A Genomic Blueprint for Safer Thiopurine Dosing
The Clinical Pharmacogenetics Implementation Consortium (CPIC) has released a crucial 2025 update to its guideline for thiopurine dosing, a cornerstone of personalized medicine in pharmacology. This update refines recommendations for adjusting starting doses of drugs like azathioprine, mercaptopurine, and thioguanine based on genetic testing for two key enzymes: thiopurine methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15). The guideline underscores that individuals carrying no-function or decreased-function genetic variants in these genes are at a significantly elevated risk of severe, potentially life-threatening myelosuppression from standard thiopurine doses. It provides specific, actionable pharmacogenomic guidance for clinicians, including how to manage patients with variants in both genes, aiming to optimize therapeutic outcomes while minimizing adverse drug reactions.
Why it might matter to you: This guideline update directly impacts clinical pharmacology and therapeutic drug monitoring by providing a concrete framework for applying pharmacogenomics to a widely used drug class. For professionals focused on pharmacokinetics and drug metabolism, it highlights the critical role of enzyme activity variants like those in cytochrome P450 pathways in determining drug toxicity and therapeutic windows. Implementing these evidence-based recommendations can enhance clinical trial design for targeted therapies and improve the safety profile of established treatments, moving the field closer to routine, pre-emptive genotyping to prevent adverse drug reactions.
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