Apixaban, concomitant medicines and spontaneous reports of haemorrhagic events

阿哌沙班、合并用药以及自发性出血事件报告

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Abstract

INTRODUCTION: Little is known about the potential safety issues associated with apixaban in clinical practice and their reporting in spontaneous adverse event (SAE) databases. OBJECTIVE: To describe SAE reports associated with the oral anticoagulant apixaban from Australia, Canada and USA and to examine associated concomitant medicine use. METHODS: SAE report databases from Australia, Canada and the USA were examined for all reports of adverse events associated with apixaban and concomitant medicines from 1 January 2012 to 30 September 2014. Disproportionality analysis (proportional reporting ratio (PRR) and reporting odds ratio (ROR)) was conducted for the quantitative detection of signals using the USA database. RESULTS: There were 97 SAE reports associated with apixaban from Australia, 77 from Canada and 2877 from the USA. Reporting of haemorrhage (any type) was common, ranging from 18% for USA to 31% for Australia. Gastrointestinal (GI) haemorrhage was the most commonly reported haemorrhage, accounting for approximately 10% of adverse event reports across all countries. Positive signals were confirmed in the USA data (haemorrhage (any type) PRR, 12.1; χ(2), 5582.2 and ROR, 13.4; 95% CI: 12.13-14.6; GI haemorrhage PRR, 11.8; χ(2), 2325.4 and ROR, 12.3; 95% CI, 10.8-14.0). Reporting of concomitant use of medicines with the potential to increase bleeding risk ranged from 47.6% in Canada to 65.5% in Australia. CONCLUSION: A large proportion of adverse event reports for apixaban were associated with use of concomitant medicines which may have increased the risk of haemorrhage.

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