Summary Safety Review - Lanoxin, Toloxin, Apo-digoxin, PMS-digoxin, (Digoxin) - Assessing the Potential Higher Risk of Death Compared to Patients not Using Digoxin

Review decision

A Summary Safety Review complements other safety related information to help Canadians make informed decisions about their use of health products. Each summary outlines what was assessed in Health Canada’s review, what was found and what action was taken by Health Canada, if any.


Issued: 2016-08-23

Product

Lanoxin, Toloxin, Apo-digoxin, PMS-digoxin, (Digoxin)

Potential Safety Issue

Increased risk of death in patients with irregular heart rhythm (atrial fibrillation) and patients with heart failure taking digoxin compared to patients with the same health issues but not using digoxin.

Key Messages

  • Digoxin is marketed in Canada for the treatment of mild to moderate heart failure and to control the heart rate in patients with chronic irregular heart rhythm.
  • This safety review was carried out by Health Canada after two published studies suggested that digoxin use may be linked with an increased risk of death, particularly in patients with irregular heart rhythm.
  • Health Canada concluded that a link between digoxin use and a higher risk of death when compared to those not using digoxin could not be established. Health Canada will continue monitoring the issue and will re-evaluate it when new information becomes available

Overview

Health Canada completed a safety review to evaluate if using digoxin was linked to a higher risk of death compared to patients not using digoxin. The issue was triggered by two publications in the scientific literature 1, 2 which investigated the link between digoxin and death. Results of the studies suggested that digoxin use may be linked with a higher risk of death when compared to patients not using digoxin, especially among patients diagnosed with an irregular heart rhythm.

Use in Canada

  • Digoxin has been marketed in Canada since 1936. It is currently marketed under the following brand names: Lanoxin, Toloxin, Apo-digoxin, PMS-digoxin, and Digoxin Injection C.S.D.
  • Digoxin is used to treat mild to moderate heart failure by improving heart pumping activity and improving the symptoms of heart failure. It is also used to control heart rate in patients with irregular heart rhythm.
  • At the time of review, the estimated number of prescriptions (including refills) for digoxin in Canada was 1.68 million per year.
  • The product information for Digoxin in Canada explains that digoxin is not to be used in patients with the condition where the lower chambers of the heart contract rapidly and uncoordinatedly so the heart pumps little or no blood (ventricular fibrillation).

Safety Review Findings

  • At the time of the review, Health Canada had received 39 Canadian cases of death a. Of the 39 cases, 22 were due to intentional overdoses (suicide) or accidental overdoses (medication errors). The remaining 16 Canadian reports (1 was reported twice) did not have a clear relationship between digoxin use and the corresponding reported deaths because the patients had other medical conditions which could have been linked to their death.
  • The World Health Organization's database showed that there were 1086 reports of death linked with digoxin use. However, only 15 of the reports contained enough information to allow for a meaningful assessment. A clear link between digoxin and death could not be made for these 15 cases because the medical conditions digoxin treats already carries the risk of death. There are also differences in local treatment guidelines and allowed uses for digoxin worldwide.
  • The review of the scientific and medical literature, including the 2 studies that triggered the safety review, showed that study outcomes were conflicting and the results of the respective studies depended on the specific study methods and design. As a result, the reviewed studies could not provide enough evidence of a link for digoxin and a higher risk of death.

Conclusions and actions

  • Based on its review of the current scientific literature and medical literature, Health Canada did not find evidence supporting a link between the use of digoxin and a higher risk of death.
  • Health Canada will continue to monitor safety information involving digoxin, as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will take appropriate and timely action when any new health risks are identified.

Additional information

The analysis that contributed to this safety review included scientific and medical literature, Canadian and international adverse reaction reports and what is known about the use of this drug both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

References

  1. 1 Vamos,M., Erath,J.W., & Hohnloser,S.H. Digoxin-associated mortality: a systematic review and meta-analysis of the literature Eur. Heart J. 36, 1831-1838 (2015)
  2. 2 Freeman,J.V. et al. Digoxin and risk of death in adults with atrial fibrillation: The ATRIA-CVRN study. Circ. Arrhythm electrophysiol. 8, 49-58 (2015)

Footnotes

  1. a Canadian reports can be accessed through the Canada Vigilance Online Database.

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