replication. The resulting decrease in DNA, RNA and protein synthesis limits the proliferation of rapidly dividing cells, including immune‑mediated inflammatory cells and malignant leukemic blasts.

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

Common Side Effects

• Nausea or vomiting: gastrointestinal upset that may require anti‑emetic therapy and can affect oral intake.
• Fatigue and mouth sores: persistent tiredness accompanied by stomatitis or ulceration, often limiting daily activities.
• Low blood cell counts (leukopenia, anemia): reduced white cells and red cells leading to infection risk, fatigue, and possible need for transfusion.

Serious or Rare Side Effects

• Severe liver toxicity or fibrosis: significant elevation of liver enzymes or progressive scarring that may require discontinuation and specialist monitoring.
• Pulmonary fibrosis or interstitial pneumonitis: inflammation and scarring of lung tissue causing breathlessness, cough, and reduced oxygen exchange.
• Life‑threatening infection or bone‑marrow suppression: profound immunosuppression that can result in sepsis, requiring immediate hospitalization and aggressive antimicrobial therapy.

Key safety considerations for methotrexate include patient monitoring and avoidance of contraindicated situations.

• Pregnancy contraindication: drug is teratogenic (Category X) and must not be used during pregnancy.
• Liver monitoring: regular liver function tests are required to detect hepatotoxicity.
• Blood count surveillance: complete blood counts should be checked frequently to identify bone‑marrow suppression.
• Renal function assessment: dose adjustment or avoidance is needed in patients with impaired kidney function.
• Concomitant drug caution: avoid NSAIDs and live vaccines while on therapy.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

Methotrexate interacts with several medicines, influencing its efficacy and toxicity.

Major Interactions (Avoid)

• NSAIDs (e.g., ibuprofen, naproxen): increase methotrexate plasma levels and risk of toxicity.
• Sulfonamide antibiotics (e.g., trimethoprim‑sulfamethoxazole): potentiate bone‑marrow suppression.
• Penicillins (e.g., ampicillin): may reduce renal clearance, raising methotrexate concentrations.

Moderate Interactions (Monitor Closely)

• Proton pump inhibitors (e.g., omeprazole): can alter methotrexate elimination and modestly increase exposure.
• Azathioprine or leflunomide: combined immunosuppression may heighten infection risk.
• Oral contraceptives: may reduce methotrexate efficacy, requiring monitoring of disease activity.