What is Constella?
Constella is a medicine that contains the active substance linaclotide, available as capsules (290 micrograms).
What is Constella used for?
Constella is indicated for the symptomatic treatment of moderate to severe irritable bowel syndrome (IBS) with constipation in adults. IBS is a chronic disorder of intestinal function characterized by abdominal pain or discomfort, accompanied by swelling and alterations of the alvus.
The medicine can only be obtained with a prescription.
How is Constella used?
The recommended dose of Constella is one capsule once a day, taken at least 30 minutes before a meal.
The doctor must periodically evaluate the need to continue the treatment. If patients do not experience an improvement in their symptoms after four weeks of treatment, the benefits and risks of continued treatment should be reconsidered.
How does Constella work?
The active ingredient of Constella, linaclotide, binds to a receptor present in the intestine, called guanylate cyclase C. In this way it reduces pain and increases the secretion of fluids in the intestine, softening the stool and improving peristalsis.
How has Constella been studied?
The effects of Constella were first tested in experimental models before being studied in humans.
Constella was examined in two main studies, involving a total of 1, 608 patients with IBS with constipation, in which it was compared with a placebo (a substance with no effect on the body). The main measures of effectiveness were the number of patients reporting at least 30% improvement in pain and discomfort and the number of patients whose IBS symptoms were significantly or completely reduced for at least 6 out of 12 weeks of treatment. One of the studies also examined the effects of Constella after 26 weeks of treatment.
What benefit has Constella shown during the studies?
Constella was more effective than placebo at improving IBS symptoms. In the first study, 55% of patients treated with Constella reported a 30% or greater improvement in pain and intestinal discomfort for at least 6 out of 12 weeks of treatment compared to 42% of placebo-treated subjects. Furthermore, there was significant improvement or complete disappearance of symptoms for at least 6 out of 12 weeks of treatment in 37% of patients treated with Constella compared with 19% of subjects treated with placebo.
Similar results were obtained in the second study, at the end of which 54% of patients treated with Constella had an improvement in pain and discomfort, while 39% found significant relief or total disappearance of symptoms for at least 6 out of 12 weeks of treatment compared to 39% and 17% of placebo-treated patients.
Results after 26 weeks of treatment showed an improvement in pain (for at least 13 weeks out of 26) in 54% of patients treated with Constella compared with 36% of subjects treated with placebo, as well as symptom relief for at least 13 weeks in 37% of patients taking Constella compared to 17% of subjects who received placebo.
What is the risk associated with Constella?
The most common side effect of Constella is diarrhea, predominantly of mild to moderate intensity, reported by 10-20 patients out of 100. In rare and more serious cases, diarrhea can lead to the onset of dehydration, hypokalemia (lack of potassium in the blood), reduction of bicarbonate in the blood, dizziness and orthostatic hypotension (drop in pressure when the patient stands up).
Constella should not be used in people who are hypersensitive (allergic) to linaclotide or any of the other ingredients. It must also not be used in patients with known or suspected gastric or intestinal blockage.
Why has Constella been approved?
The CHMP noted that Constella has been shown to have clinically important beneficial effects in patients with long-term IBS (up to six months) associated with constipation. A beneficial impact on the quality of life of patients has also been demonstrated. However, the committee noted that about half of the patients did not adequately benefit from the treatment and therefore recommended that the advisability of continuing treatment after four weeks should be reconsidered. Regarding safety, the CHMP concluded that the side effects of Constella, including diarrhea, are manageable. The CHMP therefore decided that Constella's benefits are greater than its risks and recommended that it be given marketing authorization.
More information on Constella
On 26 November 2012, the European Commission issued a marketing authorization for Constella, valid throughout the European Union.
The full EPAR for Constella can be found on the Agency's website: ema.Europa.eu/Find medicine / Human medicines / European public assessment reports. For more information about treatment with Constella, read the package leaflet (also part of the EPAR) or contact your doctor or pharmacist.
Last update of this summary: November 2012.
