Nordimet (Methotrexate)

• Methotrexate is a folate antagonist used in several autoimmune and oncologic disease pathways.
• Rheumatoid arthritis: reduces joint inflammation and slows structural damage, improving functional ability.
• Psoriasis: decreases skin cell proliferation and inflammation, leading to clearance of plaques in severe disease.
• Acute lymphoblastic leukemia: interferes with malignant cell replication, contributing to remission when used in combination chemotherapy.
• Non‑Hodgkin lymphoma: impedes tumor growth by blocking DNA synthesis in rapidly dividing lymphoid cells.

• Methotrexate inhibits dihydrofolate reductase, preventing conversion of dihydrofolate to tetrahydrofolate, a cofactor required for synthesis of purine nucleotides and thymidylate. This blockade reduces DNA, RNA and protein synthesis, particularly affecting rapidly dividing cells such as activated immune cells and malignant lymphocytes. The drug also promotes accumulation of adenosine, which exerts anti‑inflammatory effects. Additionally, methotrexate may inhibit enzymes involved in cytokine production, further contributing to its immunomodulatory profile.

Methotrexate can cause a range of adverse reactions, varying from mild to potentially life‑threatening.

Common Side Effects

• Nausea or vomiting: gastrointestinal upset often occurring early in therapy.
• Mouth sores: ulceration of oral mucosa.
• Fatigue: persistent tiredness.
• Elevated liver enzymes: mild hepatic irritation detectable in labs.

Serious or Rare Side Effects

• Bone marrow suppression: decreased blood cell production leading to anemia, infection risk.
• Severe hepatotoxicity: liver injury that may progress to fibrosis or cirrhosis.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis causing breathing difficulties.
• Renal impairment: reduced kidney function, especially with high doses.

• When prescribing methotrexate, clinicians should observe several safety precautions to minimize toxicity.
• Baseline testing: obtain complete blood count, liver and renal function before initiation.
• Monitoring: repeat labs regularly to detect hematologic or hepatic changes.
• Avoid pregnancy: drug is contraindicated in pregnancy due to teratogenicity; use effective contraception.
• Drug interactions: review concomitant medications that may increase toxicity, such as NSAIDs or penicillins.
• Patient education: inform about signs of infection, liver dysfunction, and pulmonary symptoms.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

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

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): can increase methotrexate serum levels and risk renal toxicity.
• Trimethoprim‑sulfamethoxazole: may potentiate bone marrow suppression.
• Live vaccines: immunosuppression may lead to severe infection.

Moderate Interactions (Monitor Closely)

• Penicillins and cephalosporins: may reduce renal clearance of methotrexate.
• Proton pump inhibitors: can affect renal excretion, requiring dose adjustment.
• Alcohol: may exacerbate hepatotoxicity.