Diabetes Drugs raise Cancer Risk, Genital Gangrene

Popular diabetes Invokana Lawsuitdrugs Invokana, Farxiga, and Jardiance can raise kidney and bladder cancer risk, the risk of ketoacidosis, and the risk of genital amputations.

First introduced in 2013, these SGL2 inhibitors are supposed to work by reducing a certain protein and forcing the kidneys to flush glucose out of the body instead of absorbing it.  The problem is that altering the body’s natural processes can cause other problems.

Genital Amputations, other “Side Effects”

Invokana and the other SGL2s can raise the risk of amputations of the genitals or genital amputations.

Fournier’s Gangrene or Necrotizing Fasciitis

The diabetes drugs Invokana, Farxiga, and Jardiance have been linked to causing Fournier’s gangrene of the genitals, or necrotizing fasciitis.  The FDA reported in September 2018 that it had received reports of at least 11 people who suffered Fournier’s gangrene of the genitals from Invokana and other SGL2 drugs. All of the people required painful surgery; one of them died from the condition.

$2.5 Billion in Annual Sales

Though SGL2 inhibitors have proven dangerous or deadly for many people, these drugs account for more than $2.5 billion annually in Big Pharma profits.  Invokana alone brought its maker, Johnson & Johnson, $1 billion in sales in 2018.

Diabetes Drugs linked to Kidney or Bladder Cancer

Several studies have linked Invokana, Farxiga and Jardiance to kidney and bladder cancer:

  • December 2017:  An EMPA-REG clinical trial showed that patients taking Jardiance may have twice the risk of bladder cancer.
  • October 2017:  A joint U.S / Chinese study found a higher risk for bladder cancer with SGLT2 inhibitors.
  • June 2015:  A University of Colorado study showed that patients taking Farxiga had nearly a six-fold increased risk of suffering bladder cancer.
  • February 2015:  A study by Endocrinology Network predicted  higher risk of UTIs from SGLT2 Inhibitors; UTIs can increase risk of bladder cancer.
  • November 2014:  Invokana was linked to kidney cancer in animal studies.
  • August 2014:  A University of Taiwan study found Jardiance patients showed a five (5) times greater risk of bladder cancer.  Animals given Invokana suffered higher rates of kidney cancer.

Compensation for those Diagnosed with Kidney, Bladder Cancer

Patients who have been diagnosed with bladder or kidney cancer after taking Invokana, Jardiance or Farxiga may be entitled to compensation for medical costs, pain, suffering, and other losses.

The manufacturers of these medications may be liable for damages if the makers can be shown to have known about the drugs’ dangers but failed to properly warn doctors and patients.

Cancer risks from SGLT2 diabetes drugs first appeared before 2012 in early clinical trials.  The FDA granted approval for these drugs only on the condition that their makers would conduct more safety testing in the form of post-marketing studies.  Notably, none of these drugs’ makers have added warnings about cancer in the years since, despite several studies suggesting a raised risk.

Kidney and Bladder Cancer

The good news about kidney and bladder cancer is that these types of cancer usually have high rates of treatment success.

Bladder cancer is the 6th most commonly diagnosed type of cancer among Americans.  It usually affects males 65-85.  The three types of bladder cancer are 1.) transitional cell carcinoma, 2.) squamous cell carcinoma, 3.) adenocarcinom.

Bladder Cancer Symptoms include blood in the urine, pain in the side or back, pain during urination, and frequent urination.

Treatment of bladder cancer may include chemotherapy, radiation therapy, surgery, or immunotherapy.  The survival rate with these treatments can be as high as 77%.

Kidney cancer is the 7th most common form of cancer in the U.S.  It can affect men and women of any age. The two most common kidney cancer types are renal cell carcinoma (RCC) and transitional cell carcinoma (TCC).

Common symptoms of kidney cancer include blood in the urine, a mass in the abdomen, persistent sweating, abdomen pain, weight loss.

The most common treatment for kidney cancer is surgical removal of the affected kidney or part of it.  The survival rate for kidney cancer is around 73%, though it can be as high as 92%.

Free Legal Consultation

If you or a loved one developed bladder or kidney cancer after taking an SGL2 inhibitor drug – such as Invokana, Jardiance, or Farxiga – contact us for a free legal consultation regarding a potential lawsuit against that drug’s maker.  We work on a contingency fee basis; we don’t get paid unless we achieve financial compensation for our clients.  We look forward to speaking with you.

