Invokana – Risk of Diabetic Ketoacidosis (Ketosis)
Invokana (canagliflozin) is a medication used to treat Type 2 diabetes. It is a member of the SGLT2 class of antidiabetic medication which also includes the medications empagloflozin (Jardiance) and dapagliflozin (Farxiga). Canagliflozin is also available in combination form with the antidiabetic, metformin, sold under the brand name Invokamet.
The medication was developed by a Japanese pharmaceutical company, Mitsubishi Tanabe Pharma Corporation but is licensed for manufacture and marketing in the US by Janssen, a subsidiary of the pharmaceutical giant, Johnson & Johnson which has annual estimated sales of over $74 billion.
Invokana was the first of its type in the treatment of Type 2 diabetes and was hoped to help patients who had not responded to other medications as it works differently from other antidiabetics. Unfortunately, like many other antidiabetic medications, Invokana may pose serious medical risks including the occurrence of diabetic ketoacidosis (DKA) which may be life-threatening.
About Type 2 Diabetes
Type 2 diabetes is a medical condition affecting over 9 percent of the population or an estimated 28 million Americans. It is most common in adults but the incidence is increasing in children who are overweight. Type 2 diabetes contributes to a number of other medical conditions including high blood pressure, dyslipidemia and cardiovascular death.
Insulin is required by the body to transport glucose or sugar from the blood, across cell membranes to be used as energy. When the cells are unable to transport sugar, it remains in the bloodstream, resulting in high blood glucose levels.
Over time, high blood glucose levels may damage the vascular system by destroying the small vessels known as capillaries. This may result in long-term organ damage including blindness, necrosis of the extremities (death of tissue in toes, feet and legs), kidney disease and end stage renal failure. Diabetics also suffer from chronic yeast infection and poor wound healing.
Type 2 diabetes is different from Type 1 diabetes which is caused by a lack of insulin production. Type 2 diabetics may have decreased insulin production but in most cases, cells of the body become resistant to insulin.
Physicians who treat patients with Type 2 diabetes have a number of medication choices and one of the newest groups is the SGLT2 class of antidiabetics. While new medications are often an improvement in the treatment of disease, new antidiabetic medications such as Invokana, have been particularly troublesome and resulted in a high number of serious medical injury including deaths.
About SGLT2 Inhibitors
Normally functioning kidneys work to filter glucose from the blood for release in the urine. In healthy patients, the glucose is reabsorbed back into the bloodstream by the kidney tubules so that the sugar is not lost and is useable by the body. Because Type 2 diabetics have too much blood sugar, medication is used to decrease blood glucose levels.
Most antidiabetic medications work by increasing insulin sensitivity, decreasing glucose absorption in the gastrointestinal tract or by increasing insulin secretion. The SGLT2 class of medications is scientifically known as Type 2 sodium-glucose co-transporter inhibitors and work differently from any other type of antidiabetic medications.
SGLT2 inhibitors, including Invokana, act by preventing glucose from being reabsorbed by the kidneys, leading to the excess urine to be excreted in the urine. Invokana has been shown to result in the excretion of up to 119 grams of sugar in the urine, equivalent to over 450 calories.
Like all medications, Invokana may cause a number of side effects. Many of these are mild to moderate and common in a number of medications. Unfortunately, some of the side effects of Invokana may be serious and even life-threatening.
Common side effects of Invokana may include:
- Genital yeast infection
- Vaginal yeast infection
- Vulvar yeast infection
- Jock itch, yeast infection on penis
- Urinary tract infection
- Photosensitivity (sun intolerance)
- Itching and rash
- Increased Low-density cholesterol levels (LDL)
In May 2015, the Food and Drug Administration (FDA) issued a warning statement regarding SGLT2 inhibitors, including Invokana and the increased risk of Diabetic Ketoacidosis (DKA). This warning was issued following reports of over 20 patients who had experienced DKA between March 2013 and April 2014 after taking SGLT2 inhibitors.
Diabetic ketoacidosis, also called ketosis, is caused by high levels of ketones which are produced by the body when it is unable to use glucose in the cells.
When glucose cannot be transported into the cells, the body must break down fat to be used as a fuel source. Ketones are produced as a byproduct of fat metabolism and cause the blood to become acidic in nature. Diabetic ketoacidosis can develop quickly and become life-threatening in a short period of time.
Initial symptoms of DKA which warrant medical attention may include:
- Increased thirst (polydipsia)
- Increased urination
- Abdominal pain
- Fatigue and Weakness
- Shortness of Breath
- “Fruity” Breath
As the condition progresses, additional symptoms warrant emergency medical treatment including:
- Dizziness or Fainting
- Trouble breathing
Some of these symptoms are caused by swelling of the brain and if left untreated, diabetic ketoacidosis may be fatal.
DKA is rare in Type 2 diabetics and many may not recognize the symptoms. The original prescribing information for Invokana did not mention diabetic ketoacidosis as a side effect or risk, only indicating that patients who already had DKA should not take the medication.
Other Serious Side Effects
Invokana may also pose other side effect risks, some of which may be serious including:
- Hypotension – caused by increased water loss in urine following sugar excretion
- Increased hemoglobin and potassium levels – caused by decreased blood volume and diuretic effect
- Impaired kidney function particularly if patient had prior renal damage
- Allergic or hypersensitivity reactions
Invokana is listed as Pregnancy Category C and should not be taken by pregnant or nursing women as animal studies have indicated that the drug may cause impaired renal or kidney development.
Some members of the FDA advisory committee responsible for reviewing Invokana prior to approval expressed concern about a possible increased risk of heart attack in diabetics taking the medication. The drug has been shown to increase LDL levels, however no direct link has been shown and the company was ordered to complete post-marketing studies to identify risks including: cancer, heart attack, bone degradation, pancreatitis, and pregnancy risk.,
Prior to the 2013 approval of Invokana, the consumer group, Public Citizen, objected to the drug’s potential approval. The group stated that previous mistakes had been made regarding other antidiabetic drugs including Avandia which has resulted in numerous injuries and that not enough information was available to ensure public safety and Invokana was placed on the group’s “Do Not Use” list.
Another SGLT2 inhibitor, Farxiga, had been initially rejected by the FDA due to concerns over liver damage and increased cancer risk but was later approved. Invokana was approved after a 10/15 decision by the FDA advisory committee responsible for its review, even though at least one member expressed concern about the drug’s cardiovascular risk.
In the second quarter of 2014, IMS Health, a medication data company, identified 457 serious adverse events occurring with the use of Invokana. In May 2015, The FDA issued a warning regarding the risk of diabetic ketoacidosis following the receipt of at least 20 serious adverse event reports of DKA that occurred after taking SGLT2 inhibitors between March 2013 and June 2014.
Public Citizen has recently asked the FDA to prohibit certain advertising on SGLT2 inhibitors including the non-medical claims that the medications may have the benefit of weight loss and decreased blood pressure. The group has stated that hypotension is not a benefit as it is listed as a side and that “weight loss” statements occur too close to approved use statements and may appear to be a legitimate use for the medications.
Currently, over 450,000 Invokana prescriptions are filled every three months in the U.S.
Injury caused by antidiabetic medication may require the need for hospitalization and long-term medical care. Patients who are injured by medications may be eligible for financial compensation for medical expenses, lost wages and pain and suffering. Loved ones of patients who die due to medication injury may be eligible for wrongful-death compensation.
Every case of medical injury must be considered separately and though thousands of lawsuits have been filed for other antidiabetic drugs, resulting in numerous settlements, each case must be individually considered. Learn more about Invokana lawsuits here.