Labels for Invokana, Other SGLT2 Inhibitors Updated With New Ketoacidosis, Urinary Tract Infection Warnings

Published on December 4, 2015 by Sandy Liebhard

The manufacturers of Invokana and other SGLT2 inhibitors have been ordered to add new safety warnings to their product labels, amid concerns that the Type 2 diabetes medications might cause ketoacidosis and serious urinary tract infections. The FDA also wants the drug’s manufacturers to conduct a 5-year study to analyze spontaneous post-marketing reports of ketoacidosis in patients treated with the drugs.

SGLT2 inhibitors are currently indicated to treat Type 2 diabetes, and work by inhibiting the ability of the kidneys to absorb glucose, which facilitates its removal from the body through urine. Invokana was the first SGLT2 inhibitor approved for sale in the U.S. Others in the class include Invokamet, Farxiga, Jardiance, Glyxambi, Xigduo XR and Synjardy. Though they have not been approved for use in Type 1 diabetes, the drugs are sometimes prescribed for this off-label indication.

SGLT2 Inhibitors and Ketoacidosis

Ketoacidosis is a condition caused by the accumulation of toxic blood acids called ketones that can result in hospitalization, diabetic coma and death. In May, the FDA disclosed that it was investigating a possible link between the condition and SGLT2 inhibitors.

In a Drug Safety Communication dated December 4, 2015, the agency announced that its review of adverse event reports from March 2013 to May 2015 had uncovered 73 cases of ketoacidosis that involved Type 1 and Type 2 diabetics treated with SGLT2 inhibitors. The FDA is now warning patients to stop taking their SGLT2 inhibitor and seek medical treatment immediately if they experience any symptoms associated with the condition, including:

• Nausea
• Vomiting
• Abdominal pain
• Tiredness
• Trouble breathing

Doctors have also been advised to consider certain ketoacidosis risk factors before prescribing Invokana or other SGLT2 inhibitors, including :

• Reduction of insulin dose
• Acute febrile illness
• Reduced caloric intake due to illness or surgery
• History of Type 1 diabetes or other pancreatic disorders suggesting insulin deficiency
• Alcohol abuse

SGLT2 Inhibitors and Urinary Tract Infections

From March 2013 through October 2014, the FDA received 19 reports of life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis) that started as urinary tract infections in patients taking SGLT2 inhibitors. All were hospitalized, and a few required admission to an intensive care unit or dialysis in order to treat kidney failure. The agency is now warning SGLT2 inhibitor patients to be alert to the signs and symptoms of a urinary tract infection, such as:

• Burning sensation upon urination
• The need for frequent urination
• Pain in the lower part of the stomach area or pelvis
• Fever
• Blood in the urine.