12:12.08.04 Non-selective beta-Adrenergic Agonists
Generic Name
Isoproterenol hydrochloride is available at a concentration of 0.2 mg/mL in 1- and 5-mL ampuls.2903 In addition to the drug, each mL contains sodium chloride 7 mg, sodium citrate dihydrate 2.07 mg, citric acid anhydrous 2.5 mg, edetate disodium 0.2 mg, and hydrochloric acid or sodium hydroxide to adjust the pH in water for injection.2903
pH
From 3.5 to 4.5.2903
Osmolality
The osmolality of isoproterenol hydrochloride 0.2 mg/mL was determined to be 277 mOsm/kg by freezing-point depression and 293 mOsm/kg by vapor pressure.1071
Trade Name(s)
Isuprel
Isoproterenol hydrochloride may be administered by intravenous infusion; by direct intravenous, intramuscular, or subcutaneous injection; and, in extreme emergencies, by intracardiac injection.2903 For direct intravenous injection, 1 mL of the 0.2-mg/mL injection should be diluted to 10 mL with sodium chloride 0.9% or dextrose 5% to provide a 20-mcg/mL solution.2903 Intravenous infusions are prepared by diluting 5 or 10 mL of the 0.2-mg/mL injection in 500 mL of dextrose 5% to yield solutions containing 2 or 4 mcg/mL, respectively.2903 Intravenous infusion concentrations of up to 20 mcg/mL have been used when fluid restriction is essential.2903
For intramuscular, subcutaneous, and intracardiac injection, isoproterenol hydrochloride should be administered undiluted.2903
Isoproterenol hydrochloride injection in intact containers should be stored at controlled room temperature and protected from light.2903 Ampuls should be kept in opaque containers until use.2903 The drug should not be used if the solution is pinkish or slightly darker than yellow or if a precipitate is present.2903 Exposure to air, light, or increased temperature may cause a pink to brownish pink color to develop.4; 975
Isoproterenol hydrochloride under simulated summer conditions in paramedic vehicles was exposed to temperatures ranging from 26 to 38°C over 4 weeks. Analysis found about 4% loss of the drug in 7 days and 11% loss in 4 weeks.2562
pH Effects
The pH of a solution is the primary determinant of catecholamine stability in intravenous admixtures.527 Isoproterenol hydrochloride 5 mg/L in dextrose 5% was stable for more than 24 hours at 25°C over a pH range of 3.7 to 5.7.59; 3026 However, isoproterenol hydrochloride displayed significant decomposition at a pH value above approximately 6.48; 59; 430 If drugs that may raise the pH above 6 are mixed, they should be administered immediately after preparation,59 or, preferably, administered separately.24
Visual inspection for color changes related to decomposition may be inadequate to assess the compatibility of admixtures. In one evaluation with aminophylline stored at 25°C, a color change was not noted until 24 hours had elapsed. However, no intact isoproterenol hydrochloride was present in the admixture at 24 hours.527
Filtration
Isoproterenol hydrochloride (Winthrop) 2 mg/L in dextrose 5%, sodium chloride 0.9%, and Ringer’s injection, lactated, filtered over 12 hours through a 5-µm stainless steel depth filter (Argyle Filter Connector), a 0.22-µm cellulose ester membrane filter (Ivex-2 Filter Set) and a 0.22-µm polycarbonate membrane filter (In-Sure Filter Set) showed no significant reduction due to binding to the filters.320
In another study, isoproterenol hydrochloride (Winthrop) 4 mg/L in dextrose 5% and sodium chloride 0.9% did not display significant sorption to a 0.45-µm cellulose membrane filter (Abbott S-A-I-F) during an 8-hour simulated infusion.567
Central Venous Catheter
Isoproterenol hydrochloride (Abbott) 0.02 mg/mL in dextrose 5% was found to be compatible with the ARROWg+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of the drug was found with little or no drug loss occurring. Furthermore, chlorhexidine delivered from the catheter remained at trace amounts with no substantial increase due to the delivery of the drug through the catheter.2335
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 Isoproterenol3635; 3636
| Patient Population | Concentration Standards | Dosing Units |
|---|---|---|
| Adults | 4 mcg/mL | mcg/min or mcg/kg/minutea |
| Pediatric patients (50 kg) | 20 mcg/mL 64 mcg/mL | mcg/kg/minute |
a The S4S panel recommends trying to standardize dosing units but understands that some protocols may use “flat” dosing while others may require weight-based dosing.
For a list of references cited in the text of this monograph, search the monograph titled References.