Summary Safety Review - Denosumab (Prolia and Xgeva) - Hearing loss and deafness

June 6, 2016

Product

Denosumab (Prolia and Xgeva)

Potential Safety Issue

Hearing loss and deafness

Key Messages

• Prolia (denosumab 60 mg) and Xgeva (denosumab 120 mg) are two strengths of a unique immune system protein (monoclonal antibody) that are used to slow bone loss and increase bone strength.
• Health Canada carried out a safety review after receiving a report from the European Medicines Agency of cases of hearing loss and deafness linked with the use of denosumab (Prolia or Xgeva). Health Canada’s review concluded that the information currently available is not sufficient to confirm any additional link between denosumab and hearing loss or deafness at this time.
• Hearing problems are already listed in the Canadian prescribing information for Xgeva where it is listed as a less common side effect for people with advanced bone cancer, but not for Prolia.

Overview

A safety review was carried out after Health Canada received a report from the European Medicines Agency, which linked hearing loss and deafness to the use of Prolia and Xgeva. After review of the report, Health Canada determined that there is not enough information to make such a link. The risk of hearing loss or deafness is already listed in the prescribing information for Xgeva (less common side effect for people with advanced bone cancer), but not for Prolia.

Use in Canada

• Denosumab is marketed in Canada under the brand names Prolia (denosumab 60 mg) available since 2010, and Xgeva (denosumab 120 mg) available since 2011.
• Prolia is used to treat weak and brittle bones (osteoporosis) in men and postmenopausal women who have high risk of bone breakage (fracture). It may also be used to slow bone loss and increase bone strength in women and men with a high risk of bone fracture due to treatments for certain types of cancer (breast cancer or prostate cancer).
• Xgeva is used to prevent bone fractures and other bone (skeletal) conditions in people with tumors (except multiple myeloma) that have spread to bones; or to treat giant cell tumor of bone in adults and some adolescents.

Safety Review Findings

• At the time of the review, Health Canada had received 16 Canadian reports of hearing loss associated with denosumab use, from the manufacturer. ^{Footnote _a} Due to limited information from these cases, no conclusions could be made regarding what role, if any, the drug may have played.
• Worldwide, 89 reports of hearing loss had been reported in patients using denosumab, at the time of this review. However, the rate of hearing loss related to use of denosumab is not different from the rate of hearing loss in the general public.
• It is difficult to link hearing loss and deafness to denosumab use because patients using denosumab may have additional risk factors for hearing loss such as age, and having other diseases or taking other medications at the same time.

Conclusions and Actions

• Health Canada’s review concluded that the current findings were not sufficient to confirm any additional link between denosumab (Prolia or Xgeva) and hearing loss or deafness at this time.
• Health Canada has asked the manufacturer of Prolia and Xgeva to actively monitor the risk of hearing loss and deafness in patients worldwide and to report these to Health Canada.
• Health Canada will continue to monitor side effect information for Prolia and Xgeva, 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 if and 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 currently known about the use of this drug both in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.