Xigduo XR Lawsuit
Update: Xigduo XR Litigation Centralized in New York
April 13, 2017 – The U.S. Judicial Panel on Multidistrict Litigation (JPML) has ordered that all federal lawsuits involving Farxiga and Xigduo XR be centralized for pretrial handling in the Southern District of New York. JPML agreed that the actions share factual questions arising from the allegations, thus implicating numerous common issues concerning the development, manufacture, testing, regulatory history, promotion, and labeling of Farxiga and Xigduo XR.
What’s the Problem?
Side effects of the type 2 diabetes medication Xigduo XR may include diabetic ketoacidosis (DKA), kidney failure, heart attack, stroke and more.
What is Xigduo XR?
Xigduo XR (generic: dapagliflozin and metformin HCl) is a prescription sodium-glucose cotransporter-2 (SGLT2) inhibitor used to improve glycemic control in adults with type 2 diabetes mellitus. Dapagliflozin works by helping the kidneys remove glucose from the blood, and metformin lowers glucose production in the liver and causes the intestines to absorb less glucose. Xigduo XR is manufactured by AstraZeneca, and was approved by the FDA in October 2014.
FDA Warning on Ketoacidosis Risk with SGLT2 Inhibitors
In May 2015, FDA issued a warning about an increased risk of diabetic ketoacidosis with SGLT2 inhibitor diabetes drugs. FDA’s Adverse Event Reporting System (FAERS) found at least 20 reports of ketoacidosis in patients treated with the medications from March 2013 to June 6, 2014. As a result of these problems, FDA in December 2015 updated the labeling of all SGLT2 inhibitors to include a warning about diabetic ketoacidosis.
Symptoms of diabetic ketoacidosis often develop quickly, sometimes within 24 hours. For some patients, these signs may be the first indication of type 2 diabetes. Symptoms may include:
- Excessive thirst
- Frequent urination
- Nausea and vomiting
- Abdominal pain
- Weakness or fatigue
- Shortness of breath
- Fruity-scented breath
Most patients with diabetic ketoacidosis will require treatment in a hospital. Insulin will be administered through an IV to bring ketone levels down and provide hydrating fluids that help bring your blood chemistry back into balance. Ketoacidosis is a serious medical condition which can cause diabetic coma and even death if not treated.
New Reports of Xigduo XR Ketoacidosis
According to a QuarterWatch report issued by the Institute for Safe Medication Practices (ISMP) on January 13, 2016, at least 80 cases of ketoacidosis were associated with dapagliflozin in the 12-month period ending June 30, 2015. Experts believe the actual number of incidences may be much higher, as many adverse events associated with a drug often go unreported.
FDA in June 2014 required the labeling of Xigduo XR, Invokana, Invokamet and Farxiga to carry stronger warnings about an increased risk of acute kidney complications associated with the drugs. The label change was prompted by FDA’s review of at least 101 reports of acute kidney injury in type 2 diabetes patients treated with the SGLT2 inhibitors between March 2013 and October 2015.
Xigduo XR Side Effects
Serious side effects of Xigduo XR may include:
- Diabetic Ketoacidosis (DKA, Diabetic Acidosis, Metabolic Acidosis, Ketoacidosis)
- Heart Attack (Myocardial Infarction or MI)
- Kidney Failure (Renal Failure)
- Kidney Cancer
- Kidney Infections (Pyelonephritis)
- Kidney Stones
- Bone Fractures
- Bone Abnormalities
- Testicular Cancer
- Urinary Tract Infections (UTIs)
- Lactic Acidosis
- Severe Dehydration / Fluid Imbalance
- Abnormal Weight Loss
- Hypersensitivity (Allergic Response)
- Blood Infections (Urosepsis)
- Fungal Infections
Black Box Warning
Because it contains metformin, Xigduo XR may increase the risk of lactic acidosis, which is caused by the buildup of lactic acid in the body. The condition occurs when cells make lactic acid (from glucose) faster than it can be metabolized. Xigduo XR labels contain a black box warning about the risk of lactic acidosis.
Xigduo XR Timeline
Oct 2014 – Approved by the FDA
October 30, 2014 – Xigduo XR approved by the FDA.
May 2015 – FDA warning
May 5, 2015 – FDA warns of an increased risk of diabetic ketoacidosis with SGLT2 inhibitor diabetes drugs.
Dec 2015 – SGLT2 inhibitor labels updated
December 4, 2015 – SGLT2 inhibitor labels updated to include warnings about too much acid in the blood and serious urinary tract infections (UTIs).
Jun 2016 – FDA label requirement
June 2016 – FDA requires Xigduo XR labels to carry a ‘Black Box’ warning about an increased risk of lactic acidosis which have “resulted in death, hypothermia, hypotension, and resistant bradyarrhythmias.”
Jun 2016 – FDA strengthens existing warnings
June 14, 2016 – FDA strengthens existing warnings about an increased risk of acute kidney injury with dapagliflozin (Xigduo XR, Farxiga) and canagliflozin (Invokana, Invokamet).
- “FDA 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 & Drug Administration (FDA). May 15, 2015.
- “Diseases and Conditions: Diabetic Ketoacidosis”. Mayo Clinic. August 21, 2015.
- “SGLT2 Inhibitors: Drug Safety Communication – Labels to Include Warnings About Too Much Acid in the Blood and Serious Urinary Tract Infections”. U.S. Food & Drug Administration (FDA). December 4, 2015.
- “ISMP QuarterWatch Report”. Institute for Safe Medication Practices (ISMP). January 13, 2016.
- “Xigduo XR (dapagliflozin and metformin HCl extended-release) Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)”. U.S. Food & Drug Administration (FDA). June 2016.
- “FDA Drug Safety Communication: FDA strengthens kidney warnings for diabetes medicines canagliflozin (Invokana, Invokamet) and dapagliflozin (Farxiga, Xigduo XR)”. U.S. Food & Drug Administration (FDA). June 14, 2016.
- “Canagliflozin (Invokana, Invokamet) and Dapagliflozin (Farxiga, Xigduo XR): Drug Safety Communication – Strengthened Kidney Warnings”. U.S. Food & Drug Administration (FDA). June 14, 2016.
- “Xigduo XR Approval History”. Drugs.com.