A Pharmacogenetic Roadmap for Safer Thiopurine Dosing
The Clinical Pharmacogenetics Implementation Consortium (CPIC) has issued a crucial 2025 update to its guideline for thiopurine dosing, focusing on the enzymes TPMT and NUDT15. These enzymes are responsible for metabolizing drugs like azathioprine, mercaptopurine, and thioguanine, which are used in conditions ranging from autoimmune diseases to post-transplant immunosuppression. The guideline provides specific, genotype-based recommendations for adjusting starting doses to mitigate the risk of severe, potentially life-threatening myelosuppression, a known adverse effect in patients with reduced-function genetic variants.
Why it might matter to you: For nephrologists managing immunosuppression in renal transplant patients or treating glomerular diseases with azathioprine, this guideline is a direct tool for preventing drug-induced complications. It underscores the growing necessity of pre-emptive pharmacogenetic testing to personalize therapy and avoid episodes of acute bone marrow toxicity, which can complicate patient management and lead to hospitalizations. Integrating this updated protocol represents a move toward more precise and safer long-term immunosuppressive strategies in nephrology.
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