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How Diabetes Drugs cause Dangerous Genital Infections

The US FDA announced on August 29, 2018 that certain diabetes drugs can cause dangerous genital infections.  The agency warned that people suffering from type 2 diabetes can be injured by a terrible “side effect.”  These popular drugs – Invokana, Invokamet, Farxiga and Jardiance — can increase the risk of a flesh-eating bacteria infecting the genitals.

The FDA issued a warning about sodium-glucose cotransporter-2 (SGLT2) inhibitors, drugs  commonly prescribed for treating type 2 diabetes.  These drugs were linked, over a five-year period, to a dozen rare cases of genital infection known as Fournier’s gangrene or necrotizing fasciitis. This potentially lethal malady causes the skin to die.  All 12 patients who developed it required hospitalization, according to the FDA.  One person died.

SGLT2 Inhibitors linked to Flesh-eating Bacteria

The SGLT2 inhibitors have been linked to cases of a flesh-eating bacterial infection that attacks the perineum, the skin between the anus and the vulva or the anus and the scrotum.  An infection of the perineum affecting this part of the body is called Fournier’s gangrene.  It is a rare but potentially fatal condition.

Fournier’s gangrene is more common in men than women.  It can spread to other parts of the body, according to medical experts.  It can also rapidly progress to involve the entire genital area, and even infect the abdominal wall.

The 12 cases of this infection that the FDA saw spurned the agency into requiring that all  SGLT2 inhibitors now include a warning about this risk in the prescribing information. The medications in this class include canagliflozin (Invokana & Invokamet), dapagliflozin (Farxiga), empagliflozin (jardiance) and ertugliflozin (Steglatro). The drugs are available as single-ingredient medications or in combinations, such as with metformin.

How do these infections occur?

Type 2 diabetes occurs when the body can’t remove sugar from the bloodstream.  In a diabetic, the cells fail to respond to insulin, the hormone that helps move sugar into the cells.  SGLT2 inhibitors can help lower blood sugar by causing the kidneys to remove sugar from the body through urine. This process can stabilize blood sugar levels.

Unfortunately, this process can also lead to infections, because anywhere there is higher blood sugar, there’s an increased risk of bacterial infection.  Bacteria is all over us, and a sugary environment is a great breeding ground for bacteria. When one eliminates more sugar through urine, a greater concentration of bacteria reaches into the genital area.  This area then becomes an   inviting environment for bacteria.

Bacteria can become a problem only when there is an entry point to infect, such as a small cut from shaving or a skin ulcer near the genitals.  When that happens, the infections can become serious and require many surgeries to remove all of the infected tissues, which is exactly what happened to the 12 people in the FDA report which led to the newly required warnings.

How Diabetes Drugs cause Dangerous Genital Infections

The FDA warning includes instructions for any patients taking these drugs to seek immediate medical attention if they experience any signs of swelling, itching or irritation in the genital area, or if they experience a fever above 100.4 degrees Fahrenheit (38 degrees Celsius).  The bacteria that can cause necrotizing fasciitis can spread quickly, so it’s vital to seek immediate treatment at any sign of infection and a general feeling of ill being.

Type 2 Diabetes Treatment Options Exist

SGLT2 inhibitors are not the only game in town for those who suffer from Type 2 diabetes. Good hygiene can help minimize the risk of necrotizing fasciitis, and Type 2 diabetes can be controlled in ways which don’t involve taking SGLT2 inhibitors.

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Diabetes Drugs cause Gangrene

(Sept. 24, 2018)  Diabetes drugs can cause Fournier’s gangrene.  That was the shocking conclusion of the FDA last month after the agency said it received reports that 12 people contracted gangrene or necrotizing fasciitis after taking a popular diabetes drug.

Invokana, Farxiga, Jardiance, or Steglatro can raise the risk of a nightmarish flesh-eating bacteria that can infect the genitals and cause partial amputations.

A serious genital infection has been reported with the class of type 2 diabetes medicines called sodium-glucose cotransporter-2 (SGLT-2) inhibitors.  The serous infection, called necrotizing fasciitis of the perineum, is also referred to as Fournier’s gangrene.

The U.S. FDA announced the infection warning on August 8, 2018 after receiving a dozen reports of individuals who had been diagnosed with the potentially fatal gangrene or necrotizing fasciitis after using an SGLT-2 inhibitor. Several of those infected people required multiple surgeries, and one person died from the infection.

What are SGLT-2 Inhibitors?

