Invokana Side Effects Include Lower Limb Amputation
Invokana has been strongly associated with a number of dangerous health side effects, with some risks being so serious that the FDA has required Invokana to carry a black-box warning—the FDA’s highest level of warning—informing patients of the drug’s potential harms. These harms include:
Risk of Amputation!
Large, reputable studies show that taking Invokana can double your risk of having a lower limb amputated. The FDA considered the threat to patients so great that in July 2017 it required Invokana to start carrying a black-box warning—the FDA’s highest level of warning—informing patients of the known amputation risk.
According to the FDA, “[a]n approximately 2-fold increased risk of lower limb amputations associated with Invokana was observed in…two large, randomized, placebo-controlled trials evaluating patients with type 2 diabetes.” In the first study, patients receiving Invokana suffered 5.9 amputations per 1000 patients per year, while patients taking a placebo underwent only 2.9 amputations per 1000 patients per year. The second study showed similar results, with Invokana-treated patients having 7.5 amputations per 1000 patients per year to the placebo-takers’ 4.2.
Amputations to the toe and midfoot were most prevalent, accounting for approximately 70% of the amputations across the two studies, with the other 30% being amputations of the leg, either above or below the knee. Several unfortunate patients in the studies were forced to undergo multiple amputations, sometimes of both lower limbs.
Why were these amputations necessary? The FDA identifies “lower limb infections, gangrene, and diabetic foot ulcers” as being the most common ailments necessitating lower limb amputations in the two studies, with patients who had dealt previously with peripheral vascular disease, neuropathy, diabetic foot ulcers, or who had undergone prior amputations showing the greatest risk. As a result, the FDA urges doctors to consider a patient’s medical history and predisposition toward possible amputations before prescribing Invokana and recommends that doctors continually monitor patients taking Invokana for lower limb conditions such as pain, tenderness, sores, ulcers, or infection, including osteomyelitis (an infection inside the bone). Should a doctor observe any such ailment in a patient’s lower limbs, the FDA recommends discontinuing the use of Invokana.
What are some common side effects from Invokana?
• Hypotension (Low Blood Pressure)
• Acute Kidney Injury / Impairment
• Urinary Tract Infection
• Genital Mycotic Infections
• Hypersensitivity Reactions
• Bone Fracture
• Increases in Low-Density Lipoprotein (LDL-C)
Hypotension (Low Blood Pressure)
Another possible side effect of taking Invokana is hypotension, or low blood pressure. The risk of hypotension is related to the fact that Invokana induces intravascular volume contraction, meaning the overall amount of blood circulating in the body is reduced. It is a symptom generally associated with dehydration that often results in low blood pressure.
The risk of hypotension when taking Invokana is greatest among patients who are elderly, suffer from impaired kidney function, or who are taking certain medications including diuretics and those that target the renin-angiotensin-aldosterone system. The FDA instructs doctors to “[m]onitor for signs and symptoms after initiating therapy.”
Who is at an increased risk for Hypotension when taking Invokana?
• The elderly
• Patients suffering from impaired kidney function
• Patients suffering from low systolic blood pressure
• Patients taking one or more of the following medications:
• ACE (Angiotensin-Converting-Enzyme) Inhibitors
• ARBs (Angiotensin Receptor Blockers)
• Other medications impacting the renin-angiotensin-aldosterone system
Cases of ketoacidosis—even fatal ones—have been documented in patients with type 1 and type 2 diabetes mellitus while taking Invokana or a similar drug.
What is ketoacidosis? Ketoacidosis is a condition common in those with untreated type 1 diabetes mellitus because it frequently occurs when the blood’s insulin levels are too low. With low insulin levels, the body is unable to convert sugar into energy, so the body instead turns to fat as its primary energy source. However, when the body burns fat, it creates acids known as “ketones”, which can then build up to unsafe levels. Other factors that can trigger an increase in ketone levels include illness, stress, fasting, or having an insulin reaction. Keotacidosis is a potentially life-threatening condition that may require immediate hospitalization.
