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FDA Strengthens Warning for Invokana, Invokamet

Risk of fracture and decreased bone mineral density cited

The FDA has strengthened the warning for the type-2 diabetes medicine canagliflozin (Invokana, Invokamet) related to the increased risk of bone fractures and has added information about decreased bone mineral density. To address these concerns, the agency has added a new “Warning and Precaution” section and revised the “Adverse Reactions” section of the Invokana and Invokamet drug labels.

The 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.

Bone fractures have been seen in patients as early as 12 weeks after they started taking canagliflozin, which has also been linked to decreases in bone mineral density (BMD) at the hip and lower spine.

According to Medscape, the new fracture warning is based on pooled data from nine clinical trials with a mean of 85 weeks' exposure to canagliflozin, in which the incidence rates of adjudicated bone fractures were between 1.1 and 1.5 per 100 patient-years of exposure.

Data on BMD came from an FDA-mandated post-marketing safety trial involving 714 elderly patients with type-2 diabetes (mean age, 64 years). At two years, patients randomly assigned to canagliflozin 100 mg and 300 mg had placebo-corrected declines in BMD, as measured by dual-energy X-ray absorptiometry, of 0.9% and 1.2%, respectively, at the hip, and of 0.3% and 0.7%, respectively, at the lumbar spine.

In addition, placebo-adjusted BMD declines of 0.1% were seen at the femoral neck for both canagliflozin doses, as well as a decline of 0.4% at the distal forearm for patients taking the 300-mg canagliflozin dose. No change was seen at the distal forearm with the 100-mg dose.

Health care professionals should consider factors that contribute to fracture risk prior to starting patients on canagliflozin. Patients should talk to their health care professionals about factors that may increase their risk for bone fracture.

Sources: FDA; September 10, 2015; and Medscape, September 10, 2015.

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