Clinical Pharmacology & Therapeutics· 2026Q1· Guideline
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for Thiopurine Dosing Based on TPMT and NUDT15 Genotypes: 2025 Update
- 28citations
- Q1SCImago
- 2026year
Short summary
Updated clinical guidelines recommend adjusting starting doses of mercaptopurine, thioguanine, and azathioprine based on TPMT and NUDT15 genetic variants to prevent severe myelosuppression.
AI-generated from the title and abstract; the full text is not read.
Key points
- TPMT and NUDT15 enzymes are crucial for metabolizing thiopurine drugs.
- Reduced or absent activity of TPMT/NUDT15 due to genetic variants predicts severe adverse effects, particularly myelosuppression.
- Recommendations are provided for adjusting starting doses of mercaptopurine, thioguanine, and azathioprine based on TPMT and NUDT15 genotypes.
- The guideline addresses individuals with variants in both TPMT and NUDT15 genes.
AI-generated from the title and abstract; the full text is not read.
Abstract
Thiopurine methyltransferase (TPMT) and Nudix hydrolase 15 (NUDT15) are key enzymes that catabolize thiopurines. Decreased or no-function alleles in TPMT and NUDT15 are associated with reduced or no enzyme activity and predictive of pronounced adverse effects, including severe myelosuppression, that may occur among individuals treated with standard doses of thiopurines. Genetic variants in these genes are present in all world populations; however, their frequency varies by ancestry. In this updated guideline, we provide recommendations for adjusting starting doses of mercaptopurine, thioguanine, and azathioprine based on TPMT and NUDT15 genotypes, including for individuals with variants in both genes (updates on www.clinpgx.org).
The authors' abstract, as published at the source. Clinical Pharmacology & Therapeutics, 2026 · DOI ↗
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Field: Pharmacology (Pharmacology, Toxicology and Pharmaceutics)
PharmacologyPharmacology, Toxicology and Pharmaceutics