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Practice Guideline
. 2016 Apr;99(4):363-9.
doi: 10.1002/cpt.269. Epub 2015 Nov 9.

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing

R S Gammal  1 , M H Court  2 , C E Haidar  1 , O F Iwuchukwu  3   4 , A H Gaur  5 , M Alvarellos  6 , C Guillemette  7 , J L Lennox  8 , M Whirl-Carrillo  6 , S S Brummel  9 , M J Ratain  10 , T E Klein  6 , B R Schackman  11 , K E Caudle  1 , D W Haas  12 ; Clinical Pharmacogenetics Implementation Consortium
Affiliations
Practice Guideline

Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline for UGT1A1 and Atazanavir Prescribing

R S Gammal et al. Clin Pharmacol Ther. 2016 Apr.

Abstract

The antiretroviral protease inhibitor atazanavir inhibits hepatic uridine diphosphate glucuronosyltransferase (UGT) 1A1, thereby preventing the glucuronidation and elimination of bilirubin. Resultant indirect hyperbilirubinemia with jaundice can cause premature discontinuation of atazanavir. Risk for bilirubin-related discontinuation is highest among individuals who carry two UGT1A1 decreased function alleles (UGT1A1*28 or *37). We summarize published literature that supports this association and provide recommendations for atazanavir prescribing when UGT1A1 genotype is known (updates at www.pharmgkb.org).

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Figures

Figure 1
Figure 1
Cumulative incidence of time to bilirubin‐associated discontinuation of atazanavir stratified by UGT1A1 genotype in AIDS Clinical Trials Group protocol A5257 (adapted from ref. 32). Top panels: Lines estimate the cumulative incidence of time to bilirubin‐associated discontinuation of atazanavir, stratified by UGT1A1 rs887829 genotype and self‐reported race/ethnicity. P values are given by Gray's test for testing equality of cumulative incidence functions. Dashed red lines represent rs887829 T/T, dotted green lines rs887829 C/T, and solid blue lines rs887829 C/C. Bottom panels: Proportions of individuals in this analysis with rs887829 T/T, C/T, and C/T genotypes.
See this image and copyright information in PMC

References

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