Methotrexate Accord (Methotrexate)

• Methotrexate is used in autoimmune and oncologic conditions where inhibition of folate‑dependent DNA synthesis is required.
• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: improves skin lesions and reduces plaque formation.
• Acute lymphoblastic leukemia: inhibits malignant cell proliferation and induces remission.
• Osteosarcoma: slows tumor growth and may improve survival outcomes.
• Other neoplastic diseases: provides antineoplastic activity in various malignancies.

• Methotrexate acts as a folate antagonist by inhibiting the enzyme dihydrofolate reductase. This blockade prevents the conversion of dihydrofolate to tetrahydrofolate, a cofactor required for synthesis of purine nucleotides and thymidylate. Consequently, DNA, RNA and protein synthesis are reduced, leading to decreased proliferation of rapidly dividing cells, including immune cells and cancer cells. The drug also promotes accumulation of adenosine, which contributes to its anti‑inflammatory effects.

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

Common Side Effects

• Nausea
• Fatigue
• Mouth sores
• Low blood cell counts
• Elevated liver enzymes
• Diarrhea

Serious or Rare Side Effects

• Severe liver toxicity
• Pulmonary fibrosis
• Significant bone marrow suppression
• Renal failure
• Life‑threatening infections
• Skin reactions such as Stevens‑Johnson syndrome

• When using Methotrexate, several precautions should be observed to minimize risks.
• Dose adjustment: monitor renal and hepatic function before and during therapy.
• Pregnancy: contraindicated in pregnancy; ensure effective contraception for both sexes.
• Infection risk: monitor for signs of infection and avoid live vaccines.
• Blood monitoring: perform regular complete blood count and liver function tests.
• Drug interactions: avoid concomitant use with high‑dose NSAIDs and other folate antagonists.
• Store at ambient temperature: keep in original container, protect from moisture and light.

Methotrexate interacts with several medicines, requiring careful management.

Major Interactions (Avoid)

• Other folate antagonists (e.g., pemetrexed) – may increase toxicity.
• Live vaccines – risk of infection due to immunosuppression.
• High‑dose NSAIDs – can worsen renal toxicity.
• Certain antibiotics (trimethoprim) – may enhance myelosuppression.
• Gold salts – may increase hematologic toxicity.

Moderate Interactions (Monitor Closely)

• Proton pump inhibitors – may affect absorption.
• Sulfonamides – potential additive bone marrow effects.
• Penicillins – monitor for increased toxicity.
• Oral contraceptives – may reduce efficacy, consider alternative contraception.
• Alcohol – may exacerbate liver toxicity.