Federal Court Establishes MDL 2776 for Farxiga and Xigduo Diabetes Drugs

The Judicial Panel on Multidistrict Litigation established MDL No. 2776 in New York to hear claims of diabetic ketoacidosis and kidney damage caused by the Farxiga and Xigduo diabetes drugs.

The defendants in In Re: Farxiga (Dapagliflozin) Products Liability Litigation are Bristol-Myers Squibb Co., AstraZeneca Pharmaceuticals LP, AstraZeneca LP, AstraZeneca PLC, and AstraZeneca AB. There are 18 actions that involve allegations that ingestion of the drug Farxiga may cause a variety of injuries, including diabetic ketoacidosis and kidney damage.

The JPMDL assigned the cases to Judge Lorna G. Schofield of the Southern District of New York. She is already presiding over 13 constituent and tag-along actions pending in the district

Farxiga and its sister drug Xigduo XR belong to a class of diabetes drugs known as Sodium Glucose Cotransporter 1 2 (SGLT2) inhibitors. Other SLGT2 inhibitors include Invokana (canagliflozin) and Jardiance (empagliflozin). The actions share factual questions arising from allegations that taking Farxiga or Xigduo XR may result in patients suffering kidney-related injuries, such as diabetic ketoacidosis and kidney damage. The actions thus implicate many common issues concerning the development, manufacture, testing, regulatory history, promotion, and labeling of the drugs.

As a result of ingesting Farxiga, the plaintiffs have suffered sudden onset of life-threatening diabetic ketoacidosis (often in the setting of normal blood glucose levels), and/or acute renal failure, and/or pyelonephritis (kidney infection) and/or urosepsis and continue to suffer from the sequelae of these injuries. Farxiga (dapagliflozin) is a pharmaceutical drug used to treat Type 2 Diabetes. All of these injuries were the subject of recent FDA safety advisories.

On January 8, 2014, the FDA approved Farxiga for use in treatment of type 2 diabetics.2 Farxiga is a part of the gliflozin drug class. The gliflozin class is referred to generally as SGLT2 (short for “Sodium Glucose Cotransporter 2”) inhibitors. Xigduo XR was (dapagliflozin combined with metformin) designed and made by the same defendants as Farxiga, and is an extension of the Farxiga product line. Xigduo XR was approved shortly after Farxiga, on October 29, 2014.

FDA safety warning

On December 4, 2015 the FDA issued a safety communication disclosing they had found 73 adverse events reported between March 2013 and May 2015 that required hospitalization due to ketoacidosis-related to SGLT2 inhibitors. The FDA noted adverse event reports “include only reports submitted to FDA, so there are likely additional cases about which we are unaware.”

The same safety communication also warned of “life-threatening blood infections (urosepsis) and kidney infections (pyelonephritis). In light of the data disclosed in the December 4, 2015 safety communication, the FDA changed the label for Farxiga and Xigduo XR to include a warning “about the risks of too much acid in the blood” and urged patients taking SGLT2 inhibitors to stop taking the drug and seek immediate medical attention if they have any symptoms of ketoacidosis. The FDA also required a label change to warn of urosepsis and pyelonephritis. On June 14, 2016, the FDA issued a safety announcement which advised that the existing warning about the risk of acute kidney injury on the Farxiga and Xigduo labels would be strengthened.

 

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Judge Rules that Invokana Litigation Should Stay in Federal Court

invokana-warning kidney-damage
US District Judge Mitchell Goldberg ruled that the federal court will retain jurisdiction over 106 Invokana lawsuits that were filed last year in the Philadelphia Court of Common Pleas.

The ruling did not address whether the 106 cases will remain in US District Court for Eastern District of Pennsylvania or be rolled into MDL 2750 for Invokana (Canagliflozin) Products Liability Litigation in New Jersey.

Invokana is a prescription drug used to treat Type 2 Diabetes. Plaintiffs describe a variety of ailments, including kidney failure and diabetic ketoacidosis. The case is Arthur Portnoff v. Janssen Pharmaceuticals, Inc., Case No. 16-5955.

