FDA MedWatch – Canagliflozin and Dapagliflozin

Canagliflozin (Invokana, Invokamet) and Dapagliflozin (Farxiga, Xigduo XR): Drug Safety Communication – Strengthened Kidney Warnings

AUDIENCE: Endocrinology, Internal Medicine, Nephrology, Pharmacy

ISSUE: FDA has strengthened the existing warning about the risk of acute kidney injury for the type 2 diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR).  Based on recent reports, we have revised the warnings in the drug labels to include information about acute kidney injury and added recommendations to minimize this risk.

BACKGROUND: Canagliflozin and dapagliflozin are prescription medicines used with diet and exercise to help lower blood sugar in adults with type 2 diabetes.  They belong to a class of drugs called sodium-glucose cotransporter-2 (SGLT2) inhibitors.  Canagliflozin and dapagliflozin lower blood sugar by causing the kidneys to remove sugar from the body through the urine.

From March 2013, when canagliflozin was approved, to October 2015, FDA received reports of 101 confirmable cases* of acute kidney injury, some requiring hospitalization and dialysis, with canagliflozin or dapagliflozin use (see Drug Safety Communication for the Data Summary).  This number includes only reports submitted to FDA, so there are likely additional cases about which we are unaware.

RECOMMENDATION: Health care professionals should consider factors that may predispose patients to acute kidney injury prior to starting them on canagliflozin or dapagliflozin.  These include decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs).  Assess kidney function prior to starting canagliflozin or dapagliflozin and monitor periodically thereafter.  If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.

Patients should seek medical attention immediately if they experience signs and symptoms of acute kidney injury. This is a serious condition in which the kidneys suddenly stop working, causing dangerous levels of wastes to build up in the body.  Signs and symptoms of acute kidney injury may include decreased urine or swelling in the legs or feet.  Patients should not stop taking their medicine without first talking to their health care professionals.  Doing so can lead to uncontrolled blood sugar levels that can be harmful.  Read the patient Medication Guide you receive with your canagliflozin or dapagliflozin prescriptions.  It explains the benefits and risks associated with the medicine.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

  • Complete and submit the report Online: www.fda.gov/MedWatch/report
  • Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

Read the MedWatch safety alert, including link to the Drug Safety Communication, at:

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm506554.htm