Enablex Adverse Reactions

Consistent with the pharmacological profile, the most commonly reported adverse drug reactions (ADRs) in three Phase III studies (n=1069) were dry mouth (20.2% and 35% for the 7.5 mg and 15 mg dose, respectively, respectively vs. 8.0% placebo) and constipation (14.8% and 21.0% for the 7.5 mg and 15 mg dose, respectively vs. 5.4% placebo). However, the patient discontinuation rates due to these adverse drug reactions were low (dry mouth: 0% and 0.9% for the 7.5 mg and 15 mg dose, respectively, constipation: 0.6% - 1.2% for 7.5 mg and 15 mg dose, respectively).
Adverse drug reactions from pivotal clinical trials (Table 2) with doses of 7.5 mg and 15 mg darifenacin are listed according to system organ classes in MedDRA. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first.
Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category using the following convention (CIOMS III) is also provided for each adverse drug reaction: very common (≥1/10); common (≥1/100, <1/10); uncommon (≥1/1,000, <1/100); rare (≥1/10,000, <1/1,000) very rare (<1/10,000), including isolated reports.
Most ADRs were mild or moderate and did not result in discontinuation in the majority of the patients. The incidence of serious adverse events with 7.5 mg and 15 mg darifenacin once daily was similar to placebo. (See Table 2.)

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In one flexible dose titration study (n=395) evaluating the dosing regimen approved for marketing, the overall ADR profile was comparable to that observed in the pooled analysis of three pivotal fixed-dose studies, with the most relevant difference in the very common ADRs. Dry mouth was reported in 18.7% of patients treated with darifenacin and in 8.7% of those treated with placebo. Constipation was reported in 20.9% and 7.9% of patients treated with darifenacin and placebo, respectively.
The discontinuation rates due to these ADRs in patients treated with darifenacin were low (dry mouth: 0.7%; constipation: 2.2%).
The incidence of adverse events with the doses of Enablex 7.5 mg and 15mg decreased during the treatment period up to 6 months. A similar trend is also seen for the discontinuation rates.
Adverse drug reactions from Post-marketing experience: The following adverse drug reactions have been identified based on post-marketing spontaneous reports: Generalized hypersensitivity reactions; Angioedema with or without airway obstruction (see also PRECAUTIONS) have been reported.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency (frequency unknown).