Additional Concerns Surface Over Invokana Side Effects: FDA

Washington DCUp until now there has been ongoing concern with regard to side effects associated with Invokana, the type 2 diabetes medication marketed by Janssen Pharmaceuticals Inc. (Janssen), an offshoot of pharmaceutical giant Johnson & Johnson. “Invokana Linked with Cardiovascular Injuries and Kidney Failure” is a headline no type 2 diabetes patient currently taking canagliflozin (Invokana) wishes to see.

And now there is a new concern, revealed last month by the US Food and Drug Administration (FDA) over reports of decreased bone density and increased risk for bone fracture.

The risk for bone fracture is nothing new. The FDA noted that risk for bone fracture was already a part of the prescribing label when Invokana was originally approved for the market. However, the regulator was responding to new information from clinical trials the FDA had required Janssen to undertake with regard to that particular portfolio of Invokana adverse events.

Specifically, the FDA was interested in the results of a two-year study evaluating changes to bone density in a test group of individuals - in this case, 714 elderly study participants. The study concluded that Invokana side effects fostered greater loss of bone density in the hip and lower spine than a placebo.

Most individuals lose bone density over time as a natural byproduct of aging. In this case, loss of bone density associated with the use of Invokana was more pronounced than that fostered by the natural process of aging, in the majority of the participants.

“The additional data confirm the finding that fractures occur more frequently with canagliflozin than placebo,” the FDA said, in a statement released September 10. “Fractures can occur as early as 12 weeks after starting the drug.”

The FDA, as part of the strengthened prescribing label for Invokana, urged doctors and health care professionals to weigh the risks for bone fracture prior to making any decision to prescribe canagliflozin to their patients with type 2 diabetes.

Invokana has been in the news in recent months with regard to other Invokana adverse events - namely, blood problems that have the potential to be serious. The FDA included Invokana and Invokamet (canagliflozin/metformin) in a group of six diabetes drugs put on watch for diabetic ketoacidosis. About 20 reports from March 2013 through June of last year involved patients that required hospitalization or emergency services when levels of ketones - a blood acid - were found to be elevated. Some patients had reported ongoing issues after the fact.

The FDA became concerned given that diabetic ketoacidosis is normally observed in patients with type 1 diabetes, not those taking type 2 diabetes medications, which was the case here.

“We are continuing to investigate this safety issue and will determine whether changes are needed in the prescribing information for this class of drugs,” regulators wrote, in their communiqué in May of this year. Jardiance, or empagliflozin, as well as Glyxambi (empagliflozin/linagliptin) and Xigduo XR (dapagliflozin/metformin) were also named.

Farxiga (dapagliflozin) was yet another drug identified as part of the FDA’s May 2015 safety alert.