Drug Safety

The European Medicines Agency has suspended the use of ulipristal acetate (UPA) in the treatment of uterine fibroids and is reassessing its association with a risk of liver injury. Our objectives were to characterize the post-marketing reporting of drug-induced liver injury (DILI) with UPA and investigate the underlying pharmacological basis. We queried the worldwide FDA Adverse Event Reporting System and performed a disproportionality analysis, selecting only hepatic designated medical events (DMEs) where UPA was reported as suspect. The reporting odds ratios (RORs) were calculated, and we considered a lower limit of the 95% confidence interval (LL95% CI) > 1 as significant. Physiochemical/pharmacokinetic features were extracted to assess the risk of hepatotoxicity by applying predictive DILI risk models. Mifepristone and leuprolide were selected as comparators. A significantly higher proportion of liver disorders was reported for UPA than for mifepristone (2.9 vs. 0.8%; p < 0.00001) and leuprolide (2.9 vs. 1.6%; p = 0.015). As regards hepatic DMEs, statistically significant RORs were found for autoimmune hepatitis (N = 5; LL95% CI 16.8), DILI (n = 5; LL95% CI 5.9), and acute hepatic failure (N = 5; LL95% CI 9.3). No signals of DILI emerged for mifepristone and leuprolide acetate. UPA and mifepristone showed high lipophilicity and hepatic metabolism (predicted intermediate DILI risk). Leuprolide exhibited contrasting features, resulting in no DILI concern. Inhibition of different liver transporters and the presence of a reactive metabolite were also recognised for UPA. Different drug properties previously linked to the occurrence of DILI may partially explain the reporting pattern observed with UPA. Our “bedside-to-bench” approach may support regulators in the risk–benefit assessment of UPA.

This article considers the benign yet debilitating conditions of menorrhagia, dysmenorrhoea and irregular menstrual bleeding. Surprisingly little has been reported in the literature concerning these common ailments which can detract from the quality of female life during the reproduction years. Both dysmenorrhoea and menorrhagia are subjective complaints, but despite accurate means of measuring menstrual blood loss such quantification is rarely performed. This lack of diagnostic accuracy is a cause for concern, especially as both medical and surgical treatment are not without risk. The therapeutic alternatives which are commonly prescribed in an attempt to rectify such menstrual disorders are discussed. These include the nonsteroidal anti-inflammatory agents, the combined oral contraceptives, danazol, progestogens, antifibrinolytics, haemostatics, luteinising hormone releasing hormone analogues and clomiphene. The results of clinical trials which have utilised these various agents are considered in terms of both the effectiveness of treatment and its potential adverse effects.

Empowering consumers to contribute to adverse drug reaction reporting seems a sensible innovation, particularly when traditional reports emanating from healthcare professionals are neither increasing nor improving. This work, inspired by an EU-FP7-funded project, describes an attempt by the Philippines to introduce a consumer reporting system through education and an online platform for reporting, and the lessons that were captured in the process. While participating consumers did not contribute to the adverse drug reporting process in the traditional sense as originally expected, the reports received by the drug regulatory agency revealed consumers’ concerns regarding health product legitimacy, quality and market claims, as well as the lack of available and accessible information. These reports led regulators to take action. Initial insights on consumer behavior are proposed for regulators and industry to consider in greater depth and how this may impact on consumers providing valued information that will promote other aspects of product safety.