EPINEPHrine (Systemic)

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Kit, Injection:

Adyphren Amp: 1 mg/mL [contains sodium metabisulfite]

Adyphren Amp II: 1 mg/mL [contains sodium metabisulfite]

Adyphren II: 1 mg/mL [contains sodium metabisulfite]

Epinephrine Professional: 1 mg/mL [contains edetate disodium dihydrate, sodium metabisulfite]

EpinephrineSnap-EMS: 1 mg/mL [contains edetate disodium dihydrate, sodium metabisulfite]

Epinephrinesnap-v: 1 mg/mL [contains sodium metabisulfite]

EPIsnap: 1 mg/mL [contains sodium metabisulfite]

EPY: 1 mg/mL [DSC] [contains sodium metabisulfite]

EPY II: 1 mg/mL [DSC] [contains sodium metabisulfite]

Kit, Injection [preservative free]:

Adyphren: 1 mg/mL [contains sodium metabisulfite]

Epinephrinesnap-v: 1 mg/mL [contains edetate disodium dihydrate, sodium metabisulfite]

Solution, Injection:

Adrenalin: 30 mg/30 mL (30 mL) [contains chlorobutanol (chlorobutol), disodium edta, sodium metabisulfite]

Generic: 30 mg/30 mL (30 mL [DSC])

Solution, Injection [preservative free]:

Adrenalin: 1 mg/mL (1 mL) [contains edetate disodium dihydrate, sodium metabisulfite]

Generic: 1 mg/mL (1 mL)

Solution Auto-injector, Injection:

Adrenaclick: 0.15 mg/0.15 mL (2 ea [DSC]); 0.3 mg/0.3 mL (2 ea [DSC]) [latex free; contains chlorobutanol (chlorobutol), sodium bisulfite]

Auvi-Q: 0.1 mg/0.1 mL (2 ea); 0.15 mg/0.15 mL (2 ea); 0.3 mg/0.3 mL (2 ea) [contains sodium bisulfite]

EpiPen 2-Pak: 0.3 mg/0.3 mL (2 ea) [contains sodium metabisulfite]

EpiPen Jr 2-Pak: 0.15 mg/0.3 mL (2 ea) [contains sodium metabisulfite]

Generic: 0.15 mg/0.3 mL (1 ea, 2 ea); 0.15 mg/0.15 mL (2 ea); 0.3 mg/0.3 mL (1 ea, 2 ea)

Solution Auto-injector, Injection [preservative free]:

Generic: 0.15 mg/0.3 mL (1 ea, 2 ea)

Solution Prefilled Syringe, Injection:

Generic: 1 mg/10 mL (10 mL [DSC])

Solution Prefilled Syringe, Injection [preservative free]:

Symjepi: 0.15 mg/0.3 mL (1 ea); 0.3 mg/0.3 mL (2 ea) [contains sodium metabisulfite]

Generic: 1 mg/10 mL (10 mL)

Pharmacology

Mechanism of Action

Stimulates alpha-, beta₁-, and beta₂-adrenergic receptors resulting in relaxation of smooth muscle of the bronchial tree, cardiac stimulation (increasing myocardial oxygen consumption), and dilation of skeletal muscle vasculature; small doses can cause vasodilation via beta₂-vascular receptors; large doses may produce constriction of skeletal and vascular smooth muscle

Pharmacokinetics/Pharmacodynamics

Absorption

Orally ingested doses are rapidly metabolized in GI tract and liver; pharmacologically active concentrations are not achieved

Distribution

Does not cross blood-brain barrier

Metabolism

Taken up into the adrenergic neuron and metabolized by monoamine oxidase and catechol-o-methyltransferase; circulating drug hepatically metabolized

Excretion

Urine (as inactive metabolites, metanephrine, and sulfate and hydroxy derivatives of mandelic acid; small amounts as unchanged drug)

Onset of Action

Bronchodilation: SubQ: ~5 to 10 minutes

Half-Life Elimination

IV: <5 minutes

Use: Labeled Indications

Hypersensitivity: Treatment of type I allergic reactions, including anaphylactic reactions.

Hypotension/shock: Treatment of hypotension associated with septic shock in adults (increase mean arterial blood pressure).

