ASHP INJECTABLE DRUG INFORMATION Epinephrine Hydrochloride 595

Epinephrine Hydrochloride AHFS 12:12.12

Products Epinephrine hydrochloride is rapidly destroyed by alkalies or oxidizing agents including sodium bicarbonate, halogens, Epinephrine hydrochloride 1 mg/mL is available in 1-mL ampuls, permanganates, chromates, nitrates, nitrites, and salts of easily 30-mL vials, and 0.3-mL auto-injector syringes. Epinephrine reducible metals such as iron, copper, and zinc.4 hydrochloride is also available at a concentration of 0.1 mg/mL (1:10,000) in vials and prefilled syringes. Some products also Visual inspection for color changes may be inadequate to contain sodium chloride, a bisulfite antioxidant, and an antibac- assess compatibility of epinephrine hydrochloride admixtures. terial preservative such as chlorobutanol.1(11/05) 4 In one evaluation with aminophylline stored at 25°C, a color change was not noted until 8 hours had elapsed. However, only pH 40% of the initial epinephrine hydrochloride was still present in From 2.2 to 5.4 17 the admixture at 24 hours.527 Osmolality pH Effects The osmolality of epinephrine hydrochloride (Abbott) 0.1 mg/ The primary determinant of catecholamine stability in intrave- mL was determined to be 273 mOsm/kg by freezing-point nous admixtures is the pH of the solution.527 Epinephrine hydro- depression.1071 A 1-mg/mL solution was determined to have an chloride is unstable in dextrose 5% at a pH above 5.5.48 The pH osmolality of 348 mOsm/kg.1233 of optimum stability is 3 to 4.1072 In one study, the decomposi- tion rate increased twofold (from 5 to 10% in 200 days at 30°C) Trade Name(s) when the pH was increased from 2.5 to 4.5.1259 Adrenalin Chloride, Epipen When lidocaine hydrochloride is mixed with epinephrine hydrochloride, the buffering capacity of the lidocaine hydro- Administration chloride may raise the pH of intravenous admixtures above 5.5, Epinephrine hydrochloride may be administered by subcuta- the maximum necessary for stability of epinephrine hydrochlo- neous, intramuscular, intravenous, or intracardiac injection. Intra- ride. The final pH is usually about 6. Epinephrine hydrochloride muscular injection into the buttocks should be avoided.1(11/05) 4 will begin to deteriorate within several hours. Therefore, admix- Intravenous infusion at a rate of 1 to 10 mcg/min has also been tures should be used promptly after preparation or the sepa- described.4 rate administration of the epinephrine hydrochloride should be considered. This restriction does not apply to commercial lido- Stability caine–epinephrine combinations that have had the pH adjusted 24 Epinephrine hydrochloride is sensitive to light and air.4 1259 for epinephrine stability. Protection from light is recommended. Withdrawal of doses Syringes from multiple-dose vials introduces air, which results in oxida- Epinephrine hydrochloride was diluted to 1 and 7 mg/10 mL with tion. As epinephrine oxidizes, it changes from colorless to sterile water for injection and repackaged into 10-mL glass vials pink, as adrenochrome forms, to brown, as melanin forms.4 1072 and plastic syringes with 18-gauge needles (Becton Dickinson). Discolored solutions or solutions containing a precipitate should The diluted injections were stored at room temperature protected not be used.4 The various epinephrine preparations have varying from light. Epinephrine stability was evaluated over 56 days of stabilities, depending on the form and the preservatives present. storage. The 1-mg/10-mL samples had an epinephrine loss of 4 to The manufacturer’s recommendations should be followed with 6% in 7 days and 13% in 14 days. The 7-mg/10-mL samples lost regard to storage.4 2% in the glass vials and 5% in the syringes in 56 days.1902 The stability of epinephrine hydrochloride in intact ampuls Epinephrine hydrochloride 1:10,000 in autoinjector syringes subjected to resterilization to provide a sterile outer surface was was evaluated for stability over 45 days under use conditions in evaluated. Epinephrine hydrochloride (adrenalin injection, BP) paramedic vehicles. Temperatures fluctuated with locations and ampuls were resterilized by the following methods: conditions and ranged from 6.5°C (43.7 °F) to 52°C (125.6 °F) in 1. Autoclaved at 121°C for 15 minutes. high desert conditions. No visually apparent changes occurred, 2. Autoclaved at 115°C for 30 minutes. and not more than 6% loss of epinephrine hydrochloride was 3. Exposed to ethylene oxide–freon (12:88) at 55°C for 4 hours found. Most samples exhibited no loss.2548 followed by aeration at 50°C for 12 hours. Epinephrine hydrochloride under simulated summer condi- No loss of epinephrine hydrochloride concentration was tions in paramedic vehicles was exposed to temperatures found in samples from any of these methods. However, if ampuls ranging from 26 to 38°C over 4 weeks. Analysis found no loss were resterilized by autoclaving 2 times at 121°C for 15 minutes, of the drug under these conditions. However, the buffer in the 2562 8% of the drug was lost.803 injection was altered, resulting in an increase in pH.

