Health Canada, the agency that regulates prescription drugs sold in that country, has approved Invokamet. The Type 2 diabetes medication was cleared for sale in Canada on July 20th, despite concerns about its potential association with ketoacidosis, kidney problems and other serious side effects.
Invokamet is a combination medication that contains canagliflozin, the active ingredient found in Invokana, as well as an older Type 2 diabetes drug called metformin. Invokana, was approved by Health Canada in 2014, and was the first SGLT2 inhibitor to come to market. The U.S. Food & Drug Administration (FDA) cleared Invokana in 2013, and followed up by approving Invokamet in 2014.
SGLT2 inhibitors work by preventing the absorption of glucose by the kidneys, thereby allowing for its elimination via urine. Other drugs in this class include Farxiga, Xigduo XR, and Jardiance.
In recent months, SGLT2 inhibitors, including Invokana and Invokamet, have been linked to a number of serious complications. Last December, for example, the FDA ordered that the drugs’ labels be updated with warnings about diabetic ketoacidosis, a serious condition that can result in diabetic coma or death. An agency review found that as a class, SGLT2 inhibitors had been cited in 73 ketoacidosis reports logged with its adverse event database between from March 2013 to May 2015. Forty-eight of those reports implicated canagliflozin, the active ingredient in both Invokana and Invokamet.
A recent analysis of the FDA adverse event data by the Institute for Safe Medication Practices (ISMP) indicated that reports of ketoacidosis involving SGLT2 inhibitors continued to grow in 2015. That year, Invokana was named in more than 630 ketoacidosis reports, while Farxiga was linked to more than 300 cases. Jardiance was cited in 32 incidents.
According to the ISMP, ketoacidosis cases for the three drugs were roughly similar in proportion to total reports for the medication and patient exposure.
In September 2015, the FDA announced that the labels for Invokana and Invokamet would be updated to include information about a possible increased risk of bone fractures. And just last month, the agency ordered the manufacturers of Invokana, Invokamet, Farxiga and Xigduo XR to strengthen label warnings regarding kidney complications potentially associated with their use, after the drugs were cited in more than 100 reports of acute kidney injury.
The FDA is also currently investigating a possible link between the use of Invokana and Invokamet and an increased incidence of leg and foot amputations, mostly affecting the toes.