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Allopurinol pharmacogenetics: assessment of potential clinical usefulness
Issam Zineh1, Padmaja Mummaneni, Jenna Lyndly
1Genomics Group, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation & Research, US FDA, Silver Spring, MD 20993, USA. issam.zineh@fda.hhs.gov
Abstract:
Use of pharmacogenetics to inform treatment decisions remains a priority for clinicians, patients and public health agencies. We previously developed a framework for systematically assessing whether pharmacogenetic test information would likely bring value to clinical decision-making and enjoy practical uptake. We applied this tool to allopurinol to determine potential usefulness of HLA genetic information in assessing risk for allopurinol-induced severe cutaneous adverse reactions. We quantified allopurinol use data and the magnitude of adverse event signals using US FDA databases, reviewed reported cases of allopurinol-associated severe cutaneous adverse reactions to assess whether clinical subtypes of patients could be identified, performed pooled analyses of associations between HLA variation and allopurinol-induced severe cutaneous adverse reactions and described considerations in clinical implementation of allopurinol pharmacogenetics.
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