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  5. FDA Drug Safety Podcast: Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate
  1. FDA Drug Safety Podcasts

FDA Drug Safety Podcast: Interim clinical trial results find increased risk of leg and foot amputations, mostly affecting the toes, with the diabetes medicine canagliflozin (Invokana, Invokamet); FDA to investigate

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Welcome to FDA Drug Safety Podcasts for health care professionals. This is Lesley Navin Advanced Practice Nurse from the Division of Drug Information.

On May 18, 2016, FDA is alerting the public about interim safety results from an ongoing clinical trial that found an increase in leg and foot amputations, mostly affecting the toes, in patients treated with the diabetes medicine canagliflozin (brand names Invokana, Invokamet). We have not determined whether canagliflozin increases the risk of leg and foot amputations. We are currently investigating this new safety issue and will update the public when we have more information.

Health care professionals should follow the recommendations in the canagliflozin drug labels. Monitor patients and advise them to seek medical advice for any new pain or tenderness, sores or ulcers, or infections in the legs or feet. Canagliflozin is a sodium-glucose cotransporter-2 (SGLT2) inhibitor. It is available as a single-ingredient product under the brand name Invokana and also in combination with metformin under the brand name Invokamet.

In the ongoing Canagliflozin Cardiovascular Assessment Study (CANVAS) clinical trial, the trial’s independent data monitoring committee (IDMC) identified an increased risk of leg and foot amputations. The amputations occurred about twice as often in patients treated with canagliflozin compared to patients treated with placebo. An interim analysis showed that over a year’s time, the risks of amputation for patients in the trial were equivalent to:

  • 7 out of every 1,000 patients treated with 100 mg daily of canagliflozin
  • 5 out of every 1,000 patients treated with 300 mg daily of canagliflozin
  • 3 out of every 1,000 patients treated with placebo

Patients in the CANVAS trial have been followed for an average of 4.5 years to date. The IDMC has recommended, based on an overall assessment, that the CANVAS trial continue.

The IDMC has also reported that a second, similar trial evaluating canagliflozin, the CANVAS-R trial, has not shown the same risks of increased leg and foot amputations to date. Patients in the CANVAS-R trial have been followed for an average of 9 months.

We are continuing to evaluate this safety issue and will update the public when we have more information.

Side effects involving canagliflozin should be reported to FDA’s MedWatch program at www.fda.gov/medwatch.

A link to the full communication can be found at www.fda.gov/DrugSafetyCommunications. If you have drug questions, you can reach us at druginfo@fda.hhs.gov.

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