Amiodarone hydrochloride is available as a 50-mg/mL concentrate for injection in single-dose vials containing 3, 9, and 18 mL, multidose vials containing 18 mL, and single-use plastic prefilled syringes containing 3 mL.3279; 3641; 3642 Each mL also contains polysorbate 80 100 mg and benzyl alcohol 20.2 mg in water for injection.3279; 3641; 3642 The concentrate for injection must be diluted in a compatible infusion solution prior to administration.3279; 3641; 3642
Amiodarone hydrochloride also is available in a ready-to-use formulation that does not contain polysorbate 80 or benzyl alcohol.3643 Amiodarone hydrochloride is available as an iso-osmotic premixed injection solution of 100 mL containing 150 mg of amiodarone hydrochloride (1.5 mg/mL) in dextrose or of 200 mL containing 360 mg of amiodarone hydrochloride (1.8 mg/mL) in dextrose in single-dose Galaxy containers.3643 Each mL of the 1.5-mg/mL solution also contains betadex sulfobutyl ether sodium 15 mg, citric acid anhydrous 0.362 mg, sodium citrate dihydrate 0.183 mg, and dextrose anhydrous 42.1 mg in water for injection.3643 Each mL of the 1.8-mg/mL solution also contains betadex sulfobutyl ether 18 mg, citric acid anhydrous 0.362 mg, sodium citrate dihydrate 0.183 mg, and dextrose anhydrous 41.4 mg in water for injection.3643 Sodium hydroxide or hydrochloric acid may have been added to adjust the pH.3643 No further dilution of the premixed injection solutions is required.3643 Any unused portion should be discarded.3643
pH
The pH is reported to be 4.08.1053
Amiodarone hydrochloride is administered by intravenous infusion.3279; 3641; 3642; 3643 Whenever possible, amiodarone hydrochloride should be administered through a dedicated central venous catheter.3279; 3641; 3642; 3643 An inline filter should be used for administration.3279; 3641; 3642; 3643 Amiodarone hydrochloride concentrations greater than 3 mg/mL have been associated with a high incidence of peripheral vein phlebitis; however, concentrations of 2.5 mg/mL or less appear to be less irritating.3279; 3641; 3642; 3643 For infusions lasting longer than 1 hour, amiodarone hydrochloride concentrations should not exceed 2 mg/mL, unless a central venous catheter is used.3279; 3641; 3642; 3643 Initial infusion rates should not exceed 30 mg/min.3279; 3641; 3642; 3643
For intravenous infusion of solutions prepared from vials and prefilled syringes of amiodarone hydrochloride concentrate for injection diluted to concentrations of 1 to 6 mg/mL, the solution must be administered using a volumetric pump.3279; 3641; 3642 The concentrate for injection contains polysorbate 80, a surface active agent that alters drop size.3279; 3641; 3642 Drop size reduction may lead to substantial underdosage if a drop counter infusion set is used, and thus the drug must be administered using a volumetric infusion pump.1445; 3279; 3641; 3642
Amiodarone hydrochloride should be stored at controlled room temperature in the carton to protect from light.3279; 3641; 3642; 3643 The drug should be protected from excessive heat and from freezing.3279; 3641; 3642; 3643 Light protection is not necessary during administration,3279; 3641; 3642; 3643 but exposure to direct sunlight should be avoided.2258
Manufacturers recommended that amiodarone hydrochloride concentrate for injection be diluted in dextrose 5%.3279; 3641; 3642 Information on the drug’s compatibility in sodium chloride 0.9% has been conflicting.1031; 1443 Solutions containing less than 0.6 mg/mL of amiodarone hydrochloride in dextrose 5% are unstable and should not be used.1442
Precipitation
Amiodarone hydrochloride may precipitate when diluted. Studies found little or no precipitation when the formulation was diluted to very small or very large concentrations. In the middle range, however, at concentrations between 45 mg/mL (90% amiodarone hydrochloride formulation) and about 0.0025 mg/mL in phosphate buffer (pH 7.4), the drug concentration exceeds the solubility of amiodarone hydrochloride in the mixture. Precipitation may occur immediately or on standing. Such precipitation may occur when the drug enters the bloodstream, contributing to the phlebitis associated with amiodarone hydrochloride.1818; 1819
