In the last month, the Food and Drug Administration (FDA) has issued two separate safety warnings involving the type 2 diabetes drug Invokana (canagliflozin).
On May 18, 2016, and FDA alert reported that patients in a clinical trial studying Janssen Pharmaceuticals’ Invokana and Invokamet, a combination drug containing canagliflozin, were about twice as likely to undergo amputations as patients taking a placebo.
In the alert, the FDA said that the equivalent of five of every 1,000 patients taking a 300-milligram daily dose of the active ingredient canagliflozin needed amputations, according to Law360. In addition, the equivalent of seven of every 1,000 patients taking a 100-milligram daily dose needed amputations, compared with only three of every 1,000 patients taking a placebo.
The amputations affected toes, feet and legs. FDA officials said they are working to determine whether canagliflozin actually elevates the risk of amputation, but the agency reminds patients that they should not stop taking Invokana without first consulting a doctor. Properly controlling blood sugar is crucial for people with diabetes. “Patients taking [canagliflozin] should notify their health care professionals right away if they notice any new pain or tenderness, sores or ulcers, or infections in their legs or feet,” the FDA said. People with diabetes are already at risk of amputations because the disease can cause nerve damage and impair blood circulation, according to the Mayo Clinic.
The clinical trial is examining how canagliflozin affects cardiovascular health and has followed patients for 4.5 years. The trial is expected to continue. Another trial, which followed patients for nine months, did not find the same elevated risks of amputation, the FDA said.
Officials for Janssen Pharmaceuticals, the maker of Invokana and Invokamet, say they “remain confident that canagliflozin is an important treatment option for people with Type 2 diabetes,” according to Law360.
The other warning for Invokana came on June 14, when the FDA announced it would require stronger warnings that Invokana (canagliflozin) and other diabetes drugs can cause life-threatening kidney injuries. The warning also includes dapagliflozin, sold as Farxiga and Xigduo XR. The FDA said this medication could cause worse acute kidney injury than was previously thought.
The FDA noted that from March 2013 to October 2015, there were 101 confirmed cases of acute kidney injury, with one-fifth of those cases requiring hospitalization in intensive care. Four people died, Law360 reports.
The changes to the drug labels will “include information about acute kidney injury and added recommendations to minimize this risk,” the FDA said.
In an episode of acute kidney injury, the kidneys suddenly stop working. Symptoms include “decreased urine or swelling in the legs or feet,” the FDA said. The agency warned, though, that patients should not stop taking the medicine even if they suspect acute kidney injury, because of the risk of uncontrolled blood sugar. People with kidney symptoms should seek immediate medical attention.
In addition, the FDA recommends that doctors considering prescribing these drugs take into account the patient’s predisposal to kidney issues — “decreased blood volume; chronic kidney insufficiency; congestive heart failure” and other medications that may increase the risk through interaction.