SGLT2 inhibitors — sodium-glucose cotransporter-2 – are prescribed by doctors to help lower blood sugar in adults with type 2 diabetes.  SGLT-2 drugs lower blood sugar by causing the kidneys to remove sugar through the urine.  Brand-name SGLT2 inhibitor drugs (and their active ingredients) include Invokana (canagliflozin), Farxiga (dapagliflozin), Jardiance (empagliflozin), and Steglatro (ertugliflozino).   Steglatro is also FDA approved to lower heart attack and stroke risk in adults suffering from type 2 diabetes and heart disease.

What is Fournier’s Gangrene?

Fournier’s gangrene is a life-threatening bacterial infection of tissue under the skin that surrounds the perineum’s muscles, nerves, fat, and blood vessels.  The perineum is the space between anus and scrotum in the male, and the skin between anus and vulva in the female.

Diabetes raises Risk Factors  

The FDA web site states that “having diabetes is a risk factor for developing Fournier’s gangrene.   But this condition is still rare among diabetics.  There’s a dearth of published literature regarding the occurrence of Fournier’s gangrene for men and women.  Fournier’s gangrene occurs in roughly 1.6 out of 100,000 males annually in the U.S.  It most frequently occurs in males aged 50-79 (approx. 3.3 out of 100,000).

At least 12 Diabetes Drug Gangrene Cases reported to FDA

In a five-year period since the first SGLT-2 drug was approved by the FDA — from March 2013 to May 2018 — the agency said it found 12 cases of Fournier’s gangrene in patients taking an SGLT-2 inhibitor.  That number includes only reports submitted to FDA and found in the medical literature.  The FDA admits there may be more cases about which it is not aware.  Most experts generally agree that only 1-10% of a given drug’s adverse drug events ever get reported. That would put the actual number of people injured by Fournier’s gangrene or necrotizing fasciitis from SGLT-2 drugs somewhere between 120 and 1,200.

1.7 Million SGLT-2 Prescriptions in 2017

The U.S. FDA estimates that 1.7 million patients filled a prescription for an SGLT-2 inhibitor in 2017.  The agency said the 12 Fournier’s gangrene cases it saw involved 7 men and 5 women.  All the injured people developed Fournier’s gangrene several months after filling an SGLT2 inhibitor prescription.

Diabetes Drugs cause Gangrene

The FDA said that in the 30 years prior to 2013, it had received reports of just six cases of Fournier’s gangrene (all of which occurred in men) from all other antidiabetic drug classes.

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Invokana Flesh-Eating Infection Warning

(August 30, 2018)   Invokana and other diabetes drugs like Farxiga and Jardiance can cause a flesh-eating bacterial infection in the genitals.  The U.S. FDA warned doctors and patients yesterday about the risk of infection from these popular diabetes’ drugs.  

The FDA announced that it found the flesh-eating genital infection risk linked with drugs from Johnson & Johnson, AstraZeneca, and Eli Lilly.  The agency found the “side effect” had occurred in at least 12 patients, one of whom died.

Known as Fournier’s gangrene, the condition developed in a dozen patients shortly after they began taking the medicines between March 2013 and May 2018.  The FDA reported that seven men and five women who suffered the infection were all hospitalized.  They all underwent surgery for the condition, including the patient who died.

An FDA statement said that more cases might be uncovered once the risk is better understood.

FDA’s Diabetes Drug Warning over Genital Infections

The warning covered these drugs:  Johnson & Johnson’s Invokana, AstraZeneca Plc’s Farxiga, and Eli Lilly & Co.’s Jardiance — SGLT2 inhibitors that were approved in 2013, 2013, and 2016.  They are designed to help the body lower blood-sugar levels through the kidneys, by helping excrete excess sugar through the urine.  One known side effect of these drugs is urinary tract infections. Another is that they raise the risk of amputations.

The FDA found just six reported cases of the flesh-eating bacterial condition in a review of all other diabetes drug classes for the past three decades; but one has to wonder how many cases went unreported.   How many people had the diabetes drug “side effect” of a flesh-eating genital infection without relating it to their diabetes drug?

These SGLT2 diabetes drugs are expected to generate as much as $7.1 billion in sales by 2020, says Bloomberg Intelligence.  The FDA estimates that some 1.7 million patients filled a prescription for one of these meds from a retail pharmacy in 2017.

All of the drugs in the SGLT2 class except Merck & Co.’s Steglujan have been linked to the flesh-eating infection condition.  The FDA warning demands that the drug makers add information about the risk to the prescribing information and medicine guides given to patients.  AstraZeneca said it is working with the FDA on updating its label.

Officials at J&J and Eli Lilly didn’t return phone calls and emails from Reuters News requesting comment.

FDA Recommendation

The FDA said that diabetics using these drugs should seek immediate medical help if they develop tenderness, redness or swelling of the genitals, or if they experience even a slight fever of 100.4 degrees Fahrenheit.

