The Food and Drug Administration (FDA) has added a warning to the labeling of sodium-glucose cotransporter-2 (SGLT2) inhibitors regarding the risk of a rare, serious genital infection known as necrotizing fasciitis of the perineum (also referred to as Fournier's gangrene). Used in the treatment of type 2 diabetes, SGLT2 inhibitors increase the excretion of glucose through the urine. Drugs in this class include canagliflozin (Invokana), dapagliflozin (Farxiga), empagliflozin (Jardiance), and ertugliflozin (Steglatro).

Necrotizing fasciitis is a bacterial infection affecting the tissue surrounding the muscles, nerves, fat, and blood vessels of the perineum. It spreads quickly, destroying the tissue it infects. Although diabetes is a risk factor for necrotizing fasciitis, the infection is uncommon, with an incidence of about 1.6 per 100,000 men in the United States. (While the infection has been thought to primarily affect men, the FDA observed events in both men and women in its case review.)

In conducting its review, the FDA examined the literature between March 2013, when the first SGLT2 inhibitor was approved, and May 2018, as well as case reports submitted to the agency. The FDA's review identified 12 reports of patients (seven men and five women) who reportedly developed necrotizing fasciitis of the perineum after starting an SGLT2 drug. All 12 patients required hospitalization and surgical debridement; one patient died. The agency also examined the incidence of necrotizing fasciitis in patients taking other classes of diabetes drugs. That review found six cases of the infection; all in men. The FDA concluded that SGLT2 drugs increase the risk of necrotizing fasciitis in both men and women, though the risk remains low.

Nurses should tell patients to report any early signs of genital infection including redness, swelling, and pain in the genitals and in the area from the genitals to the rectum, especially if accompanied by a fever above 100.4[degrees]F and general malaise. Nurses should explain to patients that necrotizing fasciitis is a very rare infection and encourage them to read the medication guide provided with each filled prescription for up-to-date information.

NPs should consider the possibility of necrotizing fasciitis in any patient presenting with these signs and symptoms. If a patient shows signs of the infection, the SGLT2 inhibitor should be stopped immediately and glucose should be controlled with medication from a different drug class. NPs should prescribe broad-spectrum antibiotics as soon as necrotizing fasciitis of the perineum is suspected. The patient may need an urgent referral for surgical debridement. To read the FDA Drug Safety Communication regarding SGLT2 inhibitors, go to http://www.fda.gov/Drugs/DrugSafety/ucm617360.htm.