New CPIC Guideline- UGT1A1 and atazanavir

Guidelines regarding the use of pharmacogenetic tests of UGT1A1 for atazanavir prescribing decisions have been published in Clinical Pharmacology and Therapeutics by the Clinical Pharmacogenetics Implementation Consortium (CPIC).Atazanavir is an antiretroviral protease inhibitor administered to patients infected with the human immunodeficiency virus (HIV). Atazanavir, often co-administered with low-dose ritonavir (atazanavir/r), specifically inhibits UGT1A1-mediated glucoronidation of bilirubin, leading to elevations in concentrations of plasma indirect bilirubin (hyperbilirubinemia). The resulting hyperbilirubinemia is not indicative of hepatic injury, but may result in jaundice in patients with genetic variants that negatively impact UGT1A1 function. Patient stigma due to jaundice may be of particular concern to individuals whose line of work requires them to interact frequently with the public, and may also cause individuals with visible jaundice to prematurely discontinue atazanavir. In the newly published guidelines, CPIC recommends advising patients with two decreased function UGT1A1 alleles about their increased chances of developing jaundice if prescribed atazanavir/r. The CPIC recommendations suggest that clinicians avoid prescribing atazanavir to such individuals, unless a patient does not consider jaundice to be a concern, or unless a strong argument exists in favor of prescribing atazanavir.  For patients carrying one, or no decreased function UGT1A1 alleles, CPIC deems the likelihood of bilirubin-related discontinuation of atazanavir to be low, and very low, respectively. For details, see the CPIC guideline on PharmGKB.

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