Fournier’s Gangrene Flesh-Eating Infection Risk from Invokana, Similar Diabetes Drugs Outlined in JAMA Report

The findings of a new study appear to confirm side effects of Invokana and other similar diabetes drugs may increase the risk of a flesh-eating genital infection, known as Fournier gangrene.

In a research letter published earlier this month in the medical journal JAMA Internal Medicine, researchers from Brigham and Women’s Hospital in Boston found an increase in the risk of Fournier gangrene among users of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, which is a new class of diabetes drugs including Invokana, Farxiga, Jardiance and other blockbuster treatments.

Although the risk is serious, and potentially life-threatening, researchers indicated the Fournier’s gangrene risk does not appear to outweigh the benefits provided by the drug at this time.

The findings appear to mirror those of researchers from the FDA, who first issued a warning in late August 2018, after the agency identified 12 cases of Fournier gangrene in patients taking an SGLT-2 Inhibitor.

The journal published its own analysis of the Fournier’s gangrene risk in October 2018, evaluating the FDA’s findings.

“Infections developed in all 12 patients within several months of starting an SGLT-2 inhibitor. All were hospitalized and required surgery that in some was disfiguring or resulted in complications. One patient died,” JAMA indicated in the October report. “In 2017, an estimated 1.7 million patients received a dispensed prescription for an SGLT-2 inhibitor from US outpatient retail pharmacies.”

The journal notes that while the FDA only counted Fournier’s gangrene cases submitted to the agency or found in medical literature, the actual number of cases linked to Invokana and other SGLT-2 inhibitors is likely greater.

In this latest letter, researchers indicate after evaluating additional information the risk does not rise to the point where doctors should change prescribing habits.

“The findings suggest that the small increase in the risk of Fournier gangrene that may be associated with SGLT-2 inhibitor treatment should not influence the prescribing decisions of these agents in light of other benefits of treatment,” they wrote.

Following the safety alert, the FDA required new label warnings be added to all drugs that belong to the class, including Invokana, Invokamet, Invokamet XR, Farxiga, Xigduo XR, Qtern, Jardiance, Glyxambi, Synjardy, Synjardy XR, Steglatro, Segluromet and Steglujan. Steglatro is the only drug not linked to a case of flesh-eating genital infection, but the agency is requiring it to carry a label warning anyway.

The agency indicated then that the infections developed within several months of beginning treatment with one of the drugs and all 12 patients underwent hospitalization and surgery. According to the FDA’s findings, at least one patient died, while others suffered multiple disfiguring surgeries and other complications.

Other Health Concerns Linked To Invokana and Similar Drugs

The flesh-eating genital infection warning is just the latest adverse health risk added to Invokana and similar drugs since they were first introduced on the market. The previous warnings have included kidney failure, diabetic ketoacidosis and amputations (specifically for Invokana). The drugs did not carry warnings for any of those risks when they were first approved by the FDA.

Invokana (canagliflozin) was the first SGLT-2 inhibitor introduced to the market, which was approved in March 2013 and quickly became a blockbuster treatment. The medication works in a unique way, impacting some normal kidney functions to help remove glucose from the body through urine.

In December 2015, the FDA required Johnson & Johnson to add new diabetic ketoacidosis warnings to Invokana and similar drugs, indicating that the medications increase the risk of this serious condition, which typically results in the need for emergency treatment to avoid life-threatening injury. Prior to the update, the warnings failed to alert consumers about the importance of seeking immediate medical attention if they experience symptoms like abdominal pain, fatigue, nausea, respiratory problems or vomiting.

In June 2016, the FDA required additional label warnings about the link between kidney risks and Invokana and other drugs from its class, indicating that the medications may increase the risk of acute kidney injury and other severe health problems.

In May 2017, FDA required new warnings about the Invokana amputation risks, adding information to the drug label about the increased incidence of leg, foot and toe amputations. That warning was only required for Invokana, and manufacturers of other SGLT-2 inhibitors have suggested that Invokana leg and foot amputation problems were unique to that drug, maintaining that the same risks were not seen among users of their medications.

Johnson & Johnson and Janssen have faced several thousand other Invokana lawsuits, which allege users and the medical community were not provided adequate warnings at the time the drug was first introduced. The makers of other diabetes drugs from the same class, including Farxiga and Xigduo XR, have also faced similar lawsuits; though most have been filed against the makers of Invokana.