What are the symptoms/indicators of ketoacidosis? The symptoms of ketoacidosis typically include a blood sugar level exceeding 250 mg/dL, as well as other indicators of high blood sugar, like extreme thirst, frequent urination, and dry mouth. However, the FDA notes that “ketoacidosis associated with Invokana may be present even if blood glucose levels are less than 250 mg/dL.” In some instances, this has resulted in a delayed diagnosis, so special attention should be paid to other symptoms of ketoacidosis in those taking Invokana.
Those other symptoms include:
• Vomiting for over two consecutive hours
• Extreme stomach discomfort and/or nausea
• A sweet, fruit-like odor to the breath
• Feelings of fatigue, confusion, or light-headedness
• Difficulty breathing
The FDA also cites pancreatic issues and alcohol abuse as associated with an increased risk of ketoacidosis.
One of the hallmark signs of ketoacidosis is a blood sugar level above 250 mg/dL. However, for patients taking Invokana, ketoacidosis may occur even when their blood sugar does not exceed that level. This anomaly has resulted in instances of delayed diagnoses, which can be particularly harmful in extreme cases of ketoacidosis, where time is of the essence.
Acute Kidney Injury or Impairment
Since Invokana was placed on the market, there have been numerous documented cases of acute kidney injury occurring in patients taking the drug. In some instances, the damage to the kidney has been so severe as to require hospitalization or even dialysis. And the impact has not been limited to the elderly, as some might expect. There have been multiple reports of acute kidney injury occurring in patients taking Invokana who were under the age of 65.
According to the FDA, the “[u]se of Invokana has been associated with an increased incidence of renal-related adverse reactions (e.g., increased blood creatinine, decreased glomerular filtration rate, renal impairment, and acute renal failure), particularly in patients with moderate renal impairment.” One study cited by the FDA contained a pool of patients with preexisting moderate renal impairment. Within this pool, 3.7% of patients taking a placebo experienced renal-related adverse reactions, compared to 8.9% of patients taking a 100 mg dose of Invokana and 9.3% of patients assigned a 300 mg dose. This means that patients in the study with preexisting renal impairment were more than twice as likely to suffer renal-related adverse reactions if taking Invokana than if not.
What Preexisting Factors May Increase Patients’ Chances of Suffering Acute Kidney Injury While Taking Invokana?
• Hypovolemia (Decrease in volume of blood plasma)
• Chronic Renal Insufficiency
• Congestive Heart Failure
Hyperkalamia (Elevated Blood Potassium Levels)
Taking Invokana has been linked to hyperkalemia, an elevated level of potassium in the blood, particularly in those already suffering from kidney impairment. Too much potassium in the blood can, among other things, impact the functioning of the heart, possibly resulting in an irregular heartbeat, a decreased heart rate, or a general weakening of the heart.
The FDA urges doctors to monitor regularly the blood potassium levels of patients taking Invokana who are known to suffer from impaired kidney function, as well as patients taking medications that affect potassium excretion (e.g. potassium-sparing diuretics) or the renin-angiotensin-aldosterone system.
Urinary Tract Infections (UTIs) / Pyelonephritis / Urosepsis
The use of an SGLT2 inhibitor such as Invokana increases the likelihood that a patient will develop a urinary tract infection (UTI). In some cases, patients taking Invokana have developed UTIs with complications serious enough to require hospitalization.
Pyelonephritis and urosepsis are both serious medical conditions that involve infections of the upper urinary tract. Pyelonephritis typically begins in the bladder before spreading to the kidneys, where it can do major damage if left untreated. Symptoms of pyelonephritis may vary with age and include chills, fever, and pain while urinating. The National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) recommends that those suffering from pyelonephritis drink plenty of fluids in order to assist the body in flushing bacteria from the kidneys. Antibiotics also are sometimes prescribed to help treat the infection.
Urosepsis is a sometimes-fatal condition that can be particularly dangerous if left untreated. Beyond the usual UTI symptoms, other signs of urosepsis include:
• Low blood pressure
• Difficulty concentrating
• Lack of energy
• Difficulty breathing
• Pain in kidneys (sides of lower back)
• Not urinating or urinating very little
The FDA recommends that doctors watch out for indications of UTIs in patients taking Invokana or other SGLT2 inhibitors in order to ensure that infections are treated as quickly as possible.
