Generic Name: Methotrexate
Common Brand Names: Trexall, Rheumatrex, Otrexup, Rasuvo
Introduction
Methotrexate is an antimetabolite and folate antagonist that is widely used in oncology and autoimmune diseases. It interferes with DNA synthesis, repair, and replication by inhibiting dihydrofolate reductase (DHFR).
Conditions of Use (Indications)
1. Cancer:
- Treats various malignancies, including leukemia, lymphoma, breast cancer, and osteosarcoma.
2. Autoimmune Diseases:
- Rheumatoid arthritis, psoriasis, juvenile idiopathic arthritis.
3. Ectopic Pregnancy:
- Medical management to terminate pregnancy.
Mechanism of Action
Methotrexate inhibits DHFR, blocking the conversion of dihydrofolate to tetrahydrofolate, a necessary cofactor for purine and thymidylate synthesis. This disrupts DNA and RNA synthesis in rapidly dividing cells. At low doses, methotrexate exerts anti-inflammatory effects by increasing extracellular adenosine levels.
Side Effects
1. Common Side Effects:
- Nausea, vomiting, stomatitis, diarrhea, fatigue.
- Hair thinning, rash.
2. Serious Side Effects:
- Hepatotoxicity, pulmonary toxicity, myelosuppression, severe mucositis.
- Increased risk of infection due to immunosuppression.
Harmful Interactions
1.NSAIDs:
- Increase the risk of methotrexate toxicity by reducing renal clearance.
2. Trimethoprim-Sulfamethoxazole:
- Potentiates bone marrow suppression.
3. Live Vaccines:
- Increased risk of vaccine-related infection.
Contraindications
- Pregnancy (teratogenic).
- Severe hepatic or renal impairment.
- Active infections.
Latest References
- EULAR Guidelines for Rheumatoid Arthritis (2023).
- ASCO Guidelines for Chemotherapy (2023).
Journal of Clinical Oncology (2023): Methotrexate in Cancer Therapy.