A cross-country comparison of rivaroxaban spontaneous adverse event reports and concomitant medicine use with the potential to increase the risk of harm

Drug Saf. 2014 Dec;37(12):1029-35. doi: 10.1007/s40264-014-0235-y.

Abstract

Background: Concerns with the safety profiles of the newer anticoagulants have been raised because of differences in treatment populations between pre-marketing studies (randomized controlled trials) and clinical practice. Little is known about the potential safety issues and the reporting in spontaneous adverse event databases associated with rivaroxaban.

Objectives: To analyse spontaneous adverse event reports associated with the oral anticoagulant rivaroxaban from Australia, Canada and the USA; and to examine concomitant medicine use that may increase the risk of adverse events.

Methods: Spontaneous adverse event report databases from Australia, Canada and the USA were examined for all reports of adverse events associated with rivaroxaban and concomitant medicines from 1 August 2005 to 31 March 2013. Disproportionality analysis (the proportional reporting ratio [PRR] and reporting odds ratio [ROR]) was conducted for quantitative detection of signals, using the US database.

Results: There were 244 spontaneous adverse event reports associated with rivaroxaban from Australia, 536 from Canada and 1,638 from the USA. Reporting of haemorrhage (any type) was common, ranging from 30.7% for Australia to 37.5% for Canada. Gastrointestinal haemorrhage was the most commonly reported haemorrhage, accounting for 13.9% of Australian, 16.4% of Canadian and 11.1% of US adverse event reports. Positive signals were confirmed in the US data (haemorrhage [any type] PRR 11.93, χ (2) 4,414.78 and ROR 13.41, 95% confidence interval [CI] 12.13-14.81; gastrointestinal haemorrhage PRR 12.52, χ (2) 2,018.48 and ROR 13.15, 95% CI 11.36-15.21). Reporting of concomitant use of medicines with the potential to increase bleeding risk ranged from 63.7% in Australia to 89.2% in Canada.

Conclusion: A large proportion of adverse event reports for rivaroxaban were associated with use of concomitant medicines, which may have increased the risk of adverse events-in particular, haemorrhage. Increased awareness of a patient's comorbidity and associated medicine use is needed when rivaroxaban is used in clinical practice.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adverse Drug Reaction Reporting Systems / statistics & numerical data*
  • Anticoagulants / adverse effects*
  • Australia / epidemiology
  • Canada / epidemiology
  • Female
  • Humans
  • Male
  • Middle Aged
  • Morpholines / adverse effects*
  • Odds Ratio
  • Product Surveillance, Postmarketing / statistics & numerical data
  • Risk Assessment
  • Rivaroxaban
  • Thiophenes / adverse effects*
  • United States / epidemiology

Substances

  • Anticoagulants
  • Morpholines
  • Thiophenes
  • Rivaroxaban