Mydriasis during intraocular surgery (product specific): Induction and maintenance of mydriasis during intraocular surgery. Note: Not all formulations of epinephrine injection are suitable for intraocular use; consult the prescribing information.

Use: Off Label

Acute severe asthma unresponsive to inhaled beta-agonistyes

Based on the American Heart Association (AHA) guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, subcutaneous epinephrine is an effective and recommended treatment option for acute severe asthma with respiratory failure unresponsive to an inhaled beta-agonist.

Asystole/pulseless arrest, ventricular fibrillation, or pulseless ventricular tachycardiabyes

Data from a randomized, prospective, placebo-controlled trial in patients with out-of-hospital cardiac arrest demonstrated increased survival with epinephrine (compared to placebo); however, survivors in the epinephrine group had a higher incidence of severe neurologic impairment Perkins 2018.

Based on the 2015 AHA guidelines for cardiopulmonary resuscitation and emergency cardiovascular care (Adult Advanced Cardiovascular Life Support) and the 2019 AHA focused update on advanced cardiovascular life support: use of advanced airways, vasopressors, and extracorporeal cardiopulmonary resuscitation during cardiac arrest, epinephrine may be used for ventricular fibrillation or pulseless ventricular tachycardia unresponsive to initial defibrillatory shocks, and asystole/pulseless arrest.

Bradycardia unresponsive to atropine or pacingyes

Based on the AHA guidelines for cardiopulmonary resuscitation and emergency cardiovascular care (Adult Advanced Cardiovascular Life Support), epinephrine may be used for bradycardia unresponsive to atropine or pacing.

Hypotension/shock unresponsive to volume resuscitationyes

Based on the AHA guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, epinephrine may be used for hypotension/shock unresponsive to volume resuscitation.

Inotropic supportcyes

Data from a systematic review of a number of clinical trials in cardiac surgery patients support the use of low-dose epinephrine for inotropic therapy Gillies 2005.

Based on the 2010 AHA guidelines for postcardiac arrest care in adults, epinephrine may be used for inotropic support during the postresuscitation phase of cardiac arrest.

Contraindications

There are no absolute contraindications to the use of injectable epinephrine (including Adrenaclick, Auvi-Q, EpiPen, EpiPen Jr, Symjepi, Allerject [Canadian product], and Twinject [Canadian product]) in a life-threatening situation. Some products include the following contraindications: Hypersensitivity to sympathomimetic amines; general anesthesia with halogenated hydrocarbons (eg, halothane) or cyclopropane; narrow angle glaucoma; nonanaphylactic shock; in combination with local anesthesia of certain areas such as fingers, toes, and ears; use in situations where vasopressors may be contraindicated (eg, thyrotoxicosis, diabetes, in obstetrics when maternal blood pressure is in excess of 130/80 mm Hg and in hypertension and other cardiovascular disorders).

Injectable solution (Adrenalin, Epinephrine injection, USP): There are no contraindications listed in the manufacturer's labeling.

Dosage and Administration

Dosing: Adult

Note: Adrenaclick has been discontinued in the US for more than 1 year.

Note: As of May 1, 2016, ratio expressions of epinephrine concentrations are prohibited on drug labels. Ampules, vials, and syringes of epinephrine with ratio expressions may, however, remain in inventory until replaced by products with revised labeling. Therefore, the ratio expression of 1:1,000 is equivalent to 1 mg/mL and 1:10,000 is equivalent to 0.1 mg/mL (ISMP 2015).

Acute severe asthma unresponsive to inhaled beta-agonist (off-label use): IM, SubQ: 0.01 mg/kg divided into 3 doses of approximately 0.3 to 0.5 mg every 20 minutes; the 1 mg/mL concentration is recommended (AHA [Vanden Hoek 2010]; Cydulka 2016; Shah 2012).

Asystole/pulseless arrest, pulseless ventricular tachycardia/ventricular fibrillation:

IV, Intraosseous: 1 mg (using the 0.1 mg/mL solution) every 3 to 5 minutes until return of spontaneous circulation (AHA [Panchal 2019]).

Endotracheal (alternative route): 2 to 2.5 mg every 3 to 5 minutes until IV/intraosseous access established or return of spontaneous circulation; dilute in 5 to 10 mL NS or sterile water. Note: Absorption may be greater with sterile water (Naganobu 2000). May cause false-negative reading with exhaled CO₂ detectors; use second method to confirm tube placement if CO₂ is not detected (AHA [Neumar 2010]).

