On May 15, 2015, the Food and Drug Administration (FDA) issued a drug safety communication warning that type 2 diabetes medications like Invokana (canagliflozin) could lead to a condition called “ketoacidosis,” in which the blood becomes too acidic. This is a dangerous condition that may require hospitalization and can lead to diabetic coma and even death.
The FDA later confirmed this risk and required that manufacturer Janssen Pharmaceuticals and parent company Johnson & Johnson (J&J) add related warnings to the product labels. In May 2017, the FDA also warned that the drug could increase the risk of serious leg and foot amputations.
The drug has also been linked to other dangerous side effects, including kidney stones and kidney failure, urinary tract infections, electrolyte imbalances, and more.
FDA Approves Invokana in 2013
The FDA approved Invokana in March 2013 for the treatment of type 2 diabetes. The drug is the first in a new class of diabetes drugs called “sodium-glucose co-transporter 2 (SGLT-2) inhibitors.” These drugs work by stopping the kidney from absorbing glucose. This increases the amount of glucose that the kidneys excrete through urine, which can help lower overall blood glucose levels in diabetes patients.
The FDA reviewed the results of 9 clinical trials before approving the drug. These trials involved over 10,000 patients with type 2 diabetes and showed that the drug improved both blood sugar levels and hemoglobin A1c levels (which is another measure of blood sugar control).
The administration also required Janssen to conduct an additional five postmarketing studies on Invokana. These include the following:
- Study to determine cardiovascular outcomes for those patients using the drug.
- Study to monitor for malignancies, cases of pancreatitis, photosensitivity, severe hypersensitivity, liver abnormalities, and adverse pregnancy outcomes.
- Study on bone safety.
- Two studies on how the drug works in children.
Doctors may prescribe Invokana by itself or may use it in combination with other type 2 diabetes drugs to help diabetics to keep their blood sugar levels under control. The FDA warned that the drug should not be used in the following populations because of the potential for serious side effects:
- patients with type 1 diabetes
- patients with severe kidney impairment or end-stage renal disease
- patients on dialysis
- patients with diabetic ketoacidosis
Invokana may also increase the risk of vaginal yeast infections and urinary tract infections, as well as dizziness and/or fainting.
ISMP Warns About Serious Invokana Side Effects
On May 6, 2015, the Institute for Safe Medication Practices issued its QuarterWatch report for the 2nd quarter of 2014. Immediately, they questioned the broad use of the drug:
“Also, early signals for a new kind of diabetes drug, canagliflozin (INVOKANA) raise questions about whether enough is known about this agent to be assured that its benefits outweigh its risks.”
The report goes onto state that the drug inhibits normal kidney function. Typically, kidneys don’t flush away glucose. They flush away waste materials and return glucose—which is the body’s main source of fuel—to the bloodstream.
Invokana and other SGLT2 inhibitors cause kidneys to flush away a substantial amount of glucose. The ISMP notes that in its first year on the market, the drug was associated with a number of adverse event reports indicating serious injuries involving kidney function, as well as hypersensitivity reactions.
More specifically, Invokana was linked with 457 serious adverse event reports, including 5 related to renal toxicity. This was a higher number than for 92 percent of the drugs the ISMP regularly monitors.
- 54 reports of kidney failure or impairment
- 54 reports of dehydration and fluid imbalances
- 11 kidney stones
- 50 urinary tract infections
- 52 reports of abnormal or other weight loss
- 50 reports of serious hypersensitivity, which involved symptoms like rapid swelling of the tongue, lips, face, or throat; skin rashes; and skin exfoliation
The ISMP stated that the drug came with a number of unanswered questions, including whether it helps reduce heart attacks and strokes or other vascular complications like impaired vision, kidney damage, or peripheral nerve damage in patients with type 2 diabetes.
“At the time of FDA approval,” the authors write, “canagliflozin had not been tested in a sufficient number of patients for a long enough period of time to answer that question.”
They also noted that in the clinical trials used to obtain FDA approval for Invokana, 14 percent of women and nearly 4 percent of men developed fungal infections at rates 4-6 times those in patients taking other drugs. Apparently, the increased amount of glucose in the urine increases the risk of these types of infections.
Patients on Invokana also demonstrated reduced kidney function, with “unknown effects” over longer treatment periods. Even the FDA noted in their review that the long-term consequences of canagliflozin on the kidneys were unknown and that it was “prudent to assume” that the slightly reduced kidney function seen in the studies “places patients at increased risk for clinically significant episodes of acute kidney injury.”
Higher-dose animal studies with canagliflozin showed side effects including long-term kidney damage, bone abnormalities, and kidney and testicular cancers.
Does this drug do more harm than good? That was the question raised by the ISMP report.
Study Suggests Invokana May Actually Increase Blood Sugar Levels
In addition to increasing the risk of certain side effects, might Invokana and other similar drugs actually result in a higher blood sugar level?
