Resolor Adverse Reactions

In an integrated analysis of 17 double-blind placebo-controlled studies, Prucalopride succinate (Resolor) was given orally to approximately 3300 patients with chronic constipation. Of these patients over 1500 patients received Prucalopride succinate (Resolor) at the recommended dose of 2 mg per day, while about 1360 patients were treated with 4 mg Prucalopride succinate (Resolor) daily. The most frequently reported adverse reactions associated with Prucalopride succinate (Resolor) at the 2 mg daily dose are headache (17.8%) and gastrointestinal symptoms (abdominal pain (13.7%), nausea (13.7%) and diarrhea (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.
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 (≥1/1000 to <1/100). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Frequencies are calculated based an integrated analysis of 17 double-blind placebo-controlled clinical studies. (See table.)

Click on icon to see table/diagram/image

Description of Selected Adverse Reactions: Palpitations: Palpitations were reported in 0.7% of the placebo patients, 0.9% of the 1 mg Prucalopride succinate (Resolor) patients, 0.9% of the 2 mg Prucalopride succinate (Resolor) patients and 1.9% of the 4 mg Prucalopride succinate (Resolor) patients. The majority of patients continued using Prucalopride succinate (Resolor). As with any new symptom, patients should discuss the new onset of palpitations with their physician.
Cardiovascular Safety Analysis: An evaluation was performed by an independent adjudication committee of all potential major adverse cardiovascular events (MACE) across 28 completed double-blind and open-label clinical studies for Prucalopride succinate (Resolor) in adult patients with chronic idiopathic constipation. The standardized incidence rate (IR) per 1000 subject-years for MACE for Prucalopride succinate (Resolor) was compared with the IR for placebo. The total exposure in the double-blind studies was 565.2 subject-years in the Prucalopride succinate (Resolor) group, 384 subject-years in the placebo group and 2769 subject-years in the double-blind and open-label clinical studies. The IR for MACE was 3.5 (2 subjects out of 3366) in the double-blind Prucalopride succinate (Resolor) group, 5.2 (2 subjects out of 2019) in the placebo group, and 3.3 (9 subjects out of 4472) for Prucalopride succinate (Resolor) in the combined double-blind and open-label clinical studies. The data do not indicate an increased risk of MACE attributable to Prucalopride succinate (Resolor) when compared to placebo.
Observational Cardiovascular Cohort Study: The overall (CV) safety of Prucalopride succinate (Resolor) was assessed in an observational population-based cohort study using European healthcare databases. New users of Prucalopride succinate (Resolor) (N=5715) were matched to new users of polyethylene glycol 3350 (PEG) (N=29,372) to determine the standardized incidence rate (IR) and the adjusted incidence rate ratio (IRR) per 1,000 person-years for MACE. In this cohort study, the pooled, standardized IR for MACE was 6.57 (95% CI: 3.90, 10.39) for Prucalopride succinate (Resolor) compared to an IR of 10.24 (95% CI: 6.97, 14.13) for PEG and the IRR for MACE was 0.64 (95% CI: 0.36, 1.14). These data do not indicate an increased risk of MACE in patients using Prucalopride succinate (Resolor) as compared with patients using PEG for chronic idiopathic constipation.