Hypothesis / aims of study
Anticholinergics and β3-agonists represent a cornerstone for overactive bladder (OAB) management, and their safety and efficacy profiles have been widely investigated in the literature. The aims of our study were: 1) to perform a real world analysis of nervous system disorders (NSD) related to anticholinergics and β3-agonists use, based on a market analysis from European countries; 2) to highlight strengths and weaknesses of the current information systems and registries, in order to propose any potential improvement.
Study design, materials and methods
We collected and analyzed data from the European Union Drug Regulatory Authorities (EUDRA) online database, which is managed by the European Medicine Agency (EMA) and was lunched by May 31st 2012. The chosen drugs were oxybutinin, solifenacin, fesoterodine, tolterodine, and mirabegron. We selected data on total events number, geographic distribution, and NSD seriousness grading, with no time restrictions until March 29th, 2026. We analyzed any potential available information to stratify NSD by patients age.[1,2]
Results
Individual cases for each drug are reported in Figure 1, including their stratification by patients age.
Concerning the geographic distribution, the highest reported rates of NSD (first three Countries for each drug) were:
- Oxybutinin: 378 cases in France, 271 in the Netherlands, 213 in Germany
- Solifenacin: 573 cases in France, 487 in the Netherlands, 370 in Germany
- Fesoterodine: 449 cases in France, 171 in Spain, 157 in Germany
- Tolterodine: 127 cases in Sweden, 122 in the Netherlands, 111 in Germany
- Mirabegron: 506 cases in Spain, 434 in Germany, 422 in Sweden.
The details about NSD grading (non-serious / serious / not specified) are reported in Table 1.
No data about the stratification of adverse events seriousness by age was available.
Interpretation of results
The total number of adverse events was highest for mirabegron and lowest for fesoterodine, but no information about the total number of patients / prescriptions were available, thus preventing any consistent proportion analysis or comparison between the five drugs. Among each drug, the percentage of serious adverse events was highest for tolterodine, but the same previous concern affects any further analysis. Moreover, when we focus on adverse events seriousness, no stratification by age is available from the system. This currently missing information from the market may be of help to analyze the relevant issue of NSD distribution by patients age.[3] Drug dosages are not reported, as well. An additional limitation is represented by the risk of heterogeneous adverse events reporting among different Countries, but it should not prevent a proper analysis within each Country data.
Concluding message
Currently, the EUDRA system accurately reports updated information on adverse events related to anticholinergics and β3-agonists, despite the stratification by age could be improved. Of notice, the lack of information about general prescriptions prevents any advanced analysis on the adverse events, including a comparison between the different drugs, and a stratification by patients age. A system implementation by recording the total prescriptions—along with the number of patients treated—would be advised, in order to adequately identify the amount of patients affected by adverse events, stratified by age.