Prucalopride succinate for the treatment of constipation: an update

ABSTRACT

Constipation is a disorder frequently complained about by patients in daily clinical practice. However, to date, its treatment is still commonly unsatisfactory, especially concerning patients’ quality of life, when using conventional measures. Prucalopride, a selective 5-hydroxytryptamine receptor 4 agonist, was introduced to the market in 2009 and has been commercially available in Europe since 2010. The main effect of prucalopride is to stimulate colonic motility, which explains its efficacy to treat constipated patients unresponsive to other regimens. Literature search was carrieod out to look for effects of prucalopride on constipated patients. Several papers were found demonstrating that prucalopride is effective in treatment of constipated patients. Due to its few side effects, the lack of cardiovascular effects and interactions with other drugs, prucalopride may be safely used in elderly people as well.

KEYWORDS:

• Chronic constipation
• laxatives
• prucalopride
• treatment

Financial & competing interests disclosure

G Bassotti and M Bellini have received lecture fees from Shire Pharmaceutical for educational symposia. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• Chronic constipation represents an important and frequent clinical issue in the daily practice, and often recognizes a multifactorial genesis.

• Prucalopride is a selective 5HT4 agonist, whose main effect is to increase colonic propulsive activity; the drug is safe, with few side effects (mainly headache and abdominal pain) and no cardiovascular effects.

• Prucalopride is effective on the frequency of evacuation and its correlated symptoms. In Europe, the drug is to date prescribable only in adults.

• The relatively high costs and the lack or only partial reimbursement by several National Health Systems have to date limited the use of prucalopride in some countries, and the drug is presently considered as a second-line treatment.

• By decreasing the dose at 1 mg /day, without loss of efficacy, prucalopride may be effectively used in elderly patients; in children, further data are needed to establish with certainty its safety and effectiveness.

• Preliminary data in real life suggest that prucalopride may be also effective in patients with constipation-predominant irritable bowel syndrome and in several patients with obstructed defecation. In some subjects, the drug seems to lose efficacy in the time course, possibly due to a mechanism of receptorial sensitization. In very severe forms of constipation, prucalopride may be associated to other laxatives due to its low likelihood of interactions.

• Some observations suggest that prucalopride might also be used in particular instances, such as constipation secondary to drug treatment (opioids) or other pathological conditions (Parkinson’s disease, multiple sclerosis, spinal cord injury); good results have been reported in pseudo-obstruction.

• Other reports in experimental animal model seem to indicate that 5HT4 receptor stimulation by prucalopride exerts beneficial effects in the pathophysiology of multiple sclerosis, Parkinson’s disease, and Alzheimer’s disease, and hypothesize its possible therapeutic application in these conditions.