FDA Toughens Kidney Warnings on Invokana and Farxgia

With commentary by Arshpreet Kaur, MD, geriatric fellow, University of Miami School of Medicine.

This week, the U.S. Food and Drug Administration (FDA) told two drug makers to toughen the existing warnings about the risk of kidney injury for their diabetes drugs. The two drugs are canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR).

kidney injury

Going forward, the warning on the drug labels for these medicines must include information about acute kidney injury, a serious condition in which the kidney stops working suddenly, resulting in dangerous levels of waste building up in the body, the FDA says.

The FDA also ordered the revised warnings to include recommendations to minimize the risk, such as doctors carefully considering factors that may predispose patients to the kidney problems before prescribing the drugs.

"These drugs are relatively new, so we are still getting data on long-term safety," says Arshpreet Kaur, MD, a geriatric fellow at the University of Miami School of medicine who has published about acute kidney injury with the use of this class of drugs. They are effective, she says, when they are prescribed to the appropriate patients.

Canagliflozin was approved by the FDA in March 2013 and dagpagliflozin in January 2014. Both drugs belong to a class known as SGLT2 inhibitors (sodium-glucose cotransporter-2). The drugs lower blood sugar by causing the kidneys to remove sugar from the blood via the urine.

The third approved SGLT2 drug, empagliflozin (Jardiance) was not included in the decision about tougher warnings. (At the recent American Diabetes Association meeting, researchers reported that it reduced the risk of new or worsening kidney problems.) 

Why the Stronger Warning?

From March 2013 to October 2015, the FDA says, it recorded 101 confirmable reports of acute kidney injury with the two drugs. Of those 101, 96 needed to be hospitalized, including 22 needing intensive care units. Four deaths occurred during the hospitalizations, the FDA says, but two of those were cardiac-related. And 15 patients needed dialysis. Some had previous kidney injury or disease.

The 101 reports include only those submitted to the FDA, it says, ''so there are likely additional cases about which we are unaware," reports the FDA. 

The FDA instructs doctors and other healthcare professionals to consider factors that could make patients at higher risk of acute kidney injury before prescribing the two SGLT2 drugs with the stronger warnings. Among the factors that could predispose patients to kidney problems on these drugs are:

  • Taking other medicines such as diuretics ("water pills") or some other blood pressure medicines or nonsteroidal anti-inflammatory drugs (NSAIDs)
  • Decreased blood volume
  • Chronic kidney insufficiency
  • Congestive heart failure.

Doctors should evaluate a patient's kidney function before starting either drug, the FDA says, and monitor patients while they’re on it.

Drug Companies On Board

AstraZeneca, which makes Farxiga and Xigduo XR, ''remains confident in the benefit-risk profile'' of the drugs, says Abigail Bozrth, a company spokesperson, and will continue to communicate information and evaluate new data related to any kidney issues.

The stronger label adds to information that has already been on the labels, says Kaitlin Meiser, a spokesperson for Janssen Pharmaceuticals, which makes Invokana and Invokamet. "Information regarding the renal safety profile of Invokana has been reflected in the product label since approval in 2013," Meiser says. The company has been working with the FDA to revise the warning as new information became available, she says.


''They are very effective drugs," Dr. Kauer says of the SGLT2 inhibitors involved in the new warnings, ''but we need to select patients carefully."

Who is an ideal patient for these drugs? "To me, it would be a patient who is relatively younger and does not have too many coexisting diseases and is not taking other medicine that can affect kidney function," she says, nor be at high risk of urinary tract infections.

So, the drugs may work well in patients with type 2 diabetes who are in their 30s or 40s, she says, but not so well in older patients, perhaps in their 60s or beyond, who may have coexisting medical problems and be taking several medications.

Best Course for Patients

Patients currently on these medicines should not stop taking it on their own, Dr. Kaur says. "You should always call your doctor before you stop it," she says.

Patients can be aware of certain symptoms that could point to kidney problems, she says. Urinating less often is one symptom. "Usually with these drugs you are supposed to make a lot of urine," she says. If it declines greatly, she says, call your doctor.

Another symptom that should prompt a call to the doctor is swelling in the legs or feet, the FDA says.


Updated on: November 8, 2018
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