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Duloxetine Dose Escalation and Tapering Decreases Adverse Events in Women With Stress Urinary Incontinence: Presented at ICS

By Louise Gagnon

MONTREAL, CANADA -- September 7, 2005 -- Starting at a lower dose of duloxetine appears to reduce the risk of adverse effects such as nausea in women with stress urinary incontinence (SUI) and improve patient compliance with treatment, according to research presented here at the 35^th annual meeting of the International Continence Society (ICS).

Nausea is the most common treatment-emergent adverse event in women with SUI who take duloxetine, noted Richard Bump, MD, Senior Medical Fellow, Lilly Research Labs, Eli Lilly and Company, Indianapolis, Indiana.

While the current label dose is 40 mg twice daily, Dr. Bump and colleagues randomized 516 women in a double-blind fashion to one of four regimens: 120 women were on placebo; 136 received 40 mg twice daily for 8 weeks; 127 received 40 mg once daily for 2 weeks titrated to 40 twice daily for 6 weeks; and 133 received 20mg twice daily for 2 weeks, escalated to 40mg twice daily for 6 weeks.

The women all had SUI and were 19 to 82 years old.

Following the 8-week treatment period, subjects receiving duloxetine were re-randomized to 1 of 3 double-blind taper regimens: 107 got placebo only for 4 weeks; 115 patients received duloxetine 40mg once daily for 2 weeks followed by placebo for 2 weeks; and 101 took duloxetine 20mg twice daily for 2 weeks followed by 2 weeks on placebo.

A non-inferiority analysis was conducted to determine the extent of nausea in each of the treatment arms, and significant differences were seen: 5.8% with placebo; 16.5% on initial 20 mg of duloxetine twice daily; 25.2% on initial 40 mg once daily; and 29.4% on initial 40 mg twice daily.

Because adverse effects like nausea and dizziness are likely dependent on plasma concentrations when treatment is started, twice daily dosing of 20 mg instead of once daily dosing of 40 mg produced less nausea, Dr. Bump explained.

The differences in the rates of discontinuation due to adverse events was significant across all groups: 5.8% amongst those on placebo, 7.5% among those on the initial 20 mg twice daily; 11.8% amongst those on an initial 40 mg once daily; and 16.2% amongst those on 40 mg twice daily for 8 weeks. The tapering regimen showed no significant differences in adverse events.

"The treatment dose which is the optimal dose is 40 mg twice daily, which is what all the labeling and efficacy studies indicate," Dr. Bump said.

Physicians and patients should be given the option of dose escalation, said Dr. Bump, noting there is currently a label variation of the medication in Europe.

"The option that we would recommend is 20 mg twice a day before going to 40 mg twice a day," he said. "We don't feel it's appropriate to mandate that, simply because some women would rather get as rapid an onset of treatment effect and efficacy, even if it means they get nausea, particularly given the fact that you don't eliminate nausea with the lower dose. You roughly cut it in half."

Eli Lilly and Company and Boehringer Ingelheim funded the study.


[Presentation title: The Effect of Duloxetine Dose Escalation and Tapering on the Incidence of Adverse Events (AE) in Women With Stress Urinary Incontinence (SUI). Abstract 116]

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