PRAC concludes that diabetes medicine canagliflozin may contribute to risk of toe amputation
Risk may also apply to other medicines in the same class
EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is warning that an increase in cases of lower limb amputation (mostly affecting the toes) has been observed in patients taking the type 2 diabetes medicine canagliflozin compared with those taking placebo (a dummy treatment) in two clinical trials, CANVAS and CANVAS-R. The studies, which are still ongoing, involved patients at high risk of heart problems.
Patients with diabetes (especially those with poorly controlled diabetes and pre-existing problems with the heart and blood vessels) are at increased risk of infection and ulcers (sores) which can lead to amputations. The mechanism by which canagliflozin may increase the risk of amputation is still unclear.
An increased risk has not been seen in studies with other medicines in the same class, dapagliflozin and empagliflozin. However, data available to date are limited and the risk may also apply to these other medicines.
Further data are expected from ongoing studies with canagliflozin, dapagliflozin and empagliflozin.
On the basis of the available data, the PRAC recommends that a warning on the risk of lower limb amputation (mostly affecting the toes) should be included in the prescribing information for these medicines, highlighting the importance of routine preventative foot care.
For canagliflozin, lower limb amputation should be listed as an uncommon side effect (occurring in between 1 and 10 patients in 1,000). Doctors should consider stopping treatment with canagliflozin if patients develop significant foot complications such as infection or skin ulcers.
The PRAC recommendation will now be sent to EMA’s Committee for Medicinal Products for Human Use (CHMP) for the adoption of EMA’s final opinion. Further details and advice for patients and healthcare professionals will be published at the time of the CHMP opinion.