Class Action Fairness Act

Defendants removed all 106 cases to US District Court on Nov. 9, 2016, asserting federal jurisdiction as a “mass action” pursuant to the Class Action Fairness Act (“CAFA”). The plaintiffs contested removal and filed a motion to remand arguing that Defendants’ attempt to remove those cases was untimely, and that the federal Court lacked jurisdiction under CAFA.

To remove a mass action under CAFA, there must be 100 or more plaintiffs. The initial consolidation petition was filed on September 23, 2016, but was later withdrawn on October 11, 2016. On the same day, a second petition was filed.

The plaintiffs argued unsuccessfully that a 30-day time clock started running on Sept. 23. But Judge Goldberg ruled that the first petition was “legally inoperable.” The defendants filed within the time limit starting from the Oct. 11 petition.

The plaintiffs also argued that the Second Petition contemplated consolidation for pretrial proceedings only and that the single mention of a joint trial in the Second Petition’s conclusion was a “scrivener’s error.” Plaintiff’s counsel explained that she used a previously filed petition as a template for the Second Petition and that the proposal for a joint trial contained therein was a scrivener’s error.

However, 5 other plaintiff lawyers approved the document and failed to comment on the scrivener’s error, undermining their argument.

“So long as CAFA’s other jurisdictional requirements are met, federal district courts have jurisdiction over: any civil action . . . in which monetary relief claims of 100 or more persons are proposed to be tried jointly on the ground that the plaintiffs’ claims involve common questions of law or fact, except that jurisdiction shall exist only over those plaintiffs whose claims in a mass action satisfy the jurisdictional amount requirements . . . .,” the court said.

 

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Health Canada Warns of Diabetic Ketoacidosis from Invokana Diabetes Drug

invokana-warning kidney-damageHealth Canada, the country’s equivalent of the US Food and Drug Administration, warned healthcare professionals about the risk of diabetic ketoacidosis caused by SGLT2 Inhibitors, including Invokana, (canagliflozin), Farxiga (dapagliflozin), Xigduo (dapagliflozin/metformin), and Jardiance (empagliflozin).

The leading case is Arthur Portnoff V. Janssen Pharmaceuticals, Inc., Janssen Research and Development, LLC, Johnson & Johnson Co., and Mitsubishi Tanabe Pharma Corp., Case ID: 151200653, filed In the Philadelphia Court of Common Pleas. For more info read:

FDA strengthens kidney warnings for diabetes medicines Invokana, Invokamet, Farxiga and Xigduo XR

The warning was issued to healthcare professionals including internal medicine specialists, endocrinologists, cardiologists, nephrologists, general or family practitioners, emergency healthcare professionals, critical care physicians, certified diabetes educators and pharmacists.

Key messages

  • Serious, sometimes life-threatening and fatal cases of diabetic ketoacidosis (DKA) have been reported in patients on sodium glucose co-transporter 2 (SGLT2) inhibitors for type 1 and type 2 diabetes.
  • In a number of these cases, the presentation of the condition was atypical with only moderately increased blood glucose levels observed.
  • SGLT2 inhibitors are NOT indicated for the treatment of type 1 diabetes mellitus and should not be used in type 1 diabetes.
  • It is recommended that:
    • if DKA is suspected or diagnosed, treatment with SGLT2 inhibitors should be discontinued immediately.
    • SGLT2 inhibitors should not be used in patients with a history of DKA.
    • in clinical situations known to predispose to ketoacidosis (e.g. major surgical procedures, serious infections and acute serious illness), consideration be given to temporarily discontinuing SGLT2 inhibitor therapy.
    • patients be informed of the signs and symptoms of DKA and be advised to immediately seek medical attention if they develop them.
    • caution be used before initiating SGLT2 inhibitor treatment in patients with risk factors for DKA.

A life-threatening condition

Clinical trial and post-market cases of DKA, a serious, life-threatening condition requiring urgent hospitalization have been reported in patients with type 1 and type 2 diabetes mellitus on SGLT2 inhibitor treatment.

In a number of these reports, the presentation of the condition was atypical with only moderately increased blood glucose levels observed. Such atypical presentation of DKA in patients with diabetes could delay diagnosis and treatment.

