title: Consistency of drug-drug and gene-drug interaction information in US FDA-approved drug labels.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  The FDA has recognized genetic differences in drug metabolism where clinically relevant DDIs trigger dose adjustment or use of alternative drugs.
authors: 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.
authors: Daniela J
authors: DJ
authors: Conrado
authors: Hobart L
authors: HL
authors: Rogers
authors: Issam
authors: I
authors: Zineh
authors: Michael A
authors: MA
authors: Pacanowski
mesh_terms: D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000493:pharmacokinetics; D065731:Cytochrome P-450 CYP2C19; D065729:Cytochrome P-450 CYP2C9; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics / Q000493:pharmacokinetics; D065690:Cytochrome P-450 CYP2D6 Inhibitors; D017277:Drug Approval; D004347:Drug Interactions / Q000235:genetics*; D004348:Drug Labeling; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D010597:Pharmacogenetics; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D065690:Cytochrome P-450 CYP2D6 Inhibitors; D004791:Enzyme Inhibitors; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D019389:Cytochrome P-450 CYP2D6