Metotrexat Accord (Methotrexate)

Methotrexate is used in autoimmune and oncologic conditions that involve rapid cell proliferation or immune‑mediated inflammation.

• Rheumatoid arthritis: reduces joint inflammation, pain and structural damage.
• Psoriasis: decreases skin lesion severity by limiting keratinocyte proliferation.
• Acute lymphoblastic leukemia: induces remission by inhibiting malignant lymphoblast growth.
• Non‑Hodgkin lymphoma: suppresses tumor cell replication leading to disease control.
• Breast cancer (adjuvant): impedes cancer cell division as part of combination therapy.

• Methotrexate competitively inhibits dihydrofolate reductase, preventing conversion of dihydrofolate to tetrahydrofolate, a cofactor required for synthesis of purine nucleotides and thymidylate. The resulting folate deficiency impairs DNA, RNA and protein synthesis, leading to reduced proliferation of rapidly dividing cells such as immune‑activated lymphocytes and malignant tumor cells. Additionally, at higher concentrations, methotrexate interferes with enzymes involved in adenosine metabolism, contributing to its anti‑inflammatory effects.

Methotrexate may cause a range of adverse reactions, varying in frequency and severity.

Common Side Effects

• Nausea and vomiting: gastrointestinal upset that may be mild to moderate and often improves with anti‑emetics.
• Fatigue: persistent tiredness that can affect daily activities and may fluctuate with treatment cycles.
• Oral ulcers: painful sores in the mouth or throat that can interfere with eating and speaking.
• Elevated liver enzymes: mild, usually reversible increases in ALT/AST observed in routine monitoring.

Serious or Rare Side Effects

• Bone marrow suppression: can cause anemia, leukopenia or thrombocytopenia, increasing infection and bleeding risk.
• Pulmonary toxicity: interstitial pneumonitis or fibrosis presenting with cough, dyspnea and fever, requiring prompt evaluation.
• Severe hepatotoxicity: risk of hepatic fibrosis, cirrhosis or liver failure with prolonged high‑dose therapy.

When prescribing methotrexate, several precautions and monitoring measures are recommended to ensure patient safety.

• Renal function: assess baseline creatinine and adjust dose in impaired kidney function.
• Hepatic monitoring: perform regular liver function tests to detect early enzyme elevation.
• Pregnancy avoidance: contraindicated in pregnancy; effective contraception required for women of childbearing potential.
• Drug interactions: avoid concurrent use with high‑dose NSAIDs or other folate antagonists.
• Blood counts: monitor complete blood count regularly for signs of marrow suppression.
• Store at ambient temperature: keep vials in original packaging, protect from light and moisture, and do not freeze.

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

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (high dose): can increase methotrexate plasma levels and nephrotoxicity.
• Trimethoprim‑sulfamethoxazole: may potentiate bone marrow suppression.
• Live vaccines: risk of severe infection due to immunosuppression.

Moderate Interactions (Monitor Closely)

• Proton pump inhibitors: may affect renal clearance, requiring periodic renal function checks.
• Azathioprine or mycophenolate: additive immunosuppression may increase infection risk.
• Vitamin supplements containing folic acid: can reduce therapeutic effect; timing adjustments may be needed.