Clinical Trial Finds Increased Risk of Amputations with Invokana
On May 19, 2016, the U.S. Food and Drug Administration (FDA) issued a safety alert informing the public of a potential increased risk of foot, leg and toe amputations associated with canagliflozin (the active ingredient in Invokana). FDA issued the warning after analyzing the interim results of the ongoing Canagliflozin Cardiovascular Assessment Study (CANVAS), which found that amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with a placebo. The subjects were followed for an average of 4.5 years from this point.
Results of CANVAS Trial
Over a year’s time, the risk of amputations for Invokana users was equivalent to:
- 7 out of every 1,000 patients treated with 100 mg daily of canagliflozin
- 5 out of every 1,000 patients treated with 300 mg daily of canagliflozin
- 3 out of every 1,000 patients treated with placebo
Although FDA acknowledged that the CANVAS trial has not established a causative link between Invokana and amputations, and that additional studies are needed to investigate the matter, it nevertheless advised patients to seek immediate medical attention in they experience the following symptoms in their legs or feet:
The agency also warned that patients should never switch or quit taking a prescription diabetes drug without talking to their doctor first. Doing so could result in uncontrolled blood sugar levels, nerve / kidney damage or heart disease.
“Patients should not stop or change their diabetes medicines without first talking to their health care professional,” FDA said. “Doing so can lead to uncontrolled blood sugar levels that can be harmful.”
EMA Requests Data on Amputation Risk
The European Medicines Agency’s (EMA) Pharmacovigilance Risk Assessment Committee (PRAC) has asked Janssen for more information about the amputation risk with canagliflozin, and whether any changes to the way the medication is used or prescribed need to be made in the European Union. EMA could recommend prescribing changes if the increased amputation risk is confirmed.
Type 2 Diabetes and Foot Complications
More than 60% of surgical lower limb amputations are related to diabetes, according to the Centers for Disease Control and Prevention (CDC). In the U.S., there are over 80,000 type 2 diabetic amputations per year resulting from complications of diabetes.
These number are so high because of the skyrocketing rate of type 2 diabetes in the U.S. In 1989, 6.7 million Americans said they had diabetes. By 1995, this number grew to 8 million. In 2010, 18.8 million people in the U.S. reported diabetes, but the CDC estimates another 8 million were unaware they were diabetic.
In addition to taking Invokana, other factors that may increase your risk of amputation include:
- Living alone – The number of amputations is higher among diabetes patients who live alone.
- Length of time with the disease – Risk increased in patients who have had type 2 diabetes for more than 10 years.
- Age of patient – As diabetics get older, the risk of amputation grows.
- Blood pressure – Type 2 diabetics with a high resting pulse rate but low systolic (top number) blood pressure are more at risk.
- Other health conditions – Having diabetic neuropathies and/or peripheral artery disease (PAD) also increases your diabetic amputation risk.
- Sex of patient – Men have always had higher rates of amputation than women, and the rate grows rapidly among diabetics 75 or older.
- “National Diabetes Fact Sheet, 2011”. Centers for Disease Control and Prevention (CDC). 2011.
- “FDA Drug Safety Communication: Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate”. U.S. Food & Drug Administration (FDA). May 18, 2016.
- “CANVAS – CANagliflozin cardioVascular Assessment Study (CANVAS)”. March 18, 2016.
- “EMA reviews diabetes medicine canagliflozin”. European Medicines Agency (EMA). April 15, 2016.
- “Type 2 Diabetes and Foot Complications”. American Diabetes Association (ADA). June 6, 2016.