Which are major side effects of methotrexate?

• A. Bone marrow suppression, hepatotoxicity, fetal death.
• B. Hypertension, tachycardia, diarrhea.
• C. Weight gain, edema, fatigue.
• D. Cataracts, hearing loss, rash.

Answer: (A)

Methotrexate toxicity centers on its effect on rapidly dividing cells because it blocks folate-dependent DNA synthesis. The most significant adverse effects reflect that action: bone marrow suppression, hepatotoxicity, and teratogenicity leading to fetal death.

Bone marrow suppression occurs because the drug impairs the production of blood cells, leaving the body with lowered white cells (increased infection risk), red cells (anemia), and platelets (bleeding risk). Hepatotoxicity arises from drug-related liver injury, so liver enzymes can rise and, with long-term use, there can be progressive damage if not monitored. Teratogenicity means it can cause serious fetal harm or death if pregnancy occurs during treatment or shortly after, so strict contraception is essential for anyone of childbearing potential.

These are the hallmark toxicities you’d monitor for with methotrexate, guiding frequent blood work and liver function tests, and informing counseling about pregnancy risks. Other listed effects don’t represent the primary toxicity pattern of this medication.