AHFS Class:

12:12.12 alpha- and beta-Adrenergic Agonists

Generic Name

• EPINEPHrine (CAS Registry Number: 55-31-2)

Epinephrine is available as a 1-mg/mL injection solution in 1-mL single-dose vials and 10- and 30-mL multiple-dose vials.⁴⁰⁷⁵; ⁴⁰⁷⁶ Each mL contains epinephrine 1 mg with sodium metabisulfite in water for injection; other excipients vary by manufacturer and may include sodium chloride, sodium hydroxide, tartaric acid, edetate disodium (EDTA), and hydrochloric acid to adjust pH.⁴⁰⁷⁵ Multiple-dose vials also contain chlorobutanol as a preservative.⁴⁰⁷⁵; ⁴⁰⁷⁶

Epinephrine also is available in a concentration of 0.1 mg/mL in 10-mL single-dose prefilled syringes.⁴⁰⁷⁷; ⁴⁰⁷⁸ Each mL of solution contains epinephrine 0.1 mg with sodium metabisulfite in water for injection; other excipients vary by manufacturer and may include sodium chloride, citric acid, sodium citrate, edetate disodium (EDTA), hydrochloric acid and/or sodium hydroxide.⁴⁰⁷⁷; ⁴⁰⁷⁸

Epinephrine also is available as sulfite-free, preservative-free 1-mg/mL injection solution in 2-mL ampuls.⁴⁰⁸⁰ Each mL of the preservative-free solution contains epinephrine 1 mg with sodium chloride and hydrochloric acid in water for injection.⁴⁰⁸⁰

Epinephrine also is available as a premixed solution in sodium chloride 0.9% in epinephrine concentrations of 8, 16, 20, 32, or 40 mcg/mL in 250-mL single-dose infusion bags.^4079(4079) Each bag also contains edetate disodium (EDTA) 10 mcg and tartaric acid.^4079(4079) Hydrochloric acid and/or sodium hydroxide also may be present for pH adjustment.^4079(4079) The headspace in the bags has been displaced with nitrogen.^4079(4079)

pH

Generally, from 2.2 to 5.³⁸⁶⁷; ⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁸⁰

Osmolality

The osmolality of epinephrine (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, Epipen

Epinephrine may be administered by subcutaneous or intramuscular injection, or by intravenous infusion.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁷⁷; ^4079(4079); ⁴⁰⁸⁰ Sulfite-free, preservative-free injection solutions also may be administered by ophthalmic irrigation or intracameral injection during intraocular surgery following dilution in an ophthalmic irrigation solution.⁴⁰⁸⁰ Commercially available epinephrine 0.1-mg/mL solutions in prefilled syringes are intended for administration by intravenous infusion following dilution.⁴⁰⁷⁷; ⁴⁰⁷⁸

Intramuscular or subcutaneous injections should be made into the anterolateral aspect of the thigh.⁴⁰⁷⁵; ⁴⁰⁷⁶ Injection into or near smaller muscles (e.g., deltoid muscle) is not recommended because of possible differences in absorption.⁴⁰⁷⁵; ⁴⁰⁷⁶ Injection into the digits, hands, feet, or buttocks should be avoided.⁴⁰⁷⁵; ⁴⁰⁷⁶

For intravenous infusion, epinephrine must be diluted in a compatible infusion solution prior to administration.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁷⁷; ⁴⁰⁷⁸ Diluted solutions should be administered into a large vein whenever possible.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁷⁷; ⁴⁰⁷⁸ Extravasation should be avoided.⁴⁰⁷⁵ To prepare a solution for intravenous infusion, 1 mL of a 1-mg/mL or 10 mL of a 0.1-mg/mL solution should be added to 1000 mL of a compatible diluent to yield a solution containing epinephrine 1 mcg/mL.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁷⁷; ⁴⁰⁷⁸; ⁴⁰⁸⁰ Epinephrine should be diluted in dextrose 5% or dextrose 5% and sodium chloride solution because dextrose-containing solutions provide protection against oxidation.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁷⁷; ⁴⁰⁷⁸; ⁴⁰⁸⁰ Administration in saline solution alone is not recommended.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁸⁰

Epinephrine in intact containers should be stored at controlled room temperature and protected from light and freezing.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁷⁷; ⁴⁰⁷⁸; ⁴⁰⁷⁹ Solutions should be clear and colorless; do not use if the solution is colored, cloudy, or contains particulate matter.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁷⁷; ⁴⁰⁷⁸; ^4079(4079)

Premixed infusion bags should be stored in the foil overwrap and should be discarded after 24 hours of opening the overwrap.^4079(4079)

Multiple-dose vials should be discarded 30 days after initial use.⁴⁰⁷⁵; ⁴⁰⁷⁶

Epinephrine is sensitive to light and air.¹²⁵⁹ The drug should be protected from light and alkalis and oxidizing agents.⁴⁰⁷⁶; ⁴⁰⁷⁷; ⁴⁰⁷⁸ As epinephrine oxidizes, it changes from colorless to pink, as adrenochrome forms, to brown, as melanin forms.¹⁰⁷²; ⁴⁰⁷⁵; ⁴⁰⁷⁶

The stability of epinephrine in intact ampuls subjected to resterilization to provide a sterile outer surface was evaluated. Epinephrine (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 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

Visual inspection for color changes may be inadequate to assess compatibility of epinephrine 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 was still present in the admixture at 24 hours.⁵²⁷

Autoclaving

No loss of epinephrine was found when ampuls (adrenalin injection, BP) were autoclaved once at 115°C for 30 minutes or 121°C for 15 minutes.⁸⁰³ However, 8% drug loss was observed when ampuls were autoclaved 2 times at 121°C for 15 minutes.⁸⁰³

pH Effects

The primary determinant of catecholamine stability in intravenous admixtures is the pH of the solution.⁵²⁷ Epinephrine 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, the buffering capacity of the lidocaine hydrochloride may raise the pH of intravenous admixtures above 5.5, the maximum necessary for stability of epinephrine. The final pH is usually about 6. Epinephrine will begin to deteriorate within several hours. Therefore, admixtures should be used promptly after preparation or the separate administration of the epinephrine should be considered. This restriction does not apply to commercial lidocaine-epinephrine combinations that have had the pH adjusted for epinephrine stability.²⁴

Light Effects

Epinephrine is sensitive to light and should be stored protected from light.⁴⁰⁷⁵; ⁴⁰⁷⁶; ⁴⁰⁷⁷; ⁴⁰⁷⁸

Syringes

Epinephrine 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 1:10,000 (0.1 mg/mL) 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 was found. Most samples exhibited no loss.²⁵⁴⁸

Epinephrine 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 (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

^aThe concentrations for epinephrine and norepinephrine are intentionally different to avoid confusion as recommended by the S4S panel and ISMP.^bBabies 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

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 March 7, 2025. © Copyright, 2025. American Society of Health-System Pharmacists^®, 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.