The symptoms can worsen quickly, the agency said; so it’s important to get help right away.

Invokana Lawsuits

Invokana may also increase the risk of ketoacidosis, which is potentially fatal kidney failure.  The U.S. FDA confirmed on May 16, 2017 that the Invokana label needed to include a black-box warning.

Invokana Flesh-Eating Infection Warning – Lawsuit Consultation

If you or someone you love suffered a flesh-eating genital infection following the use of Invokana, Invokamet, Farxiga, or Jardiance, contact our law firm for a free legal consultation regarding a potential diabetes drug lawsuit against the drug’s maker.

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Diabetes Drug Raises Risk of Foot, Leg Amputations

The diabetes drug Invokana raises the risk of foot and leg amputations. As a result, the FDA required Johnson & Johnson to add new warnings to the Invokana drug label in 2017.

The agency required the warnings after two clinical trials showed leg and foot amputations occurred about twice as often in patients with type 2 diabetes treated with Invokana (canagliflozin), as those given a placebo. The FDA announcement came May 17, 2017, along with a posting on its website.

FDA Boxed Warning
The FDA said the warnings include a boxed warning, which is reserved for the most serious possible adverse events.

Diabetes Drug Invokana
Invokana is part of a newer class of type 2 diabetes drugs called SGLT-2 inhibitors. These drugs are promoted to help remove excess blood sugar through urine. Other drugs in the class include AstraZeneca’s Farxiga and Eli Lilly’s Jardiance.

Amputation Risk Doubles for Invokana – Study
The FDA noted that results of one clinical trial showed the risk of amputation in patients treated with Invokana was equivalent to 5.9 out of 1,000 in a year’s time, compared with 2.8 out of 1,000 for patients given a placebo drug.

A second trial showed the risk of amputation was equivalent to 7.5 out of every 1,000 patients treated with Invokana compared with 4.2 out of every 1,000 patients given a placebo.

Diabetes Drug Raises Risk of Foot, Leg Amputations
The FDA said amputations of the toe and middle of the foot were the most common, but that partial leg amputations also occurred below and above the knee.

The National Diabetes Statistics Report from 2017 said that some 23.1 million people – or 7.2% of the U.S. population – had diagnosed diabetes. The total included 132,000 children and adolescents younger than 18; 193,000 children and adolescents younger than 20. About 5% of people with diabetes are estimated to have type 1 diabetes.

Among U.S. adults 18 or older, data for 2013–2015 indicated American Indians/Alaska Natives had the highest prevalence of diagnosed diabetes for both men (14.9%) and women
(15.3%) Prevalence varied by region, from 6.0% among Alaska Natives to 22.2% among American Indians in certain areas of the Southwest.

Overall, prevalence was higher among American Indians/Alaska Natives (15.1%), non-Hispanic blacks (12.7%), and people of Hispanic ethnicity (12.1%) than among non-Hispanic whites (7.4%) and Asians (8.0%). Among Hispanics, Mexicans had the highest prevalence (13.8%), followed by Puerto Ricans (12.0%), Cubans (9.0%), and Central/South Americans (8.5%).

Among Asians, Asian Indians had the highest prevalence (11.2%), followed by Filipinos (8.9%), and Chinese (4.3%). Other Asian groups had a prevalence of 8.5%. Prevalence varied sharply by education level, which is an indicator of socioeconomic status. Specifically, 12.6% of adults with less than a high school education had diagnosed diabetes versus 9.5% of those with a high
school education and 7.2% of those with more than a high school education.

Untreated type 2 diabetes can cause blindness, nerve and kidney damage and heart disease.

Invokana Lawsuit Help

Anyone who has taken Invokana and suffered an amputation could be eligible for financial compensation for pain and suffering, loss of income and quality of life.  Contact an experienced drug injury attorney now for a free legal consultation.

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Invokana Drug Amputations drive Lawsuit Filings

(March 5, 2018) – Invokana drug amputations have prompted two new lawsuit filings. Lawsuits were filed last month in New Jersey for two people who lost a leg below the knee after using Invokana.  The suits came after the FDA concluded in 2016 that the drug made by Johnson & Johnson, Co. and Janssen Pharmaceuticals, Inc. – a sodium-glucose co-transporter-2 (SGLT2) inhibitor diabetes treatment – can cause an increased risk of toe, feet, and leg amputations.  The FDA warning applies to Invokana, Invokamet, and Invokamet XR.

In addition, the European Medicines Agency (EMA) has also warned about a potentially increased risk of amputations for anyone taking SGLT2 inhibitors.

