In 2013, Johnson & Johnson introduced Invokana, a new type 2 diabetes medication, to the U.S. market as a “much-needed” innovation in blood glucose management. Invokana lowers blood sugar levels in a markedly different way from other diabetes medicines and quickly grew in popularity, with roughly 4 million prescriptions written each year.

Will Invokana-Linked Complications Spur Recall?

But although it’s only been four years since Invokana’s release, the U.S. Food and Drug Administration has already had to issue multiple safety warnings, prompted by disturbing clinical trial results and patient complaints. In recent years, Invokana has been linked to life-altering complications, including diabetic ketoacidosis and amputations.

The drug is still on the market, for now, but will growing evidence of dangerous unexpected side effects eventually lead to an Invokana FDA recall?

Increased Risk Of Lower Limb Amputations

In May of 2015, the FDA’s first major Safety Communication regarding Invokana cautioned the public that the drug could cause patients to develop ketoacidosis, described as a “serious condition” characterized by high levels of blood acidity.

But more recently, federal safety authorities have notified the medical community of another risk, one that is expected to draw thousands of patients into legal proceedings. Invokana, the FDA says, causes an increase in the risk of lower limb amputations.

Announced in May 2017, the risk was observed in an analysis of final results from two enormous long-term studies of the type 2 diabetes drug. People taking Invokana were around twice as likely to undergo foot and toe amputations as type 2 diabetes patients on a placebo. And that’s true even assuming that patients with diabetes already live at risk for amputations of the lower extremities.

FDA Publishes Invokana Ketoacidosis Alert

This warning applies not only to Invokana, but also to other medications containing an active ingredient from the sodium-glucose co-transporter2 (SGLT2) inhibitor drug class, including Farxiga (dapagliflozin) and Jardiance (empagliflozin).

The FDA decided an alert was necessary after receiving numerous reports of Invokana patients falling victim to ketoacidosis and ending up in the emergency room for the condition. Since ketoacidosis is not among the listed side effects on the drug’s label, the FDA needed to make sure that patients and doctors would be aware of the potential risks.

The Safety Communication informed consumers:

  • Those taking SLGT2 inhibitors need to monitor themselves vigilantly for signs of ketoacidosis, such as difficult breathing, nausea, vomiting, fatigue, stomach pain, and feelings of confusion or lightheadedness. Patients experiencing such symptoms should obtain medical attention immediately.
  • If doctors suspect ketoacidosis, they should perform acidosis testing and promptly discontinue prescriptions of SGLT2 inhibitors upon confirmation of the condition.
  • Any unexpected SGLT2 inhibitor side effects or complications should be reported to the FDA to help the agency monitor patient reactions to the drugs

The complete announcement can be found on the official FDA website.

What Causes Ketoacidosis?

The elevated blood acidity that characterizes ketoacidosis arises when the body makes too many “ketone bodies,” which are byproducts of fat metabolism. Typically, glucose is the body’s choice energy source. Whenever glucose is either unavailable or somehow unusable, the body turns to fat for fuel. But constantly metabolizing fat for long periods of time causes a buildup of acidic ketone bodies and can eventually lead to dangerously high blood acid levels.

One of the main triggers for fat metabolism is the absence of insulin, the hormone that signals cells to absorb glucose from the bloodstream. In healthy individuals, insulin levels are low when blood glucose levels are low, so ketoacidosis can be caused by a sustained lack of food, whether from intentional fasting or from starvation.

Exceedingly Common in Type 1 Diabetics

Ketoacidosis most commonly occurs in patients with type 1 diabetes, a disease in which the body produces little or no insulin. Unless the patient’s insulin is raised to normal levels through scheduled injections, fat will be burned by default to meet the body’s energy needs.

Ketoacidosis is so common in type 1 diabetes that it’s considered a major symptom / complication of the disease, and is given a special term—diabetic ketoacidosis (DKA). However, ketoacidosis is very rare among those with type 2 diabetes, because in this form of the disease, insulin levels are usually normal though the patient’s cells are resistant to the hormone’s effects.

This is why reports of patients taking Invokana (only prescribed for type 2 diabetes) succumbing to ketoacidosis acted as an immediate red flag to the FDA. Such atypical circumstances could possibly signal that these ketoacidosis cases were caused by undetected side effects of the drug.

Why Is It Dangerous?

The FDA was also concerned about the ketoacidosis reports received because they all described cases that were serious enough to require hospitalization. How does ketoacidosis pose a health threat?

