Metotreksat Sandoz (Methotrexate)

Methotrexate is indicated for several autoimmune and oncologic conditions that involve abnormal cell proliferation or immune dysregulation.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: diminishes skin plaque formation and severity.
• Psoriatic arthritis: alleviates joint pain and prevents structural damage.
• Acute lymphoblastic leukemia: interferes with malignant cell replication to achieve remission.
• Gestational trophoblastic disease: induces regression of trophoblastic tissue.
• Osteosarcoma: limits tumor growth as part of multimodal therapy.

• Methotrexate inhibits the enzyme dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate, a cofactor required for synthesis of purine nucleotides and thymidylate. This blockade impairs DNA synthesis and cell replication, particularly in rapidly dividing cells such as activated lymphocytes and malignant blasts. The drug also promotes the release of adenosine, which contributes to its anti‑inflammatory and immunosuppressive actions.

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

Common Side Effects

• Nausea and vomiting: gastrointestinal upset that may affect appetite.
• Fatigue or malaise: persistent tiredness not relieved by rest.
• Mouth sores (stomatitis): painful ulcerations in the oral cavity.
• Elevated liver enzymes: mild hepatic enzyme rise detectable in blood tests.

Serious or Rare Side Effects

• Severe liver toxicity (hepatitis or fibrosis): significant liver injury that may require discontinuation.
• Pulmonary fibrosis or interstitial pneumonitis: inflammation and scarring of lung tissue causing breathing difficulty.
• Bone marrow suppression leading to pancytopenia: marked reduction of blood cells increasing infection and bleeding risk.

When using methotrexate, several precautions should be observed to minimize risks.

• Liver monitoring: perform baseline and periodic liver function tests.
• Blood count monitoring: check complete blood count regularly for cytopenias.
• Pregnancy avoidance: contraindicated in pregnancy; effective contraception required for both sexes.
• Renal function assessment: adjust dose or avoid use in significant renal impairment.
• Drug interaction vigilance: avoid concomitant use with known major interacting agents.
• Store at below 25°C: keep in original packaging, protect from moisture and direct sunlight.

Methotrexate interacts with several medicines; some require avoidance while others need careful monitoring.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase methotrexate toxicity.
• Trimethoprim‑sulfamethoxazole: can cause severe bone marrow suppression.
• Live vaccines: risk of uncontrolled infection due to immunosuppression.

Moderate Interactions (Monitor Closely)

• Proton pump inhibitors: may raise methotrexate plasma levels.
• Phenytoin and carbamazepine: may reduce methotrexate efficacy.
• Vitamin C and folic acid supplements: can alter drug activity and require dose adjustment.