Related: Invokana Lawsuit

The two lawsuits were filed last month in New Jersey State Court – the Superior Court of New Jersey Law Division, Middlesex County.  Defendants named in the suits are Johnson & Johnson, Co. and Janssen Pharmaceuticals, Inc.  The plaintiffs are two men who each lost a limb which they allege was a result of their use of Invokana.

One plaintiff is an Alabama resident, Robert E. Shook.  His lawsuit petition sstates that he began treatment with Invokana in January 2015.  Mr. Shook lost his left foot and part of his leg below the knee on or about December 15, 2015 and January 15, 2016.

The second Invokana lawsuit was filed for Michael A. Wilkinson. The 53-year-old Iowa man alleges that after he began taking Invokana in April 2015, he suffered a below the right knee amputation on or about December 14, 2015

Both lawsuits contend Johnson & Johnson and Janssen concealed and continue to conceal their knowledge of Invokana’s unreasonably dangerous risks of lower limb amputations. The lawsuits also allege the defective nature of Invokana can cause other problems.  Besides the tragic amputations suffered by Mr. Shook and Mr. Wilkinson, the suits allege people who were prescribed and took Invokana risked or suffered additional severe and permanent personal injuries, including amputations, kidney failure, diabetic ketoacidosis, stroke, and heart attack.

Invokana Approved in 2013
The U.S. FDA approved Invokana (canagliflozin) in March 2013 for the treatment of type 2 diabetes. The European Medicines Agency (“EMA”) allowed Invokana sales in the European Union in November 2013.  Despite its frightening risks, Invokana has been one of Janssen and Johnson & Johnson’s top selling drugs.  J&J reported worldwide Invokana sales of $1.31 billion in 2015 and $1.41 billion in 2016.

Invokana Amputation Risk Warning from Europe
On February 24, 2017, the EMA issued information “about a potential increased risk of lower limb amputation (mostly affecting the toes) in people taking the SGLT2 inhibitors canagliflozin [Invokana], dapagliflozin [Farxiga] and empagliflozin [Jardiance].” The EMA review of SGLT2 inhibitors was triggered by an increase in lower limb amputations reported for patients taking canagliflozin (Invokana) in two large clinical trials, CANVAS and CANVAS-R, even though the final results of those trials had not yet been made public. The EMA wrote: “[A]n increase in lower limb amputations has not been seen in studies with other medicines in the same class, dapagliflozin and empagliflozin.  However, data available to date are limited and the risk may also apply to these other medicines.”

FDA Warning of Invokana Amputation Risk
On May 16, 2017, the FDA issued a Drug Safety Communication that confirmed an “increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR).”  The Drug Safety Communication noted: “[B]ased on new data from two large clinical trials, the U.S. Food and Drug Administration (FDA) has concluded that the type 2 diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR) causes an increased risk of leg and foot amputations.”

Clinical Trials Out Invokana
The two clinical trials the FDA relied on in requiring new Invokana label warnings were the  CANVAS (Canagliflozin Cardiovascular Assessment Study) and CANVAS-R (A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus).

The FDA also announced in the May 16, 2017 Drug Safety Communication that it was “requiring new warnings, including our most prominent Boxed Warning, to be added to the canagliflozin drug labels to describe this risk.”  The “Boxed Warning,” also known as a “Black Box Warning,” was added in the United States to the Invokana label/package insert on July 25, 2017.  It states:

WARNING: LOWER LIMB AMPUTATION
See full prescribing information for complete boxed warning.

In patients with type 2 diabetes who have established cardiovascular disease (CVD) or at risk for CVD, INVOKANA has been associated with lower limb amputations, most frequently of the toe and midfoot; some also involved the leg (5.1)
Before initiating, consider factors that may increase the risk of amputation. Monitor patients receiving INVOKANA for infections or ulcers of the lower limbs, and discontinue if these occur. (5.1)

The EMA commendably notified people promptly about the potential for an increased risk of lower limb amputations with the use of any SGLT2 inhibitor before the final CANVAS and CANVAS-R study results were published. The FDA also acted swiftly in requiring a label change after the publication of the final results from the two clinical trials that “showed that leg and foot amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with placebo, which is an inactive treatment.”

The FDA also noted that the risk of leg and foot amputations may be even higher for some people, “including those who have peripheral vascular disease, neuropathy (nerve damage), or diabetic foot ulcers (sores), or who have a history of prior amputation.”

