Adverse reactions : תופעות לוואי

4.8   Undesirable effects

Summary of the safety profile
In an integrated analysis of 17 double-blind placebo-controlled studies, Resolor was given orally to approximately 3,300 patients with chronic constipation. Of these, over 1,500 patients received Resolor at the recommended dose of 2 mg per day, while approximately 1,360 patients were treated with 4 mg prucalopride daily. The most frequently reported adverse reactions associated with Resolor 2 mg therapy are headache (17.8%) and gastrointestinal symptoms (abdominal pain (13.7%), nausea (13.7%) and diarrhoea (12.0%)).
The adverse reactions occur predominantly at the start of therapy and usually disappear within a few days with continued treatment. Other adverse reactions have been reported occasionally. The majority of adverse events were mild to moderate in intensity.

Tabulated list of adverse reactions
The following adverse reactions were reported in controlled clinical studies at the recommended dose of 2 mg with frequencies corresponding to very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.
Frequencies are calculated based on the integrated analysis of 17 double-blind placebo- controlled clinical studies.
    Table 1: Adverse Drug Reactions (ADRs) Associated with Resolor


System/Organ Class            Incidence Category              Adverse Drug Reaction Metabolism and nutrition      Common                          Decreased appetite disorders
Nervous system disorders      Very common                     Headache Common                          Dizziness
Uncommon                        Tremors, migraine
Cardiac disorders             Uncommon                        Palpitations Ear and labyrinth disorders   Uncommon                        Vertigo Gastrointestinal disorders    Very common                     Nausea, diarrhoea, abdominal pain
Common                          Vomiting, dyspepsia,
flatulence, gastrointestinal sounds abnormal
Uncommon                        Rectal haemorrhage


Renal and urinary disorders   Uncommon                        Pollakiuria General disorders and         Common                          Fatigue administration site
Uncommon                        Pyrexia, malaise conditions

Description of selected adverse reactions
After the first day of treatment, the most common adverse reactions were reported in similar frequencies (incidence no more than 1% different between prucalopride and placebo) during Resolor therapy as during placebo, with the exception of nausea and diarrhoea that still occurred more frequently during Resolor therapy, but less pronounced (differences in incidence between Resolor and placebo of 1.3% and 3.4%, respectively).

Palpitations were reported in 0.7% of the placebo patients, 0.9% of the 1 mg prucalopride patients, 0.9% of the 2 mg prucalopride patients and 1.9% of the 4 mg prucalopride patients.
The majority of patients continued using prucalopride. As with any new symptom, patients should discuss the new onset of palpitations with their physician.


Suicidal Ideation and Behaviour
In the double-blind trials, one patient reported a suicide attempt 7 days after the end of treatment with RESOLOR 2 mg once daily; none were reported in patients on placebo. In the open-label trials, two patients reported a suicide attempt and another patient reported suicidal ideation. Completed suicide was reported in two patients, previously treated with RESOLOR 2 mg or 4 mg; both discontinued RESOLOR for at least one month prior to the event.


Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form per the following link:  https://sideeffects.health.gov.il