Summary Safety Review - KEPPRA (levetiracetam) - Assessing the Potential Risk of Acute Kidney Injury (Acute renal failure/Interstitial nephritis)

January 6, 2017

Product

Keppra (levetiracetam) and generics

Potential Safety Issue

Acute kidney injury (acute renal failure/interstitial nephritis)

Key Messages

• Levetiracetam is authorized for sale in Canada, to help reduce the number of seizures when taken together with other seizure medicines.
• Health Canada reviewed the potential risk of acute kidney injury with the use of levetiracetam, because of an article that was published by the World Health Organization (WHO) suggesting this risk.
• Health Canada's review concluded that there may be a link between the use of levetiracetam and the risk of acute kidney injury. The current product information for Keppra informs that cases of acute kidney injury have been reported in patients treated with levetiracetam. Health Canada has requested that the other manufacturers of levetiracetam-containing products also update their product information with the same wording.

Overview

Health Canada reviewed the potential risk of acute kidney injury with the use of levetiracetam, because of an article that was published by the WHO suggesting this risk. Health Canada assessed the risk of acute kidney injury, which is defined as a sudden loss of kidney function, including kidney failure and interstitial nephritis. Interstitial nephritis is the inflammation of the kidneys and is one of the conditions that may lead to kidney failure.

Use in Canada

• Levetiracetam is a prescription drug authorized for sale in Canada, to help reduce the number of seizures when taken together with other seizure medicines.
• Levetiracetam is available in Canada as oral tablets. It has been marketed under the brand name Keppra since 2003. Generic products are also available.
• There were about 583 000 prescriptions of levetiracetam-containing products filled in 2015.

Safety Review Findings

• At the time of the review, Health Canada had not received any Canadian reports of acute kidney injury related to levetiracetam use.
• A search in the World Health Organization's Adverse Drug Reaction Database (Vigibase) found more than 150 international reports of acute kidney injury with the use of levetiracetam. The WHO reviewed 39 of these 150 reports in depth and concluded that levetiracetam had possibly caused acute kidney injury.
• In addition, there were 6 cases of acute kidney injury linked to the use of levetiracetam, published in the scientific literature. While the cases noted other factors such as pre-existing diseases, other medications taken at the same time, or other additional medical conditions, a link between the use of levetiracetam and acute kidney injury could not be ruled out.

Conclusions and Actions

• Health Canada's review found a possible link between the use of levitiracetam and the risk of acute kidney injury.
• The current product information for Keppra informs that cases of acute kidney injury have been reported in patients treated with levetiracetam. Health Canada has requested that the other manufacturers of levetiracetam-containing products also update their product information with the same wording.
• Health Canada will continue to monitor side effects information involving levetiracetam, 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, 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.