Farxiga and Chronic Kidney Disease: FDA Confusion

On June 14, 2016, the Food and Drug Administration strengthened its warning on certain medications prescribed for people with type 2 diabetes. Canagliflozin and dapagliflozin are sold under the brand names Invokana and Farxiga (pronounced FARSEEGA). The warning was about kidney injury.

The agency went on to state:

“A search of the FDA Adverse Event Reporting System (FAERS) database from March 29, 2013, to October 19, 2015, identified 101 cases of acute kidney injury with sufficient detail to confirm the diagnosis and demonstrate a temporal relationship with canagliflozin (73 patients) and dapaglifozin (28 patients).”

FDA Approves Farxiga To Treat Chronic Kidney Disease:

If you look at the “indications” for which Farxiga has been approved, you will discover that the FDA says the drug is helpful:

“To reduce the risk of sustained eGFR [estimated glomerular filtration rate, a measure of kidney function] decline, end-stage kidney disease, cardiovascular death, and hospitalization for heart failure in adults with chronic kidney disease at risk of progression.”

Why Is There Confusion?

On the one hand, the FDA has warned health care professionals that when drugs like Invokana and Farxiga are prescribed to treat type 2 diabetes there is a risk of “acute kidney injury.” On the other hand, the FDA has granted the drug company that makes Farxiga permission to promote the medicine to:

1. Slow the progression of CKD [chronic kidney disease]
2. Reduce the risk of end-stage kidney disease, which can lead to dialysis
3. Keep you living life by reducing the risk of CV [cardiovascular] death

You might understand why some patients are a bit confused.

Farxiga for Chronic Kidney Disease:

Here is a question from a reader:

Q. I’ve had chronic kidney disease for more than twenty years. Over the past eight months, my kidney function has worsened quite a bit.

My nephrologist has put me on Farxiga to try to prevent further deterioration. Fortunately, I have not yet suffered from any side effects, but I have not found any information on how successful this treatment will be. Is this medication capable of significantly stabilizing my loss of kidney function and is it worth the cost involved in purchasing Farxiga?

A. Farxiga (dapagliflozin) was originally approved to treat type 2 diabetes in 2014. Subsequently, it has been shown to reduce the risk of heart failure and complications of chronic kidney disease (CKD).

A placebo-controlled trial found that people taking Farxiga were only half as likely to have further serious decline in kidney function (Lancet. Diabetes & Endocrinology, Jan. 2021).

As you note, Farxiga is pricey, at about $650 for a month’s supply. Because the FDA has approved the drug’s use for CKD, your insurance company should cover it.

Side effects may include fungal infections in the genital area, urinary tract problems, constipation, nausea and dizziness upon standing. People with diabetes may be more susceptible to a condition called ketoacidosis. Symptoms include digestive upset, fatigue and difficulty breathing. Diabetic ketoacidosis is a medical emergency!

Limitations on the Use of Farxiga:

The FDA requires these cautions in the official prescribing information:

“• FARXIGA is not recommended for use to improve glycemic [blood sugar] control  in adults with type 2 diabetes mellitus with an eGFR less than 45 mL/min/1.73 m2. FARXIGA is likely to be ineffective in this setting based upon its mechanism of action.

“•FARXIGA is not recommended for the treatment of chronic kidney disease in patients with polycystic kidney disease or patients requiring or with a recent history of immunosuppressive therapy for the treatment of kidney disease. FARXIGA is not expected to be effective in these populations.”

The agency warns that certain conditions may make a patient more vulnerable:

“VOLUME DEPLETION: Before initiating FARXIGA, assess volume status and renal function in the elderly, patients with renal impairment or low systolic blood pressure, and in patients on diuretics. Monitor for signs and symptoms during therapy.”

Beware necrotizing fasciitis of the perineum (Fournier’s Gangrene):

“Serious, life-threatening cases have occurred in patients with diabetes, both females and males. Assess patients presenting with pain or tenderness, erythema, or swelling in the genital or perineal area, along with fever or malaise. If suspected, institute prompt treatment.”

Many people may not know what the “perineal area” is. In a man, this is the area between the anus and the penis. In a woman, this is the area between the vagina and the anus. Any discomfort or irritation in that area requires immediate medical attention to prevent Fournier’s gangrene. You do not want this!