The FDA Is Investigating Whether Farxiga And Jardiance Are Also Associated With Higher Rates Of Bone Breaks
(Posted by Tom Lamb at DrugInjuryWatch.com)
There is new evidence about another safety issue with Invokana and Invokamet that has resulted in recent label changes with increased warnings for these popular new diabetes drugs.
From this September 2015 FDA document, "Invokana and Invokamet (canagliflozin): Drug Safety Communication - New Information on Bone Fracture Risk and Decreased Bone Mineral Density", we get this overview of the latest problems with these drugs:
FDA has strengthened the warning for the type 2 diabetes medicine canagliflozin (Invokana, Invokamet) related to the increased risk of bone fractures, and added new information about decreased bone mineral density. To address these safety concerns, FDA added a new Warning and Precaution and revised the Adverse Reactions section of the Invokana and Invokamet drug labels.
FDA is continuing to evaluate the risk of bone fractures with other drugs in the SGLT2 inhibitor class, including dapagliflozin (Farxiga, Xigduo XR) and empaglifozin (Jardiance, Glyxambi, Synjardy), to determine if additional label changes or studies are needed. Health care professionals and patients are urged to report side effects involving canagliflozin or other SGLT2 inhibitors to the FDA MedWatch program.
And from a related item, "FDA Drug Safety Communication: FDA revises label of diabetes drug canagliflozin (Invokana, Invokamet) to include updates on bone fracture risk and new information on decreased bone mineral density", we get these additional facts:
Information about the risk of bone fractures was already in the Adverse Reactions section of the drug label at the time of canagliflozin’s approval. Based on updated information about bone fractures from several clinical trials, we revised the drug label and added a new Warning and Precaution. The additional data confirm the finding that fractures occur more frequently with canagliflozin than placebo, which is an inactive treatment. Fractures can occur as early as 12 weeks after starting the drug. In the clinical trials, when trauma occurred prior to a fracture, it was usually minor, such as falling from no more than standing height.
In addition, we have added new information about the risk of decreased bone mineral density to the canagliflozin label. A clinical trial that we required the manufacturer of canagliflozin to conduct evaluated changes to bone mineral density over two years in 714 elderly individuals and showed that canagliflozin caused greater loss of bone mineral density at the hip and lower spine than a placebo. This new safety information has been added to the Adverse Reactions section of the drug label.
We get some background information about these latest safety concerns for Invokana and Invokamet -- as well as, possibly, other drugs in the SGLT2 inhibitor class, including dapagliflozin (Farxiga, Xigduo XR) and empaglifozin (Jardiance, Glyxambi, Synjardy) -- from this September 2015 news report, "FDA Strengthens Fracture Warning for Canagliflozin":
The topic of SGLT2 inhibitors and bone was discussed in an article published earlier this year in Lancet Diabetes and Endocrinology by Simeon I. Taylor, MD, professor of medicine at University of Maryland School of Medicine in Baltimore, and colleagues. They explain that SGLT2 inhibitors increase concentrations of phosphate in serum, probably via increased tubular reabsorption, which has the potential to adversely affect bone....
Dr Taylor told Medscape Medical News, "Although not proven, I believe that increased risk of bone fracture is likely a class effect. Nevertheless, individual drugs differ with respect to selectivity for SGLT2 vs SGLT1, and also with respect to where on the dose-response curve the approved dose falls. So, it is certainly possible that the magnitude of the risk could vary among individual SGLT2 inhibitors."
And about that Lancet Diabetes and Endocrinology medical journal Comment article mentioned above, "Possible adverse effects of SGLT2 inhibitors on bone", here is some earlier news reporting from back in December 2014, "Look into SGLT2 Fracture Risk, Researchers Urge":
Look deeper into the potential relationship between SGLT2 inhibitors and bone fractures, researchers urged in a comment in the Lancet Diabetes & Endocrinology.
It's biologically plausible that this class of drug -- which includes canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) -- could have an impact on fracture, according to Simeon Taylor, MD, PhD, of the National Institute of Diabetes and Digestive and Kidney diseases, and colleagues.
"I think that bone fracture risk, if it is eventually confirmed to be real, is important for patients, especially postmenopausal women who are already at increased risk," Taylor told MedPage Today.
Several studies have shown a possible link with fracture, across all drugs in the class....
"There are plausible pathophysiological mechanisms with the potential to mediate adverse effects on bone," they wrote. "Future mechanistic research might identify patients who are most susceptible to development of drug-induced bone fractures, and could suggest therapeutic approaches to minimize the risk."
We will continue to watch for developments regarding increased bone fracture risks for patients using the increasingly popular diabetes drugs Invokana, Jardiance, and Farxiga.