Bradycardia (symptomatic; unresponsive to atropine or pacing): IV infusion: 2 to 10 mcg/minute or 0.1 to 0.5 mcg/kg/minute (7 to 35 mcg/minute in a 70 kg patient); titrate to desired effect (AHA [Neumar 2010]; AHA [Peberdy 2010]).

Hypersensitivity reaction (eg, anaphylaxis): Note: IM administration in the anterolateral aspect of the middle third of the thigh is preferred in the setting of anaphylaxis (AHA [Vanden Hoek 2010]; WAO [Simons 2011]).

Endotracheal (alternative route): 2 to 2.5 mg every 3 to 5 minutes until IV/intraosseous access established; dilute in 5 to 10 mL NS or sterile water (AAAAI [Lieberman 2015]; AHA [Neumar 2010]; Campbell 2014). Note: Absorption may be greater with sterile water (Naganobu 2000).

IM: 0.2 to 0.5 mg or 0.01 mg/kg (maximum dose: 0.5 mg) using the 1 mg/mL solution; repeat every 5 to 15 minutes in the absence of clinical improvement (AAAAI [Lieberman 2015]; AHA [Vanden Hoek 2010]; WAO [Simons 2011]). Note: May administer epinephrine as a continuous IV infusion in patients not responding to IM injections (AAAAI [Lieberman 2015]; Campbell 2014).

IV: Note: In general, IV administration should only be done in patients who are unresponsive or profoundly hypotensive after failure to respond to IV fluid replacement and several epinephrine IM injections (WAO [Simons 2011]).

Slow IV bolus (off-label dose): 0.05 to 0.1 mg using the 0.1 mg/mL solution (further diluted in 10 mL of NS) administered over 5 to 10 minutes (AHA [Vanden Hoek 2010]; Barach 1984). If the patient is in cardiopulmonary arrest, use of higher IV/intraosseous bolus doses (ie, 1 mg every 3 to 5 minutes) should be employed (AAAAI [Lieberman 2015]; AHA [Neumar 2010]; Campbell 2014). Note: Rapid IV bolus administration is associated with cardiac arrhythmias, only use in this way if absolutely necessary (Campbell 2014).

Continuous infusion (off-label dose): May initiate with an infusion at 1 to 15 mcg/minute (with fluid resuscitation) (AAAAI [Lieberman 2015]; AHA [Vanden Hoek 2010]; Brown 2004; Campbell 2014).

Self-administration following severe allergic reactions (eg, insect stings, food): Note: The World Health Organization (WHO) and Anaphylaxis Canada recommend the availability of one dose for every 10 to 20 minutes of travel time to a medical emergency facility. If anaphylactic symptoms persist after first dose, may repeat dose in 5 to 15 minutes (AHA [Vanden Hoek 2010]; WAO [Simons 2011]); more than 2 sequential doses should only be administered under direct medical supervision.

Adrenaclick: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Adrenaclick injector

Allerject [Canadian product]: IM: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Allerject injector

Auvi-Q: IM, SubQ: Weight ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated

EpiPen: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional EpiPen

Symjepi: IM, SubQ: Weight ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated

Twinject [Canadian product]: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated in 5 to 15 minutes using the same device after partial disassembly

Inotropic support (off label use): IV infusion: Initial: 0.01 to 0.5 mcg/kg/minute; titrate to desired response (AHA [Peberdy 2010]; Gillies 2005; Hollenberg 2004). Note: Inotropic actions predominate at lower doses with vasoconstrictive actions at higher doses (Hollenberg 2004; Manaker 2019).

Mydriasis during intraocular surgery, induction and maintenance (product specific): Intraocular: Must dilute 1 mL of a 1 mg/mL single-use solution to a concentration of 1 to 10 mcg/mL prior to intraocular use: May use as an irrigation solution as needed during the procedure or may administer intracamerally (ie, directly into the anterior chamber of the eye) with a bolus dose of 0.1 mL of a 2.5 to 10 mcg/mL dilution. Note: Not all formulations of epinephrine injection are suitable for intraocular use; consult the prescribing information (ISMP 2017).

