A renal transplant recipient on azathioprine maintenance is started on allopurinol for gout. Three weeks later he develops profound leukopenia. The most likely explanation is:

• A Allopurinol induces cytochrome P450, increasing azathioprine activation
• B Allopurinol inhibits xanthine oxidase, reducing conversion of 6-mercaptopurine to 6-thiouric acid ✓
• C Allopurinol displaces azathioprine from plasma protein binding sites
• D Allopurinol directly suppresses granulocyte colony formation

Explanation

Azathioprine is a prodrug converted to 6-mercaptopurine, which is normally inactivated partly by xanthine oxidase to 6-thiouric acid. Allopurinol blocks this pathway, shunting more drug toward active thioguanine nucleotides and causing life-threatening myelosuppression unless the azathioprine dose is cut to roughly one quarter to one third. Protein displacement and P450 induction are not relevant mechanisms, and allopurinol is not myelotoxic alone at gout doses.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.