It’s been three years since the Food and Drug Administration (FDA) approved Johnson & Johnson’s Janssen Pharmaceutical’s drug Invokana (canagliflozin) as a treatment for type 2 diabetes. Since then, the FDA and other drug regulators have issued numerous warnings over new Invokana side effects that have emerged outside initial clinical trials.
Invokana was the first drug approved in the United States in a class known as sodium glucose cotransporter 2 (SGLT2) inhibitors. Prescriptions for the drug have since soared, generating hundreds of millions in revenue.
In May 2015, the FDA issued a Safety Communication warning that Invokana and two other SGLT2 inhibitors, Jardiance and Farxiga, could cause ketoacidosis, a serious condition in which too much acid builds up in the blood. If left untreated, ketoacidosis can lead to diabetic coma and death. The FDA urged health care professionals to report cases of ketoacidosis in patients treated with these drugs.
In December 2015, the FDA had received additional reports of ketoacidosis and ordered manufacturers of SGLT2 inhibitors to add stronger warnings to their safety labels. The agency had also received reports of serious urinary tract infections that in some cases progressed to life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis) that required dialysis to treat kidney failure in patients treated with SGLT2 inhibitors. New warnings for serious urinary tract infections were also added to the drug’s label.
In September 2015, the FDA announced that it was strengthening warnings for Invokana over an increased risk of bone fractures and decreased bone mineral density. The agency said it was also reviewing this risk with other SGLT2 inhibitors.
Last month, the European Medicines Agency (EMA) announced that it was reviewing a link between Invokana and an increased risk of lower limb amputations, mostly of the toe. Type 2 diabetics are at an increased risk of amputations due to neuropathy, but researchers are concerned a disproportionate number of patients taking Invokana are at greater risk for amputations.