The U.S. Food and Drug Administration has issued a new safety alert regarding a possible increase in the risk of leg or foot amputation after taking the antidiabetic medication, Invokana. Previous safety warnings were also issued about an increased risk of severe urinary tract infection and diabetic ketoacidosis which has required hospitalization and dialysis due to kidney failure.
Invokana, a medication used to treat Type 2 diabetes, may have caused serious injury in some patients. Patients who have taken Invokana may have experienced leg, foot or toe amputation, kidney failure, heart attack or other events which were life-threatening or resulted in permanent injury. Many of these patients or their family members have filed an Invokana lawsuit against the manufacturer of Invokana, stating that the company failed to warn the public and the medical community about the potential risks of the medication.
If you or a loved one required amputation, experienced kidney failure with dialysis, heart attack or other serious injuries after taking Invokana, you may be eligible for legal compensation.
What is Invokana?
Invokana (canagliflozin) is a newer type of anti-diabetic medication used to treat Type 2 diabetes. It is a member of the class “SGLT2 inhibitors” (sodium-glucose-co-transporter 2) medications that work to lower blood sugar by encouraging the body to release excess sugar into the urine.
Normally, insulin is secreted by the body to help move sugar or glucose from the bloodstream into the cells where it can be used as energy. Type 2 diabetics are often resistant to insulin, causing the sugar to remain in the blood stream, unusable by the cells. This excess sugar is excreted into the urine but is reabsorbed by the kidneys. Over time, high blood sugar may cause permanent damage to body tissues and may result in the death of certain tissues.
Damage to the blood vessels may decrease the ability of the vascular system to supply oxygen and nutrients to distant tissues, particularly in the legs and feet. This may cause cellular death, requiring surgical removal of affected tissue or amputation. The results of a new study show that Invokana may increase the risk of the need for amputation.
Invokana and other SGLT2 inhibitors work to stop the kidneys from reabsorbing the sugar to lower blood sugar. This increased amount of sugar being released in the urine, may increase the risk for urinary tract infection. Serious UTI can result in kidney failure and the need for dialysis and may be potentially life-threatening.
Invokana may also increase the risk of ketoacidosis, a severe and potentially fatal side effect. In type 2 diabetics, the body is unable to use sugar in the blood and begins to break down fat to use as energy. This causes ketones, an acidic metabolic byproduct, to build up in the blood. When the blood is acidic due to ketoacidosis, potassium levels in the circulation may also rise to dangerous levels and may increase the chance for heart attack.
Invokana is not the only member of the SGLT2 type of antidiabetic which may have caused serious injury and many lawsuits have been filed against the manufacturers. Invokana lawsuits have been filed against Invokana’s manufacturer Janssen Pharmaceuticals and its parent company, Johnson and Johnson and the recent FDA safety alerts may indicate that more are expected.
The SGLT2 inhibitor class of antidiabetics includes a number of medications. All of these medications are being investigated for an increased risk of severe urinary tract infection, kidney failure, diabetic ketoacidosis (DKA), and myocardial infarction (heart attack), while Invokana has been implicated in a possible increased risk of amputation.
All of these conditions are severe and potentially life-threatening.
SGLT2 inhibitors and combinations include:
- Invokana – canagliflozin
- Invokamet – canagliflozin and metformin
- Farxiga – dapagliflozin
- Xigduo XR – dapagliflozin and metformin
- Jardiance – empagliflozin
- Glyxambi – empagliflozin and linagliptin
Risks of Invokana
Invokana may cause a number of side effects but the most severe are potentially life-threatening. Patients taking Invokana may be at risk for:
Amputation may be required when tissues of the extremities have died. Cell death is due to the lack of the vascular system’s ability to supply oxygen and nutrients through the bloodstream. When cellular death has occurred, an infection known as “gangrene” may develop. Gangrenous tissue will require surgical removal and may include amputation. Amputation of the toes is most common but more advanced cases may involve the feet and legs.
