Summary Safety Review - PROLIA (denosumab) - Cardiovascular events
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: 2015-05-29
Product
PROLIA (denosumab)
Potential Safety Issue
Cardiovascular events
Overview
Use in Canada
- Denosumab is marketed under the brand name PROLIA and has been available in Canada since 2010. Denosumab is also present in another medicine called XGEVA.
- PROLIA is a unique immune system protein (monoclonal antibody), which works by binding to and inhibiting specific cells that remove bone mass to slow bone loss and increase bone strength.
- It is used to treat postmenopausal women and men with weak and brittle bones (osteoporosis) at high risk of breaking their bones (fracture).
- It is used to increase bone mass in men with prostate cancer that has not spread (nonmetastatic) and who are taking medicine to block the production of male hormones (androgen deprivation therapy).
- It is used to increase bone mass in women with breast cancer that has not spread (nonmetastatic), who are taking medicine to block the production of female hormones (adjuvant aromatase inhibitor therapy).
Safety Review Findings
- In the safety review, the term "cardiovascular adverse events" was used to explain coronary artery disease, heart failure, and cardiac arrhythmia. Coronary artery disease occurs when plaques build up in the arteries of the heart, which could lead to a heart attack. Heart failure is a chronic condition in which the heart muscle is unable to pump enough blood to meet the body's needs for blood and oxygen. Cardiac arrhythmia refers to any change in the normal rhythm of the heart's electrical impulses.
- As of June 30, 2014, Health Canadaa identified three cases of heart rhythm problems (QT interval prolongation) as possibly related to low blood calcium (hypocalcemia) due to use of PROLIA. Because hypocalcemia is known to be associated with the use of PROLIA, the Canadian prescribing information already labels for this risk.
- In a review of international safety data provided by the manufacturer, the majority of the reports of the cases of cardiovascular adverse events occurred in patients who had other pre-existing risk factors or where information about the patients was incomplete. It was therefore difficult to determine whether the cardiovascular adverse events were caused by the use of PROLIA or were due to other reasons. Overall, the evidence did not suggest an increased risk of cardiovascular adverse events associated with the use of PROLIA.
- A review of the scientific and medical literature identified four research articles relevant to the topic of cardiovascular adverse events associated with the use of PROLIA. However, the frequency of cardiovascular adverse events associated with the use of PROLIA was comparable to placebo (sugar pill). As such, the link between the use of PROLIA and cardiovascular adverse events could not be concluded.
Conclusions and actions
- At this time, the available evidence does not support an association between PROLIA and the risk of cardiovascular adverse events. In addition, the risk of low blood calcium and its effects on heart rhythm (e.g. QT interval prolongation) is already described in the Canadian prescribing information for PROLIA.
- Health Canada will continue to monitor adverse reaction information involving PROLIA, 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 known about the use of this drug both in Canada and internationally.
For additional information, contact the Marketed Health Products Directorate.
Footnotes
- Canadian reports can be accessed through the Canada Vigilance Adverse Reaction Database.