Methotrexate Morningside Healthcare (Malta) (Methotrexate)

Methotrexate is used in several disease categories where inhibition of cell proliferation is therapeutic.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: decreases skin cell turnover, improving plaque severity.
• Acute lymphoblastic leukemia: impedes leukemic cell growth, contributing to remission.
• Non‑Hodgkin lymphoma: targets malignant lymphocytes, enhancing treatment response.
• Gestational trophoblastic disease: eliminates trophoblastic tissue, facilitating cure.

• Methotrexate competitively inhibits dihydrofolate reductase, an enzyme required for conversion of dihydrofolate to tetrahydrofolate. This blockade depletes intracellular folate pools, impairing synthesis of purine nucleotides and thymidylate, which are essential for DNA replication and repair. The resulting inhibition of DNA, RNA and protein synthesis preferentially affects rapidly dividing cells, including immune‑mediated inflammatory cells and malignant clones. Consequently, the drug exerts both immunosuppressive and antineoplastic effects.

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

Common Side Effects

• Nausea: mild to moderate gastrointestinal upset.
• Fatigue: generalized tiredness.
• Oral ulcers: painful sores in the mouth.
• Elevated liver enzymes: mild hepatic enzyme rise.

Serious or Rare Side Effects

• Bone marrow suppression: risk of anemia, leukopenia, thrombocytopenia.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis.
• Severe hepatotoxicity: significant liver injury or cirrhosis.

When prescribing methotrexate, clinicians should observe several safety precautions to minimize toxicity.

• Renal function: assess baseline creatinine and adjust dose in impairment.
• Hepatic monitoring: perform regular liver function tests during therapy.
• Hematologic surveillance: check complete blood count periodically.
• Concomitant folic acid: supplement to reduce mucosal and hematologic toxicity.
• Pregnancy contraindication: avoid use in women of childbearing potential; ensure effective contraception.
• Store at below 25°C: keep in original packaging, protect from moisture and light.

Methotrexate has notable drug interactions that can alter its efficacy or increase toxicity.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase methotrexate serum levels and risk of renal toxicity.
• Proton pump inhibitors (e.g., omeprazole): may reduce renal clearance, enhancing toxicity.
• Penicillins (e.g., ampicillin): can decrease methotrexate elimination, raising plasma concentrations.

Moderate Interactions (Monitor Closely)

• Sulfonamides and trimethoprim: may potentiate bone marrow suppression.
• Azathioprine or 6‑mercaptopurine: additive immunosuppression risk.
• Live vaccines: increased infection risk; avoid concurrent administration.