A 30-year-old man on maintenance 6-mercaptopurine for acute lymphoblastic leukemia develops acute gouty arthritis. His physician considers starting allopurinol. What adjustment is mandatory?

• A Increase the 6-mercaptopurine dose to maintain efficacy
• B Switch 6-mercaptopurine to methotrexate before adding allopurinol
• C No change needed as there is no clinically significant interaction
• D Reduce the 6-mercaptopurine dose to approximately one quarter of the original ✓

Explanation

Xanthine oxidase is responsible for catabolism of 6-mercaptopurine to 6-thiouric acid. Allopurinol blocks this pathway, shunting more drug toward conversion to active thioguanine nucleotides, producing severe and potentially fatal bone marrow suppression. The standard teaching from Katzung is to cut the 6-mercaptopurine dose to roughly 25 percent when allopurinol must be coadministered. Switching agents is unnecessary when simple dose adjustment suffices.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.