Summary Safety Review - Sodium Glucose Cotransporter 2 (SGLT2) Inhibitors INVOKANA (canagliflozin) and FORXIGA (dapagliflozin) - Evaluation of a Potential Risk of Acute Kidney Injury

October 16, 2015

Product

SGLT2 Inhibitors

Potential Safety Issue

Acute kidney injury

Key Messages

• Invokana and Forxiga are SGLT2 inhibitors, which are drugs that can be used on their own with diet and exercise or with other products to decrease blood sugar levels in adults with type 2 diabetes.
• This safety review of Invokana and Forxiga on acute kidney injury was triggered by new safety information received from the manufacturer of Invokana following the marketing of this product.
• Health Canada's safety review found a link between events of acute kidney injury and the use of Invokana and Forxiga. Health Canada is working with the manufacturers on an update to the Canadian prescribing information of Invokana and Forxiga to strengthen the wording relating to kidney injury to reflect this risk.

Overview

A safety review was done to evaluate the potential risk of acute kidney injury and the use of two SGLT2 inhibitors, Invokana (canagliflozin) or Forxiga (dapagliflozin). This issue was identified following new safety information received from the manufacturer of Invokana following the marketing of this product.

Use in Canada

• The SGLT2 inhibitors are medicines used to treat type 2 diabetes by reducing high blood sugar levels. Type 2 diabetes is a disease where the pancreas does not produce enough insulin leading to an inability to control blood sugar levels.
• Type 2 diabetes may lead to several health problems, such as eye disorders (diabetic retinopathy), kidney disorders (diabetic nephropathy), nervous system disorders (diabetic neuropathy) and cardiovascular disorders (such as heart attacks).
• The review focused on Invokana and Forxiga, marketed since June 2014 and January 2015, respectively. Invokana and Forxiga use has been steadily increasing since the time of their marketing in Canada.
• A third SGLT2 inhibitor, Jardiance (empagliflozin) was marketed in August 2015. This product was not included in the review due to its recent approval; however, it already contains wording in its labelling for acute kidney failure (acute renal failure).

Safety Review Findings

• This safety review considered serious reports of acute kidney injury, acute renal failure and renal failure (severe renal impairment). These kidney problems occur when the kidneys suddenly become unable to filter waste products from the blood.
• At the time of the review, Health Canada had received two reports of acute kidney injury in Invokana users.
• Additional international reports of kidney injury suspected to be linked with either Invokana or Forxiga were provided by their Canadian manufacturers. The review of these cases showed that there was a link between events of acute kidney injury and the use of these SGLT2 inhibitors.
• A review of the scientific literature linking Invokana or Forxiga to acute kidney injury provided limited evidence on this topic, although their renal effects were noted as a potential problem.
• At the time of the review, the product information for both Invokana and Forxiga already included some warnings on the use of these products in patients who have severe kidney problems or are on dialysis. The product labeling also reports the occurrence of decreased kidney function in patients treated with SGLT2 inhibitors.

Conclusions and Actions

• Health Canada's safety review concluded that the evidence supported the existence of a link between the use of SGLT2 inhibitors and the risk of acute kidney injury.
• Health Canada is working with the manufacturers on an update to the Canadian prescribing information of Invokana and Forxiga to reflect the risk of acute kidney injury and will notify Canadians when changes have occurred. Currently, the product labeling reports the occurrence of decreased kidney function in patients treated with SGLT2 inhibitors.
• Health Canada will continue to monitor side effect information involving SGLT2 inhibitors, 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 was carried out for this safety review took into consideration information from scientific and medical literature, Canadian and international adverse reaction reports as well as what is known about the use of this drug in Canada and internationally.

For additional information, contact the Marketed Health Products Directorate.