The aqueous solubility of amiodarone hydrochloride is not substantially altered over the pH range of 1.5 to 7.5,925 but precipitation may occur in alkaline media.791; 1032
Amiodarone hydrochloride (Wyeth-Ayerst) 1.2 mg/mL in 250 mL of dextrose 5% has been reported to develop cloudiness upon standing when prepared in evacuated glass bottles (Abbott). The precipitation was attributed to the acetate buffers present in the small amount of residual fluid left in evacuated bottles from steam sterilization.1982
Syringes
Amiodarone hydrochloride (Sanofi) 600 mg/24 mL in dextrose 5% in a 50-mL polypropylene syringe (BD) was physically stable for 48 hours at room temperature.3545
Sorption
Amiodarone hydrochloride concentrate for injection prepared at concentrations of 1 to 6 mg/mL in dextrose 5% in polyolefin or glass containers is physically compatible with no loss of the drug in 24 hours.3279; 3641; 3642 In polyvinyl chloride (PVC) containers, however, amiodarone hydrochloride loss due to sorption occurs; acceptable potency (less than 10% loss) exists for only 2 hours.3279; 3641; 3642 Consequently, the manufacturers state that all infusions longer than 2 hours must be prepared in glass or polyolefin containers of dextrose 5%.3279; 3641; 3642 Evacuated glass containers should not be used.3279; 3641; 3642
Similarly, amiodarone hydrochloride is lost due to sorption to PVC infusion sets.1443; 3279; 3641; 3642 However, the manufacturers state that these losses are accounted for by the recommended dosage schedule.3279; 3641; 3642 Consequently, PVC sets should be used with this drug, but the recommended infusion regimen must be followed.3279; 3641; 3642
Amiodarone hydrochloride 1 mg/mL in dextrose 5% in VISIV polyolefin bags was tested for 24 hours at room temperature near 23°C. Little or no loss due to sorption was found within the 24-hour study period.2660
Plasticizer Leaching
Amiodarone hydrochloride leaches diethylhexyl phthalate (DEHP) plasticizer from PVC tubing.3279; 3641; 3642 The degree of plasticizer leaching depends on the concentration and rate of administration, with higher concentrations and slower administration rates leaching more plasticizer.3279; 3641; 3642 Polysorbate 80, a component of amiodarone hydrochloride concentrate for injection, also is known to leach DEHP from PVC.3279; 3641; 3642
Filtration
An inline filter should be used for administration of amiodarone hydrochloride.3279; 3641; 3642; 3643
Amiodarone hydrochloride (Labaz) 0.6 mg/mL in dextrose 5% and sodium chloride 0.9% was filtered through a 0.22-µm cellulose ester membrane filter (Ivex-HP, Millipore) over 6 hours. No significant drug loss due to binding to the filter was noted.1034
Standardize 4 Safety
One or more standardized concentrations for this drug have been established through Standardize 4 Safety (S4S), a national patient safety initiative to reduce medication errors, especially during transitions of care. (See Standardize 4 Safety in Users Guide.) Recommendations developed to date through this initiative are available at www.ashp.org/pharmacy-practice/standardize-4-safety-initiative.
Table 1: Standardize 4 Safety Continuous IV Infusion Standard Concentrations for Amiodarone3635; 3636
| Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
| Adults | 1.8 mg/mL | mg/minute |
| Pediatric patients (50 kg) | 1.8 mg/mL 3.6 mg/mL | mcg/kg/minute (note dosing units differ from concentration units) |
Drugs in Syringe Compatibility
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Infusion Solutions
In a simulated Y-site administration study, amiodarone hydrochloride (Baxter) 1.8 mg/mL in dextrose 5% was physically compatible with Normosol R for up to 4 hours at 21°C protected from light.3719
For a list of references cited in the text of this monograph, search the monograph titled References.