Annotation of Health Canada Santé Canada (HCSC) label information
for darifenacin
and CYP2D6
Summary
The product monograph for darifenacin notes that CYP2D6 poor metabolizers may have higher levels of the drug as compared to extensive metabolizers. However, it also notes that there are no special dosing requirements for poor metabolizers.
Annotation
Darifenacin (ENABLEX) is indicated for the treatment of overactive bladder. Excerpt from the darifenacin product monograph:
Variability in metabolism: A subset of individuals are devoid of CYP 2D6 enzyme activity (i.e. approximately 7% of the Caucasian population). Therefore, the metabolism of darifenacin in these poor metabolizers (PMs) will be principally mediated via CYP 3A4. The darifenacin ratios (poor metabolizers: extensive metabolizer) for Cmax and AUC following darifenacin 15 mg once-daily at steady state were 1.9 and 1.7, respectively. Population pharmacokinetic analyses of Phase 3 data indicated that on average PMs have 55% higher steady-state exposure than EMs. However, there is considerable overlap between the ranges of exposures seen in EM and PM populations and clinical experience confirms that there are no special dosing requirements for PMs.
For the complete product monograph text with sections containing pharmacogenetic information highlighted, see the darifenacin product monograph.
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