Annotation

Darifenacin (Emselex) is indicated for the treatment of urge incontinence and/or increased urinary frequency and urgency. It is metabolized by CYP3A4 and CYP2D6. The EMA EPAR contains information regarding dose adjustments for darifenacin if taken concomitantly with potent CYP2D6 inhibitors or moderate CYP3A4 inhibitors. Concomitant use of potent CYP3A4 inhibitors is contraindicated.

Excerpts from the darifenacin (Emselex) EPAR:

Darifenacin is metabolised by CYP3A4 and CYP2D6. Due to genetic differences, about 7% of the Caucasians lack the CYP2D6 enzyme and are said to be poor metabolisers. A few percent of the population have increased CYP2D6 enzyme levels (ultrafast metabolisers). The information below applies to subjects who have normal CYP2D6 activity (extensive metabolisers) unless otherwise stated.

The metabolism of darifenacin in CYP2D6 poor metabolisers is principally mediated by CYP3A4. In one pharmacokinetic study the steady-state exposure in poor metabolisers was 164% and 99% higher during treatment with 7.5 mg and 15 mg once daily, respectively. However, a population pharmacokinetic analyses of Phase III data indicated that on average steady-state exposure is 66% higher in poor metabolisers than in extensive metabolisers. There was considerable overlap between the ranges of exposures seen in these two populations (see section 4.2).

For the complete drug label text with sections containing pharmacogenetic information highlighted, see the darifenacin (Emselex) EMA drug label.

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