Products affected
Brand Name Medicinal Ingredients Manufacturer
INVOKANA® canagliflozin Janssen Inc.
FARXIGA® dapagliflozin AstraZeneca Canada Inc.
XIGDUO® dapagliflozin and metformin AstraZeneca Canada Inc.
JARDIANCE empagliflozin Boehringer Ingelheim (Canada) Ltd.

Background information

Sodium glucose co-transporter type 2 (SGLT2) inhibitors are a class of drugs indicated as oral antihyperglycemic agents for the treatment of patients with type 2 diabetes.

The underlying mechanism for SGLT2 inhibitor-associated ketoacidosis is not clearly established. DKA usually develops when insulin levels are too low to prevent ketoacid accumulation. DKA occurs most commonly in patients with type 1 diabetes and is usually accompanied by high blood glucose levels (>14 mmol/L). However, the cases referred to above also concern patients with type 2 diabetes and in a number of cases blood glucose levels were only slightly increased, in contrast to typical cases of DKA.

The majority of the patients described in the above reports required hospitalization. To date, many of them have occurred during the first 2 months of treatment.  In many cases, just before or at the same time as the ketoacidosis occurred, patients experienced dehydration, low food intake, weight loss, infection, surgery, vomiting, a decrease in their insulin dose or poor control of diabetes.

A substantial proportion of the cases concerned use of SGLT2 inhibitors in patients with type 1 diabetes. SGLT2 inhibitors are NOT indicated for treatment of type 1 diabetes mellitus.

Who is affected

Information for consumers

Diabetic ketoacidosis (DKA) is a serious complication of diabetes caused by low insulin levels. Rare cases of this condition, including life-threatening and fatal ones, have occurred in patients taking SGLT2 inhibitors [INVOKANA®(canagliflozin), FORXIGA® (dapagliflozin), XIGDUO® (dapagliflozin/metformin), JARDIANCETM (empagliflozin)] for type 1 and type 2 diabetes.

A number of these cases have been unusual, with patients having blood sugar levels that are not as high as typically expected in DKA, which can lead to a delay in diagnosis and treatment.

Patients taking any of these medicines should be aware of the symptoms of DKA, including loss of appetite, nausea or vomiting, stomach pain, feeling very thirsty, rapid breathing, confusion, feeling unusual tiredness, a sweet smell to the breath, a sweet or metallic taste in the mouth, or a different odour to urine or sweat.

Patients should immediately seek medical advice if they develop any of these symptoms. Patients should also inform their healthcare professional about medical issues or factors (see below) that may predispose them to ketoacidosis.

SGLT2 inhibitors are NOT indicated for treatment of type 1 diabetes mellitus and should not be used in type 1 diabetes.

Information for health care professionals

Before initiating treatment with SGLT2 inhibitors, factors in the patient history that may predispose to ketoacidosis should be considered. These factors include:

  • patients on a very low carbohydrate diet (as the combination may further increase ketone body production),
  • an acute serious illness,
  • pancreatic disorders suggesting insulin deficiency (e.g., type 1 diabetes, history of pancreatitis or pancreatic surgery),
  • sudden insulin dose reduction (including insulin pump failure),
  • alcohol abuse,
  • conditions that lead to severe dehydration,
  • hospitalization for major surgery or serious medical illness.

SGLT2 inhibitors should be used with caution in these patients. In addition, patients should be informed of these risk factors.

SGLT2 inhibitors should not be used in patients with a history of DKA.

A substantial proportion of the cases concerned off-label use in patients with type 1 diabetes. Prescribers are reminded that type 1 diabetes is NOT an approved indication for SGLT2 inhibitors.

Patients on SGLT2 inhibitors should be tested for ketones when they present with symptoms of acidosis in order to prevent delayed diagnosis and patient management.  If ketoacidosis is suspected, treatment with SGLT2 inhibitors should be discontinued.

Prescribers should inform patients of signs and symptoms of metabolic acidosis and advise them to immediately seek medical advice if they develop such signs and symptoms.

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