Methotrexate Accord (Methotrexate)

Methotrexate is used in several disease categories where rapid cell proliferation or immune activation is a key factor.

• Rheumatoid arthritis: reduces joint inflammation and slows disease progression.
• Psoriasis: decreases skin cell turnover and improves plaque lesions.
• Acute lymphoblastic leukemia: induces remission by targeting rapidly dividing lymphoblasts.
• Osteosarcoma: used as part of combination chemotherapy to inhibit tumor growth.

• Methotrexate acts as a folate antagonist by competitively 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 impaired cell replication, particularly in rapidly dividing immune cells and malignant cells. The drug also promotes accumulation of polyglutamated metabolites that further enhance intracellular retention and cytotoxicity.

Methotrexate may cause a range of adverse reactions, varying from mild to severe, depending on dose and patient factors.

Common Side Effects

• Nausea and vomiting
• Fatigue or weakness
• Oral mucosal ulceration
• Elevated liver enzymes
• Transient low white blood cell count
• Alopecia (hair thinning)

Serious or Rare Side Effects

• Severe hepatic toxicity or fibrosis
• Bone marrow aplasia leading to pancytopenia
• Pulmonary fibrosis or interstitial pneumonitis
• Acute renal failure
• Life‑threatening infections
• Hypersensitivity reactions including Stevens‑Johnson syndrome

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

• Liver monitoring: perform baseline and periodic liver function tests.
• Hematologic monitoring: check complete blood count regularly.
• Renal assessment: evaluate kidney function before and during therapy.
• Infection risk: avoid use in active infections and monitor for signs of sepsis.
• Contraception: require effective contraception for both men and women of reproductive potential.
• Pregnancy and lactation: discontinue before conception and avoid breastfeeding.
• Store at ambient temperature: keep in original container, protect from moisture and light.

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

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): increase methotrexate plasma levels.
• Trimethoprim‑sulfamethoxazole: potentiates bone marrow suppression.
• Live vaccines: risk of severe infection due to immunosuppression.
• Alcohol: heightens risk of hepatic injury.
• High‑dose penicillins: may reduce renal clearance of methotrexate.

Moderate Interactions (Monitor Closely)

• Azathioprine: additive immunosuppressive effect.
• Proton pump inhibitors: may affect renal excretion.
• Vitamin supplements containing folic acid: can diminish therapeutic effect if not timed correctly.
• Sulfonylureas: potential for enhanced hypoglycemia.
• Anticonvulsants (e.g., phenytoin): may alter methotrexate metabolism.