Shock: Note: Vasopressors should be used if patient is hypotensive during or after fluid resuscitation to maintain goal mean arterial pressure (MAP) ≥65 mm Hg (AHA [Peberdy 2010]; Levy 2018). Titrate to lowest effective dose. Institutional protocols may vary with weight-based or nonweight dose regimens.

Cardiogenic shock or post-cardiac arrest (off-label dose): IV infusion: 0.01 to 0.5 mcg/kg/minute (AHA [Peberdy 2010]; AHA [van Diepen 2017]). Note: Consider for initial use in patients with bradycardia or evidence of end organ hypoperfusion and shock (AHA [Peberdy 2010]; AHA [van Diepen 2017]).

Septic shock (adjunctive agent) (off-label dose): IV infusion: 0.01 to 0.7 mcg/kg/minute (Annane 2007; Dellinger 2017). Note: Consider for use in addition to norepinephrine (preferred vasopressor for septic shock) to achieve target MAP (SCCM [Rhodes 2017]).

Manufacturer's labeling: Dosing in the prescribing information may not reflect current clinical practice. IV infusion: Initial: 0.05 to 2 mcg/kg/minute (3.5 to 140 mcg/minute in a 70 kg patient); titrate to desired MAP. May adjust dose every 10 to 15 minutes by 0.05 to 0.2 mcg/kg/minute to achieve desired blood pressure goal.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: As of May 1, 2016, ratio expressions of epinephrine concentrations are prohibited on drug labels. Ampules, vials, and syringes of epinephrine with ratio expressions may, however, remain in inventory until replaced by products with revised labeling. Therefore, the ratio expression of 1:1,000 is equivalent to 1 mg/mL and 1:10,000 is equivalent to 0.1 mg/mL (ISMP 2015). Adrenaclick has been discontinued in the US for more than 1 year.

Asystole or pulseless arrest (PALS [Duff 2018]; PALS [Kleinman 2010]): Infants, Children, and Adolescents:

IV, Intraosseous: 0.01 mg/kg (0.1 mL/kg of 0.1 mg/mL solution) (maximum single dose: 1 mg); every 3 to 5 minutes until return of spontaneous circulation.

Endotracheal: 0.1 mg/kg (0.1 mL/kg of 1 mg/mL solution) (maximum single dose: 2.5 mg) every 3 to 5 minutes until return of spontaneous circulation or IV/intraosseous access established. Note: Recent clinical studies suggest that lower epinephrine concentrations delivered by endotracheal administration may produce transient beta 2-adrenergic effects which may be detrimental (eg, hypotension, lower coronary artery perfusion pressure). IV or intraosseous are the preferred methods of administration.

Bradycardia (PALS [Kleinman 2010]): Infants, Children, and Adolescents:

IV, Intraosseous: 0.01 mg/kg (0.1 mL/kg of 0.1 mg/mL solution) (maximum dose: 1 mg or 10 mL); may repeat every 3 to 5 minutes as needed.

Endotracheal: 0.1 mg/kg (0.1 mL/kg of 1 mg/mL solution) (maximum single dose: 2.5 mg); doses as high as 0.2 mg/kg may be effective; may repeat every 3 to 5 minutes as needed until IV/intraosseous access established. Note: Recent clinical studies suggest that lower epinephrine concentrations delivered by endotracheal administration may produce transient beta 2-adrenergic effects which may be detrimental (eg, hypotension, lower coronary artery perfusion pressure). IV or intraosseous are the preferred methods of administration.

Cardiac output increase or maintenance/post-resuscitation stabilization: Infants, Children, and Adolescents: Continuous IV or intraosseous infusion: 0.05 to 1 mcg/kg/minute; doses <0.3 mcg/kg/minute generally produce beta-adrenergic effects and higher doses (>0.3 mcg/kg/minute) generally produce alpha-adrenergic vasoconstriction; titrate dosage to desired effect (ACCM [Davis 2017]; PALS [Kleinman 2010]).

Hypersensitivity reaction/Anaphylaxis: Infants, Children, and Adolescents: Note: The preferred route of administration is IM administration in the anterolateral aspect of the middle third of the thigh; SubQ administration results in slower absorption and is less reliable (Campbell 2014; AAAAI [Lieberman 2015]; WAO [Simons 2011]).

