BACKGROUND: A generic formulation of amiodarone was recently approved by the Food and Drug Administration based on single-dose equivalence data. Because amiodarone has complex pharmacokinetic properties, a narrow therapeutic range, and a significant adverse effect profile, concern about equivalency persists. OBJECTIVE: To compare steady-state plasma concentrations of the brand-name reference product Cordarone with the AB-rated generic formulation, Pacerone, in patients exposed to both products. METHODS: A retrospective analysis was performed at the Minneapolis Veterans Affairs Medical Center on 138 patients who were taking a stable dose of amiodarone before and after an amiodarone generic product substitution. RESULTS: Seventy-seven patients had steady-state plasma concentrations documented for each product at the same dose. The mean steady-state plasma concentrations of amiodarone were not significantly different for Cordarone compared with Pacerone (1.07 +/- 0.48 vs. 1.19 +/- 0.66 micro g/mL, respectively); similarly, the concentrations of the active metabolite (desethylamiodarone) did not differ (0.95 +/- 0.30 vs. 0.96 +/- 0.49 micro g/mL, respectively). However, the variability in plasma drug concentrations between products was increased as compared to variability within each product. CONCLUSIONS: This study indicates that comparable steady-state concentrations can be achieved with a change in formulation from Cordarone to Pacerone. However, individual responses vary, suggesting that monitoring of plasma concentrations is prudent 1-3 months after any change from one product to another.
BACKGROUND: A generic formulation of amiodarone was recently approved by the Food and Drug Administration based on single-dose equivalence data. Because amiodarone has complex pharmacokinetic properties, a narrow therapeutic range, and a significant adverse effect profile, concern about equivalency persists. OBJECTIVE: To compare steady-state plasma concentrations of the brand-name reference product Cordarone with the AB-rated generic formulation, Pacerone, in patients exposed to both products. METHODS: A retrospective analysis was performed at the Minneapolis Veterans Affairs Medical Center on 138 patients who were taking a stable dose of amiodarone before and after an amiodarone generic product substitution. RESULTS: Seventy-seven patients had steady-state plasma concentrations documented for each product at the same dose. The mean steady-state plasma concentrations of amiodarone were not significantly different for Cordarone compared with Pacerone (1.07 +/- 0.48 vs. 1.19 +/- 0.66 micro g/mL, respectively); similarly, the concentrations of the active metabolite (desethylamiodarone) did not differ (0.95 +/- 0.30 vs. 0.96 +/- 0.49 micro g/mL, respectively). However, the variability in plasma drug concentrations between products was increased as compared to variability within each product. CONCLUSIONS: This study indicates that comparable steady-state concentrations can be achieved with a change in formulation from Cordarone to Pacerone. However, individual responses vary, suggesting that monitoring of plasma concentrations is prudent 1-3 months after any change from one product to another.
Authors: Meytal A Tsadok; Cynthia A Jackevicius; Elham Rahme; Vidal Essebag; Mark J Eisenberg; Karin H Humphries; Jack V Tu; Hassan Behlouli; Jennifer Joo; Louise Pilote Journal: CMAJ Date: 2011-07-11 Impact factor: 8.262