Adverse events reported for Mirena levonorgestrel-releasing intrauterine device in France and impact of media coverage.

AIMS: In 2017, concerns regarding adverse events (AEs) associated with the Mirena levonorgestrel intrauterine device were largely echoed in the media in France. This resulted in a tremendous reporting of AEs to pharmacovigilance centres. The aim of this study was to describe the reporting of AEs regarding Mirena in France and to study the impact of media coverage on this reporting. METHODS: All cases reports involving Mirena recorded in the French national pharmacovigilance database from marketing (21 July 1995) until 04 August 2017 were extracted. To allow studying the influence of mediatisation, reports were described separately for the periods preceding and following the observed media coverage peak (15 May 2017). RESULTS: Overall, 3224 reports were considered, 510 (15.8%) recorded before the media coverage peak, and 2714 (84.2%) after. Before the peak, 76.5% of reports originated from health professionals; median time-to-report was of 5.5 months (interquartile range: 1.7-18.6), and median number of AEs per report was 1 (range: 1-17). After the peak, 98.6% originated from patients; median time-to-report was 21 months (interquartile range: 8.1-45.5), and median number of AEs per report was 6 (range: 1-37). After the peak, most reports mentioned anxio-depressive disorders (38.8 vs 10.6% before) or sexual disorders (47.3 vs 6.9%). Other emphasised AEs were weight increase (42.3 vs 10.2%) and pain (gastrointestinal, 19.1 vs 3.5%; musculoskeletal, 22.2 vs 4.5%). CONCLUSION: This study highlighted the importance of mediatisation impact on spontaneous reporting with changes concerning amounts of reports, type of reporter, and type of reported AEs. For Mirena, this led to generate signals regarding anxio-depressive and sexual disorders.

Safety of levonorgestrel 52 mg intrauterine system compared to copper intrauterine device: a population-based cohort study.

OBJECTIVE: To compare the risk of all-cause death, hospitalizations (any cause), ectopic pregnancy, pelvic inflammatory disease or infection, uterine perforation, device removal, neuro-psychiatric drugs initiation, or new psychiatric visit(s) between levonorgestrel (LNG) 52 mg intrauterine system (IUS) and copper intrauterine device (IUD) users in France. STUDY DESIGN: We identified a historical cohort of women aged 20-55 years with a first dispensing of either LNG 52 mg IUS or copper-IUD between January 1, 2010, and December 31, 2014, in the French National Claims database, SNDS. We used propensity score matching to balance the two groups on baseline sociodemographic and clinical characteristics to minimize confounding. We estimated Cox proportional hazards models to compare health outcomes between LNG 52 mg IUS and copper-IUDs users. RESULTS: We matched 9318 LNG 52 mg IUS users (mean age 36.2±6.8 years) to 10,185 copper-IUD users (mean age 35.4±7.1 years). After matching and age-adjustment, LNG 52 mg IUS users had a slightly higher risk of anxiolytic drugs initiation (HR 1.08, 95%CI 1.01-1.15) and device removal (HR 1.05, 95%CI 1.01-1.10) compared to copper-IUD users, with no differences for other studied outcomes. CONCLUSION: French IUS users report slightly more anxiolytic treatment initiation and IUD removal compared to copper-IUD users. These results are consistent with a potential pharmacovigilance signal of anxiety-related disorders in LNG 52 mg IUS users. IMPLICATIONS STATEMENT: In French LNG 52 mg IUS users, there was slightly more anxiolytic treatment initiation and IUD removal compared to copper-IUD users. No risk difference was found for all-cause death, hospitalizations, ectopic pregnancy, pelvic disorders, and uterine perforation. We cannot exclude that the associations are related to differences in characteristics of women who chose each type of type of IUD.