EUROPEAN PUBLIC ASSESSMENT REPORT (EPAR) YENTREVE

EPAR summary for the public

What is Yentreve?

Yentreve is a medicine containing the active substance duloxetine. It is available as blue (20 mg) and orange (40 mg) capsules.

What is Yentreve used for?

Yentreve is used to treat moderate to severe stress urinary incontinence (SUI) in women. SUI is accidental leaks of urine during physical exertion or when coughing, laughing, sneezing, lifting or exercising.

The medicine can only be obtained with a prescription.

How is Yentreve used?

The recommended dose of Yentreve is 40 mg twice a day. Some patients may benefit from starting treatment at a dose of 20 mg twice a day for two weeks before increasing to 40 mg twice a day, to reduce nausea (feeling sick) and dizziness. The benefit of treatment should be re-assessed at regular intervals. Combining Yentreve with pelvic floor muscle training may provide additional benefit.

How does Yentreve work?

The active substance in Yentreve, duloxetine, is a serotonin-noradrenaline re-uptake inhibitor (SNRI). It works by preventing the neurotransmitters 5-hydroxytryptamine (also called serotonin) and noradrenaline from being taken back up into nerve cells in the brain and spinal cord.

Neurotransmitters are chemicals that allow nerve cells to communicate with one another. By blocking their re-uptake, duloxetine increases the amount of these neurotransmitters in the spaces between these nerve cells, increasing the level of communication between the cells. How duloxetine works in SUI is not clear but it is thought that, by increasing the levels of 5-hydroxytryptamine and noradrenaline at the level of the nerves that control the muscle of the urethra (the tube that leads from the bladder to outside), duloxetine causes a stronger closure of the urethra during urine storage. By closing the urethra more powerfully, Yentreve prevents the unwanted loss of urine during physical stress such as coughing or laughing.

How has Yentreve been studied?

Yentreve has been studied in a total of 2,850 women with SUI. The four main studies involved 1,913 women and lasted 12 weeks, comparing Yentreve (mostly as 40 mg twice daily) with placebo (a

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dummy treatment). The main measures of effectiveness were incontinence episode frequency (IEF, the number of episodes of incontinence per week) recorded in patient diaries and the patients’ scores on an incontinence-specific quality-of-life questionnaire (I-QOL).

What benefit has Yentreve shown during the studies?

In all four studies, the patients treated with Yentreve had fewer episodes of incontinence after 12 weeks, with about four or five fewer episodes of incontinence per week, in comparison with the number before the study. The IEF decreased by 52% in the Yentreve group, compared with a decrease of 33% in the placebo-treated group. The I-QOL questionnaire scores were also improved in the Yentreve group compared with the placebo group. Yentreve was more effective than placebo only in patients who had more than 14 incontinence episodes per week (moderate to severe SUI) at the start of the study.

What is the risk associated with Yentreve?

The most common side effects with Yentreve (seen in more than 1 patient in 10) are nausea, dry mouth, constipation and fatigue (tiredness). For the full list of all side effects reported with Yentreve, see the Package Leaflet.

Yentreve should not be used in people who may be hypersensitive (allergic) to duloxetine or any of the other ingredients. Yentreve should not be used in patients with certain types of liver disease or with severe kidney disease. Yentreve should not be used with monoamine oxidase inhibitors (a group of antidepressants), fluvoxamine (another antidepressant), or ciprofloxacin or enoxacin (types of antibiotic). Treatment with Yentreve should not be started in patients with uncontrolled high blood pressure, because of a risk of hypertensive crisis (sudden, dangerously high blood pressure).

Why has Yentreve been approved?

The Committee for Medicinal Products for Human Use (CHMP) decided that Yentreve’s benefits are greater than its risks for the treatment of moderate to severe SUI. The Committee recommended that Yentreve be given marketing authorisation.

Other information about Yentreve:

The European Commission granted a marketing authorisation valid throughout the European Union for Yentreve to Eli Lilly Nederland B.V. on 11 August 2004.

The full EPAR for Yentreve is available here.

This summary was last updated in 05-2008.

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