Brand names: Adrenaclick, Adrenalin, Auvi-Q, EpiPen
Drug class: alpha- and beta-Adrenergic Agonists
VA class: AU100
CAS number: 51-43-4

Medically reviewed by Drugs.com on Feb 21, 2024. Written by ASHP.

Introduction

Epinephrine is an endogenous catecholamine that is the active principle of the adrenal medulla; epinephrine acts directly on both α- and β-adrenergic receptors.^a

Uses for Epinephrine

Sensitivity Reactions

Drug of choice in the emergency treatment of severe acute anaphylactic reactions, including anaphylactic shock.^{163 169 172 193 195 196 197 200 212 228}

Used to relieve anaphylactic symptoms (e.g., urticaria, pruritus, angioedema, hypotension, respiratory distress) caused by reactions to drugs, contrast media, insect stings, foods (e.g., milk, eggs, fish, shellfish, peanuts, tree nuts), latex, or other allergens; also used for idiopathic or exercise-induced anaphylaxis.^{163 195 197 212}

Administer immediately by IM injection as soon as anaphylaxis is diagnosed or strongly suspected.^{196 197 228}

Administration by IM injection preferred, mainly because of safety considerations.^{196 197 198 199 200 201 228} However, IV administration may be necessary in extreme situations (e.g., anaphylactic shock, cardiac arrest, unresponsive or severely hypotensive patients who have failed to respond to multiple IM injections).^{196 197 198 199 200 201 228} Close hemodynamic monitoring is recommended during IV administration.¹⁹⁶

Also used for its vasopressor effects in the treatment of anaphylactic shock and cardiac arrest associated with anaphylaxis.^{196 212}

Manage cardiac arrest secondary to anaphylaxis with standard ACLS measures; consider alternative vasoactive drugs (e.g., vasopressin, norepinephrine) in patients who do not respond to epinephrine.¹⁹⁶ (See ACLS and Cardiac Arrhythmias under Uses.) Consider other interventions (e.g., antihistamines, inhaled β₂-adrenergic agents, IV corticosteroids) as clinically indicated.^{196 197}

Risk of paradoxical response to epinephrine in patients receiving β-adrenergic blocking agents; consider glucagon and/or ipratropium for treatment of anaphylaxis in these patients.^{197 228}

ACLS and Cardiac Arrhythmias

Used for its α-adrenergic effects to increase blood flow and facilitate return of spontaneous circulation (ROSC) during cardiac arrest.^{172 179 193 212 400 401 402 403} Principal benefits of the drug result from increases in aortic diastolic blood pressure and in coronary and cerebral blood flow during resuscitation.^{400 401 403}

High-quality CPR and defibrillation are the only proven interventions to increase survival to hospital discharge in ACLS.^{400 401} Other resuscitative efforts, including drug therapy, are considered secondary and should be performed without compromising the quality and timely delivery of chest compressions and defibrillation.^{400 401}

Principal goal of pharmacologic therapy during cardiac arrest is to facilitate ROSC, and epinephrine is the drug of choice for this use.^{400 401}

ACLS guidelines state that administration of epinephrine may be reasonable in adults with VF or pulseless VT resistant to initial CPR attempts and at least one defibrillation shock; optimal timing of administration (particularly in relation to defibrillation) not known and may vary based on patient-specific factors and resuscitation conditions.^{400 401} In adults with asystole or pulseless electrical activity (PEA), epinephrine may be administered as soon as feasible after onset of cardiac arrest.^{400 401}

Also may be used in the postresuscitation period to optimize BP, cardiac output, and systemic perfusion after ROSC.^{402 403 404}

Used during the periarrest period for treatment of symptomatic bradycardia in adults; although not a first-line drug, may be considered in patients who are unresponsive to atropine or as a temporizing measure while awaiting availability of a pacemaker.⁴⁰¹

Also used in the emergency treatment of infants and children with bradycardia and cardiopulmonary compromise (with a palpable pulse) when bradycardia persists despite ventilation, oxygenation, and chest compressions.⁴⁰³

Drugs are rarely needed during resuscitation of neonates; because hypoxemia and inadequate lung inflation are common causes of bradycardia, establishing adequate ventilation is the most important corrective measure in these patients.^{213 214}

Also has been used in the treatment of syncope resulting from AV nodal block.^{172 193 401} However, permanent pacemaker implantation is the treatment of choice for third-degree and advanced second-degree AV nodal block (complete heart block).¹⁸²

Septic Shock

Used for treatment of hypotension associated with septic shock, generally as a second-line agent.^{195 204 205 207 208 209 235 238}