Invokana / Invokamet Lawsuit
Invokana and Invokamet appear to double the risk of lower limb amputations.  Anyone suffering the tragic loss of toes or a foot or limb as the result of using a dangerous drug is deserving of financial compensation, in our view.  Our law firm exists to seek justice for those injured by dangerous drugs and medical devices.  If you or someone you love lost a limb following use of Invokana, Invokamet or some other SGLT2 inhibitor used for type 2 diabetes, contact us for a free legal consultation in a potential lawsuit.

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Invokana Dangers seen Early

Invokana dangers were seen early on by researchers. FDA reviewers were divided over the safety and effectiveness of Invokana before approving it for the market in 2013. At that time, the agency acted against the advice of prominent physicians and researchers in approving the drug for the treatment of Type-2 Diabetes. Since then, Invokana label warnings have been adjusted twice, so far, to reflect Invokana’s dangers.

Invokana Warnings
The Invokana label was first updated in 2015 to reflect Invokana’s propensity to increase the risk of ketoacidosis and possibly heart attacks.

What is (Diabetic) Ketoacidosis?
Diabetic ketoacidosis (DKA) is a dangerous rise in blood acidity. This life-threatening condition develops when the body’s cells can’t get the sugar (glucose) they need for energy due to insulin shortage. When sugar can’t enter cells, it stays in the blood. The kidneys filter some of the sugar from the blood and remove it from the body through urine. When cells cannot receive sugar for energy, the body starts to break down fat and muscle for it. This process causes ketones – or fatty acids – to form and enter the bloodstream. This triggers a chemical imbalance (metabolic acidosis) called diabetic ketoacidosis, which can cause coma and even death.

Invokana Heart Attack Links
Another apparent problem with Invokana is its link to heart attacks (myocardial infarction) of which both the drug’s maker – Janssen (of Johnson & Johnson) – and the FDA were aware.

FDA Invokana Fail
A January 2013 meeting occurred between the FDA Endocrinologic and Metabolic Drugs Advisory Committee (EMDA) and representatives of Janssen Pharmaceuticals (drug maker Mitsubishi Tanabe’s U.S. marketing partner). Janssen gave several presentations on the growth of Type 2 diabetes among the population and pushed the need for effective treatments (of the patent medicine, chemical kind, of course). The drug maker also promoted the wonders of its latest product, Invokana. During the question-and-answer session which followed, Dr. Sidney Wolfe – co-founder and director of Public Citizen’s Health Research Group – raised several questions. He pointed out that Janssen’s request for FDA approval was “based solely on surrogate efficacy of HbA1c lowering.” This is a measure of how well a patient’s blood sugar is controlled.

Invokana Dangers seen Early
Dr. Sidney Wolfe said that as with all recently approved Type 2 diabetic drugs, there was no evidence of any improved clinical outcomes, contrary to an older diabetes drug such as metformin. He said that this “surrogate efficacy needs to be balanced against a number of serious safety signals” seen in the clinical trials.

Dr. Wolfe’s primary concern was “thrombotic events” (blood clots) that could lead to heart attacks. He pointed out that in the studies presented, thirteen people on Invokana suffered “cardiovascular events.” Using available data from a related drug of the gliflozin class, Farxiga (dapagliflozin), Dr. Wolfe demonstrated that the risks for Invokana heart attack would be significantly greater: He said, “There is much more of an increase in hematocrit in the people getting canagliflozin [Invokana], 1.5 times as much as the dapa [gliflozin] group.”

Hematocrit refers to the concentration of red blood cells, which is increased by gliflozin drug’s mechanism of action. Normal concentration is 40% for women and 45% for men. Levels higher than that increase the likelihood that a person will develop a blood clot, causing a stroke or heart attack. According to Dr. Wolfe, at least 25% of patients on Invokana would wind up with a red blood cell concentration of 47%, which he described as “a very dangerous range.”

Additionally, FDA Reviewer Dr. Hyon Kwon testified at the committee hearing that there was “an imbalance in early cardiovascular events” observed in the CANVAS trial, a 4,300-subject study assessing the cardiovascular effects of Invokana. When FDA Biostatistician Dr. Mat Soukop testified, it became apparent how profound this “imbalance” is. Dr. Soukop testified that, in the first 30 days of use, Invokana had a cardiovascular events “Hazard Ratio” of 6.9; that is, patients who were taking Invokana had a 690% higher likelihood of suffering a cardiovascular event than the patients who were taking a placebo.

