AHFS Class:

12:12.12 alpha- and beta-Adrenergic Agonists

Generic Name

• EPINEPHrine Hydrochloride

Epinephrine hydrochloride 1 mg/mL is available in 1-mL ampuls, 30-mL vials, and 0.3-mL auto-injector syringes. Epinephrine hydrochloride is also available at a concentration of 0.1 mg/mL (1:10,000) in vials and prefilled syringes. Some products also contain sodium chloride, a bisulfite antioxidant, and an antibacterial preservative such as chlorobutanol.^1(11/05); ⁴

pH

From 2.2 to 5.³⁸⁶⁷

Osmolality

The osmolality of epinephrine hydrochloride (Abbott) 0.1 mg/mL was determined to be 273 mOsm/kg by freezing-point depression.¹⁰⁷¹ A 1-mg/mL solution was determined to have an osmolality of 348 mOsm/kg.¹²³³

Trade Name(s)

Adrenalin Chloride, Epipen

Epinephrine hydrochloride may be administered by subcutaneous, intramuscular, intravenous, or intracardiac injection. Intramuscular injection into the buttocks should be avoided.^1(11/05); ⁴ Intravenous infusion at a rate of 1 to 10 mcg/min has also been described.⁴

Epinephrine hydrochloride is sensitive to light and air.⁴; ¹²⁵⁹ Protection from light is recommended. Withdrawal of doses from multiple-dose vials introduces air, which results in oxidation. As epinephrine oxidizes, it changes from colorless to pink, as adrenochrome forms, to brown, as melanin forms.⁴; ¹⁰⁷² Discolored solutions or solutions containing a precipitate should not be used.⁴ The various epinephrine preparations have varying stabilities, depending on the form and the preservatives present. The manufacturer’s recommendations should be followed with regard to storage.⁴

The stability of epinephrine hydrochloride in intact ampuls subjected to resterilization to provide a sterile outer surface was evaluated. Epinephrine hydrochloride (adrenalin injection, BP) ampuls were resterilized by the following methods:

1. Autoclaved at 121°C for 15 minutes.
2. Autoclaved at 115°C for 30 minutes.
3. Exposed to ethylene oxide-freon (12:88) at 55°C for 4 hours followed by aeration at 50°C for 12 hours.

No loss of epinephrine hydrochloride concentration was found in samples from any of these methods. However, if ampuls were resterilized by autoclaving 2 times at 121°C for 15 minutes, 8% of the drug was lost.⁸⁰³

Epinephrine hydrochloride is rapidly destroyed by alkalies or oxidizing agents including sodium bicarbonate, halogens, permanganates, chromates, nitrates, nitrites, and salts of easily reducible metals such as iron, copper, and zinc.⁴

Visual inspection for color changes may be inadequate to assess compatibility of epinephrine hydrochloride admixtures. In one evaluation with aminophylline stored at 25°C, a color change was not noted until 8 hours had elapsed. However, only 40% of the initial epinephrine hydrochloride was still present in the admixture at 24 hours.⁵²⁷

pH Effects

The primary determinant of catecholamine stability in intravenous admixtures is the pH of the solution.⁵²⁷ Epinephrine hydrochloride is unstable in dextrose 5% at a pH above 5.5.⁴⁸ The pH of optimum stability is 3 to 4.¹⁰⁷² In one study, the decomposition rate increased twofold (from 5 to 10% in 200 days at 30°C) when the pH was increased from 2.5 to 4.5.¹²⁵⁹

When lidocaine hydrochloride is mixed with epinephrine hydrochloride, the buffering capacity of the lidocaine hydrochloride may raise the pH of intravenous admixtures above 5.5, the maximum necessary for stability of epinephrine hydrochloride. The final pH is usually about 6. Epinephrine hydrochloride will begin to deteriorate within several hours. Therefore, admixtures should be used promptly after preparation or the separate administration of the epinephrine hydrochloride should be considered. This restriction does not apply to commercial lidocaine-epinephrine combinations that have had the pH adjusted for epinephrine stability.²⁴

Syringes

Epinephrine hydrochloride was diluted to 1 and 7 mg/10 mL with sterile water for injection and repackaged into 10-mL glass vials and plastic syringes with 18-gauge needles (Becton Dickinson). The diluted injections were stored at room temperature protected from light. Epinephrine stability was evaluated over 56 days of storage. The 1-mg/10-mL samples had an epinephrine loss of 4 to 6% in 7 days and 13% in 14 days. The 7-mg/10-mL samples lost 2% in the glass vials and 5% in the syringes in 56 days.¹⁹⁰²

Epinephrine hydrochloride 1:10,000 in autoinjector syringes was evaluated for stability over 45 days under use conditions in paramedic vehicles. Temperatures fluctuated with locations and conditions and ranged from 6.5°C (43.7°F) to 52°C (125.6°F) in high desert conditions. No visually apparent changes occurred, and not more than 6% loss of epinephrine hydrochloride was found. Most samples exhibited no loss.²⁵⁴⁸

Epinephrine hydrochloride under simulated summer conditions in paramedic vehicles was exposed to temperatures ranging from 26 to 38°C over 4 weeks. Analysis found no loss of the drug under these conditions. However, the buffer in the injection was altered, resulting in an increase in pH.²⁵⁶²

Central Venous Catheter

Epinephrine hydrochloride (American Regent) prepared at an epinephrine 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 Epinephrine³⁶³⁵; ³⁶³⁶

^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.

Solution Compatibility

Additive Compatibility

Drugs in Syringe Compatibility

Y-Site Injection Compatibility (1:1 Mixture)

Additional Compatibility Information

Infusion Solutions

In a simulated Y-site administration study, epinephrine (BPI Labs) concentrations of 16 and 32 mcg/mL in dextrose 5% were physically compatible with Normosol R for up to 4 hours at 21°C protected from light.³⁷¹⁹

Alprostadil

Alprostadil (Pfizer) 20 mcg/mL in dextrose 5% with epinephrine bitartrate (Braun) 0.2 mg/mL in dextrose 5% protected from light was physically compatible for up to 4 hr at 22 to 25°C during a simulated Y-site administration study.³⁶⁶⁴; ³⁶⁸⁰

For a list of references cited in the text of this monograph, search the monograph titled References.

ASHP^® Injectable Drug Information^TM. Selected Revisions September 12, 2024. © Copyright, 2024. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.