Invokana Loses the Black Box Amputation Warning, But Fournier's Gangrene Risk Still Looms

Invokana no longer carries a black box warning for amputation, but the drug is still associated with a dangerous, flesh-eating bacterial infection.

In late 2020, the U.S. Food and Drug Administration (FDA) removed a Boxed Warning from the Invokana drug label. The black box warning was added in 2017 when regulators learned of an increased amputation risk with the diabetes medication. The warning removal stems from new data showing amputation risk at a lower level than previously reported.

Despite losing its black box warning, Invokana still carries serious risks, some of which are the subject of active litigation.

Consumers have filed over 1,200 Invokana (canagliflozin) lawsuits to date. Plaintiffs claim the drug manufacturer failed to warn them of serious side effects like Fournier's Gangrene and kidney failure. Without accurate information, patients were unable to make informed decisions about Invokana. If you or a loved one developed Fournier's Gangrene while taking Invokana, you may be eligible for compensation.

New Data Shows Invokana Amputation Risk Is Lower Than Expected

In 2017, the FDA used data from the CANVAS and CANVAS-R clinical trials to evaluate amputation risk. In those trials, patients using Invokana appeared to have twice the amputation risk of those receiving placebo. As such, the FDA added its most serious warning, the black box warning, to the Invokana label.

However, a study published in the BMJ (formerly the British Medical Journal) came to different conclusions. Rather than comparing to placebo, the newer study compared Invokana patients to those receiving routine care for diabetes. The researchers found a slightly elevated risk of amputation with Invokana.

The study determined risk by calculating how many amputations would occur per 1,000 patients receiving Invokana versus routine care. They found Invokana treatment resulted in one additional amputation per year of therapy. This risk increased slightly to 4 additional amputations per year in patients 65 and older.

The BMJ study authors also noted the CANVAS trials studied patients with an average age of 63 years. This means the CANVAS trials may have accidentally studied a higher risk group. Thus, the CANVAS data may have overestimated Invokana's amputation risk.

In light of this new information, the FDA removed Invokana's boxed warning for amputation. However, the drug label still warns about amputation, along with a slew of other side effects.

Invokana Still Associated with Rare, Serious Fournier's Gangrene

The first regular warning listed on the Invokana label is now "Lower Limb Amputation." Several lines below, the drug label warns of "Necrotizing Fasciitis of the Perineum." This condition is also known as Fournier's gangrene (FG).

FG affects the skin and tissues of the perineal, genital or perianal regions. It is a mixed infection composed of multiple kinds of bacteria. Experts say FG warrants aggressive, multimodal treatment for the best outcomes.

If it is not treated promptly, FG may quickly cause serious complications, including:

  • Severe infection of deeper tissues, including blood vessels
  • Blockage of small blood vessels, leading to compromised blood supply and tissue death
  • Release of caustic materials leading to septic shock and potentially death

Between March 2013 and January 2019, 21 cases of FG were reported in patients using Invokana. It is unclear what the true incidence of FG is in the general population or those taking Invokana. Regardless, FG was added to the Invokana label in 2018, five years after it was initially approved.

This means patients may have been unknowingly at an increased risk of FG for years before it was added to the Invokana label. Patients have cited this fact in lawsuits against Invokana manufacturer Janssen Pharmaceuticals. Hundreds of these lawsuits are currently pending in federal court. Only time will tell if the justice system will compensate patients who developed FG after taking Invokana.

Authored by Katy Moncivais, Ph.D.Medical Editor
Photo of Katy Moncivais, Ph.D.
Katy Moncivais holds a Ph.D. in Biomedical Engineering from The University of Texas at Austin. She’s an experienced Regenerative Medicine Consultant with a demonstrated history of working in the hospital & healthcare industry. Skilled in adult stem cells, medical devices, biomechanics, bacterial and mammalian cell culture, and regenerative medicine, she provides guidance on an array of topics affecting consumers. In her role at ConsumerSafety.org, Dr. Moncivais works alongside the writing and research staff to help deliver fact-based news stories to consumers. Her unique professional history alongside her rigorous educational background allows her to contribute to a variety of consumer-focused topics with a fresh perspective. In addition, Dr. Moncivais reviews portions of medically driven content to ensure scientific accuracy.
Editorial Standards Full Bio