Antiarrhythmic effects of solvents: III Effects of propylene glycol and benzyl alcohol on contractile force of isolated rabbit heart

Comparative Effects of Rapid Bolus Administration of Aqueous Amiodarone Versus 10-Minute Cordarone I.V. Infusion on Mean Arterial Blood Pressure in Conscious Dogs

“…Amio-Aqueous does not contain pharmacologically active excipients, while each ampule of Cordarone IV contains 300 mg polysorbate 80 and 60.6 mg benzyl alcohol [20]. However, neither benzyl alcohol nor polysorbate 80 is an inert ingredient [21][22][23][24][25][26]. Polysorbate 80 has a negative inotropic effect [21], causes peripheral vasodilatation [21,23,24], and decreases arterial blood pressure [21,22,28,29].…”

“…Polysorbate 80 has a negative inotropic effect [21], causes peripheral vasodilatation [21,23,24], and decreases arterial blood pressure [21,22,28,29]. In animal studies, benzyl alcohol was also found to be cardiotoxic and resulted in negative inotropy, vasodilatation, and decreased arterial blood pressure [25,26]. The benzyl alcohol in the standard formulation is the reason that Cordarone IV and its generic formulations are recommended to not be given to infants due to the risk of fatal gasping syndrome [20].…”

“…Intravenous amiodarone without polysorbate 80 decreased the heart rate and did not cause hypotension, while polysorbate 80 alone caused severe hypotension and reflex tachycardia with a magnitude similar to that seen with Cordarone IV [21,22,29,30]. Benzyl alcohol was also found to be a potent negative inotropic [25] and hypotensive [26] agent. These studies provided evidence of the untoward pharmacologic properties of the excipients of the standard intravenous amiodarone formulation.…”

“…The hypotension seen with intravenous amiodarone has been attributed to the solvents of Cordarone IV [21][22][23][24][25]. Cordarone IV and the generic preparations are amiodarone hydrochloride in a solution of two chemicals, polysorbate 80 and benzyl alcohol, both known to exhibit negative inotropy and hypotensive effect [20][21][22][23][24][25][26].…”

“…Cordarone IV and the generic preparations are amiodarone hydrochloride in a solution of two chemicals, polysorbate 80 and benzyl alcohol, both known to exhibit negative inotropy and hypotensive effect [20][21][22][23][24][25][26]. The polysorbate 80 and benzyl alcohol are employed to keep the amiodarone in solution, because amiodarone itself is very poorly water-soluble.…”