Kidney failure occurs when the kidneys stop working. The kidneys are responsible for filtering metabolic waste products out of the bloodstream. The waste products are then excreted into the urine and passed through the bladder. They are also important in blood pressure control, and fluid and electrolyte balance. Invokana’s action means that there is more sugar in the urinary tract infection, increasing the risk of UTI and kidney failure. If the kidneys are not working, waste products and fluids may build up in the bloodstream which may increase the blood pressure and lead to toxicity. The loss of kidney function may also disrupt electrolyte balance which may lead to weakness, confusion, abnormal heart rhythm, lethargy and even death.
Myocardial infarction, also known as heart attack, occurs when cells of the heart muscle are suddenly deprived of oxygen. Oxygen is transported in the blood to supply muscle cells and other tissues but when blood supply is restricted by blockage, the heart tissue is suddenly starved. This may result in cardiac weakness and irregular heart rhythm and if oxygen is not restored, will cause cell death. Excess potassium levels, known as hyperkalemia, can increase the risk of irregular heart rhythm and sudden death.
Ketoacidosis occurs when sugar cannot be used as cellular energy and the body is forced to break down fat stores to use as fuel. When fat is metabolized, a byproduct known as ketones is produced. Ketones are acidic in nature, causing the blood to become acidic. If left untreated, ketoacidosis continues to worsen, causing difficulty breathing, fatigue, confusion, coma and death. When blood becomes acidic, multiple body systems are affected, including a significant rise in potassium which may increase the chance for heart failure.
Patients who are taking SGLT2 inhibitor medications for type 2 diabetes should be warned of the symptoms of gangrene, kidney failure, cardiac events, acidosis, hyperkalemia and other side effects. They should be advised to seek medical attention for symptoms such as:
- numbness in feet, legs or skin
- foot or skin infection
- black areas of toes, feet or on skin
- urinary pain
- flank pain
- muscle weakness
- difficulty breathing
- increased urination
- extreme thirst
- abdominal pain
- excessive fatigue
- increased heart rate
- chest pain
Patients who are taking Invokana or other SGLT2 medications should not stop or quit taking medication without the advice of a doctor but should seek medical attention. Emergency medical attention may be warranted if symptoms occur suddenly or are severe.
Type 2 diabetics taking Invokana should notify their health care provider of any other medical conditions that may increase Invokana risks such as:
- High or low blood pressure
- Electrolyte imbalances like hyperkalemia (high potassium levels)
- Heart disease
- Decreased liver function or liver failure
- Decreased kidney function or kidney failure
- Low salt diet
- Other medication use, particularly other antidiabetics
Women who are pregnant, intend to get pregnant or are breastfeeding should discuss Invokana’s risk with their health care provider and may not be able to take the medication.
The U.S. Food and Drug Administration (FDA) has issued three safety warnings regarding Invokana. The most recent safety announcement indicates that Invokana may be linked to an increased risk of amputation. Prior safety announcements have advised that patients should be notified of the risks and advised to seek immediate medical assistance if they experience any symptoms of ketoacidosis such as nausea, vomiting, and abdominal pain, tiredness, confusion, dizziness, or difficulty breathing.
Invokana was approved by the FDA in March of 2013. In 2014, the combination of canagliflozin and metformin (another antidiabetic medication) was approved under the name Invokamet. By May of 2015, increasing numbers of diabetic ketoacidosis reports resulted in a drug safety warning issued to medical professionals regarding the SGLT2 inhibitors, including Invokana. The May 2015 safety warning stated that the medications carried an increased risk of diabetic ketoacidosis which left untreated, is potentially fatal.
In December of 2015, the FDA further ordered manufacturers of SGLT2 inhibitors, including Janssen/Johnson & Johnson, to add warnings regarding an increased risk of ketoacidosis and increased risk of urinary tract infections in patients who take Invokana.
A May 2016 safety alert was issued after interim analysis of a long-term study comparing two doses of Invokana to placebo. The mid-term results showed an increase in the number of patients requiring amputation when Invokana was taken. Patients taking placebo had a 3 out of 1000 risk of amputation, usually the toes. The risk increased to 5 out of 1000 in patients taking 100 mg Invokana daily and increased further to 7 out of 1000 when 300 mg of Invokana was taken daily.
The FDA safety announcement indicates that the agency has not confirmed that there is a direct link but states that the investigation will continue. The European Medicines Agency (EMEA) is also investigating Invokana and the increase occurrence of amputation.