It’s possible, according to a 2014 study. Researchers first studied dapagliflozin, another SGLT2 inhibitor, in men with diabetes. They found that though the drug increased glucose excretion in the urine and lowered fasting blood sugar levels, it also increased the body’s production of glucose and increased glucagon levels. (Glucagon is a hormone that raises blood sugar.) These increases offset about half the amount of blood sugar flushed away because of the drug.
Researchers found similar results in a second study published a month earlier. This time, they gave patients empagliflozin, another drug similar to Invokana. Again, the kidneys excreted more glucose, but the body also produced more, and glucagon levels were increased.
The researchers concluded that the body was doing what the body does best—balancing it all out. It sensed the loss of glucose through the urine, so it compensated by releasing more glucose into the bloodstream.
Invokana May Increase Risk of Cardiovascular Problems
The FDA required Janssen to perform additional studies on the drug and its effects on the cardiovascular system because the initial clinical trials showed a small increased risk of stroke and heart attacks in the first 30 days of treatment. The drug was also related to an increase in “bad” LDL cholesterol, as well as in “good” HDL cholesterol.
FDA Warns About Invokana Ketoacidosis
The body naturally maintains an equilibrium between acids and bases, maintaining a healthy pH balance. The kidneys and the respiratory system work together to keep the blood pH between 7.38 and 7.42. An imbalance may occur when something changes to affect how the kidneys and lungs are doing their jobs.
Invokana can be that disruptive force. According to the FDA’s drug safety communication, all SGLT2 inhibitors (which include Invokana, Farxiga, and Jardiance) can increase risk of diabetic ketoacidosis (DKA)—a condition in which the body makes too many blood acids (also called “ketones), shifting the pH balance into an unhealthy place. Researchers believe it has something to do with disrupting kidney function, as kidneys usually flush out ketones to maintain pH balance.
Blood that is too acidic can lead to the following symptoms:
- difficulty breathing
- nausea and vomiting
- abdominal pain
- unusual fatigue
- dry or flushed skin
- fruity odor on the breath
The American Diabetes Association (ADA) also notes that early signs of DKA may include:
- thirst or a very dry mouth
- frequent urination
- high blood glucose levels
- high levels of ketones in the urine
Both the FDA and the ADA warn that DKA is a very serious condition and that patients experiencing any of these symptoms should see a doctor immediately.
The FDA initially investigated the issue based on 20 cases of DKA reported in patients taking SGLT2 inhibitors between March 2013 and June 2014. All patients ended up in the hospital. Since June 2014, more reports have come in concerning the same condition in other patients.
Following the safety review, the FDA required product labels to include new warnings alerting patients and physicians to the risk for ketoacidosis. They noted that ketoacidosis could occur even when blood sugar levels were not very high and advised patients to be aware of symptoms including nausea, vomiting, abdominal pain, tiredness, and trouble breathing. The new warnings also warn about serious urinary tract infections.
Meanwhile, healthcare professionals have been advised to be aware of the risks and to report any other adverse events to the FDA.
FDA Warns About Risk of Amputations
On May 6, 2017, the FDA required an additional prominent boxed warning for Invokana, alerting doctors and patients to a risk for serious leg and foot amputations. They based their conclusion on a review of two clinical trails, which showed that leg and foot amputations occurred about twice as often in patients treated with Invokana compared to patients treated with a placebo.
Amputations of the toe and middle of the foot were most common. Amputations of the leg, both above and below the knee, also occurred. Some patients required more than one amputation, in some instances involving both limbs.
The FDA advised physicians to consider risk factors before prescribing Invokana, and to think twice before prescribing it to patients with peripheral vascular disease, neuropathy, or diabetic foot ulcers. They also advised patients to watch for symptoms like new pain or tenderness, sores and ulcers, and infections in the legs and feet.
Types of Invokana Side Effects
Considering all of the above evidence, we now know that Invokana may cause the following side effects:
- allergic reactions
- yeast infections
- urinary tract infections
- kidney stones
- decreased kidney function/kidney failure
- increased LDL “bad” cholesterol
- heart attack
- dehydration and fluid imbalances
- leg and foot amputations
“This is not a drug I’d be enthusiastic about,” Dr. David M. Nathan of Harvard Medical School, Boston, told Medscape.
An Invokana Lawyer Can Help
Chaffin Luhana is currently accepting Invokana-induced personal injury lawsuits. If you or a loved one suffered serious side effects after taking this drug, our Invokana attorneys may be able to help. We understand that manufacturers like Janssen Pharmaceuticals are responsible for making sure their products are safe before releasing them on the market. They are also responsible for making sure doctors and patients are well aware of the risks before prescribing or taking their drugs.
At Chaffin Luhana, we are on top of the developments concerning Invokana and are happy to give you a free case consultation. Call today at 1-888-316-2311.