Methotrexate Afortas (Methotrexate)

Methotrexate is used across several disease categories, primarily as an immunosuppressant and antineoplastic agent.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: decreases skin cell proliferation and improves plaque severity.
• Acute lymphoblastic leukemia: interferes with malignant cell replication to achieve remission.
• Non‑Hodgkin lymphoma: impairs tumor growth as part of combination chemotherapy.
• Ectopic pregnancy: terminates trophoblastic tissue when surgical management is not chosen.

• Methotrexate inhibits the enzyme dihydrofolate reductase, blocking conversion of dihydrofolate to tetrahydrofolate. This reduces the cellular pool of tetrahydrofolate needed 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 activated immune cells and malignant lymphocytes. Additionally, at higher concentrations methotrexate can inhibit enzymes involved in folate metabolism, contributing to its cytotoxic activity.

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

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset that may be accompanied by vomiting.
• Fatigue: persistent tiredness that can affect daily activities.
• Oral ulcers: painful sores in the mouth that may interfere with eating.

Serious or Rare Side Effects

• Bone marrow suppression: reduced production of blood cells leading to anemia, leukopenia, or thrombocytopenia.
• Severe hepatotoxicity: significant liver enzyme elevation that can progress to fibrosis or cirrhosis with long‑term use.
• Pulmonary toxicity: inflammation of lung tissue causing interstitial pneumonitis or, rarely, fibrosis.

When prescribing methotrexate, several precautions should be observed to minimize risks and ensure safe therapy.

• Baseline testing: obtain liver function, renal function and complete blood count before initiation.
• Monitoring: repeat laboratory assessments regularly to detect toxicity early.
• Contraindications: avoid use in pregnancy, breastfeeding and in patients with severe hepatic or renal impairment.
• Drug interactions: review concomitant medications for potential additive toxicity, especially NSAIDs and other folate antagonists.
• Folate supplementation: consider prescribing folic acid to reduce mucosal and hematologic side effects.
• Store at ambient temperature: keep tablets in the original container, protect from moisture and heat, and store below 25 °C.

Methotrexate interacts with several medicines; understanding the level of interaction guides clinical decisions.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase risk of renal toxicity and elevate methotrexate levels.
• Proton pump inhibitors (e.g., omeprazole): may reduce renal clearance and heighten toxicity.
• Trimethoprim‑sulfamethoxazole: potentiates bone marrow suppression.

Moderate Interactions (Monitor Closely)

• Azathioprine or mycophenolate: additive immunosuppression may increase infection risk.
• Live vaccines: reduced efficacy and potential for vaccine‑derived infection.
• Phenytoin: may lower methotrexate plasma concentrations, reducing efficacy.