United Kingdom’s and European Union’s Drug Agencies Call for Increased Amputation Warnings for Invokana
The Medicines and Healthcare products Regulatory Agency (MHRA), which regulates drugs and devices in the United Kingdom—similar to the U.S. Food and Drug Administration (FDA) in the United States—just updated its advice regarding increased risks of lower limb amputation associated with the Type 2 diabetes drug. Invokana (canaglifozin), The Pharmaceutical Journal reported.
UK’s move follows a recommendation from the European Medicines Agency (EMA)—the agency that evaluates drug products for use in Europe—that a warning concerning potential risks of toe amputation should be included on the prescribing information for canagliflozin and other sodium-glucose co-transporter 2 (SGLT2) inhibitor drugs, according to The Pharmaceutical Journal. In a March 22, 2017 drug safety update, the MHRA confirmed that canagliflozin’s prescribing information will also indicate lower limb amputation as an uncommon side effect occurring in less than 10 patients per 1,000.
The MHRA and EMA updates followed a review of information from two ongoing canagliflozin clinical trials, the Canagliflozin Cardiovascular Assessment Study (CANVAS) and A Study of the Effects of Canagliflozin on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus (CANVAS-R). The research reveals that the SCLT2 inhibitor potentially raises risks for lower limb amputation. According to the trial data the MHRA reviewed, six of 243 British patients involved in the trials underwent amputations. Once the European Commission (EU) approves it, the warning about an increased risk of amputation will be added to the summary of product characteristics and package leaflet for canagliflozin and for two other SGLT2 products: Farxiga (dapagliflozin) and Jardiance (empagliflozin). The changes were recommended by the EMA’s Committee for Medicinal Products for Human Use at its meeting February 23, 2017, The Pharmaceutical Journal reported.
Preliminary CANVAS study data revealed that the prevalence of lower limb amputations—which generally impacted toes—was seven in 1,000 patient years with Invokana (canagliflozin) 100mg daily and five in 1,000 patient-years with canagliflozin 300mg daily. The amputation rate was three in 1,000 patient-years for patients who were given a placebo. The CANVAS-R research found that the rate of lower limb amputation was eight in 1,000 patient-years with Invokana when compared to the four in 1,000 patient-years in the placebo group, The Pharmaceutical Journal wrote. The EMA noted that the preliminary data are not final given that the two studies remain ongoing and that “no imbalances were seen in other studies.”
The EMA noted that, in March 2016, the trials’ independent data monitoring committee—the committee has access to all so-called “unblended” outcome side effect data—recommended that the studies should continue and participants should be informed of the risk. The MHRA drug safety update indicates that evidence does not show an increased risk for dapagliflozin and empagliflozin; however, the risk may be a class effect, according to The Pharmaceutical Journal. Because of this, the MHRA advises healthcare professionals to monitor patients who are taking Invokana and who have risk factors for amputation, including poor control of diabetes and heart and blood vessels problems. Physicians are advised to consider stopping the drug if patients develop foot complications such as infection, skin ulcers, osteomyelitis (inflammation of bone caused by infection), or gangrene (tissue death caused by loss of blood supply; fingers, toes, and limbs are most often affected). Patients receiving any SGLT2 inhibitor should be advised of the importance of routine preventive foot care and adequate hydration.
SGLT2 inhibitor-containing medicines marketed in the UK include: Invokana (canagliflozin; Janssen), Vokanamet (canagliflozin and metformin; Janssen), Forxiga (dapagliflozin; AstraZeneca), Xigduo (dapagliflozin and metformin; AstraZeneca), Jardiance (empagliflozin; Boehringer Ingelheim), and Synjardy (empagliflozin and metformin; Boehringer Ingelheim), notes The Pharmaceutical Journal.
Parker Waichman LLP has decades of experience representing clients in product liability and personal injury litigation. The firm continues to offer free legal consultations to individuals with questions about filing an Invokana amputation lawsuit.
U.S. Federal Agency Increases Amputation Risk Warnings Associated with Invokana, Invokamet
The U.S. Food and Drug Administration (FDA) recently placed its most serious boxed warning, also known as a “black box” warning, on Invokana, Invokamet, and Invokamet XR. The agency confirmed in safety announcement issued May 16, 2017 that the three drugs cause an increased risk of leg and foot amputations. The announcement and boxed warning were based on data from the two large clinical trials—CANVAS and CANVAS-R.
The FDA reviewed data from the two studies prior to placing the black box warning on the drugs. Federal regulators revealed that patients taking canagliflozin experience a two-fold risk of leg and foot amputations compared to individuals taking a placebo. In the CANVAS trial, the risk of amputation in patients taking canaglifozin over a one-year period was equivalent to 5.9 out of every 1,000 patients; the risk was 2.8 out of every 1,000 patients who were given a placebo.
The FDA advises Invokana and Invokamet users to speak to their doctors immediately should they develop new pain or tenderness, sores or ulcers, or infections of the legs or feet—patients should not stop taking their diabetes medication without first speaking to their healthcare professional.
Regulators in the U.S. also noted that lower limb infections, gangrene, diabetic foot ulcers, and ischemia (inadequate blood supply to an organ or part of the body) typically preceded amputations. Patients were likelier to undergo amputations if they underwent a prior amputation. The agency announcement was an update from last May, when the FDA indicated that interim data suggested an increased risk of leg and foot amputations, mostly affecting the toes among Invokana and Invokamet users.
SGLT2 inhibitors stimulate the kidneys to remove sugar from the body through the urine, lowering blood sugar in patients diagnosed with Type 2 diabetes. The drugs are meant to be used along with with diet and exercise. According to the FDA, other side effects tied to Invokana include low blood pressure, ketoacidosis, kidney problems, high blood potassium, serious urinary tract infections, low blood sugar when taken with other diabetes drugs, bone breaks and increased cholesterol.
The FDA updated the warning on Invokana and other SGLT2 inhibitors in May 2015 to warn about the risk of ketoacidosis. Symptoms of ketoacidosis include abdominal pain, confusion, difficulty breathing, nausea, unusual fatigue or sleepiness, and vomiting. In June 2016, the FDA increased its warning on Invokana and other SGLT inhibitors to warn about the risk of acute kidney injury, in which the kidneys suddenly stop working.
Filing an Invokana Side Effects Lawsuit
Parker Waichman has years of experience representing clients in medical device and drug injury lawsuits. If you or someone you know is interested in filing an Invokana lawsuit, contact one of our experienced defective drug lawyers today. Our firm offers free, no-obligation case evaluations. For more information, fill out our online form or call 1-800-YOURLAWYER (1-800-968-7529).