Gender differences in the adverse events associated with cardiovascular drugs in a spontaneous reporting system in South Korea.

Background Studies on disease-related gender differences in pharmacodynamics and pharmacokinetics are prevalent; however, gender differences in the drug-related adverse events have not been systemically described. Objective To explore gender differences in the adverse events associated with cardiovascular drugs using a spontaneous reporting system. Setting This study was conducted using the Korea adverse event reporting system and national health insurance databases. Methods The number of reported adverse events was divided by the number of patients diagnosed with cardiovascular diseases (Korean Standard Classification of Disease, 7th Revision, I05-I70) and prescribed cardiovascular drugs. We calculated adverse event reporting rates per 100,000 persons and the reporting ratio for women, compared with men. Main outcome measures Reporting ratios across the groups of adverse events and cardiovascular drugs. Results We identified 27,533 adverse events associated with cardiovascular drugs and 9,413,666 patients with cardiovascular disease. Compared with men, reporting ratios of women were higher in the following categories: Overall (1.09, 95% CI, 1.06-1.11), beta blockers (1.20, 95% CI, 1.05-1.39), and calcium channel blockers (1.14, 95% CI, 1.03-1.27). For the adverse events, the reporting ratio was 1.34 (95% CI, 1.14-1.58) for musculoskeletal disorders and 2.54 (95% CI, 2.10-3.07) for oedema in women. Conclusion Our findings on differential adverse events reporting rates associated with the cardiovascular drugs between women and men provide an evidence on possible gender differences in wide range of pharmacotherapy. A clear understanding of the relationship between drug-induced adverse events and gender will aid in the development of therapeutic interventions being tailored to the individual patients.

Gender differences in adverse event reports associated with antidiabetic drugs.

Little is known about gender-specific reporting of adverse events (AEs) associated with antidiabetic drugs. This study was to assess the gender-related difference in AEs reporting associated with antidiabetic agents. The number of antidiabetic drug-AE pairs associated was identified using the Korea Adverse Event Reporting System database. Prevalence of diabetes was estimated using the Health Insurance Review and Assessment Service-National Patients Sample database. Reporting rate per 10,000 people was calculated by dividing drug-AE pairs with the number of antidiabetic drug users by gender. Gender difference was presented with risk ratio (reporting rate ratio) of women to men. Antidiabetic agent-associated AEs were more frequently reported by women than men throughout body organs and drug classes. 13 out of 17 system organ class level disorders with significant gender differences were reported more often by women than men. By drug class, gender-specific reporting rates were observed in most of the drug classes, especially in newer classes such as glucagon-like peptide-1 analog (GLP1-RA), sodium glucose co-transporter-2 inhibitor (SGLT2i), and thiazolidinedione (TZD). Looking into preferred term level for each drug class, women dominated the reports of class-specific AEs of newer antidiabetic drugs such as urinary tract/genital infection (all reported by women) in SGLT2i, edema in TZD (risk ratio (RR) 12.56), and hyperglycemia in insulin users (RR 15.35). Gender differences in antidiabetic-associated AE reporting often attributed to women. Explanations for these different report levels by gender should be further investigated.

Pattern of adverse events induced by aflibercept and ranibizumab: A nationwide spontaneous adverse event reporting database, 2007-2016.

Data regarding the safety of anti-vascular endothelial growth factor (anti-VEGF) treatment is limited.To compare the adverse events (AEs) induced by aflibercept and ranibizumab using a spontaneous reporting system and determine the signals.We used data from the Korea Institute of Drug Safety & Risk Management-Korea Adverse Event Reporting System Database (KIDS-KD), collected between 2007 and 2016. Differences in patient demographics, report type, reporter, causality, and serious-AEs between aflibercept and ranibizumab were compared. Metrics including proportional reporting ratio (PRR), reporting odds ratio (ROR), and information component (IC), were used to compare signals with the AEs on the drug labels in the United States of America and Korea. Logistic regression analysis was performed to identify AEs that are more likely to occur with drug use.A total of 32 aflibercept and 103 ranibizumab cases of AEs were identified. The proportion of AEs that were reported voluntarily was higher with aflibercept (50.5%) use than ranibizumab (4.9%), whereas the AEs reported by post-marketing surveillance were higher with ranibizumab (46.6%) use than aflibercept (31.3%). The percentage of AEs in patients >60 years old, reports by consumers, and the ratio of SAEs to AEs associated with aflibercept (84. %, 9.4%, and 75.0%, respectively) were higher than those of ranibizumab (77.7%, 1.9%, and 19.4%, respectively). The number of newly detected AEs after aflibercept and ranibizumab treatment was 3 and 8, respectively. Among these, conjunctivitis and medicine ineffective were not included on the aflibercept and ranibizumab labels, respectively. Endophthalmitis (OR 6.96, 95% CI 2.74-17.73) was more likely to be reported in patients with aflibercept than in patients without aflibercept, whereas medicine ineffective (OR 18.49, 95% CI 2.39-143.29) and retinal disorder (OR 7.03, 95% CI 1.60-30.96) were more likely to be reported in patients with ranibizumab than in patients without ranibizumab.New signals have been identified for aflibercept and ranibizumab. Further research is necessary to evaluate the causality of AEs that were detected as signals in this study.