Methotrexate Pfizer (Methotrexate)

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

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: limits skin cell proliferation and improves plaque lesions.
• Acute lymphoblastic leukemia: interferes with malignant cell replication.
• Non‑Hodgkin lymphoma: hampers growth of lymphoma cells.
• Ectopic pregnancy: medically terminates non‑viable implantation.

• Methotrexate inhibits dihydrofolate reductase, an enzyme required for tetrahydrofolate regeneration. This blockade reduces the synthesis of purine nucleotides and thymidylate, leading to impaired DNA, RNA and protein production. The resulting antiproliferative effect is most pronounced in rapidly dividing cells, such as activated immune cells and malignant lymphocytes, providing both immunosuppressive and antineoplastic activity.

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

Common Side Effects

• Nausea or vomiting.
• Fatigue or malaise.
• Oral mucosal ulceration (stomatitis).
• Elevated liver enzymes.
• Decreased white blood cell or platelet counts.
• Alopecia (hair thinning or loss).

Serious or Rare Side Effects

• Severe hepatic toxicity or fibrosis.
• Pulmonary fibrosis or interstitial pneumonitis.
• Life‑threatening infection due to bone‑marrow suppression.
• Aplastic anemia or pancytopenia.
• Acute renal failure.
• Severe cutaneous reactions such as Stevens‑Johnson syndrome.

Before initiating therapy, several safety considerations should be addressed.

• Pregnancy: contraindicated (Category X) – avoid use in women of childbearing potential.
• Renal function: assess creatinine clearance; dose adjustment may be required.
• Hepatic function: monitor liver enzymes regularly; discontinue if significant elevation occurs.
• Hematologic monitoring: perform complete blood counts before and during treatment.
• Concomitant drugs: avoid high‑dose NSAIDs and other myelosuppressive agents without supervision.
• Store at ambient temperature: keep in original packaging, protect from moisture and light.

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

Major Interactions (Avoid)

• Live vaccines: risk of severe infection.
• Azathioprine or other immunosuppressants: additive bone‑marrow suppression.
• Trimethoprim‑sulfamethoxazole: heightened myelosuppression.

Moderate Interactions (Monitor Closely)

• NSAIDs (especially high‑dose): may increase methotrexate levels.
• Penicillins: may reduce methotrexate clearance.
• Oral contraceptives: reduced hormonal efficacy, consider alternative contraception.