General dosing or health care settings: IM, SubQ: 0.01 mg/kg (0.01 mL/kg/dose of 1 mg/mL solution) not to exceed: Prepubertal child: 0.3 mg/dose; adolescent: 0.5 mg/dose; administered every 5 to 15 minutes (Hegenbarth 2008; AAP [Sicherer 2017]; WAO [Simons 2011]).

Self/caregiver-administration following severe allergic reactions (eg, insect stings, food): Autoinjector dose: Note: If anaphylactic symptoms persist after first dose, may repeat dose in 5 to 15 minutes (WAO [Simons 2011]).

Manufacturer's labeling (eg, Adrenaclick, Auvi-Q, EpiPen Jr, EpiPen): IM, SubQ:

7.5 to <15 kg: 0.1 mg; if anaphylactic symptoms persist, dose may be repeated based on severity and response to initial dose; more than 2 sequential doses should only be administered under direct medical supervision.

15 to <30 kg: 0.15 mg; if anaphylactic symptoms persist, dose may be repeated based on severity and response to initial dose; more than 2 sequential doses should only be administered under direct medical supervision.

≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated based on severity and response to initial dose; more than 2 sequential doses should only be administered under direct medical supervision.

Alternate dosing: AAP Recommendations (Sicherer 2017): Limited data available:

7.5 to <25 kg: 0.15 mg.

≥25 kg: 0.3 mg.

Refractory cases (unresponsive to IM doses): Continuous IV infusion: Prepared 1 mcg/mL solution: Initial: 0.1 mcg/kg/minute; titrate dose to response. Usual range: 0.1 to 1 mcg/kg/minute; maximum dose: 10 mcg/minute (Campbell 2014; Cheng 2011; AAAAI [Lieberman 2015]). Note: Suggested concentration of initial solution is more dilute than those typically utilized in other clinical conditions; evaluate infusion concentration with continued therapy and patient fluid status.

Hypotension/shock, fluid-resistant: Infants, Children, and Adolescents:

Continuous IV infusion: 0.1 to 1 mcg/kg/minute; rates >0.3 mcg/kg/minute associated with vasopressor activity; doses up to 5 mcg/kg/minute may rarely be necessary; for fluid-resistant shock, may be combined with inotropic support (ACCM [Davis 2017]; Hegenbarth 2008).

SubQ: 0.01 mg/kg (0.01 mL/kg of 1 mg/mL solution) (maximum single dose: 0.5 mg) every 20 minutes for 3 doses (Hegenbarth 2008).

Mydriasis during intraocular surgery, induction, and maintenance (product specific): Note: Not all formulations of epinephrine injection are suitable for intraocular use; consult product labeling prior to use. Infants, Children, and Adolescents: Intraocular: Must dilute 1 mL of a 1 mg/mL preservative-/sulfite-free, single-use solution to a concentration of 1 mcg/mL to 10 mcg/mL prior to intraocular use: May use as an irrigation solution as needed during the procedure or may administer intracamerally (ie, directly into the anterior chamber of the eye) with a bolus dose of 0.1 mL of a 2.5 mcg/mL to 10 mcg/mL dilution.

Reconstitution

Endotracheal (off-label route): Dilute in NS or sterile water.

Intraocular: Dilute 1 mL of 1 mg/mL solution in 100 mL to 1,000 mL of an ophthalmic irrigation fluid for a final concentration of 1 to 10 mcg/mL); may use this solution as an irrigation as needed during the procedure. May also prepare a dilution of 2.5 to 10 mcg/mL for intracameral administration.

Intravenous: Although the manufacturer recommends dilution in dextrose containing solutions (provides protection against significant loss of potency by oxidation) and does not recommend dilution in NS alone, dilution in NS has been reported to be physically compatible (Trissel 2014).

Administration

Epinephrine solutions for injection can be administered IM, intraosseous, endotracheally, IV, or SubQ. Note: Adrenaclick, Allerject [Canadian product], Auvi-Q, EpiPen, EpiPen Jr, and Symjepi contain a single, fixed-dose of epinephrine and may only be administered IM (preferred) or SubQ. Twinject Auto-Injectors [Canadian product] contain two doses; the first fixed-dose is available for auto-injection; the second dose is available for manual injection following partial disassembly of device.

