Summary Safety Review - YERVOY (ipilimumab) - Posterior Reversible Encephalopathy Syndrome (PRES)
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: 2014-12-01
issue
A safety review was conducted to evaluate the currently available information regarding the possible risk of posterior reversible encephalopathy syndrome (PRES), a serious condition which affects the brain, with the use of YERVOY (ipilimumab), an anti-cancer agent. The review was prompted by a published case report of PRES during YERVOY therapy in the scientific publication, Journal of Clinical Oncology (Maur et al, 2012).
Background
Approved use of YERVOY in Canada
YERVOY is a prescription medicine used to treat melanoma (a kind of skin cancer) that has spread or cannot be removed by surgery. It is administered into a vein (intravenous infusion) for the treatment of melanoma in adults.
Posterior reversible encephalopathy syndrome (PRES)
Posterior reversible encephalopathy syndrome (PRES) is characterized by seizures, mental status changes, visual disturbances, severe headache, nausea, vomiting, and/or difficulties in communicating. This condition usually starts rapidly. It is reversible if identified and treated appropriately. However, if undetected, PRES may lead to permanent neurologic damage or death.
Objective
To assess the risk of a person developing PRES while taking YERVOY. The evidence considered included Canadian adverse reaction reports, scientific and medical literature, international safety data, and what is known about the use of this product both in Canada and internationally.
Key findings
Use of YERVOY in Canadaa
YERVOY was introduced on the Canadian market in March 2012. It is given in a hospital or clinic under medical supervision.
Canadian reports of PRES associated with YERVOY
No Canadian cases of PRES had been reported in association with YERVOY at the time of this review.
Scientific reports
A 2012 publication identified a possible case of PRES in the medical literature (Maur et al, 2012). It occurred in a 58 year-old woman treated with YERVOY for melanoma. The patient also had renal failure and hypertension.
International datab
At the time of this review, the World Health Organization (WHO) Database (VigiBase) contained a single case of PRES following YERVOY exposure in a 50 year-old man. The potential risk of PRES with the use of YERVOY is also being investigated by other regulators.
Conclusions and actions
PRES is a disorder that is not yet fully understood. In addition, there is no clear explanation of how YERVOY may cause PRES. Given that this product is new to the Canadian market, there is limited information concerning this possible risk. It has been determined that information is too limited to accurately assess the risk of PRES with the use of YERVOY.
Therefore, Health Canada has asked the manufacturer of YERVOY to perform continued surveillance of this adverse event with Periodic Safety Update Reports (or PSURs), which provide an update of the worldwide safety experience of a health product.
Health Canada will also continue its ongoing monitoring of adverse reaction information involving YERVOY, as it does for all health products, to identify and assess potential harms. Health Canada will keep Canadians informed and take action, as appropriate, if any new safety information is identified.
References
- Maur M, Tomasello C, Frassoldati A, et al. Posterior reversible encephalopathy syndrome during ipilimumab therapy for malignant melanoma. J Clin Oncol 2012;30(6):e76-8.
- Pharmacovigilance Risk Assessment Committee (PRAC). Pharmacovigilance Risk Assessment Committee (PRAC) - Minutes of the meeting on 10-13 June 2014. London (UK): European Medicines Agency, 2014. (accessed 2014 October 9).
Footnotes
- IMS utilization data provided by: IMS Health Canada Inc. An external party cannot refer to nor use IMS data, which have been generated by Health Canada, without a Third Party Agreement in place.
- World Health Organization (WHO) adverse reaction information provided by: The WHO Collaborating Centre for International Drug Monitoring. This information is not homogeneous with respect to the sources of the information or the likelihood that the pharmaceutical product caused the suspected adverse reaction. Also, this information does not represent the opinion of the WHO.
- This list of references is not intended to be exhaustive. References have been selected as suggestions for further reading and reflect the most current information at the time of the safety review.