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Fesoterodine – A New Treatment Option for Overactive Bladder
variables (p<0.05), except the frequency of micturitions (see Table 6). versus 6.2% for placebo.
The dry mouth rate reported for solifenacin is
The treatment response rate was raised to 77% with fesoterodine 8mg 10.9% for the 5mg dose and 27.6% for the 10mg dose, versus 4.2% for
at 12 weeks, significantly higher than the 69% rate reached with placebo. The constipation rate reported for solifenacin is 5.4% for the 5mg
fesoterodine 4mg (see Table 6). At weeks two, eight and 12 (end of dose and 13.4% for the 10mg dose, versus 2.9% for placebo.
treatment), the effect of fesoterodine 8mg on UUI episodes per 24 hours Discontinuation rates from dry mouth and constipation were low (<1%) for
was more profound throughout the time-course than that of fesoterodine. Finally, no CNS-related adverse effects occurred with an
fesoterodine 4mg (see Figure 3). incidence greater than that of placebo.
Pooled Analysis of Health-related Quality of Life Data Summary and Conclusions
Recently, the pooled analysis of HRQoL data from the phase II clinical trial on Both the 4 and 8mg doses of fesoterodine demonstrated rapid and
fesoterodine has been reported.
HRQoL was assessed using the King’s sustained treatment responses. This successful profile can be attributed
Health Questionnaire (KHQ), International Consultation on Incontinence to the agent’s unique pharmacokinetic and pharmacological profile.
Questionnaire-Short Form (ICIQ-SF), a six-point Likert scale measuring the Unlike antimuscarinic agents, which are metabolised in the liver to
severity of bladder-related problems and treatment response. Both doses of
fesoterodine produced significant improvements on most KHQ domains (see
Table 7). At baseline, scores for the Likert scale were approximately 3.6,
Thanks to its potent, dose-related
which indicates moderate to severe problems. At the end of the study,
scores ranged from 2.3 to 2.8, which is indicative of minor problems. A
efficacy and good tolerability at both
major improvement in bladder condition (a two-point change on the six-
doses, fesoterodine emerges as a very
point Likert scale) was reported by 33% of patients on fesoterodine 4mg
promising treatment option for patients
and 38% of patients on fesoterodine 8mg versus 21% of placebo-treated
patients (p<0.0001). with overactive bladder.
Safety of Fesoterodine
Fesoterodine displayed the expected safety profile for an antimuscarinic produce their active metabolites, liver enzymes are not involved in the
agent. Data from the pivotal phase III study SP583 demonstrated that conversion of fesoterodine. Instead, its active metabolite, 5-HMT, is
treatment with tolterodine or the maximum recommended dose of produced through the action of ubiquitously expressed non-specific
fesoterodine (8mg) was safe and generally well tolerated (see Table 8).
esterases. Given the ubiquitous localisation of these enzymes, there is low
The most common AE in all groups was dry mouth, followed by variability in 5-HMT formation between subjects. Another advantageous
constipation, and most cases were mild to moderate. More patients feature of fesoterodine is its low lipophilicity, which ensures a lower risk
treated with the maximum recommended dose of fesoterodine (8mg) has of the drug crossing the blood–brain barrier and potential toxicity in the
dry mouth compared with those treated with tolterodine ER or placebo. CNS. In fact, with both doses of fesoterodine the incidence of CNS
adverse effects did not exceed the incidence seen with placebo. Both
To put the safety findings in perspective, dry mouth rates reported for other doses of fesoterodine are well tolerated. The adverse effects of
antimuscarinic agents are 20.2 and 35.3% for darifenacin 7.5 and 15mg, fesoterodine are largely mild to moderate. Thanks to its potent, dose-
respectively, versus 8.2% for placebo.
The constipation rate reported for related efficacy and good tolerability at both doses, fesoterodine emerges
darifenacin is 14.8% for the 7.5mg dose and 21.3% for the 15mg dose, as a very promising treatment option for patients with OAB. ■
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