The manufacturer of canagliflozin has written to healthcare professionals, in agreement with the European Medicines Agency, advising of an increased risk of lower limb amputations seen in the CANVAS study.
Canagliflozin (Invokana®, Vokanamet®) is licensed for the treatment of adults with type 2 diabetes mellitus to improve glycaemic control. The CANVAS study is a long-term study investigating cardiovascular outcomes. Adverse event monitoring in this study has observed a two-fold increase in the risk of a lower limb amputation, primarily the toe.
The risk rate in study participants taking canagliflozin is 6 lower limb amputations per 1,000 patient years compared to a risk of 3 per 1,000 patient years in patients taking placebo. No dose response had been noted.
Healthcare professionals are advised that:
- Routine preventative foot care management remains important
- Patients with other risk factors for amputation, such as peripheral vascular disease or peripheral neuropathy should be carefully monitored
- Consideration should be given to suspending treatment in patients who develop significant lower limb complications such as ulcers, osteomyelitis or gangrene
- Patients should be advised to maintain adequate hydration and monitored for signs or symptoms of volume depletion, especially those who are also taking diuretics
Regulatory agencies will continue to monitor and investigate this issue.
Action: Clinicians should be aware of this new safety information. Risk factors for amputation should be considered before starting new treatment and consideration given to stopping treatment if complications develop during treatment.