IV: When administering as a continuous infusion, central line administration is preferred. IV infusions require an infusion pump. If central line not available, as a temporary measure, may administer through a large vein. Avoid use of hand, foot, and ankle veins (due to potential for gangrene), leg veins in elderly patients, or leg veins in those suffering from occlusive vascular diseases (eg, diabetic endarteritis, Buerger disease, arteriosclerosis, atherosclerosis).

Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate phentolamine (or alternative antidote). Apply dry warm compresses (Hurst 2004; Reynolds 2014).

Phentolamine: Dilute 5 to 10 mg in 10 to 20 mL NS and administer into extravasation site as soon as possible after extravasation; may readminister if patient remains symptomatic (Reynolds 2014).

Alternatives to phentolamine:

Nitroglycerin topical 2% ointment (based on limited data): Apply a 1-inch strip to the site of ischemia; may repeat every 8 hours as necessary (Reynolds 2014).

Terbutaline (based on limited case reports): Infiltrate extravasation area using a solution of terbutaline 1 mg diluted in 10 mL NS (large extravasation site; administration volume varied from 3 to 10 mL) or 1 mg diluted in 1 mL NS (small/distal extravasation site; administration volume varied from 0.5 to 1 mL) (Reynolds 2014; Stier 1999).

Subcutaneous: SubQ administration results in slower absorption and is less reliable.

IM: IM administration in the anterolateral aspect of the middle third of the thigh is preferred in the setting of anaphylaxis (AHA [Vanden Hoek 2010]; WAO [Simons 2011]). Administer through clothing if necessary. Although the manufacturers of auto-injectors recommend varying lengths of time for holding the device in the thigh (range: 2 to 10 seconds), longer times have occasionally resulted in injury. For all devices, the needle should remain in the thigh for the least amount of time as possible. With nearly every device, the full dose is delivered within 3 seconds. For EpiPen, holding the device against the leg followed by removing the cap and then compressing has been described for easier administration. Never reinsert needles (Baker 2011; Brown 2016; Kränke 2012; Lieberman 2011). Do not administer repeated injections at the same site. Do not inject into the buttocks or into digits, hands, or feet. Adrenaclick, Adrenalin, Allerject [Canadian product], Auvi-Q, EpiPen, EpiPen Jr, Symjepi, and Twinject [Canadian product] should only be injected into the anterolateral aspect of the thigh.

Obesity: In overweight or obese children, because skin surface to muscle depth is greater in the upper half of the thigh, administration into the lower half of the thigh may be preferred. In very obese children, injection into the calf will provide an even greater chance of intramuscular administration (Arkwright 2013).

Intraocular (product specific): May administer diluted solution (concentration: 1 to 10 mcg/mL) as an irrigation solution as needed during the procedure or may administer intracamerally (ie, directly into the anterior chamber of the eye). Note: Not all formulations of epinephrine injection are suitable for intraocular use; consult the prescribing information. Appropriate products should have mydriasis during intraocular surgery as an approved indication and should not contain any sulfites or preservatives (ISMP 2017).

Endotracheal (cardiac arrest): Dilute in NS or sterile water. Absorption may be greater with sterile water (Naganobu 2000). Stop compressions, spray drug quickly down tube. Follow immediately with several quick insufflations and continue chest compressions. May cause false-negative reading with exhaled CO₂ detectors; use second method to confirm tube placement if CO₂ is not detected (AHA [Neumar 2010]).

Storage

Epinephrine is sensitive to light and air. Protection from light is recommended. Oxidation turns drug pink, then a brown color. Solutions should not be used if they are discolored or contain a precipitate.

Adrenaclick: Store between 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze or refrigerate.

Adrenalin: Store between 20°C to 25°C (68°F to 77°F); do not freeze. Diluted solution for infusion may be stored for up to 4 hours at room temperature or for 24 hours refrigerated.

Allerject [Canadian product]: Store between 15°C to 30°C (59°F to 86°F); do not refrigerate.

Auvi-Q: Store between 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not refrigerate.

Epinephrine injection, USP: Store between 20°C to 25°C (68°F to 77°F); do not refrigerate; protect from freezing.

