Invokana is the brand name of canagliflozin, a popular medication used to treat Type 2 diabetes. It works to lower blood sugar levels by blocking glucose reabsorption in the kidneys so that extra sugar is lost through urination. Canagliflozin, the active ingredient in Invokana is also one of the active ingredients in the combination products, Invokamet.
Invokana is a member of the SGLT2 Inhibitor class of antidiabetics which also include brand name medications Farxiga and Jardiance, along with combination products Xigduo, Glyxambi, and Synjardy. Since Invokana’s approval in 2013, it has been shown to increase the risk for serious side effects including:
- Diabetic ketoacidosis
- Severe urinary tract infection
- Kidney disease and renal failure
- Increased bone fracture risk
In May of 2016, a safety alert was issued regarding interim results of two clinical studies which showed a doubling of the risk of amputation in patients taking Invokana. Final study results from the CANVAS and CANVAS-R trials, reported in 2017, confirmed the increased risk. Based on these final results, the FDA issued the most serious safety alert possible, a “black box warning” which includes information about the amputation risk.
This boxed warning has been included on Invokana labeling and has been added to the information already printed on Invokamet labeling regarding an increased risk for lactic acidosis because of the other ingredient, metformin.
CANVAS trial results
The black box information about increased risk of amputation was identified during two, large clinical trials which were undertaken to study Invokana’s long-term effects on the heart. Janssen Pharmaceuticals and parent company, Johnson & Johnson had hoped to find positive cardiac results for the diabetes medication but instead, found an increased risk for amputation.
Patients in the CANVAS and CANVAS-R trials were followed for 5 years. Patients taking Invokana were compared to those taking a placebo and the study found amputation risk was as follows:
- Patients taking placebo experienced amputation at a rate of 3/1000 patients per year
- Patients taking 100 mg Invokana daily experienced amputation at a rate of 5/1000 patients per year
- Patients taking 300 mg Invokana daily experienced amputation at a rate of 7/1000 patients per year
This shows an increased risk that is two-thirds higher on a low dose of Invokana and more than twice the risk of amputation with a higher dose.
Amputation risk patient warnings
The FDA safety alert regarding the black box warning also states that health care practitioners should consider general patient health and specific factors before prescribing Invokana. Conditions such as peripheral vascular disease, neuropathy, foot or leg ulcers and prior history of amputation may add to the increased risk for amputation because of lack of blood flow and inability to sense injury. Practitioners are warned to closely monitor patients foot and leg health and discontinue Invokana if complications occur.
Patients are advised to report any symptoms affecting skin or extremity health such as pain, tenderness, sores or infection but should not discontinue the medication without advice from a healthcare professional.
Other safety alerts
The black box warning was only the most recent alert in a string of notifications about Invokana.
Invokana was the first SGLT2 Inhibitor approved in March of 2013. By mid-2015, the FDA noted that it had received numerous adverse event reports involving Invokana and other SGLT2 inhibitors for diabetic ketoacidosis (DKA) events which had required hospitalization. A safety alert regarding this development was issued in May of 2015, which was followed in September by labeling changes about bone density loss that contributed to increased risk of fracture.
In December of 2015, another safety warning about DKA was issued which included warnings about increased risk for severe urinary tract infection which may contribute to kidney failure. Labeling was updated to include UTI, DKA, and kidney failure information.
In May of 2016, the first amputation risk warning was issued based on interim CANVAS study results and was followed a month later in June to strengthen warnings about kidney injury. In May of 2017, the most recent, black box warning was issued about Invokana and Invokamet’s potential of doubled amputation risk.
Johnson & Johnson continuing problems
Janssen Pharmaceuticals is a subsidiary of the pharmaceutical giant, Johnson & Johnson which has annual estimated revenue of nearly $72 billion. The company has faced multiple medical injury crises due to problems with a number of their products ranging from medical devices and surgical products to consumer products like baby powder to several of their drugs like Invokana.
Invokana injuries are being evaluated by regulators around the world including the EU, where European medical regulators at the European Medicines Agency’s Risk Assessment Committee have asked Johnson & Johnson for more information regarding Invokana’s amputation risk. Other diabetes drugs including SGLT-2 Inhibitors, Farxiga, and Jardiance are also under fire but neither drug has the same warning as of yet.
Multiple Invokana lawsuits have already been filed by patients or family members of those who have experienced serious side effects of the medication. Invokana lawsuits have included diabetic ketoacidosis, bone fracture, kidney failure and other serious injuries and more may be expected due to amputation.
If you or a loved one were required to have the amputation of the toe, foot or leg after taking Invokana, you may be eligible for compensation and should seek legal expertise.
Brooks, M., (15 May 2015), SGLT2 inhibitor diabetes drugs may cause ketoacidosis: FDA, Medscape, accessed on 14 August 2017 http://www.medscape.com/viewarticle/844754
Cefalu, W. et al, (2015), SGLT2 Inhibitors: The Latest “New Kids on the Block”!, Diabetes Care, accessed on 14 August 2017 http://care.diabetesjournals.org/content/38/3/352.full
Food and Drug Administration, (15 May 2015), Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood, U.S. Food and Drug Administration, accessed on 14 August 2017 http://www.fda.gov/Drugs/DrugSafety/ucm475463.htm
Food and Drug Administration, (04 December 2015), Drug Safety Communication: FDA revised labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infection, U.S. Food and Drug Administration, U.S. Food and Drug Administration, accessed on 14 August 2017 http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm May
Food and Drug Administration, (18 May 2016), 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 and Drug Administration, accessed on 14 August 2017 http://www.fda.gov/Drugs/DrugSafety/ucm500965.htm
ISMP, (06 May 2015), Questions about Canagliflozin (INVOKANA), Quarter Watch, 2., Institute for Safe Medication Practices, accessed on 14 August 2017 http://www.ismp.org/QuarterWatch/pdfs/2014Q2.pdf
Nainggolan, Lisa, (15 April 2016), EMA Probes Link with Diabetes Drug Canagliflozin, Toe Amputation, Medscape Medical News, accessed on 14 August 2017 http://www.medscape.com/viewarticle/862009
National Library of Medicine, (2016), Invokana-canagliflozin tablet prescribing information, U.S. National Library of Medicine, accessed on 14 August 2017 http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b9057d3b-b104-4f09-8a61-c61ef9d4a3f3