Methotrexate Hospira Uk (Methotrexate)

Methotrexate is used across several disease families, primarily as an antimetabolite that interferes with rapidly dividing cells.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: diminishes skin plaque formation and severity.
• Acute lymphoblastic leukemia: induces remission by inhibiting leukemic cell proliferation.
• Non‑Hodgkin lymphoma: contributes to tumor control as part of chemotherapy regimens.
• Gestational trophoblastic disease: promotes resolution of abnormal trophoblastic tissue.

• Methotrexate inhibits dihydrofolate reductase, blocking the conversion of dihydrofolate to tetrahydrofolate. This impairs synthesis of purine nucleotides and thymidylate, leading to reduced DNA replication and cell division, particularly affecting rapidly proliferating tissues such as immune cells, malignant cells, and trophoblastic tissue.

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

Common Side Effects

• Nausea and vomiting: gastrointestinal upset occurring shortly after administration.
• Fatigue: persistent tiredness not relieved by rest.
• Oral mucositis: painful sores or ulcers in the mouth.
• Myelosuppression: decreased white blood cells, red blood cells, or platelets.
• Elevated liver enzymes: mild transaminase increases indicating hepatic stress.
• Alopecia: temporary hair thinning or loss.

Serious or Rare Side Effects

• Severe hepatic toxicity: potential for fibrosis or cirrhosis with prolonged use.
• Pulmonary fibrosis: interstitial lung disease presenting with dyspnea.
• Life‑threatening infection: due to profound immunosuppression.
• Renal failure: acute kidney injury from precipitation of drug crystals.
• Severe bone marrow aplasia: pancytopenia requiring transfusion support.
• Anaphylaxis: rare hypersensitivity reaction with rapid onset.

Methotrexate requires careful monitoring and specific safety measures.

• Liver function monitoring: perform baseline and periodic liver enzyme tests.
• Hematologic monitoring: regular complete blood counts to detect myelosuppression.
• Renal function assessment: adjust dosing in patients with impaired clearance.
• Pregnancy contraindication: avoid use in women who are pregnant or may become pregnant; employ effective contraception.
• Drug interaction vigilance: review concomitant medications for potential additive toxicity.
• Store at ambient temperature: keep in original container, protect from light and moisture.

Methotrexate interacts with several drug classes, necessitating awareness of potential additive effects.

Major Interactions (Avoid)

• Other folate antagonists (e.g., trimethoprim): may amplify toxicity.
• High‑dose NSAIDs: increase risk of renal impairment and gastrointestinal ulceration.
• Live vaccines: heightened risk of infection due to immunosuppression.
• Proton pump inhibitors (high dose): may reduce renal clearance of methotrexate.
• Sulfonamide antibiotics: potential for severe bone marrow suppression.

Moderate Interactions (Monitor Closely)

• Penicillins: may increase methotrexate plasma levels.
• Azathioprine: additive myelosuppressive effect.
• Phenytoin: may alter hepatic metabolism.
• Vitamin supplements containing folic acid: can reduce efficacy if not timed appropriately.
• Alcohol: exacerbates hepatic toxicity.