DOI: 10.37573/9781585286850.143 596 Epinephrine Hydrochloride ASHP INJECTABLE DRUG INFORMATION

Central Venous Catheter the drug was found with little or no drug loss occurring. Further- more, chlorhexidine delivered from the catheter remained at Epinephrine hydrochloride (American Regent) 0.1 mg/mL in trace amounts with no substantial increase due to the delivery dextrose 5% was found to be compatible with the ARROW- of the drug through the catheter.2335 g+ard Blue Plus (Arrow International) chlorhexidine-bearing triple-lumen central catheter. Essentially complete delivery of

Compatibility Information Solution Compatibility

Epinephrine HCl

Test Soln Name Mfr Mfr Conc/L or % Remarks Ref C/I

Dextrose 2.5% in half-strength Ringer’s injection AB PD 4 mg Physically compatible 3 C

Dextrose 5% in Ringer’s injection AB PD 4 mg Physically compatible 3 C

Dextrose 5% in half-strength Ringer’s injection, AB PD 4 mg Physically compatible 3 C lactated

Dextrose 2.5% in Ringer’s injection, lactated AB PD 4 mg Physically compatible 3 C

Dextrose 5% in Ringer’s injection, lactated AB PD 4 mg Physically compatible 3 C

Dextrose 5% in Ringer’s injection, lactated TRa PD 1 mg Stable for 24 hr at 5°C 282 C

Dextrose 10% in Ringer’s injection, lactated AB PD 4 mg Physically compatible 3 C

Dextrose 2.5% in sodium chloride 0.45% AB PD 4 mg Physically compatible 3 C

Dextrose 2.5% in sodium chloride 0.9% AB PD 4 mg Physically compatible 3 C

Dextrose 5% in sodium chloride 0.225% AB PD 4 mg Physically compatible 3 C

Dextrose 5% in sodium chloride 0.45% AB PD 4 mg Physically compatible 3 C

Dextrose 5% in sodium chloride 0.9% AB PD 4 mg Physically compatible 3 C

Dextrose 5% in sodium chloride 0.9% TRa PD 1 mg Stable for 24 hr at 5°C 282 C

Dextrose 10% in sodium chloride 0.9% AB PD 4 mg Physically compatible 3 C

Dextrose 2.5% AB PD 4 mg Physically compatible 3 C

Dextrose 5% AB PD 4 mg Physically compatible 3 C

Dextrose 5% TRa PD 1 mg Stable for 24 hr at 5°C 282 C

Dextrose 5% AB PD 4 mg Physically compatible and stable. At 25°C, 527 C 10% loss is calculated to occur in 50 hr in light and in 1000 hr in the dark

Dextrose 5% BAb ANT 16 mg 5% loss in 20.75 days at 5°C protected 1610 C from light

Dextrose 5% BAa AMR 87 mg No epinephrine loss in 24 hr at 23°C 2085 C protected from light

Dextrose 10% AB PD 4 mg Physically compatible 3 C

Ionosol B in dextrose 5% AB PD 4 mg Physically compatible 3 C

Ionosol MB in dextrose 5% AB PD 4 mg Physically compatible 3 C

Ionosol T in dextrose 5% AB PD 4 mg Haze or precipitate within 6 to 24 hr 3 I

Ringer’s injection AB PD 4 mg Physically compatible 3 C