More About Invokana

What Is Invokana?

Invokana is a diabetes drug that 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

In addition to the more severe Invokana side effects such as diabetic ketoacidosis and kidney failure described below, patients may experience a variety of other possible side effects. These adverse reactions may be mild, moderate, or severe. You should always discuss any side effects you experience while taking Invokana with your doctor, especially if they are persistent or severe.

Most Common Invokana Side Effects

  • Abdominal pain
  • Allergic reactions
  • Bone fractures
  • Constipation
  • Dehydration
  • Falls
  • Fatigue
  • Hyperkalemia (high potassium)
  • Hypersensitivity reactions
  • Increased cholesterol
  • Increased urination
  • Kidney problems
  • Low blood pressure
  • Low blood sugar
  • Nausea
  • Urination discomfort
  • Urinary tract infections
  • Vaginal itching

Amputations

Due to poor circulation, nerve damage, peripheral arterial disease, and other health issues, diabetes patients are at risk of developing various foot problems. This risk can significantly increase when taking Invokana. Based on an interim study conducted over a period of four and a half years, the FDA found that diabetes patients who take drugs containing canagliflozin are more likely to require an amputation than those who don’t take the medication.

In May 2017, the FDA added a black box warning (its most severe alert) for an increased risk of leg and foot amputations with Invokana, Invokamet, and Invokamet XR. This decision followed a review of the results of two large clinical trials, the Canagliflozin Cardiovascular Assessment Study (CANVAS) and A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants with Type 2 Diabetes Mellitus (CANVAS-A).

The FDA found that patients who took Invokana required leg and foot amputations twice as often as those who took a placebo. Toe and middle-of-the-foot amputations were most common, but leg amputations above and below the knee also occurred. Some patients had to have more than one limb amputated.

Ketoacidosis

Invokana should not be harmful if the body’s insulin supply is sufficient for metabolizing glucose in the bloodstream. But combine a lack of insulin with the drug, and patients are at risk of developing diabetic ketoacidosis (DKA), a severe complication that occurs when high levels of blood acids (ketones) accumulate in the blood. If left untreated, DKA can be fatal, causing critical dehydration, brain swelling, and coma.

After receiving 20 reports of DKA among Invokana patients in a one-year period, the FDA issued a warning in May 2015 that the drug and other SGLT2 inhibitors may cause this life-threatening diabetic complication. But it wasn’t until December of that year that the agency ordered Invokana labels to carry a warning about the risk of excessive ketones.

Symptoms of DKA include:

  • Abdominal pain
  • Breathing difficulty
  • Fatigue
  • Fruit-smelling breath
  • Nausea
  • Vomiting

If you experience any of these symptoms while taking Invokana or another SGLT2 inhibitor, seek medical assistance.

Kidney Failure

When functioning normally, the kidneys absorb as much as 90 percent of waste glucose back into the bloodstream via the SGLT2 protein. Invokana prevents the kidneys from reabsorbing glucose molecules by blocking SGLT2, leading to lower blood sugar levels.

The kidneys are also responsible for filtering out waste materials like creatinine, a byproduct of normally functioning muscles. Clinical trials have shown that patients who take Invokana tend to have increased levels of creatinine, indicating that the kidneys are not filtering out the acid properly.

Since kidney failure (also known as renal failure) is extremely serious and can lead to death, the FDA has issued multiple warnings about the possibility of kidney damage in patients who take Invokana and other medicines containing canagliflozin. In May 2016, the agency updated Invokana’s warning label to include information about the possibility of severe kidney damage. This was spurred by multiple reports of renal failure in patients who took the drug, including some hospitalizations and the need for dialysis. Those who already have kidney disease or damage may also face a higher risk of death when taking Invokana.

Some patients taking Invokana are at greater risk of developing severe kidney disease than others. This includes patients who are also taking ACE inhibitors, angiotensin II receptor blockers (ARBs), diuretics, or non-steroidal anti-inflammatory drugs (NSAIDs). Those who have experienced chronic renal insufficiency, congestive heart failure, or hypovolemia also have an increased risk.

Other Severe Side Effects of Invokana

Blood Infections: Urinary tract infections (a common minor side effect) can turn into dangerous blood infections (urosepsis) in patients taking Invokana. From March 2013 to October 2014, the FDA identified nearly 20 cases of kidney infections and blood infections, prompting them to issue a warning in December 2015 indicating that the drug can increase the risk of these life-threatening complications.

Acute Pancreatitis: A rare but serious Invokana side effect is the sudden inflammation of the pancreas, the body’s insulin-producing organ. Known as acute pancreatitis, researchers believe that the condition arises due to Invokana’s diuretic (or dehydrating) effects. Left untreated, the condition can lead to more severe health problems and even death. Mild cases can typically be treated with antibiotics. One study by the Journal of Basic and Clinical Pharmacy found that after taking Invokana for just four days, one patient developed DKA caused by acute pancreatitis. After receiving several reports of cases like this, from April to June 2016 the FDA noted in its FDA Adverse Event Reporting System (FAERS) list that it was evaluating whether regulatory action was required.

Cardiovascular Problems: According to the official minutes of a January 2013 meeting of the FDA’s Endocrinologic and Metabolic Drug Advisory Committee (prior to Invokana’s approval), clinical trials showed signs that the drug may be associated with an increased risk of major adverse cardiovascular events, including blood clots, strokes, and heart attacks. A majority of the panel expressed some concern, but described a “general comfort with the data overall.” At that point, the FDA required Janssen to perform post-marketing studies and a clinical trial. Although results of its CANVAS study showed the drug was not associated with an increased risk for cardiovascular events, many researchers still question the risk.

Approved Uses of Invokana

The U.S. Food & Drug Administration first approved Invokana in January 2013 to treat Type 2 diabetes in adults. The recommendation came after the FDA reviewed results from more than 10,000 patients across nine different studies, showing that the drug could effectively help the kidneys reabsorb glucose into the body. Since then, the FDA has repeatedly updated Invokana’s warnings and indications, most recently requiring the addition of a black box warning on the label informing patients of an increased risk of amputation after taking the drug.

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 Drug Details

BRAND NAMES
Invokana, Invokamet, Sulisent

GENERIC NAME
canagliflozin

TREATS/PREVENTS
Type 2 diabetes

MANUFACTURER
Janssen Pharmaceuticals (subsidiary of Johnson & Johnson)

COMMON DOSAGES
100 mg, 300 mg

FDA HISTORY
First approved in March 2013; label updated in June 2016

Invokana Contraindications

Invokana and SGLT2 inhibitors can affect each person differently. The drug should not be taken by women who are pregnant, breastfeeding, or planning to become pregnant. You should also tell your doctor if you have a history of:

  • Alcoholism, heavy drinking, or heavy episodic drinking (binge-drinking)
  • Allergic reactions to Invokana or other SCLT2 inhibitors
  • Urinary tract infections or urination issues
  • Kidney problems
  • Liver problems
  • Low-sodium or modified diet
  • Problems with your pancreas
  • Surgical procedures

Invokana Litigation

Due to the dangers of canagliflozin, patients who were injured by the drug have filed Invokana lawsuits against the manufacturers. 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 the drugs.