EpiPen, EpiPen Jr, and Symjepi: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze or refrigerate.

Twinject [Canadian product]: Store between 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze or refrigerate. Protect from light.

Drug Interactions

Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Benperidol: May diminish the therapeutic effect of EPINEPHrine (Systemic). Monitor therapy

Benzylpenicilloyl Polylysine: Alpha-/Beta-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Consider therapy modification

Beta-Blockers (Beta1 Selective): May diminish the therapeutic effect of EPINEPHrine (Systemic). Monitor therapy

Beta-Blockers (Nonselective): May enhance the hypertensive effect of EPINEPHrine (Systemic). Exceptions: Arotinolol; Carvedilol; Labetalol. Monitor therapy

Beta-Blockers (with Alpha-Blocking Properties): May diminish the therapeutic effect of EPINEPHrine (Systemic). Monitor therapy

Blonanserin: May diminish the therapeutic effect of EPINEPHrine (Systemic). Avoid combination

Bretylium: May enhance the therapeutic effect of Alpha-/Beta-Agonists (Direct-Acting). Monitor therapy

Bromperidol: May diminish the therapeutic effect of EPINEPHrine (Systemic). Avoid combination

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Chloroprocaine: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Monitor therapy

CloZAPine: May diminish the therapeutic effect of Alpha-/Beta-Agonists. Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

COMT Inhibitors: May decrease the metabolism of COMT Substrates. Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Ergot Derivatives: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

Hyaluronidase: May enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Consider therapy modification

Inhalational Anesthetics: May enhance the arrhythmogenic effect of EPINEPHrine (Systemic). Management: Administer epinephrine with added caution in patients receiving, or who have recently received, inhalational anesthetics. Use lower than normal doses of epinephrine and monitor for the development of cardiac arrhythmias. Consider therapy modification

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Lurasidone: EPINEPHrine (Systemic) may enhance the hypotensive effect of Lurasidone. Avoid combination

Monoamine Oxidase Inhibitors: May enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy

Promethazine: May diminish the vasoconstricting effect of EPINEPHrine (Systemic). Management: When vasoconstrictive effects are desired in patients receiving promethazine, consider alternatives to epinephrine. Consider use of norepinephrine or phenylephrine, and avoid epinephrine, when treating hypotension associated with promethazine overdose. Consider therapy modification

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Consider therapy modification

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Monitor therapy

Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Consider therapy modification

Adverse Reactions

Frequency not defined:

Cardiovascular: Angina pectoris, cardiac arrhythmia, cardiomyopathy (stress), cerebrovascular accident, chest pain, hypertension, increased cardiac work, ischemic heart disease, limb ischemia, localized blanching, myocardial infarction, palpitations, peripheral vasoconstriction, supraventricular tachycardia, tachyarrhythmia, tachycardia, vasoconstriction, ventricular arrhythmia, ventricular ectopy, ventricular fibrillation

Central nervous system: Anxiety, apprehension, cerebral hemorrhage, disorientation, dizziness, drowsiness, exacerbation of Parkinson disease, headache, memory impairment, panic, paresthesia, psychomotor agitation, restlessness, tingling sensation

Dermatologic: Diaphoresis, gangrene of skin or other tissue (at injection site), pallor, piloerection

Endocrine & metabolic: Hyperglycemia, hypoglycemia, hypokalemia, insulin resistance, lactic acidosis

Gastrointestinal: Nausea, vomiting

Local: Tissue necrosis at injection site

Neuromuscular & skeletal: Asthenia, tremor

Renal: Renal insufficiency

Respiratory: Dyspnea, pulmonary edema, rales

Warnings/Precautions

Concerns related to adverse effects:

