Methotrexate Ebewe Pharma (Methotrexate)

Methotrexate is an antimetabolite that modulates cell proliferation in autoimmune and oncologic disease pathways.

• Rheumatoid arthritis: reduces joint inflammation and slows structural damage, improving functional ability.
• Psoriasis: diminishes keratinocyte hyperproliferation, leading to clearance of plaques and reduced scaling.
• Acute lymphoblastic leukemia: induces remission by inhibiting DNA synthesis in rapidly dividing lymphoblasts.
• Osteosarcoma: contributes to tumor control when used in combination chemotherapy regimens.
• Gestational trophoblastic disease: promotes resolution of abnormal trophoblastic tissue, facilitating cure.

These indications reflect its role in both inflammatory and malignant conditions.

• Methotrexate competitively inhibits dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate. This blockade reduces the cellular pool of tetrahydrofolate, a cofactor required for synthesis of purine nucleotides and thymidylate, thereby impairing DNA, RNA, and protein synthesis. The resulting antiproliferative effect is most pronounced in rapidly dividing cells, including immune cells and malignant clones. Additionally, at higher doses it may increase adenosine release, contributing to its anti‑inflammatory properties.

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

Common Side Effects

• Nausea: gastrointestinal upset leading to vomiting or loss of appetite.
• Mouth sores: painful ulcerations of the oral mucosa.
• Fatigue: persistent tiredness affecting daily activities.
• Elevated liver enzymes: mild, transient increase in hepatic transaminases.

Serious or Rare Side Effects

• Severe liver toxicity: hepatitis or hepatic failure requiring discontinuation.
• Pulmonary fibrosis: interstitial lung disease presenting with dyspnea and cough.
• Bone marrow suppression: pancytopenia with risk of infection and bleeding.
• Severe skin reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.

When prescribing methotrexate, clinicians should observe several safety measures to minimize risk.

• Monitor blood counts: perform regular complete blood count testing to detect cytopenias.
• Assess liver function: schedule periodic liver enzyme evaluations for hepatotoxicity.
• Evaluate renal function: check serum creatinine before initiation and during therapy.
• Avoid use in pregnancy: drug is teratogenic and contraindicated for women of childbearing potential.
• Store at room temperature: keep tablets in the original container, protect from moisture and light.

Methotrexate’s pharmacokinetics and toxicity profile can be altered by several concomitant medicines.

Major Interactions (Avoid)

• NSAIDs: increase methotrexate plasma levels and risk of renal toxicity.
• Live vaccines: heightened risk of infection due to immunosuppression.
• Trimethoprim‑sulfamethoxazole: additive bone‑marrow suppression.

Moderate Interactions (Monitor Closely)

• Proton pump inhibitors: may affect gastrointestinal absorption of methotrexate.
• Sulfonamide antibiotics: increase potential for myelosuppression.
• Alcohol: can exacerbate hepatic injury when combined with methotrexate.