Metotrexato Accord (Methotrexate)

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

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: decreases skin cell proliferation and plaque formation.
• Acute lymphoblastic leukemia: induces remission by inhibiting malignant lymphoblast growth.
• Non‑Hodgkin lymphoma: impedes tumor cell replication in certain lymphoma subtypes.
• Gestational trophoblastic disease: promotes resolution of abnormal trophoblastic tissue.

• Methotrexate inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate, a cofactor required for thymidylate and purine synthesis. This blockade reduces DNA, RNA and protein synthesis, leading to decreased proliferation of rapidly dividing cells, including immune cells and malignant cells.

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

Common Side Effects

• Nausea or vomiting: gastrointestinal upset occurring shortly after administration.
• Fatigue: persistent tiredness not relieved by rest.
• Mouth sores: ulceration of oral mucosa.
• Elevated liver enzymes: mild hepatic irritation detectable on labs.
• Low blood counts: mild leukopenia or anemia.

Serious or Rare Side Effects

• Severe liver toxicity: potential for hepatitis or fibrosis with prolonged use.
• Pulmonary fibrosis: progressive lung scarring causing breathlessness.
• Severe bone marrow suppression: pancytopenia requiring medical intervention.
• Renal impairment: reduced kidney function affecting drug clearance.

Methotrexate requires careful monitoring and patient education.

• Pregnancy contraindication: drug is teratogenic and must not be used in pregnancy (Category X).
• Renal function: assess creatinine clearance before initiation and periodically thereafter.
• Hepatic monitoring: perform baseline and regular liver function tests.
• Blood counts: conduct complete blood count monitoring to detect cytopenias.
• Drug interactions: avoid concomitant use with high‑dose NSAIDs or other folate antagonists.
• Store at 2-8°C: keep refrigerated, protect from light, do not freeze or shake.

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

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (high‑dose NSAIDs): increase risk of renal toxicity.
• Proton pump inhibitors: may raise methotrexate plasma levels.
• Trimethoprim‑sulfamethoxazole: potentiates myelosuppression.

Moderate Interactions (Monitor Closely)

• Azathioprine or mycophenolate: additive immunosuppression.
• Live vaccines: risk of infection due to immunosuppression.
• Alcohol: may exacerbate hepatic toxicity.