During high-dose methotrexate therapy, which medication should be discontinued?

• A. Granisetron
• B. Leucovorin
• C. Bactrim
• D. IV hydration

Answer: (C)

During high-dose methotrexate therapy the aim is to clear the drug efficiently while protecting normal cells, using leucovorin rescue and supportive measures like IV hydration to reduce toxicity. A medication that can dramatically raise methotrexate toxicity is trimethoprim-sulfamethoxazole, known as Bactrim. It can interfere with how methotrexate is cleared by the kidneys and add to folate pathway disruption, increasing the risk of serious side effects such as bone marrow suppression, mucositis, and nephrotoxicity. Because of this, Bactrim should be stopped during high-dose methotrexate treatment.

The other options fit into the supportive management rather than raising toxicity. Granisetron is an antiemetic used to prevent chemotherapy-induced nausea and does not impair methotrexate clearance. Leucovorin is given after high-dose methotrexate to rescue normal cells from toxicity and should not be discontinued. IV hydration supports kidney clearance of methotrexate and should be continued to prevent drug precipitation in the kidneys.