• Cardiac effects: May precipitate or aggravate angina pectoris or induce cardiac arrhythmias; use with caution especially in patients with cardiac disease or those receiving drugs that sensitize the myocardium.
• Extravasation: IV administration: Vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
• Pulmonary edema: Due to peripheral constriction and cardiac stimulation, pulmonary edema may occur.
• Renal effects: Due to renal blood vessel constriction, decreased urine output may occur.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular diseases (eg, arrhythmias, cerebrovascular disease, coronary artery disease, heart disease, hypertension).
• Diabetes: Use with caution in patients with diabetes mellitus; may transiently increase blood glucose levels.
• Hypovolemia: Correct blood volume depletion before administering any vasopressor.
• Parkinson disease: Use with caution in patients with Parkinson disease; psychomotor agitation or temporary worsening of symptoms may occur.
• Pheochromocytoma: Use with caution in patients with pheochromocytoma.
• Thyroid disease: Use with caution in patients with thyroid disease.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in elderly patients.
• Pediatric: Lacerations, bent needles, and embedded needles have been reported in young children who are uncooperative during injection for hypersensitivity reaction. To minimize risk, hold the child's leg firmly in place and limit movement prior to and during injection. Although the manufacturers of auto-injectors recommend varying lengths of time for holding the device in the thigh (range: 2 to 10 seconds), longer times have occasionally resulted in injury. For all devices, the needle should remain in the thigh for the least amount of time as possible (~3 seconds) (Brown 2016) (also see Administration: IM).

Dosage form specific issues:

• Accidental injection: Accidental injection into digits, hands, or feet may result in local reactions including injection-site pallor, coldness, and hypoesthesia or injury resulting in bruising, bleeding, discoloration, erythema, or skeletal injury. Patient should seek immediate medical attention if this occurs.
• Intraocular use: Not all formulations of epinephrine injection are suitable for intraocular use; consult the prescribing information prior to selecting a product. Appropriate products should have an indication for induction and maintenance of mydriasis during intraocular surgery and should not contain any sulfites or preservatives (ISMP 2017). Prior to intraocular use of an appropriate product, must dilute single-use 1 mg/mL (1 mL) solution to a concentration of 1 mcg/mL to 10 mcg/mL. Corneal endothelial damage has occurred when products containing sodium bisulfite have been used undiluted; therefore, dilution is advised prior to any intraocular use. In addition, products containing chlorobutanol must also not be used intraocularly (may be harmful to corneal endothelium).
• IV administration: Rapid IV administration may cause death from cerebrovascular hemorrhage or cardiac arrhythmias. However, rapid IV administration during pulseless arrest is necessary.
• Sulfites: Some products may contain sulfites as preservatives. The presence of sulfites in some products should not deter administration during a serious allergic or other emergency situation even if the patient is sulfite-sensitive.

Other warnings/precautions:

• Appropriate use: Hypersensitivity reactions: Do not inject into the buttock; may not effectively treat anaphylaxis and has been associated with Clostridial infections (gas gangrene). Serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported rarely at the injection site. Cleansing skin with alcohol may reduce bacteria at the injection site, but alcohol cleansing does not kill Clostridium spores. Preferred injection site is anterolateral aspect of the thigh. Do not administer repeated injections at the same site (tissue necrosis may occur). Monitor for signs/symptoms of injection-site infection.

Monitoring Parameters

Heart rate, blood pressure (invasive blood pressure monitoring recommended while receiving continuous infusion); monitor site of infusion for blanching/extravasation; continuous cardiac monitoring required during continuous infusion. If using to treat hypotension, assess intravascular volume prior to and during therapy; support as needed; monitor for cardiac arrhythmias, hyperlactatemia, and hyperglycemia.

Consult individual institutional policies and procedures.

Pregnancy

Pregnancy Considerations

Epinephrine crosses the placenta (Sandler 1964).

Epinephrine is recommended for the treatment of anaphylaxis in pregnant women. Specific dosing is not available; use with caution and monitor hemodynamic response (Hepner 2013). Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant woman. Doses and indications should follow current Advanced Cardiovascular Life Support guidelines. Appropriate medications should not be withheld due to concerns of fetal teratogenicity (Jeejeebhoy [AHA] 2015).

Patient Education

What is this drug used for?

• It is used to treat a very bad allergic response.
• It is used to treat low blood pressure.
• It is used during eye surgery.
• It is used when the heart is not beating.
• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Anxiety
• Tremors
• Nausea
• Vomiting
• Agitation
• Sweating a lot
• Pale skin

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Severe headache
• Dizziness
• Passing out
• Vision changes
• Unable to pass urine
• Change in amount of urine passed
• Chest pain
• Fast heartbeat
• Abnormal heartbeat
• Shortness of breath
• Severe loss of strength and energy
• Infection at injection site
• Injection site redness, burning, edema, pain, or irritation
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.