Advice for healthcare professionals: post-marketing cases of Fournier’s gangrene (necrotising fasciitis of the genitalia or perineum) have been associated with the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors

Fournier’s gangrene is a rare but serious and potentially life-threatening infection

if Fournier’s gangrene is suspected, stop the SGLT2 inhibitor and urgently start treatment (including antibiotics and surgical debridement as required)

urogenital infection or perineal abscess may precede necrotising fasciitis

advise patients to seek urgent medical attention if they experience severe pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise

report suspected adverse drug reactions to a SGLT2 inhibitor to the Yellow Card Scheme without delay

Review of cases of Fournier’s gangrene

SGLT2 inhibitors are indicated for the treatment of type 2 diabetes. Medicines in the UK are those containing dapagliflozin, canagliflozin, empagliflozin, and ertugliflozin▼.

An EU review has assessed reported cases of Fournier’s gangrene across the class of SGLT2 inhibitors. Although diabetes mellitus is a risk factor for the development of Fournier’s gangrene, some of the EU post-marketing reports were considered possibly to be related to the use of SGLT2 inhibitors. Fournier’s gangrene usually occurs almost exclusively in men. However, around a third of the EU cases reviewed were reported in women. We are also aware of rare occurrences of Fournier’s gangrene in patients on SGLT2 inhibitors in the USA (see FDA safety announcement).

We have received 6 Yellow Card reports (4 in men and 2 in women) of UK cases of Fournier’s gangrene in association with SGLT2 inhibitors up to January 2019. This corresponds to a UK estimated exposure to SGLT2 inhibitors of 548,565 patient-years of treatment.

Warnings about Fournier’s gangrene will be added to the product information for all SGLT2 inhibitors. A letter has also been sent to advise healthcare professionals of the risk.

Patients taking SGLT2 inhibitors should be advised to seek urgent medical attention if they experience severe pain, tenderness, erythema, or swelling in the genital or perineal area accompanied by fever or malaise. If Fournier’s gangrene is suspected, SGLT2 inhibitor treatment should be stopped and treatment started urgently (including antibiotics and surgical debridement) as appropriate.

Background

SGLT2 inhibitors authorised in the UK include Edistride (dapagliflozin), Forxiga (dapagliflozin), Ebymect (dapagliflozin/metformin), Xigduo (dapagliflozin/metformin), Qtern (dapagliflozin/ saxagliptin), Invokana (canagliflozin), Vokanamet (canagliflozin/metformin), Jardiance (empagliflozin), Synjardy▼ (empagliflozin/metformin), Glyxambi▼ (empagliflozin/linagliptin), Steglatro▼ (ertugliflozin), Segluromet▼ (ertugliflozin/metformin), and Steglujan▼ (ertugliflozin/sitagliptin).

Report suspected drug reactions on a Yellow Card

Please continue to report suspected adverse drug reactions (ADRs) associated with SGLT2 inhibitors on a Yellow Card. Reporting suspected ADRs, even those known to occur in association with the medicine, adds to knowledge about the frequency and severity of these reactions and can be used to identify patients who are most at risk. Your report helps the safer use of medicines.

Healthcare professionals, patients, and caregivers can report suspected ADRs via the Yellow Card website or via the Yellow Card app. Download the app today via iTunes Yellow Card for iOS devices or via PlayStore Yellow Card for Android devices.

Further information

PRAC signal report for 26-29 November 2018 meeting.

FDA safety announcement

Direct Healthcare Professional Communication.

Article citation: Drug Safety Update volume 12, issue 7: February 2019: 3.