Methotrexat Lederle (Methotrexate Disodium)

Methotrexate is used in several therapeutic areas, primarily targeting inflammatory and malignant cell proliferation.

• Rheumatoid arthritis: reduces joint inflammation, slows disease progression, and improves functional ability.
• Psoriasis: decreases hyperproliferation of skin cells, leading to reduced plaque thickness and symptom relief.
• Acute lymphoblastic leukemia: interferes with leukemic cell DNA synthesis, forming a key component of multi‑agent chemotherapy regimens.
• Osteosarcoma: incorporated into combination chemotherapy to inhibit tumor cell replication and support surgical outcomes.
• Gestational trophoblastic disease: promotes regression of abnormal trophoblastic tissue, aiding in disease remission.

• Methotrexate inhibits the enzyme dihydrofolate reductase, preventing the conversion of dihydrofolate to tetrahydrofolate, a cofactor required for synthesis of purine nucleotides and thymidylate. This blockade reduces DNA, RNA and protein synthesis, particularly affecting rapidly dividing cells such as activated lymphocytes and malignant tumor cells. The resulting antiproliferative and immunosuppressive actions underlie its efficacy in autoimmune diseases and cancer therapy and inflammatory conditions.

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

Common Side Effects

• Nausea and vomiting, often occurring shortly after oral administration.
• Oral mucosal ulceration or painful sores in the mouth and throat.
• Fatigue or generalized weakness affecting daily activities.
• Elevated liver enzymes indicating hepatic stress or injury.
• Diarrhea or abdominal discomfort, sometimes with cramping.

Serious or Rare Side Effects

• Bone marrow suppression leading to pancytopenia, increasing infection and bleeding risk.
• Severe hepatic toxicity or progressive fibrosis, potentially resulting in liver failure.
• Pulmonary toxicity such as interstitial pneumonitis, presenting with cough and dyspnea.

Key safety considerations for methotrexate include patient assessment and monitoring.

• Pregnancy: contraindicated (Category X); avoid use in women of childbearing potential unless effective contraception is ensured.
• Renal function: evaluate creatinine clearance before initiation and adjust therapy as needed.
• Hepatic function: monitor liver enzymes regularly; discontinue if significant elevation occurs.
• Hematologic monitoring: perform complete blood counts to detect bone marrow suppression.
• Drug interactions: review concomitant medications for potential additive toxicity.
• Store at ambient temperature: keep tablets in the original container, protect from moisture and light.

Methotrexate can interact with several medicines, altering its efficacy or toxicity.

Major Interactions (Avoid)

• Non‑steroidal anti‑inflammatory drugs (NSAIDs): can impair renal clearance of methotrexate and increase gastrointestinal toxicity, so concurrent use should be avoided.
• Penicillins (e.g., ampicillin, amoxicillin): may reduce methotrexate elimination, leading to elevated plasma concentrations and heightened adverse effects.
• Live vaccines: immunosuppressive action of methotrexate can cause severe infection from live attenuated vaccines; therefore they are contraindicated during treatment.

Moderate Interactions (Monitor Closely)

• Sulfonamide antibiotics: may potentiate myelosuppression, necessitating regular complete blood count monitoring.
• Azathioprine or other immunosuppressants: combined use can increase risk of bone‑marrow suppression and infection, requiring dose adjustments and close observation.