Hypoglycemia (Low Blood Sugar)
Invokana can increase the chances of hypoglycemia, or low blood sugar levels, when used in conjunction with insulin or an insulin secretagogue. Consuming carbohydrates oftentimes helps alleviate the symptoms of hypoglycemia, which include:
• Trouble communicating
Genital Mycotic Infections
Taking Invokana increases the risk of genital mycotic infections, particularly in uncircumcised males or individuals who have previously suffered from a genital mycotic infection.
Genital mycotic infections are known as vulvovaginal candidiasis in females and Candida balanitis in males. Individuals with diabetes are especially susceptible to genital mycotic infections because high blood glucose levels are not only conducive to the growth of yeast but also impede upon the immune system’s ability to resist.
Beyond maintaining healthy blood glucose levels, those suffering from genital mycotic infections have a number of treatment options available, including topical creams and oral medications.
In some instances, patients have suffered hypersensitivity reactions such as angioedema and anaphylaxis when taking Invokana, most often within just hours or days of when they first start taking the drug.
Angioedema and anaphylaxis are both allergic reactions that are, in these cases, likely brought on by the body’s exposure to Invokana. Angioedema is a condition that, like hives, involves a swelling of tissue, except that angioedema occurs beneath the skin. Anaphylaxis, sometimes called anaphylactic shock, is a severe allergic response that involves many of the body’s organs and systems. It is the same kind of dangerous reaction experienced by individuals with severe allergies to peanuts or bee stings.
What are some signs that a person is going into anaphylactic shock (anaphylaxis)?
• Loss of Consciousness / Fainting
• Nausea, diarrhea, vomiting, stomach cramps
• Low blood pressure
• Hives or other redness or swelling of the skin
• Difficulty swallowing / Swollen throat
• Trouble breathing
• Tightness in the chest
According to the FDA, patients have shown an increased risk of bone fracture within as little as 12 weeks of Invokana treatment. In a pool of clinical trials in which the mean duration of Invokana treatment was 85 weeks, those taking a 100 mg dose of Invokana were approximately 25% more likely to suffer a fractured bone, while those taking a 300 mg dose had their chances increased by 35% over patients taking a placebo. Patients were at greatest risk of suffering fractures to an upper extremity and to do so while falling from standing height or lower. Doctors are urged to take into account a patient’s predisposition for bone fractures when considering Invokana as a treatment option.
The documented increase in bone fractures for patients taking Invokana is likely due at least in part to the decrease in bone mineral density (BMD) observed in those taking Invokana for multiple years. In a study involving 714 adults with a mean age of 64 years old, those taking a 300 mg dose of Invokana for a period of two years showed a 1.2% placebo-corrected decline in BMD in the hip (The figure was 0.9% for those taking the 100 mg dose). BMD declines in the Invokana-taking groups were also observed in the lumbar spine, femoral neck, and distal forearm (300 mg dose only).
Increases In Low-Density Lipoprotein Cholesterol (LDL-C)
Research has demonstrated that taking Invokana increases a patient’s low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). The observed increases were highly dose-dependent.
In a study whose participants began with mean baseline LDL-C levels of 104 to 110 mg/dL, those taking a 100 mg dose of Invokana saw a mean placebo-corrected increase of 4.4 mg/dL, or 4.5%, while a 300 mg dose resulted in an increase of 8.2 mg/dL, or 8.0%. Similarly, a 100 mg dose resulted in a mean increase of 1.5% in non-HDL-C, while a 300 mg dose caused a mean increase of 3.6%. Results like these have led the FDA to warn doctors that they should be aware of any preexisting conditions making patients susceptible to increases in LDL-C and/or non-HDL-C when considering Invokana treatment.
On This Page
Invokana Common Side Effects
Invokana Hypertension Risk
Invokana Acute Kidney Injury Risk
Articles Related To: Invokana
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National Institute of Diabetes and Digestive and Kidney Diseases Medical News Today US National Library of Medicine, Medline Plus, “Sepsis” source: FDA Medication Guide, Invokana WebMD.com US National Library of Medicine – MedlinePlus US National Library of Medicine, PubMed.gov US National Library of Medicine, MedlinePlus, “Angioedema” US National Library of Medicine, MedlinePlus, “Anaphylaxis”