Metoject (Methotrexate)

Methotrexate is employed in the management of autoimmune disorders and certain malignancies by targeting rapidly dividing cells and modulating immune response.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression, improving pain and function.
• Psoriasis: decreases skin plaque formation and severity by suppressing abnormal immune activity.
• Acute lymphoblastic leukemia: inhibits leukemic cell proliferation, contributing to remission when used in chemotherapy protocols.
• Non-Hodgkin lymphoma: impedes lymphoma cell growth, enhancing response to combination chemotherapy regimens.
• Osteosarcoma: limits tumor expansion and metastasis as part of multimodal cancer treatment.
• Ectopic pregnancy: terminates trophoblastic tissue, allowing non‑surgical management of early ectopic implantation.

• Methotrexate acts as a folate antagonist by competitively inhibiting dihydrofolate reductase, an enzyme required for tetrahydrofolate regeneration. This blockade reduces the synthesis of purine nucleotides and thymidylate, impairing DNA, RNA and protein production in rapidly dividing cells. The resulting antiproliferative effect, together with modulation of cytokine release, underlies its immunosuppressive and antineoplastic activities. Consequently, methotrexate interferes with cell cycle progression, particularly affecting the S‑phase.

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

Common Side Effects

• Nausea and vomiting: mild gastrointestinal upset.
• Fatigue: general tiredness.
• Mouth sores: ulceration of oral mucosa.
• Elevated liver enzymes: transient hepatic irritation.
• Low blood counts: mild neutropenia or anemia.

Serious or Rare Side Effects

• Severe liver toxicity: potential fibrosis or cirrhosis with prolonged use.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis.
• Renal impairment: acute kidney injury from precipitation.
• Severe bone marrow suppression: pancytopenia leading to infection risk.
• Cutaneous reactions: Stevens‑Johnson syndrome or toxic epidermal necrolysis.

Methotrexate requires careful monitoring and specific safety measures.

• Pregnancy: contraindicated (Category X) due to teratogenic risk.
• Renal function: assess before initiation and monitor; dose adjust if impairment.
• Liver function: baseline tests required; avoid in active liver disease.
• Hematologic status: monitor blood counts regularly; discontinue if severe cytopenia.
• Concomitant drugs: avoid use with NSAIDs or other folate antagonists without supervision.
• Patient education: advise on signs of infection, bleeding, or pulmonary symptoms.
• 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 increase toxicity.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase risk of renal toxicity and gastrointestinal ulceration.
• Proton pump inhibitors (e.g., omeprazole): may raise methotrexate serum levels, especially at high doses.
• Trimethoprim‑sulfamethoxazole: potentiates bone marrow suppression.

Moderate Interactions (Monitor Closely)

• Live vaccines: immunosuppression may reduce vaccine efficacy and increase infection risk.
• Antifolate agents (e.g., pemetrexed): additive toxicity to folate pathways.
• Azathioprine or 6‑mercaptopurine: enhanced myelosuppression.