FDA Warns of Serious Genital Infection With SGLT2 Inhibitors

Miriam E. Tucker

Disclosures

August 29, 2018

The US Food and Drug Administration (FDA) is warning about cases of necrotizing fasciitis of the perineum in patients taking sodium-glucose cotransporter-2 (SGLT2) inhibitors.

The new warning will be added to the prescribing information and the patient medication guides for all single and combination agents in the glucose-lowering SGLT2 inhibitor class of drugs approved to treat type 2 diabetes. Those drugs include the following:

  • Canagliflozin (Invokana, Invokamet, Invokamet XR; Janssen)

  • Dapagliflozin (Farxiga, Xigduo XR, Qtern, AstraZeneca)

  • Empagliflozin (Jardiance, Glyxambi, Synjardy, Synjardy XR; Boehringer Ingelheim/Eli Lilly)

  • Ertugliflozin (Steglatro, Segluromet, Stelujan; Merck)

Necrotizing fasciitis of the perineum, also called Fournier's gangrene, is an extremely rare but life-threatening bacterial infection of the tissues underlying the skin surrounding the perineal muscles, nerves, fat, and blood vessels. It is estimated to occur in about 1.6 of 100,000 males annually in the United States, most often among those aged 50 to 79 years (3.3/100,000).

However, from March 2013 to May 2018, the FDA received reports of 12 cases of Fournier's gangrene among patients taking SGLT2 inhibitors, of whom five were women and seven were men. The condition has rarely been reported among women. The patients ranged in age from 38 to 78 years.

The condition developed within an average of 9.2 months of starting the SGLT2 inhibitor (range, 7 days to 25 months). The drug was stopped in most cases.

Multiple Surgeries, One Death

Reports included all of the drugs in the SGLT2 inhibitor class except ertugliflozin, but that agent "would be expected to have the same risk for this rare and serious infection as other SGLT2 inhibitors," the FDA said in a statement.

All 12 patients were hospitalized and required surgical debridement. Five required more than one surgery, and one required skin grafting. Four patients developed complications, including diabetic ketoacidosis, acute kidney injury, and septic shock. One patient died, and two were transferred to a rehabilitation hospital.

Because diabetes itself increases the risk for Fournier's gangrene, data were examined for patients taking other glucose-lowering agents. Between 1984 and 2018, just six cases of Fournier's gangrene were identified, all in men.

In 2017, an estimated 1.7 million patients received a dispensed prescription for an SGLT2 inhibitor from US outpatient retail pharmacies.

Patients taking SLGT2 inhibitors should be advised to seek medical attention immediately if they experience tenderness, redness, or swelling of the genitals or the area from the genitals to the rectum and have a temperature higher than 100.4° F.

Healthcare professionals should assess patients for Fournier's gangrene if they present with tenderness, erythema, swelling in the genital or perineal area, fever, malaise, and have pain out of proportion to the physical examination.

If the condition is suspected, broad-spectrum antibiotics should be started immediately, and surgical debridement performed if necessary. The SGLT2 inhibitor should be discontinued, the patient's blood glucose levels should be carefully monitored, and alternative blood glucose-lowering medications should be provided.

The FDA urges healthcare professionals to report any side effects in patients taking SGLT2 inhibitors or other medicines to FDA MedWatch by calling 855-543-DRUG (3784) and pressing 4, emailing druginfo@fda.hhs.gov, or completing the online form https://www.fda.gov/downloads/AboutFDA/ReportsManualsForms/Forms/UCM163919.pdf.

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