Increased Risk of Leg & Foot Amputations

FDA Issues MedWatch on Invokana

On May 16, 2017, the FDA had concluded that Invokana, a type 2 diabetes drug, causes an increased risk of leg and foot amputations. Because of the increased amputation risk, the FDA is requiring new warnings, including a box warning to be added to the drug’s packaging.

Based on new data from two large clinical trials, leg and foot amputations were twice s likely in patients treated with Invokana.  See the FDA Drug Safety Communication for additional information, including a data summary.

Facts About Canagliflozin (Invokana)

  • Canagliflozin is a prescription medicine that is used with diet and exercise to lower blood sugar in adults with type 2 diabetes. It belongs to a class of drugs called sodium-glucose cotransporter-2 (SGLT2) inhibitors.
  • Canagliflozin is available as a single-ingredient product under the brand name Invokana, and also in combination with the diabetes medicine metformin under the brand names Invokamet and Invokamet XR.
  • Canagliflozin lowers blood sugar by causing the kidneys to remove sugar from the body through the urine.
  • Other side effects of canagliflozin include low blood pressure, a condition of too much acid in the blood called ketoacidosis; kidney problems; a high amount of potassium in the blood; serious urinary tract infections; low blood sugar when combined with other prescription diabetes medicines; yeast infections; bone breaks; and increased cholesterol.

What Did The Clinical Trials Show?

Final results from two clinical trials – the CANVAS  and CANVAS-R  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 CANVAS trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to:

  • 5.9 out of every 1,000 patients treated with canagliflozin
  • 2.8 out of every 1,000 patients treated with placebo

The CANVAS-R trial showed that over a year’s time, the risk of amputation for patients in the trial were equivalent to:

  • 7.5 out of every 1,000 patients treated with canagliflozin
  • 4.2 out of every 1,000 patients treated with placebo

Amputations of the toe and middle of the foot were the most common; however, amputations involving the leg, below and above the knee, also occurred. Some patients had more than one amputation, some involving both limbs.

The Olinde Firm is currently accepting Invokana amputation cases in all 50 states. If you or somebody you know was injured by taking Invokana, you should contact our lawyers immediately for a free case consultation. Please use the form below to contact our Defective Medical Device Litigation Group or call toll free 24 hours a day at 1-800-587-1889.

If you or somebody you know was injured by taking Invokana, you us immediately for a free case consultation.

Clinical Trial

The following results are from the FDA’s website. You can read the entire article here.
An approximately two-fold increased risk of lower limb amputations associated with canagliflozin use was observed in two large, randomized, placebo-controlled trials evaluating patients with type 2 diabetes who had either established cardiovascular disease or were at risk for cardiovascular disease. These trials were 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). Patients in the CANVAS and CANVAS-R trials were followed for an average of 5.7 and 2.1 years, respectively.

In CANVAS, the risk of lower limb amputations was 5.9 amputations per 1,000 patients per year for canagliflozin compared to 2.8 amputations per 1,000 patients per year for placebo (Number Needed to Harm: 323). In CANVAS-R, the risk of lower limb amputations was 7.5 amputations per 1,000 patients per year for canagliflozin compared to 4.2 amputations per 1,000 patients per year for placebo (Number Needed to Harm: 270). The risk of lower limb amputations was observed at both the 100 mg and 300 mg doses. The amputation results for CANVAS and CANVAS-R are shown in Tables 1 and 2 below.

Overall, amputations of the toe and mid-foot were the most frequent (99 out of 140 patients with amputations receiving canagliflozin in the two trials); however, amputations involving the leg, below and above the knee, were also observed (41 out of 140 patients with amputations receiving canagliflozin in the two trials). Some patients had more than one amputation, some involving both limbs. Lower limb infections, gangrene, diabetic foot ulcers, and ischemia were the most common precipitating medical events leading to an amputation. The risk of amputation was highest in patients with a baseline history of prior amputation, peripheral vascular disease, and neuropathy.

Table 1. CANVAS Amputations

Placebo N=1,441Canagliflozin 100 mg N=1,445Canagliflozin 300 mg N=1,441Canagliflozin (pooled) N=2,886
Patients with an amputation, n (%)22 (1.5)50 (3.5)45 (3.1)95 (3.3)
Total amputations*338379162
Amputation incidence rate (per 1,000 patient-years)2.86.25.55.9
Hazard ratio (95% CI)2.24 (1.36, 3.69)2.01 (1.20, 3.34)2.12 (1.34, 3.38)

* Some patients had more than one amputation.

Table 2. CANVAS-R Amputations

Placebo
N=2,903
Canagliflozin 100 mg (with up-titration to 300 mg)
N=2,904
Patients with an amputation, n (%)25 (0.9)45 (1.5)
Total amputations*3659
Amputation incidence rate (per 1,000 patient-years)4.27.5
Hazard ratio (95% CI)1.80 (1.10, 2.93)

* Some patients had more than one amputation.

If you or somebody you know was injured by taking Invokana, you us immediately for a free case consultation.

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