Johnson & Johnson — Vokanamet EMA EPAR variation assessment report (EMEA/H/C/002656, 2014)
Johnson & Johnson · 2014 · EMA EPAR variation assessment report · company profile →
Report summary
The EMA's PRAC assessed the risk of lower limb amputations with SGLT2 inhibitors, particularly canagliflozin, due to observed increases. Safety data from trials for canagliflozin, dapagliflozin, and empagliflozin were reviewed. The PRAC concluded that lower limb amputation is an identified risk for canagliflozin, with increased incidence (primarily toe amputations) noted in T2DM patients with cardiovascular risk. For dapagliflozin and empagliflozin, it's considered a potential class effect, though data are less conclusive. Consequently, product information for all three drugs was updated to include warnings about lower limb amputation risk, and enhanced pharmacovigilance was recommended.
Key findings — cited to the page
| Annualised incidence rate of amputations (placebo group) | 5 events per 1000 patient-years exposure | CANVAS-R · p.4 |
| Annualised incidence rate of amputations (canagliflozin group) | 7 events per 1000 patient-years exposure | CANVAS-R · p.4 |
| Death from cardiovascular causes (placebo) | 5.9 % | EMPA-REG · p.5 |
| Relative risk reduction for death from cardiovascular causes (empagliflozin vs placebo) | 38 % | EMPA-REG · p.5 |
| Death from cardiovascular causes (empagliflozin) | 3.7 % | EMPA-REG · p.5 |
| Hospitalization for heart failure (placebo) | 4.1 % | EMPA-REG · p.5 |
| Relative risk reduction for hospitalization for heart failure (empagliflozin vs placebo) | 35 % | EMPA-REG · p.5 |
| Death from any cause (empagliflozin) | 5.7 % | EMPA-REG · p.5 |
| Death from any cause (placebo) | 8.3 % | EMPA-REG · p.5 |
| Relative risk reduction for death from any cause (empagliflozin vs placebo) | 32 % | EMPA-REG · p.5 |
| Hospitalization for heart failure (empagliflozin) | 2.7 % | EMPA-REG · p.5 |
| Incidence of non-traumatic, lower-extremity amputations (canagliflozin 100 mg) | 3.3 % | CANVAS · p.6 |
Source: Johnson & Johnson ↗ · License: EMA - reuse permitted with acknowledgement. Summary and findings are extracted from the published document; every figure cites its page. Informational only — not investment advice. Explore the Metabolic library →