Frequent Adverse Drug Reactions, and Medication Groups under Suspicion

Abstract

Background: The adverse drug reaction database of the German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM) contains reports of suspected adverse drug reactions (ADRs) that are spon- taneously submitted by physicians, pharmacists, or patients. The aim of the present study was a descriptive analysis of all of these spontaneous reports.

Methods: 345 662 spontaneously submitted reports were analyzed with respect to the number of reports per year, the sources of the reports, demographic variables, the most commonly reported ADRs, and the drug classes most commonly suspected.

Results: The number of reports submitted spontaneously each year has grown steadily since 1978. At the least detailed level of analysis, "drugs for the treatment of nervous system disorders" were the most common class of drugs under suspicion of causing the reported adverse drug reactions (23.1%). In a more detailed analysis by therapeutic subgroup, the three subgroups most commonly reported as suspected of causing side effects were antithrombotic agents, systemic antibiotics, and psycholeptics-causing thrombocytopenia, diarrhea, and drug dependency as the most frequently reported ADRs, respectively. The order of drug classes most commonly causing ADRs differed markedly between the physicians' reports (diazepines, fluoroquinolones, heparins) and the patients' reports (interferons, anti- thrombotic drugs, selective immunosuppressant drugs). Patients more commonly reported subjectively perceived ADRs, while physicians more commonly reported findings or diagnoses that require medical expertise.

Conclusion: The increasing number of spontaneous reports is mainly due to reports forwarded from pharmaceutical companies to the BfArM. This, in turn, is probably a result of increasingly strict legal reporting requirements in Germany. The detected differences between physicians' and patients' ADR reports can be taken to indicate that patients should be more specifically informed and questioned about potential ADRs. By reporting adverse drug reactions, physicians may improve drug safety.

Figure 1

Number of spontaneous reports received per year according to primary reporting source. (The primary source refers to the person who generated the ADR report, not to the sender [such as the pharmaceutical company] who submitted the report to the German Federal Institute for Drugs and Medical Devices). The color-coded curves indicate the respective 95% confidence intervals. In 6% of the 345 662 cases, more than one reporting source was named (for example, physician and patient both reported the same case independently from each other). To avoid double counting, this analysis was based on reports that only named one source. HCP, healthcare professionals

Figure 2

Number of spontaneous reports per year that are forwarded by pharmaceutical companies to the German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM).

Figure 3

Quotient of spontaneous reports per 100 000 population, per 100 000 prescriptions, or per 100 physicians, over time. Limitations of the analysis over time are described in eBox 3.

eFigure 1

Flow chart depicting generation of final dataset German Federal Institute for Drugs and Medical Devices (Bundesinstitut für Arzneimittel und Medizinprodukte, BfArM); SMQ, standardized MedDRA queries; MedDRA, Medical Dictionary for Regulatory Activities

eFigure 2

Description and schematic depiction of ATC^* (anatomical, therapeutic, chemical) classification using morphine as an example

eFigure 3

Stratification of spontaneous reports by age and sex eFigure 3 shows the cumulative stratification of spontaneous reports with respect to age (in 5-year age groups) of affected patients and their sex. Reports within one age group can be from different years. In addition to the sex ratio (female/male), the odds ratio for each age group with respect to the other age groups was calculated using the Bonferroni confidence interval adjustment.