Severe injection site reactions after subcutaneous administration of Sayana(c).
PURPOSE: Sayana(R) was introduced as the first depot medroxyprogesterone acetate-containing contraceptive that is administered via subcutaneous injection. Within 10 months, the Regional Pharmacovigilance Centre (RPVC) Zurich received several anonymous reports of serious local reactions after Sayana(R) administration. In this retrospective study, individual case safety reports (ICSRs) on local adverse drug reactions (ADRs) related to Sayana(R) were analysed from the WHO pharmacovigilance database. METHODS: International, national and regional ICSRs during Sayana(R) administration up to 1 January 2016 were examined. Data on ADRs were retrieved from the WHO Global Database VigiBase. Demographic data, drug administration information, duration of Sayana(R) treatment, latency time of the ADR, and its course, severity and outcomes were analysed. RESULTS: Worldwide, 398 ICSRs after Sayana(R) use were registered in the database. We identified 20 reported terms that were potentially used to describe a persistent lipodystrophy. When only cases containing one or more of these 20 reported terms were selected, 323 (81.2%) international ICSRs remained for analysis. Of those, 91.6% (n = 296) were categorised as serious. The majority of the reactions (n = 193, 54.4%) did not recover. In the 67 Swiss ICSRs, 77 ADRs were reported using 10 different terms including severe or persistent local reactions like lipodystrophy, atrophy or fat necrosis. Thirty-two patients (47.7%) did not recover. All 11 regional cases reported to the RPVC Zurich were categorised as serious ADRs. For the majority of the patients (n = 7, 63.6%) the interval between the application of Sayana(R) and development of the lipodystrophy was between 2 and 4 months. Most of the reactions were irreversible (n = 9, 81.8%). One patient underwent plastic surgery for artificial infill of the dent. CONCLUSIONS: Persistent local injection site reactions such as lipodystrophy, fat tissue necrosis or atrophy occur frequently after subcutaneous Sayana(R) use. These adverse drug reactions were recently integrated in the Swiss product information. Physicians and patients should be informed and advised about these potentially irreversible effects.