Despite the safety warnings regarding Invokana, the FDA has not forced Invokana’s manufacturer, Janssen Pharmaceuticals to recall the medication. The company has also not withdrawn the drug voluntarily and Invokana remains on the market, though the company has been required to include additional warnings in drug labeling and prescribing information.
Multiple Invokana lawsuits have been filed against Janssen and its parent company, Johnson and Johnson due to medical injuries that have occurred after the medication’s use. These lawsuits, filed in both the U.S. and Canada, claim that Janssen knew about the risks of Invokana but continued to promote and sell the medication anyway, without additional warnings. If health care practitioners and patients had been warned about increased risks, many would not have used the medication.
When multiple lawsuits regarding the same medication and medical issues are filed against one company, the individual lawsuits are often combined into one large group of cases known as “multidistrict litigation” (MDL). MDL cases remain separate and do not require that a plaintiff must agree to a lesser compensation in advance. MDL cases will be initially approached by a “bellwether” trial in which one or two representative cases will be tried before a judge. When the bellwether trial results in a judgment in favor of the plaintiff, many manufacturers settle cases out of court. They often prefer to settle each individual case at the same time but no patient is forced to agree to the settlement offer and can continue to ask for their own trial.
Combining individual cases into one MDL helps to ensure that each plaintiff has the same access to information and helps to ensure that cases are settled fairly and appropriately. This is different from a “class action lawsuit”.
Though many previous antidiabetic medication lawsuits have been successful and resulted in judgements for the plaintiff, there are no guarantees when a lawsuit is filed. Each case is unique and each set of circumstances must be evaluated separately. Patients who have been injured may be eligible for compensation for medical bills, future medical treatment costs, lost wages, and pain and suffering. In some cases, victims or family members may be eligible for punitive damages as well, if it can be proven that the company was aware of the dangers, but continued to sell the medication anyway.
Patients who suffered kidney failure, diabetic ketoacidosis, heart attack or other serious injury may be eligible for compensation from Janssen and should seek legal advice right away.
- Brooks, M., (15 May 2015), SGLT2 inhibitor diabetes drugs may cause ketoacidosis: FDA, Medscape, accessed on 19 May 2016 http://www.medscape.com/viewarticle/844754
- Cefalu, W. et al, (2015), SGLT2 Inhibitors: The Latest “New Kids on the Block”!, Diabetes Care, accessed on 19 May 2016 http://care.diabetesjournals.org/content/38/3/352.full
- Food and Drug Administration, (15 May 2015), Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of too much acid in the blood, U.S. Food and Drug Administration, accessed on 19 May 2015 http://www.fda.gov/Drugs/DrugSafety/ucm475463.htm
- Food and Drug Administration, (04 December 2015), Drug Safety Communication: FDA revised labels of SGLT2 inhibitors for diabetes to include warnings about too much acid in the blood and serious urinary tract infection, U.S. Food and Drug Administration, U.S. Food and Drug Administration, accessed on 19 May 2015 http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm
- Food and Drug Administration, (18 May 2016), Drug Safety Communication: Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate, U.S. Food and Drug Administration, accessed on 19 May 2015 http://www.fda.gov/Drugs/DrugSafety/ucm500965.htm
- ISMP, (06 May 2015), Questions about Canagliflozin (INVOKANA), Quarter Watch, 2., Institute for Safe Medication Practices, accessed on 19 May 2016 http://www.ismp.org/QuarterWatch/pdfs/2014Q2.pdf
- Mayo Clinic, (23 October 2013). Diabetic ketoacidosis, Mayo Clinic, accessed on 19 May 2016 http://www.mayoclinic.org/diseases-conditions/diabetic-ketoacidosis/basics/definition/con-20026470
- Nainggolan, Lisa, (15 April 2016), EMA Probes Link with Diabetes Drug Canagliflozin, Toe Amputation, Medscape Medical News, accessed 19 May 2016 http://www.medscape.com/viewarticle/862009
- National Library of Medicine, (2016), Invokana-canagliflozin tablet prescribing information, U.S. National Library of Medicine, accessed 19 May 2016 http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b9057d3b-b104-4f09-8a61-c61ef9d4a3f3
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