Summary Safety Review - Cyclosporine - Assessing the Potential Risk of Hearing Impairment

• Health Canada’s safety review did not find sufficient evidence in the post-market setting regarding the link between cyclosporine and the risk of hearing impairment to support changes to the current product safety information in the Canadian product monograph (CPM).

• Health Canada will continue to monitor the safety of cyclosporine.

Health Canada reviewed the potential risk of hearing impairment with the use of cyclosporine. The safety review was triggered by a labelling update for cyclosporine-containing products by the European Medicines Agency.

• Cyclosporine is a prescription drug authorized for sale in Canada for the prevention and treatment of rejection after an organ or bone marrow transplant, the prevention and treatment of graft-versus-host-disease (a complication of bone marrow transplantation) and the treatment of certain autoimmune diseases.

• Cyclosporine has been marketed in Canada since the early 1980s. Systemic cyclosporine is currently available as a solution for infusion into a vein (intravenous), oral capsules and oral solution under the brand names Sandimmune IV and Neoral. Generic versions of cyclosporine are also available in Canada.

• The number of prescriptions dispensed by Canadian retail pharmacies for cyclosporine has been relatively consistent over the past 5 years, at around 80,000 prescriptions annually. Cyclosporine is also used in the hospital setting.

• Health Canada reviewed the available information provided by manufacturers, and from searches of the Canada Vigilance database^a, international databases and the scientific literature.

• Health Canada reviewed 2 international cases of hearing impairment in patients taking cyclosporine that were reported in the scientific literature. Both cases were found to be possibly linked to the use of cyclosporine. However, the cases reviewed provided limited evidence for a definitive link due to study limitations and other contributing factors that may have resulted in hearing impairment.

• Health Canada also reviewed 11 articles published in the scientific literature. Overall, the scientific literature provided insufficient evidence to support a link between cyclosporine and hearing impairment in the post-market setting due to conflicting study findings, limitations in study design, and the underlying conditions of patients that may have contributed to the risk.

• Health Canada’s review of the available information did not find sufficient evidence in the post-market setting regarding the link between cyclosporine and the risk of hearing impairment to support changes to the CPM.

• Health Canada encourages consumers and healthcare professionals to report any side effects related to the use of cyclosporine, and other health products, to the Canada Vigilance Program.

• Health Canada will continue to monitor safety information involving cyclosporine, 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 should new health risks be identified.

The analysis that contributed to this safety review included scientific literature, Canadian and international information and what is known about the use of cyclosporine both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.

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