Invokana Side Effects
(Updated Feb. 13, 2018)
Note: We are no longer taking Invokana and Invokamet cases.
Invokana belongs to a class of drugs known as sodium-glucose cotransporter-2 (SGLT2) inhibitors. These drugs lower blood sugar levels in type 2 diabetes patients, but they may also cause serious side effects like diabetic ketoacidosis (DKA), limb amputations, and kidney problems.
Some patients have filed lawsuits against Johnson & Johnson and other drug companies, claiming that drug makers did not sufficiently warn about these side effects.
Diabetic Ketoacidosis (DKA)
Diabetic ketoacidosis (DKA) is a severe diabetes complication that occurs when the body produces high levels of blood acids called ketones.
Ketones are produced when cells don’t receive the energy they need from glucose and begin to break down fat for energy. Ketone accumulation acidifies the blood and can poison the body. DKA may send the patient into a diabetic coma and can even be fatal.
In May 2015, the FDA warned that Invokana and other SGLT2 inhibitors may lead to DKA.
In May 2015, the U.S. Food and Drug Administration (FDA) warned that Invokana and other SGLT2 inhibitors may lead to DKA. The FDA based the warning on 20 cases of DKA reported to the agency over a one-year period. This is an unusually high number of cases considering that DKA most commonly occurs in patients with type 1 diabetes. All of the patients required hospitalization and/or a visit to an emergency room.
In December 2015, the FDA declared that SGLT2 inhibitors would now be required to carry warnings about the risk of excessive blood acids. The FDA added that the drugs must also warn against serious urinary tract infections.
Symptoms of DKA include:
- Abdominal pain
- Difficulty breathing
- Fruity-smelling breath
Invokana's Other Health Risks
DKA is not the only serious side effect associated with SGLT2 inhibitors. The drugs are also linked to:
- Kidney failure
- Kidney stones
- Breast and bladder cancer
- Cardiovascular side effects
- Bone fractures
- Severe urinary tract infections (UTIs)
- Yeast infections
SGLT2 inhibitors are not recommended for people with impaired kidney (renal) function. This is because the drugs act on the kidneys and promote urine production.
While kidney injury and impairment is mentioned in SGLT2 inhibitor prescribing information, manufacturers may not have gone far enough in warning about severe renal side effects when the drugs were first marketed.
The Institute for Safe Medication Practices (ISMP) published a 2015 report identifying more than 450 Invokana adverse events, including:
- Kidney failure or impairment
- Dehydration and fluid imbalances
- Kidney stones
The ISMP raised questions about whether Invokana has been sufficiently tested, and whether its benefits outweigh its risks. The report stated, “The current data are insufficient to address unanswered questions raised in the FDA reviews about whether long-term use might result in a steady decline in kidney function.”
"The current data are insufficient to address... whether long-term [Invokana] use might result in a steady decline in kidney function."
In June 2016, the FDA issued a drug safety bulletin that said Invokana, Invokamet, Farxiga, and Xigduo XR must strengthen their kidney warnings. The FDA based this decision on more than 100 cases of acute kidney injury—some requiring hospitalization—which were reported to the agency from March 2013 (when Invokana was approved) to October 2015.
In about half of the cases, signs of kidney injury developed within a month of patients starting the drug. Most patients improved after they went off the drug.
Symptoms of acute kidney injury include decreased urine and swelling in the legs or feet.
Foot and Leg Amputations
In May 2017, the FDA ordered a black box warning—its strongest advisory—for Invokana’s increased risk of foot and leg amputations. Two clinical trials showed that patients with type 2 diabetes were twice as likely to need an amputation if they took Invokana than if they took a placebo.
Trials showed that patients were twice as likely to need an amputation if they took Invokana.
The FDA reported that amputations of the toe and foot were the most common, but that leg amputations above and below the knee also occurred.
In 2015, the FDA ordered a labeling change to Invokana over patients’ increased risk of bone fracture. A post-marketing study that the FDA ordered Janssen to conduct showed that Invokana is more likely than a placebo to cause bone fractures.
Three case reports demonstrate a rare but potentially deadly Invokana side effect: acute pancreatitis (inflammation of the pancreas).
A Journal of Basic and Clinical Pharmacy report details a 50-year-old man who was prescribed Invokana four days prior to being admitted to the hospital complaining of malaise, weakness, abdominal pain, and vision loss. The patient stopped using Invokana and his symptoms subsided.
Another case study, in Therapeautics and Clinical Risk Management, details a similar experience with a 33-year-old woman. The woman was admitted to the emergency room with nausea, vomiting, and severe abdominal pain. She discontinued Invokana and, like the male patient, subsequently recovered.
A third case of this kind was covered by the American Journal of Therapeutics.
Invokana’s label still does not warn against this potentially deadly side effect.
All new diabetes drugs approved in the U.S. must be clinically evaluated for cardiovascular risk because diabetes can increase the risk of heart attack, stroke, coronary artery disease, and other cardiovascular complications.
There was controversy at the time of Invokana’s approval over an apparent increase in heart attacks and strokes among clinical trial patients. One study showed that Invokana produced 13 cardiovascular events compared to just one in the placebo group.
Eight of 15 panel members expressed concerns about cardiovascular risks—particularly strokes.
In a vote, eight of 15 panel members expressed concerns about cardiovascular risks—particularly strokes—citing insufficient data. Despite these concerns, the FDA panel voted 10-to-5 to approve Invokana. The FDA did order five post-marketing studies, including a cardiovascular outcomes trial.
Meanwhile, Invokana is being prescribed to hundreds of thousands of patients and generating roughly $1.5 billion per year for drug maker Janssen.
Invokana currently has no warnings about cardiovascular side effects.