Reports linking Invokana to serious kidney problems have prompted U.S. health regulators to announce changes to the safety information included on the drug’s label. Similar modifications are being made to the labels of Invokamet, Farxiga and Xiduo XR.
All four of these drugs belong to a class of Type 2 diabetes medications called SGLT2 inhibitors. They lower blood glucose levels by preventing the reabsorption of sugar by the kidneys, allowing for its elimination from the body via the urine.
In a Drug Safety Communication issued on June 14th, the FDA said that it had received101 reports of acute kidney injury in patients taking either Invokana/ Invokamet (canagliflozin), or Farxiga / Xiduo XR (dapaglifozin). Canagliflozin was implicated in 73 reports, while dapaglifozin was named in 28 cases. All of the reports were logged with the agency’s adverse event database from March 29, 2013, to October 19, 2015.
The median age of the affected patients was 57 years. Among the 84 cases that reported an age, more than half were 60 years or younger. Fifty-one of the 101 cases reported concomitant ACE inhibitor use, 26 reported concomitant diuretic use, and 6 reported concomitant NSAID use. A prior history of chronic kidney disease was reported in 10 of the 101 cases. In some, dehydration or hypotension was reported.
Ninety-six patients were hospitalized and 22 cases required admission to an intensive care unit. Four deaths occurred during hospitalization, two of which were cardiac-related. Fifteen patients received dialysis. In 58 of the cases, acute kidney injury occurred within one month or less of initiating the drug. In the 78 cases reporting discontinuation of the medication, 56 saw improvement. However, 11 patients – including the four who died – did not recover.
As a result of these reports, the labels for Invokana, Invokamet, Farxiga and Xiduo XR are being updated with information about acute kidney injury, as well as recommendations to minimize this risk.
This is not the first time that Invokana has been the subject of an FDA alert. In December, the agency announced that information regarding diabetic ketoacidosis would be added to the “Warnings and Precautions” section on all SGLT2 inhibitors labels. The labels were also modified with information about life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis) that originate as urinary tract infections.
September 2015, the FDA announced that the labels for Invokana and Invokamet would be updated to include information regading bone fractures. And just last month, the agency said it was investigating a possible link between the drugs and an increased risk of leg and foot amputations, mostly involving the toes.