For optimal organ function, blood pH must be maintained within a narrow range. Outside of this range, body chemistry gets thrown off and organ damage may occur. An extended state of ketoacidosis may necessitate a trip to the emergency room, or even lead to coma or death if not treated.

In emergency treatment for ketoacidosis, the patient’s lost fluids and electrolytes are replenished by an IV infusion. Additionally, the fat metabolizing pathways that produce ketone bodies are halted by administering insulin. However, such treatment can also cause problems:

  • Low Blood Potassium (Hypokalemia).  IV fluid and insulin treatment can severely lower potassium levels. Complications can be physical (muscle pain, cramping) as well as psychological (hallucinations, depression).
  • Low Blood Glucose (Hypoglycemia) Blood sugar levels can crash if administered insulin causes cells to absorb glucose too quickly. Nerve damage and seizures can occur after extended periods of hypoglycemia.
  • Brain Swelling (Cerebral Edema) An accelerated drop in blood glucose can also cause the brain to swell. This swelling can lead to headaches, coma and even death, if the brain swells against the skull enough to cut off circulation.

Alert Warns Of Bone Health Problems

Just 5 months after the FDA’s ketoacidosis warning was sent out, the agency had to issue another safety communication, this time specifically for Invokana and Invokamet.

skeleton with focus on hipbones Results from a series of clinical trials indicated that elderly patients suffered from an increased risk of bone fractures in as little as 3 months after first taking Invokana / Invokamet, compared to patients on a placebo. Troublingly, these fractures occurred after only minor trauma (defined by the FDA as “falling from no more than standing height”) and the risks were especially pronounced in patients aged 75 years and older.

Another set of studies the FDA discussed in the warning showed that bone mineral density measurements decreased, particularly in the hip and lower spine, after patients started their Invokana / Invokamet prescriptions. Bone mineral density is a leading indicator of bone strength and anything that contributes to its decline can become a major cause for concern in older patients.

FDA Initiates Label Revisions To Protect Patients

Weakened and fractured bones pose a significant threat to patient health and well-being. Broken bones are often extremely painful and patients may require assistance with day-to-day activities while the healing process takes place. Some bones, such as the hip, may require surgery to fix and even put a patient’s life at risk if broken. According to the U.S Department of Health & Human Services, 1 in 5 women over 50 will die within a year of breaking the hipbone.

Thus, it’s not surprising that the FDA felt it was urgent to update Invokana / Invokamet labeling so that patients would be informed of potential bone health risks:

  • The FDA created a whole new section detailing risks of bone mineral density loss, which had not been mentioned at all on the original labels
  • The existing increased bone fracture risk warnings was strengthened, and the FDA added another precaution and warning about fractures

Will Invokana And Related Drugs Ever Be Recalled?

Invokana and its sister drugs Farxiga and Jardiance have already been tentatively linked to ketoacidosis and several other serious side effects (Farxiga was even initially denied FDA approval due to bladder cancer concerns).

But even if further research and patient complaints continue to indicate significant risks, the drugs may never be pulled from the market. Shockingly, many “dangerous drugs” remain available for use even with overwhelming evidence of harm.

Avandia: Never Recalled Despite Severe Warnings

One prominent example of this alarming trend is the type 2 diabetes medication Avandia, released by GlaxoSmithKline in 1999. A comprehensive 2007 study, in which the authors analyzed results from 42 clinical trials, linked Avandia to a very large increase (43%) in heart attack risk.

After learning of the study, the FDA struck Avandia with a severe “black box” warning and placed restrictions on sales of the drug.

However, even after more than 50,000 Avandia heart attack lawsuits were filed against GlaxoSmithKline—including a lawsuit from the U.S. Department of Justice alleging that the manufacturer hid safety test data from the FDA—Avandia has still not been recalled.

Fighting Back Through Legal Action

As we’ve seen, the FDA has acknowledged that possible Invokana side effects could be causing a grave threat to patient health, and the agency has taken measures to warn patients. But Invokana still remains on the market, and many patients are now claiming that unexpected side effects of the drug have caused them to develop serious health conditions.

Hundreds of product liability lawsuits have already been filed by injured patients, and the legal community expects many more claims will surface in the near future.

If you think you may have an Invokana claim, you can contact Banville Law for a free case evaluation. Our experienced legal team can answer all of your pressing questions regarding your potential claim.