Summary Safety Review - EYLEA (aflibercept) - Assessing the Risk of Side Effects Outside the Eye (systemic side effects)

May 10, 2016

Product

Eylea (aflibercept)

Potential Safety Issue

Possible risk of side effects outside the eye

Key Messages

• Eylea is a medicine that is injected into the eye to treat vision impairment caused by diseases that affect the blood vessels in the sensory layer at the back of the eye (the retina).
• Health Canada carried out a safety review after new published literature suggested that the body takes a longer time to remove Eylea from the circulating blood (prolonged systemic exposure) compared to a similar product used for the same condition, which may put patients at greater risk of side effects in areas outside the eye.
• Health Canada's safety review concluded that despite the presence of low levels of Eylea in the rest of the body, the risk of experiencing side effects was not different from that of the similar product.Health Canada continues to monitor the safety of Eylea and encourages health care professionals to report any side effects related to the use of this health product.

Overview

A safety review was carried out by Health Canada to evaluate the risk of harmful side effects in areas of the body other than the eye (systemic toxicity) associated with Eylea. The review was triggered by 3 scientific studies which observed that following injection into the eye, Eylea is removed from the body's bloodstream slower than alternative products, and this could possibly lead to systemic toxicity.^{Reference 1},^{Reference 2},^{Reference 3} The rare side effects of these medications include stroke, heart disease, high blood pressure, bleeding and signs of harm to the kidneys such as passing protein in the urine.

Use in Canada

• Eylea (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor. It is a type of biologic medicine (recombinant fusion protein) which blocks the effects of VEGF which is normally produced in the body to help in the growth or repair of blood vessels.
• Eylea is in a formulation that is directly injectable into the eye (intravitreal injection) and acts to prevent the formation of new blood vessels that could damage the sensory layer at the back of the eye (the retina). Eylea is used to treat diseases of the retina including "wet" age-related macular degeneration, diabetic macular edema or macular edema resulting from retinal blood vessel occlusion.
• Eylea has been marketed in Canada since late 2013.

Safety Review Findings

• At the time of the review Health Canada received 4 Canadian reports ^{Footnote 4} of systemic side effects that were all related to bleeding. However, the reports either involved cases of bleeding at the injection site (hemorrhage into the eye) or did not contain enough information to conclude that Eylea itself was the cause of bleeding in another part of the body.
• The published studies showed that Eylea (mainly in its inactive form) is removed from the body slower than a similar product used for the same purpose.
• However, the review of the published studies and safety data from international reports found that, overall, the occurrence and severity of systemic side effects was comparable between the 2 products.

Conclusions and Actions

• Health Canada's review found that there was not enough evidence to conclude that Eylea is associated with a greater risk of systemic side effects. The potential for experiencing some side effects in areas of the body other than the eye is already mentioned in the Canadian product safety information for Eylea.
• Health Canada will continue to monitor safety information associated with the use of Eylea as it does for all health products on the Canadian market, to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.

Additional Information

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

For additional information, contact the Marketed Health Products Directorate.

References