Introduction Cordarone IV is an effective antiarrhythmic agent; however, a high incidence of drug related hypotension was reported in clinical trials. The hypotension was not dose related, but related to the rate of infusion. As a result, labeling calls the standard formulation (including generics) to be administered over 10 minutes. The standard formulation contains polysorbate 80 and benzyl alcohol and each causes hypotension. A new aqueous formulation of amiodarone (AA) does not contain these solubilizing agents and therefore may cause less hypotension. This hypothesis was tested in conscious dogs.
Methods Six mature beagle dogs were surgically instrumented with a telemetric device for monitoring of heart rate and blood pressure. The study was run on 5 separate days. On the first 2 days, a 10-minute IV infusion or a bolus of 5% dextrose in water (D5W) was administered (placebo). Over the following 3 days, the dogs received (in randomized order, one per day) a 10-minute infusion of 2.5 mg/kg of Cordarone® IV (C) and bolus administrations of 2.5 mg/kg and 5.0 mg/kg of AA injected over 2 to 5 seconds. The dogs were monitored for 2 hours after dosing (1-min intervals).
Results Bolus administration of AA at either 2.5 mg/kg or 5.0 mg/kg produced no statistically significant changes in the mean arterial blood pressure (MABP) relative to D5W bolus (p>0.25, ANOVA). In contrast, 10-minute infusion of 2.5 mg/kg C produced statistically significant decreases in MABP relative to D5W infusion that lasted for at least 2 hours (p<0.001). The decrease in MABP became statistically significant at 3 min. post dosing (91 vs. 105 mm Hg, p<0.05) with a further drop in MABP to 62 mm Hg (p<0.001) at 10 min post dose. The MABP remained significantly lower until the end of the study (80 vs. 98 mm Hg, p<0.05). Compared to AA boluses, MABP was significantly lower following C infusion.
Conclusion Aqueous amiodarone did not cause hypotension when administered as a rapid bolus. In contrast, 10 minute infusion of the standard preparation, Cordarone IV resulted in a sustained and significant hypotension. The hemodynamic profile of the aqueous formulation was significantly better than C, permitting a more rapid administration.