Daniela J Conrado1, Hobart L Rogers, Issam Zineh, Michael A Pacanowski. 1. Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation & Research, US FDA, 10903 New Hampshire Avenue, White Oak Building 51, Room 3112, Silver Spring, MD 20993, USA.
Abstract
AIM: To characterize concordance between clinically relevant drug-drug interactions (DDIs) related to CYP2C19, CYP2D6 and CYP2C9 and their analogous gene-drug interactions (GDIs) in US FDA-approved drug labeling. METHODS: We selected prototypical CYP2C19, CYP2D6 and CYP2C9 inhibitors and abstracted all respective interacting drugs via a tertiary resource used in the clinical setting. We then selected only CYP2C19, CYP2D6 and CYP2C9 metabolism-related DDIs requiring enhanced clinical monitoring, dose adjustment or use of alternative drugs. Labeling and management strategies on DDIs and GDIs were compared. RESULTS: Among the drug labels with DDI information, 73% of them describe the analogous GDI. Of the 65 drug labels, 43 and 17% had specific management recommendations for DDIs and GDIs, respectively. In general, GDI management recommendations were concordant with DDI management recommendations in terms of specific dose adjustments or use of alternative drugs. CONCLUSION: The FDA has recognized genetic differences in drug metabolism where clinically relevant DDIs trigger dose adjustment or use of alternative drugs.
AIM: To characterize concordance between clinically relevant drug-drug interactions (DDIs) related to CYP2C19, CYP2D6 and CYP2C9 and their analogous gene-drug interactions (GDIs) in US FDA-approved drug labeling. METHODS: We selected prototypical CYP2C19, CYP2D6 and CYP2C9 inhibitors and abstracted all respective interacting drugs via a tertiary resource used in the clinical setting. We then selected only CYP2C19, CYP2D6 and CYP2C9 metabolism-related DDIs requiring enhanced clinical monitoring, dose adjustment or use of alternative drugs. Labeling and management strategies on DDIs and GDIs were compared. RESULTS: Among the drug labels with DDI information, 73% of them describe the analogous GDI. Of the 65 drug labels, 43 and 17% had specific management recommendations for DDIs and GDIs, respectively. In general, GDI management recommendations were concordant with DDI management recommendations in terms of specific dose adjustments or use of alternative drugs. CONCLUSION: The FDA has recognized genetic differences in drug metabolism where clinically relevant DDIs trigger dose adjustment or use of alternative drugs.
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