A Genetic Blueprint for Safer Thiopurine Dosing
The Clinical Pharmacogenetics Implementation Consortium (CPIC) has released its 2025 update on thiopurine dosing guidelines. These drugs, including azathioprine, mercaptopurine, and thioguanine, are used to treat conditions like leukemia and autoimmune diseases. The updated guideline provides specific recommendations for adjusting starting doses based on a patient’s genetic profile for two key enzymes: thiopurine methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). Individuals carrying reduced or no-function genetic variants in these genes are at high risk for severe, potentially life-threatening myelosuppression when given standard doses. The update is critical as these genetic variants are found across all global populations, though their frequency varies, underscoring the need for personalized medicine approaches to prevent adverse drug reactions.
Why it might matter to you: For professionals focused on infectious diseases and antimicrobial resistance, this guideline highlights a parallel frontier in managing drug toxicity. The principles of pharmacogenomics—using genetics to predict and prevent severe adverse events—are directly applicable to optimizing antibiotic and antiviral therapies. Understanding these frameworks can inform strategies for deploying high-risk antimicrobials more safely, a key consideration in an era of increasing multidrug-resistant organisms. This represents a move towards precision medicine that could reduce treatment-related morbidity and improve patient outcomes across therapeutic areas.
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