With Dr. Wolfe’s expert testimony and the FDA’s own biostatistical analysis, one might assume Janssen and Mitsubishi Tanabe would have been ordered to conduct more studies before FDA would approve the drug to be administered to patients in the United States. The FDA, by contrast, gave approval for sales of Invokana, on the condition that Janssen monitor it for adverse events. The company was also ordered to conduct a “post-market” double-blind study to determine how many patients actually experienced Invokana heart attacks. The FDA gave Johnson & Johnson’s subsidiary four years to do so.

FDA Ignores Physician/Researcher’s Analysis
The official position of the FDA is that such decisions are based on analyses of risks versus benefits. But FDA simply ignored the advice of prominent physicians and researchers who clearly showed that Invokana offered “no evidence of any improved clinical outcomes.”

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•   Invokana Lawsuit Attorney
•   Invokana Dangers seen Early

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Invokana Amputation Warning

An Invokana amputation warning will be added to the Invokana label. On May 16, 2017, the U.S. FDA confirmed that this black-box warning must be included in the Invokana label. The revised label will state that Invokana raises the risk of people needing to have their legs or feet amputated.  A black box warning is the strongest label warning in the FDA’s rusty tool box.(It habitually comes too late for many. How do dangerous drugs like this ever get FDA approval in the first place? Could the agency be compromised by the drug industry with which it works so closely?)

Related: Invokana Lawsuit

The FDA first sent out an alert May 18, 2016, which said patients in Invokana clinical trials were twice as likely to need amputations as those on a placebo. On May 16, 2017, the FDA issued the final results from those two clinical trials. Those dire results triggered the new warning label.

Invokana / Invokamet / Canagliflozin
Invokana, Invokamet and Invokamet XR are brand names for canagliflozin, which is used to treat Type 2 diabetes. Janssen Pharmaceuticals, a division of baby-powder-beleaguered Johnson & Johnson, makes and markets Invokana (Canagliflozin).

Invokana Clinical Trials show Double Risk of Amputations
In the first clinical trial – CANVAS – 5.9 of 1,000 patients on the drug needed an amputation in a year, vs. the placebo totals of 2.8 of 1,000. In the second trial – CANVAS-R – 7.5 of 1,000 patients needed amputation compared with 4.2 of 1,000 on the placebo.

Most of the amputations were of the foot or a toe, said FDA, while others lost legs. Some patients needed more than one amputation.

FDA Safety Communication
The FDA said in a safety communication: “Patients taking canagliflozin should notify your health care professionals right away if you develop new pain or tenderness, sores or ulcers, or infections in your legs or feet. Talk to your healthcare professional if you have questions or concerns.”

FDA also cautioned Invokana users not to stop taking the medication without first speaking with a “health care professional.”

Janssen Speaks
A Janssen spokesmodel, William Foster, said, “At Janssen, patient safety is our highest priority. (We) are working with FDA to include (this) in the prescribing information for canagliflozin and look forward to the presentation of the full CANVAS Program results at the American Diabetes Association Scientific Sessions in June.”

Invokana Amputation Warning

Invokana (canagliflozin) was approved despite concerns about cardiovascular health and bone safety. The FDA has since updated the drug’s labels to reflect risks of bone fractures, blood disorders, and urinary tract infections.

SGLT2 Inhibitors
Other drug makers and drugs in Invokana’s class of sodium-glucose cotransporter 2 (or SGLT2) inhibitors include:

•  AstraZeneca PLC – Farxiga and Xigduo XR

•  Boehringer Ingelheim – GmbH

•  Eli Lilly and Co. – Jardiance and Glyxambi

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FDA Invokana Reviewers’ Tepid Approval

FDA reviewers  Invokana Lawsuitexpressed concern over the safety and efficacy of Invokana before voting to approve it for sale. In fact, just 67% of them decided that letting Invokana hit the market was a good thing. An FDA committee met on January 10, 2013 to assess Invokana and determine whether it made sense to let Johnson & Johnson’s Jannsen Pharmaceuticals market it for help with diabetes.

FDA Reviewers Vote 8-7 and 10-5

An FDA committee of 15 people discussed new drug application (NDA) 204042 for canagliflozin tablets, or Invokana. It was submitted by Janssen Research and Development, LLC. A member of the sodium-glucose co-transporter 2 (SGLT2) inhibitors, Canagliflozin was, said FDA, developed to improve glycemic control in adults with type 2 diabetes mellitus.

The FDA report of the January 10, 2013 meeting says, “The committee members generally agreed that the benefit-risk profile of canagliflozin in patients with type 2 diabetes and moderate renal impairment should be considered differently from the general population. The committee members expressed concern about usage in these patients, owing to a decreased efficacy, especially when combined with an increased incidence of side effects. The committee members further discussed a discomfort with the relatively small volume of data to support use in this population (emphasis ours). (One) committee member also mentioned a concern over the cardiovascular risks of the drug, given an existing elevated cardiovascular risk in patients with renal impairment.”

