Invokana works by blocking sodium/glucose cotransporter 2 – a protein that helps reabsorb glucose into the blood. This reabsorption happens when blood is filtered through the kidneys. Normally, the kidneys would reabsorb glucose (sugar) and return it to the bloodstream; however, canagliflozin prevents that process from taking place, causing glucose to be expelled through the urine and lowering the patient’s blood sugar level.

In most cases, Invokana is taken in conjunction with a modified diet. It might also be prescribed for use with metformin (sold under the brand name Invokamet). It may be combined with insulin and other drugs as well, depending on various factors.

Invokana is created by Janssen, a Johnson & Johnson company, and is taken by 1.5 million people annually.

Invokana Side Effects and Risks

There are a number of safety concerns related to Invokana, from mild side effects to more serious conditions, which recently prompted the FDA to require a new black box warning on the drug.

Invokana and Kidney Failure

When functioning normally, the kidneys will usually absorb as much as 90% of waste glucose (sugar) back into the bloodstream. This is done through a set of proteins known as sodium/glucose cotransporters. Invokana prevents the kidneys from reabsorbing glucose molecules by blocking sodium/glucose cotransporter 2.

One of the functions of the kidneys is to filter out waste materials like creatinine, a byproduct of normally working muscles. Clinical trials have shown that patients who take Invokana tend to have increased levels of creatinine, which can indicate that the kidneys are not filtering out creatinine properly.

As a result, the FDA has issued multiple warnings about the possibility of kidney damage in patients who take medicines containing canagliflozin, such as Invokana. In May 2016, the FDA updated the required warning label on Invokana to include information about the possibility of severe kidney damage. Up to that point, the agency had received multiple reports of renal failure in patients who took the drug, including some instances that led to hospitalization and the need for dialysis.

The risk of developing severe kidney disease due to Invokana is greater in some people than others. For example, people on certain medications such as ACE inhibitors, non-steroidal anti-inflammatory drugs (NSAIDs), diuretics, or angiotensin II receptor blockers (ARBs), have an increased risk of developing kidney problems when taking a drug containing canagliflozin. Those who have experienced congestive heart failure, hypovolemia, or chronic renal insufficiency are also at a greater risk.

Amputations and Deaths

More than a mere side effect, in 2016 the FDA reported that people who take Invokana have a higher risk of needing leg and foot amputations. Many people with diabetes are already at risk of developing various foot problems, due to poor circulation, nerve damage, peripheral arterial disease, and other health effects. However, based on an interim study conducted over a 4.5-year period, the FDA found that those who take drugs containing canagliflozin have an even greater risk of needing an amputation than those with diabetes who do not take the drug.

Due to the possibility of ketoacidosis, it is possible that Invokana could cause death to occur. As long as the body’s insulin supply is sufficient for metabolizing glucose in the bloodstream, there may not be a problem. However, a lack of insulin combined with Invokana can cause uncontrolled ketogenesis, which could lead to death very quickly if the person is not treated right away.

Death may also occur as a result of kidney failure (also known as renal failure). Individuals who take certain medications may be at a greater risk of death while taking Invokana. Those who already have kidney disease or damage also may be at a higher risk of dying from Invokana.

Other Severe Side Effects

In addition to the possibility of kidney failure, patients taking Invokana may be subject to a number of other possible side effects.

Fractures: Patients who use canagliflozin have a greater chance of breaking their bones. This can take place as soon as 12 weeks after starting the prescription.

Falls: According to the FDA, patients who take Invokana are also at a higher risk of falling down, with the risk increasing at higher dosages of the drug.

Dehydration: Invokana has a diuretic effect which can lead to dehydration. Symptoms include dizziness, faintness, lightheadedness, or weakness. Individuals who are taking diuretics while also taking Invokana may be at a greater risk of becoming dehydrated.

Ketoacidosis: This is a severe condition in which the body cannot properly regulate the production of ketone bodies. It can be triggered in those who have diabetes when the body does not have access to enough glucose. Invokana has been shown to trigger ketoacidosis in some patients.

Yeast Infections: Urinary tract infections, yeast infections, and vaginal itching may also be common side effects of taking the drug.

Approved Uses of Invokana

 Brand NamesInvokana, Invokamet, Sulisent
 Generic Namecanagliflozin
TreatsType 2 diabetes
Common Dosages100 mg, 300 mg
FDA ApprovalFirst approved in March 2013; label updated in June 2016

Invokana is only approved in the United States to treat adults with type 2 diabetes mellitus. Its approval is based on being taken along with a proper diet and exercise to reduce blood glucose levels. There are no other approved uses of the drug.

The FDA has explicitly stated that Invokana is not for use with individuals who have type 1 diabetes or diabetic ketoacidosis.

Invokana Lawsuits

Due to the dangers of canagliflozin, including the possibility of severe damage or even death from kidney failure and ketoacidosis, a number of lawsuits have been filed on behalf of patients who took the drug and experienced these adverse effects. The primary complaint in many of these legal actions are that Janssen and other drug manufacturers did not properly warn patients about the risk of taking drugs like Invokana and Invokamet.

In October 2015, a woman named Paula Brazil sued Janssen and its parent company Johnson & Johnson—also the defendant in thousands of lawsuits over the brand’s baby powder products. Paula had lost an extraordinary amount of weight and was subjected to recurrent vomiting and nausea from the drug, which ultimately led her to seek emergency care at Hamilton Medical Center in Dalton, Georgia. The Brazil lawsuit contained claims of strict liability, negligence, fraud, misrepresentation, and consumer protection against Janssen, and it sought punitive damages for the harm done to the plaintiff.

In another case, Wardell Fleming sued Janssen, Johnson & Johnson, and Mitsubishi Tanabe due to the failure of his kidneys after starting to take Invokana in 2013. The lawsuit was filed in December 2015, making claims related to physical and emotional injuries, economic losses, and a loss of enjoyment of life due to the adverse effects of the drug.

Ultimately, both of these lawsuits were dismissed for different reasons. However, Janssen and its parent company, Johnson & Johnson, face additional lawsuits due to the dangers of Invokana. As of September 2016, there were at least 56 cases in 11 federal district courts across the U.S. with similar claims as Brazil and Fleming, and another 41 cases were pending in Pennsylvania state court alone. Motions have been filed to treat these cases similarly to other product liability lawsuits using multidistrict litigation (MDL).

In October 2016, Janssen told the Judicial Panel on Multidistrict Litigation that it agreed with those plaintiffs who wanted to have their cases transferred to an MDL. The proposed venue for the MDL is the District of New Jersey.