Drug–drug interactions (DDIs) are frequent contributors to adverse drug reactions (ADRs) and represent a preventable component of medication-related harm. The study compared pharmacovigilance outcomes for DDI reporting between Switzerland and Austria to explore whether differences in system design and expert involvement affect reporting patterns and report quality. Switzerland and Austria were selected because they have similar population sizes, age distributions, universal healthcare coverage, and largely overlapping pharmaceutical markets, while differing in organisation of national pharmacovigilance activities.
The analysis used individual case safety reports (ICSRs) retrieved from VigiBase®, the World Health Organization global database of ICSRs, with data extraction performed on 3 April 2024. The study included all ICSRs coded under the MedDRA higher-level term “Drug Interaction” from the first report in each country through 1 April 2024, covering the period from 1 January 2008 to 1 April 2024. Interaction subtypes (for example drug–drug, drug–herb, drug–alcohol) were captured using MedDRA preferred-term subcategories, and multiple interaction types could be present in a single case.
This was a retrospective, cross-sectional observational analysis reported according to STROBE guidance. The investigators analysed 1,499 DDI-related ICSRs in total. Cases were stratified by age into children (<18 years), adults (18–64 years), and elderly (>64 years), and plausibility checks excluded reported ages ≥120 years. Primary variables included frequency of DDI reports, patient demographics, reporter categories, seriousness of outcome (hospitalization, life-threatening events, fatality), ADR types, completeness of case documentation (completeness score), and pharmacological plausibility of the reported ADR–drug combinations. Drug classes were analysed using ATC coding where applicable.
Overall, 1,499 DDI reports were identified: 1,159 from Switzerland and 340 from Austria. Switzerland submitted 3.4 times more DDI cases than Austria, corresponding to mean monthly reporting rates of 5.8 versus 1.7 cases per month. Patient demographic distributions were comparable between the two countries, although the proportions of reporter categories (for example health professionals versus others) differed. The majority of reports were classified as serious in both settings: 80% of Swiss reports and 84% of Austrian reports met seriousness criteria.
Polypharmacy was strongly associated with serious outcomes in both national datasets. In Switzerland, the reporting odds ratio (ROR) for polypharmacy and serious outcome was 3.71 (95% CI 3.26–4.23, p < 0.0001). In Austria, polypharmacy was also associated with increased odds of seriousness, with an ROR of 1.98 (95% CI 1.60–2.44, p < 0.0001). These results indicate a robust association between multiple concomitant medications and reporting of serious ADRs in the context of DDIs in both countries.
The content and clinical framing of reports differed across countries. Swiss reports more frequently described mechanistic aspects of the interaction (for example pharmacokinetic or pharmacodynamic mechanisms), whereas Austrian reports more commonly recorded clinical symptoms or manifestations. The study also identified differences in pharmacological consistency between the reported ADR and the implicated drugs, suggesting variability in the depth of clinical assessment or documentation practices between the two pharmacovigilance systems. Case completeness was assessed using a completeness score (maximum 1) to quantify clinically relevant information present in ICSRs.
The authors attribute observed cross-national disparities in reporting volume, content, and apparent report quality at least partly to differences in national pharmacovigilance system design. In Switzerland, reporting is managed centrally through the Electronic Vigilance System (ELViS) with reports assessed at clinical pharmacology units, while Austria’s Federal Office for Safety in Health Care (BASG) oversees pharmacovigilance without routine mandatory involvement of clinical pharmacology specialists in report assessment. The study suggests that specialist involvement—clinical pharmacologists and pharmacists—may influence the detection, description, and pharmacological assessment of DDIs in submitted ICSRs.
Data were derived from VigiBase® and therefore subject to the known constraints of spontaneous reporting, including lack of a defined denominator and underreporting. The authors note that access to the VigiBase® data is restricted by Uppsala Monitoring Centre data-sharing agreements, and the investigators are not authorised to share raw VigiBase® extracts. Other limitations inherent to registry-based, observational analyses—such as reporting bias and heterogeneity in reporting practices—apply and were considered by the authors.
Cross-national differences in DDI reporting between Switzerland and Austria were substantial in volume and composition. Switzerland reported more DDI cases and more mechanistic detail, while Austria reported fewer cases and more symptom-focused entries. Polypharmacy was consistently associated with serious outcomes in both countries. The findings imply that pharmacovigilance system architecture and the involvement of clinical pharmacology specialists may shape reporting patterns and report quality. The authors recommend further investigation into structured integration of clinical pharmacologists and pharmacists in ADR processing as a potential approach to strengthen DDI-related pharmacovigilance and inform regulatory or policy interventions.