June 22, 2016

FDA Strengthens Warnings for Two SGLT2 Drugs

The US Food and Drug Administration (FDA) has strengthened its drug label warnings about the risk for acute kidney injury that can result from the use of the type 2 diabetes prescription medications canagliflozin (Invokana, Invokamet, Janssen) and dapagliflozin (Farxiga, Xigduo XR, AstraZeneca), according to an agency news release. The revised warnings include information about acute kidney injury and recommendations for minimizing this risk.

These medications are sodium-glucose cotransporter-2 (SGLT2) inhibitors and are used with diet and exercise to lower blood sugar in adults with type 2 diabetes. The dangers are beginning to show now that these drugs have been in use for over two years. I can just about bet there will be other problems come to the fore over the next five years.

The FDA approved canagliflozin in March 2013 and dapagliflozin was approved in January 2014. In these cases, approximately half of the patients experienced acute renal injury within one month of beginning the medication, and some were younger than 65 years. Most improved after discontinuing the drug. Some of the affected patients were dehydrated, had low blood pressure, or were taking other drugs that can affect the kidneys. Some of these patients required hospitalization and dialysis. The FDA believes there are additional cases that have not been reported.

There is no mention of any warning with another SGLT2 inhibitor, empagliflozin (Jardiance, Boehringer Ingelheim) in this FDA communication, but it has not been on the market long enough.

The FDA does advise healthcare professionals to consider factors that may predispose patients to acute kidney injury before starting them on either of the medications. These factors include decreased blood volume; chronic renal insufficiency; congestive heart failure; and taking medications such as diuretics, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers, and nonsteroidal anti-inflammatory drugs.

Clinicians should assess the patient's kidney function before beginning canagliflozin or dapagliflozin and monitor it periodically after the patient begins either medication. Clinicians should discontinue the medication promptly and treat the renal impairment if acute kidney injury occurs.

SGLT2 inhibitors have also been associated rarely with fractures and diabetic ketoacidosis, and the FDA strengthened the warning with regard to fracture and canagliflozin specifically last September.

Patients who experience signs and symptoms of acute kidney injury should seek immediate medical attention, says the FDA. These can include decreased urination or swelling in the legs or feet. The FDA warns patients that acute renal injury is a serious condition in which the kidneys abruptly stop working and dangerous levels of waste can accumulate in the body.

The warnings do instruct patients not to discontinue their medication without first talking to their healthcare providers because uncontrolled blood glucose levels can develop. Patients are instructed to read the medication guide that comes with their canagliflozin or dapagliflozin prescriptions.

Healthcare professionals and patients should report adverse events or side effects related to the use of these medications 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 preaddressed form, or submit by fax to 1-800-FDA-0178

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