SGLT2 Inhibitors Hit By New FDA Warnings
The manufacturers of Invokana (canagliflozin) and Farxiga (dapagliflozin) will now be required to formally warn patients about a risk of drastic kidney impairment. The warnings will also be added to related products Invokamet and Xigduo XR.
The FDA received 101 confirmed reports of acute kidney injury between March 2013, when Invokana was first approved, and October 2015. Some patients required hospitalization and dialysis. The case reports were submitted directly to the FDA and, in the agency’s words, “there are likely additional cases” that have not been reported.
Both Invokana and Farxiga are SGLT2 inhibitors, a new class of type 2 diabetes drugs that impair the kidney’s ability to excrete excess blood glucose in urine. A third SGLT2 inhibitor, Jardiance, is not included in the warning. Recent clinical trial results have found that Jardiance can actually reduce the risk of worsening kidney disease by 39%.
The new warning for acute kidney injury comes just seven months after the FDA announced a link between SGLT2 inhibitors and diabetic ketoacidosis, a condition caused by increasing blood acid levels. The FDA’s new warning requirements were publicized on June 14, 2016.
Acute Kidney Injury
Acute kidney injury, or AKI, is “a syndrome that results in a sudden decrease in kidney function or kidney damage within a few hours or few days,” according to the National Kidney Foundation. After suffering impairment, the kidneys become unable to filter waste products from the blood, leading ultimately to myriad forms of organ failure. This isn’t a specific medical condition. In most cases, acute kidney injury is a cluster of effects caused by some other condition, usually ones like heart failure or severe dehydration that reduce blood flow to the kidneys.
AKI is particularly prevalent among hospitalized patients, particularly elderly patients and those being treated in an intensive care unit (ICU). While the condition isn’t well-known, it is shockingly common. Up to 1 in 5 hospitalized patients will suffer acute kidney injury, although the proportion doubles among patients in the ICU. Death can be a surprisingly frequent, and always tragic, result. Up to half of all severely ill patients who develop AKI will die from the condition.
Among the 101 reports reviewed by the FDA, around half of the patients developed acute kidney injury within one month of starting an SGLT2 inhibitor. Most of the cases improved after the patient was taken off Invokana or Farxiga.
Risk Factors For AKI
Before prescribing patients with either SGLT2 inhibitor, the FDA says that physicians should consider factors which predispose patients to acute kidney injury, including:
- decreased blood volume
- chronic kidney insufficiency
- congestive heart failure
- taking other medications like diuretics, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and nonsteroidal anti-inflammatory drugs
In its recent press release, the FDA made clear that some of the reported cases of acute kidney injury involved patients who were dehydrated or had low blood pressure, both of which may affect the body’s blood volume. Other patients were reportedly taking additional drugs that alter kidney function.
The FDA’s additional recommendations for healthcare providers include checking a patient’s kidney function prior to prescribing Invokana or Farxiga.
Perhaps most important, patients taking SGLT2 inhibitors should remain vigilant for the signs and symptoms of acute kidney injury. In chronic kidney disease, the kidneys deteriorate gradually over a long period of time. Acute kidney disease is different, a condition that worsens quickly but often shows few signs at first. When patients experience symptoms, these usually include:
- nausea and vomiting
- abdominal pain and backaches
- high blood pressure
Again, around 50% of the acute kidney injury cases developed during the first month of treatment with an SGLT2 inhibitor.