12:12.12 alpha- and beta-Adrenergic Agonists
Generic Name
Norepinephrine bitartrate is available as 1 mg/mL of norepinephrine base in 4-mL vials. Each mL of solution also contains sodium metabisulfite 0.2 mg and sodium chloride for isotonicity in water for injection.1(6/07)
pH
Osmolality
Norepinephrine bitartrate injection is adjusted to isotonicity with sodium chloride.1(6/07)
Trade Name(s)
Levophed
Norepinephrine bitartrate is administered by intravenous infusion into a large vein, using a pump or other flow rate control device. Extravasation may cause tissue damage and should be avoided. A 4-mcg/mL dilution of norepinephrine base for infusion is usually prepared by adding 4 mg of base (4 mL) to 1000 mL of dextrose 5% with or without sodium chloride. The concentration and infusion rate depend on the patient’s requirements.1(6/07); 4
Norepinephrine bitartrate in intact containers should be stored at controlled room temperature and protected from light.1(6/07); 4 Dextrose 5% and dextrose 5% in sodium chloride 0.9% are the recommended diluents for infusion because their dextrose content provides protection against significant drug loss due to oxidation. The drug gradually darkens upon exposure to light or air and must not be used if it is discolored or has a precipitate.4
pH Effects
Norepinephrine bitartrate is stable at pH 3.6 to 6 in dextrose 5%.48; 77 The pH of a solution is the primary determinant of catecholamine stability in intravenous admixtures.527 At a concentration of 5 mg/L in dextrose 5% at pH 6.5, norepinephrine bitartrate loses 5% in 6 hours; at pH 7.5, it loses 5% in 4 hours.77 The rate of loss also increases with exposure to increasing temperatures.1929
Caution should be employed in mixing additives that may result in a final pH above 6 since norepinephrine bitartrate is alkali labile.6; 24; 77
Visual inspection for color change may be inadequate to assess compatibility of admixtures. In one evaluation with aminophylline stored at 25°C, a color change was not noted until 48 hours had elapsed. However, no intact norepinephrine bitartrate was present in the admixture at 48 hours.527
Syringes
Norepinephrine bitartrate (Aguettant) 0.24 mg/mL in sodium chloride 0.9% was packaged in 50-mL polypropylene syringes (Becton Dickinson) and stored at 2 to 8°C with light protection.3508 Solutions were physically stable with less than 10% loss in 30 days.3508
Norepinephrine bitartrate (manufacturer unspecified) prepared at norepinephrine concentrations of 0.5 and 1.16 mg/mL in dextrose 5% was packaged as 48 mL in 50-mL clear polypropylene and amber polypropylene syringes (Becton Dickinson) and stored at 20 to 25°C.3509 Solutions both with and without light protection were physically stable with little to no loss of drug in 48 hours.3509
Noradrenaline (as the tartrate salt) (Aguettant) prepared at norepinephrine concentrations of 6 mg/50 mL and 12 mg/50 mL in sodium chloride 0.9% in a 50-mL polypropylene syringe (BD) was physically stable for 48 hours at room temperature.3545
Filtration
Norepinephrine bitartrate 4 mg/L in dextrose 5% and sodium chloride 0.9% was filtered at a rate of 120 mL/hr for 6 hours through a 0.22-µm cellulose ester membrane filter (Ivex-2). No significant drug loss due to binding to the filter was noted.533
Central Venous Catheter
Norepinephrine bitartrate prepared at a norepinephrine concentration of 0.1 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 Norepinephrine3635; 3636
| Patient Population | Concentration Standardsa | Dosing Units |
|---|---|---|
| Adults | 16 mcg/mL 32 mcg/mL 128 mcg/mL | mcg/kg/minute |
| Pediatric patients (50 kg) | 16 mcg/mLb 32 mcg/mL 64 mcg/mL | mcg/kg/minute |
a The concentrations for epinephrine and norepinephrine are intentionally different to avoid confusion as recommended by the S4S panel and ISMP.b Babies weighing under 500 grams may require a lower concentration.
Drugs in Syringe Compatibility
Y-Site Injection Compatibility (1:1 Mixture)
Additional Compatibility Information
Infusion Solutions
In a simulated Y-site administration study, norepinephrine bitartrate (Claris) at a norepinephrine concentration of 16 mcg/mL in dextrose 5% was physically compatible with Normosol R for up to 4 hours at 21°C protected from light.3719 However, at a norepinephrine concentration of 32 mcg/mL in dextrose 5%, turbidity increased within 1 hour when mixed with Normosol R in the simulated Y-site administration.3719
For a list of references cited in the text of this monograph, search the monograph titled References.