Metotreksat Ebewe (Methotrexate)

Methotrexate acts on rapidly dividing cells and inflammatory pathways, making it useful across several disease families.

• Rheumatoid arthritis: reduces joint inflammation and slows structural damage.
• Psoriasis: decreases skin cell proliferation and plaque formation.
• Acute lymphoblastic leukemia: interferes with malignant cell DNA synthesis to achieve remission.
• Non‑Hodgkin lymphoma: impedes tumor growth by blocking folate metabolism.
• Ectopic pregnancy: halts trophoblastic tissue development to allow non‑surgical resolution.

• Methotrexate inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate, a cofactor required for purine and pyrimidine synthesis. This blockade reduces DNA, RNA, and protein production, leading to decreased proliferation of immune cells and malignant cells. Additionally, intracellular accumulation of adenosine mediates anti‑inflammatory effects.

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

Common Side Effects

• Nausea or vomiting: gastrointestinal upset occurring shortly after dosing.
• Fatigue: persistent tiredness not explained by disease activity.
• Oral ulceration: painful sores on the mucous membranes of the mouth.
• Elevated liver enzymes: mild transaminase rise detected on routine labs.

Serious or Rare Side Effects

• Severe hepatotoxicity: significant liver injury requiring discontinuation.
• Pulmonary fibrosis: progressive lung scarring presenting with dyspnea.
• Bone marrow failure: pancytopenia leading to infection, anemia, or bleeding.

Before initiating therapy, clinicians should assess baseline organ function and counsel patients on safety measures.

• Liver monitoring: perform baseline and periodic liver function tests.
• Hematologic surveillance: check complete blood counts regularly to detect cytopenias.
• Pregnancy avoidance: contraindicated in pregnancy; ensure effective contraception.
• Renal dose adjustment: reduce dose or increase monitoring in patients with impaired renal function.
• Drug-specific counseling: advise patients to report signs of infection or respiratory difficulty promptly.
• Store at ambient temperature: keep in the original container, protect from moisture and direct sunlight.

Methotrexate’s efficacy and toxicity can be altered by concomitant medicines.

Major Interactions (Avoid)

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

Moderate Interactions (Monitor Closely)

• Azathioprine or other immunosuppressants: additive myelosuppression requiring blood‑count monitoring.
• Proton‑pump inhibitors: may modestly raise methotrexate concentrations.
• Antacids containing aluminum or magnesium: can reduce absorption, potentially lowering efficacy.