FDA Warns of Ketoacidosis, UTIs With SGLT2 Inhibitors

Manufacturers to Add Warning to Diabetes Drug Labels

December 08, 2015 04:42 pm News Staff

On Dec. 4, the FDA issued a Drug Safety Communication(www.fda.gov) explaining the agency is adding warnings to the labels of sodium-glucose cotransporter-2 (SGLT2) inhibitors about the drugs' risk of causing ketoacidosis and urinary tract infections (UTIs), which could lead to hospitalization. SGLT2 inhibitors are indicated for the management of type 2 diabetes.

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In light of these concerns, the FDA suggests physicians assess patients who are taking SGLT2 inhibitors for symptoms of ketoacidosis or UTI.

Patients who continue to take SGLT2 inhibitors also should be taught to recognize symptoms of ketoacidosis, which include nausea, vomiting, abdominal pain, tiredness and trouble breathing. Furthermore, they should be able to detect the signs and symptoms of a UTI, such as a burning sensation when urinating or the need to urinate often or right away; pain in the lower part of the stomach area or pelvis; fever; and blood in the urine.

If any of these signs or symptoms persist, patients should be told to stop taking their SGLT2 inhibitor and seek medical attention immediately.

SGLT2 inhibitors are approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. The SGLT2 inhibitor class includes canagliflozin (Invokana), dapagliflozin (Farxiga) and empagliflozin (Jardiance).

In addition to the new warning labels, the FDA also is requiring manufacturers of SGLT2 inhibitors to conduct an enhanced pharmacovigilance study and analyze spontaneous postmarketing reports of ketoacidosis in patients treated with their SGLT2 inhibitors. Manufacturers are to follow these consumers for five years to collect additional information.

The FDA first warned(www.fda.gov) health care professionals and patients about the risk of ketoacidosis with SGLT2 inhibitor use back in May.

A review of the FDA Adverse Event Reporting System (FAERS) database(www.fda.gov) from March 2013 to May 2015 identified 73 cases of ketoacidosis in patients with type 1 or type 2 diabetes who were treated with SGLT2 inhibitors.

All of these patients required hospitalization or treatment in an emergency department, and in many of the cases, ketoacidosis was not immediately recognized because the patient's blood glucose levels were below those typically expected for diabetic ketoacidosis. As a result, treatment of ketoacidosis was delayed in some patients.

The FDA also noted that FAERS includes only reports voluntarily submitted to the agency, so there likely are additional cases that have gone unreported.

In addition, the agency identified 19 cases of urosepsis and pyelonephritis in patients using SGLT2 inhibitors that were reported to FAERS from March 2013 through October 2014. All 19 patients were hospitalized, and a few required admission to an intensive care unit or dialysis to treat kidney failure.

Physicians are encouraged to report any side effects their patients experience from SGLT2 inhibitor use to the FDA MedWatch(www.fda.gov) program.

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