The 15 committee members were asked to vote on two important questions to determine whether Invokana were worthy of market approval.

Tiny Approval Margin

The first question J&J fails its Credo with Pelvic Meshput before the committee was: “Based on the data submitted and considering the points of discussion in question 3 [which involved Invokana cardiovascular risk], do you have any concern regarding a conclusion that a risk margin of 1.8 has been excluded for canagliflozin?”

The 15 members voted 8-7 to say that the drug passed an acceptable risk measure. That razor-thin margin can hardly be called a vote of confidence in the drug’s safety profile.

The next question put before the committee was all important: “Based on the information included in the briefing materials and presentations today, has the applicant provided sufficient efficacy and safety data to support marketing of canagliflozin for the treatment of Type 2 diabetes mellitus? The committee voted 10-5 on that question, better than 8-7 but once again hardly a ringing vote of confidence in the new drug.

Unknown Cardiovascular Risks
The FDA reviewer taking the minutes of the meeting cautioned that, “The committee members who voted ‘no’ cited similar concerns over unknown cardiovascular risk and usage in moderate renal impairment, which were frequently stated as overriding concerns (emphasis ours). One committee member who voted ‘no’ expressed comfort with the benefit-risk profile in combination therapy, but described a lack of comfort with usage as monotherapy since the drug had not been compared against metformin, which is the standard initial therapy in Type 2 diabetes. An additional committee member voiced concerns over the potential for renal damage, (emphasis ours) and suggested a possibility of prolonging hypoglycemia in the elderly.”

FDA Invokana Reviewers’ Tepid Approval

With such tepid Janssen_logo-JnJapproval, and now with the risk of ketoacidosis made much more clear with strengthened FDA Warnings for Invokana and Ketoacidosis, it is difficult to see why such a drug ever made it to the market in the first place. Not surprisingly, problems with Invokana and its link with ketoacidosis began to show up almost immediately after the drug’s approval.

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Invokana Warnings FDA Strengthened

Invokana warnings Invokana-197x300were strengthened by FDA June 14, 2016. The announcement topped the existing FDA warning made May 18, 2016. The agency wrote that recent reports prompted it to revise the warnings on Invokana’s label to include information about acute kidney injury. FDA also said that it added recommendations to minimize the risk of acute kidney injury from the type 2 diabetes medicines. In addition to Invokana, drugs included in the warning include Invokamet and Dapagliflozin (Farxiga, Xigduo XR).

Type 2 Diabetes Medications

Canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR) are prescription medicines used to help lower blood sugar in adults with type 2 diabetes. These drugs belong to a class called sodium-glucose cotransporter-2 (SGLT2) inhibitors. Canagliflozin and dapagliflozin lower blood sugar by causing kidneys to remove sugar through the urine.

FDA said in the June 2016 announcement that from canagliflozin’s approval in March 2013 through October 2015, it had received 101 confirmable case reports of acute kidney injury. Some required hospitalization and dialysis, with canagliflozin or dapagliflozin use. That number includes only reports submitted to FDA; the agency says there are likely additional cases not reported. (In point of fact, it is generally known that only some 10 percent of adverse drug reactions are reported to the FDA.)

Invokana Warnings FDA Strengthened

The FDA recommended that health care professionals consider factors that may predispose people to acute kidney injury before starting those people on canagliflozin or dapagliflozin. The agency said factors that may predispose people to kidney injury include “decreased blood volume; chronic kidney insufficiency; congestive heart failure; and taking other medications such as diuretics, blood pressure medicines called angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs), and nonsteroidal anti-inflammatory drugs (NSAIDs).” The agency recommends assessing kidney function before beginning canagliflozin or dapagliflozin, and monitoring the patient periodically thereafter. FDA also said, “If acute kidney injury occurs, promptly discontinue the drug and treat the kidney impairment.”
Acute Kidney Injury

Acute kidney injury occurs when the kidneys quit working, which causes dangerous wastes to build in the body. Signs and symptoms of acute kidney injury can include low urine output, or swollen legs or feet. FDA cautioned that people should not quit their medicine without first consulting health care professionals. Stopping medication can trigger harmful, uncontrolled blood sugar levels.

Invokana Adverse Events

FDA requests that healthcare professionals and patients report adverse events or side effects related to the use of these drugs. Reports can be made to FDA’s MedWatch Safety Information and Adverse Event Reporting Program.

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