FDA Adds Boxed Warning to Canagliflozin Due To Increased Leg and Foot Amputation Risk

Canagliflozin use is associated with increased risk of toe, foot, and leg amputations.
Canagliflozin use is associated with increased risk of toe, foot, and leg amputations.

Data from 2 large clinical trials have confirmed that treatment of type 2 diabetes with canagliflozin (Invokana®, Invokamet®, and Invokamet XR®; Janssen Pharmaceuticals, Inc.) may lead to an increased risk of leg and foot amputations, according to a US Food and Drug Administration (FDA) Drug Safety Communication.1

The announcement — an update to a similar communication issued in May 20162 — cites data from CANVAS (Canagliflozin Cardiovascular Assessment Study; ClinicalTrials.gov identifier NCT01032629) and CANVAS-R (A Study of the Effects of Canagliflozin [JNJ-28431754] on Renal Endpoints in Adult Participants With Type 2 Diabetes Mellitus; ClinicalTrials.gov identifier NCT01989754), which found that leg and foot amputations occurred “about twice as often in patients treated with canagliflozin compared to patients treated with placebo,” according to the FDA announcement.

Over one year, amputation risk for patients in CANVAS and CANVAS-R was equivalent to 5.9 and 7.5 out of every 1000 patients treated with canagliflozin, respectively, compared with 2.8 and 4.2 out of every 1000 patients treated with placebo. The most common amputations resulting from canagliflozin therapy were of the toe and middle of the foot, although above-knee and below-knee leg amputations were also reported.

As a result, the FDA will require canagliflozin drug labels to include prominent boxed warnings describing the risk to patients.

Health care professionals and patients are advised to report adverse effects and serious issues resulting from canagliflozin use to the FDA MedWatch program

Reference

  1. FDA Drug Safety Communication: FDA confirms increased risk of leg and foot amputations with the diabetes medicine canagliflozin (Invokana, Invokamet, Invokamet XR). Silver Spring, MD: US Food and Drug Administration. https://www.fda.gov/Drugs/DrugSafety/ucm557507.htm. Published May 16, 2017. Accessed May 16, 2017.
  2. FDA Drug Safety Communication: 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. Silver Spring, MD: US Food and Drug Administration. https://www.fda.gov/Drugs/DrugSafety/ucm500965.htm. Published May 18, 2016. Accessed May 16, 2017.
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