Metotrexat Sandoz (Methotrexate)

Methotrexate is a disease‑modifying antirheumatic drug (DMARD) that targets inflammatory and proliferative pathways.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: decreases skin cell proliferation and improves plaque lesions.
• Certain leukemias and lymphomas: interferes with cancer cell DNA synthesis to inhibit tumor growth.
• Ectopic pregnancy: halts trophoblastic tissue development to allow non‑surgical resolution.

• Methotrexate inhibits dihydrofolate reductase, leading to reduced tetrahydrofolate availability and impaired synthesis of purine and pyrimidine nucleotides. This blockade diminishes DNA, RNA and protein production, limiting the proliferation of rapidly dividing cells such as immune lymphocytes, cancer cells and trophoblastic tissue. The drug also promotes the release of adenosine, which contributes to its anti‑inflammatory effects.

Methotrexate may cause a range of adverse reactions that vary in frequency and severity.

Common Side Effects

• Nausea or vomiting: gastrointestinal upset occurring in many patients.
• Oral mucositis: painful sores or ulceration of the mouth lining.
• Fatigue: persistent tiredness that can affect daily activities.
• Elevated liver enzymes: mild hepatic irritation detectable on blood tests.
• Decreased blood counts: mild anemia, leukopenia or thrombocytopenia.

Serious or Rare Side Effects

• Severe liver toxicity: potential for hepatitis or fibrosis with prolonged use.
• Pulmonary fibrosis: interstitial lung disease presenting with cough and breathlessness.
• Bone marrow suppression: profound pancytopenia increasing infection and bleeding risk.
• Severe infection: opportunistic infections due to immunosuppression.
• Allergic reactions: rash, fever or anaphylaxis in hypersensitive individuals.
• Kidney failure: impaired renal clearance leading to drug accumulation.

Before initiating therapy, several safety considerations should be reviewed.

• Pregnancy contraindication: avoid use in women who are pregnant or may become pregnant.
• Liver function monitoring: perform baseline and periodic liver enzyme tests.
• Renal function monitoring: assess creatinine clearance before and during treatment.
• Hematologic monitoring: conduct regular complete blood counts to detect cytopenias.
• Avoid live vaccines: immunization with live agents may cause infection.
• Store at below 25°C: keep in the original packaging, protect from moisture and direct sunlight.

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

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase methotrexate plasma levels and toxicity.
• Sulfonamide antibiotics (e.g., trimethoprim‑sulfamethoxazole): risk severe bone‑marrow suppression.
• Live vaccines: may lead to uncontrolled infection in immunosuppressed patients.

Moderate Interactions (Monitor Closely)

• Azathioprine: additive immunosuppressive effect requiring blood count surveillance.
• Cyclosporine: can raise methotrexate concentrations, necessitating dose adjustment.
• Folic acid supplements: may reduce therapeutic efficacy if not timed appropriately.