The Surviving Sepsis Campaign International Guidelines for Management of Sepsis and Septic Shock recommend norepinephrine as the first-line vasopressor of choice in adults with septic shock; if adequate BP not achieved, epinephrine may be added.^{204 205 208}

Vasopressor therapy is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes.²¹² Correct blood volume depletion as fully as possible before administration of epinephrine.¹⁹⁵

Should not be used in cardiogenic shock (because it increases myocardial oxygen demand) or in hemorrhagic or traumatic shock.^{172 206 208 212}

Local Vasoconstriction

May be added to solutions of some local anesthetics to decrease the rate of vascular absorption (to localize and prolong the duration of anesthesia and decrease the risk of systemic toxicity).^{172 215 216}

Has been applied topically to control superficial bleeding from arterioles or capillaries in the skin, mucous membranes, or other tissues.^a Bleeding from larger vessels is not controllable by topical application.^a

Premature Labor

Has been used to relax uterine musculature and inhibit uterine contractions in premature labor^{† [off-label]} (tocolysis); however, the cardiovascular and other adverse effects limit its usefulness.^a (See Pregnancy under Cautions.) Other β-agonists (e.g., terbutaline) preferred.^{165 173}

Bronchospasm

Has been used as an oral bronchodilator for symptomatic treatment of asthma.^{166 191 192 194 236} However, an epinephrine preparation for oral inhalation no longer commercially available in US.^{166 223 236}

While orally inhaled epinephrine was once widely used in the treatment of asthma,^{191 194} the drug has been replaced by more selective and rapid-acting agents (e.g., inhaled β₂-adrenergic agonists).^{160 192 202 203}

Also has been used IV for treatment of severe asthma exacerbations; however, no evidence that the drug improves outcomes compared with selective inhaled β₂-adrenergic agonists.^{193 196}

Upper GI Hemorrhage

Has been used as an endoscopic treatment modality (as a dilute solution injected into and around ulcer base) to produce tamponade and achieve hemostasis in patients with acute nonvariceal upper GI bleeding^{† [off-label]}.^{229 230 231 232 233 234} Should not be used as monotherapy; use in combination with additional treatment modality (e.g., clips, thermocoagulation).^{229 230 231 232 233 234}

Epinephrine Dosage and Administration

Effective May 1, 2016, USP changed its labeling standard for all single-entity preparations of epinephrine injection, USP to require that dosage strengths be expressed only in terms of strength per mL (e.g., mg/mL).²²⁷ Use of ratio expressions (e.g., 1:1000 or 1:10,000) no longer is acceptable.^{226 227} Labeling change was prompted by numerous reports of serious medication errors caused by confusion with different ratio expressions.^{200 226}

Usually administered parenterally (by IM, sub-Q, or IV injection or by continuous IV infusion).^{163 169 172 193 195 212}

Select appropriate concentration and route of administration carefully; serious adverse effects (e.g., cerebral hemorrhage) have occurred after concentrated solutions of epinephrine intended for IM administration were administered IV.^{163 197 199 200 201 212 221} Generally administer IV only in extreme situations (e.g., septic or anaphylactic shock, cardiac arrest, or when patient is unresponsive to multiple IM injections).^{196 197 198 199 200 201 204 228} Always use dilute solutions of epinephrine (e.g., 0.1 mg/mL) when administering IV.^{101 172 200 212} Commercially available epinephrine solutions for IM or sub-Q injection are more concentrated (1 mg/mL) and should not be administered IV without dilution.^{172 212}

Also has been administered by intraosseous (IO) injection or infusion^{† [off-label]} in the ACLS setting, generally when IV access not readily available; onset of action and systemic concentrations are comparable to those achieved with venous administration.^{401 403}

May be administered endotracheally if vascular access (IV or IO) cannot be established during cardiac arrest.^{175 193 401 403}

Also has been administered by intracardiac injection (into the left ventricular chamber) during cardiac arrest;^{161 172 193 212} however, this route of administration not recommended in current ACLS guidelines.^{400 401 403}

Solutions of epinephrine have been applied topically to the skin, mucous membranes, or other tissues for local hemostasis.^a

Also has been administered by oral inhalation in the treatment of asthma; however, an oral inhalation preparation no longer commercially available in the US.^{166 223 236}

IM or Sub-Q Injection

Injections containing 1 mg/mL may be administered IM or sub-Q; avoid IM injections in the buttock.^{169 195 197 219 221} When epinephrine is used for the treatment of anaphylaxis, inject into anterolateral aspect of thigh; injection into or near smaller muscles (i.e., deltoid muscle) not recommended because of possible differences in absorption.^{169 195 197 219 221} When administered sub-Q, absorption and subsequent achievement of peak plasma concentrations is slower and may be substantially delayed if shock is present.¹⁹⁶

Commercially available as a prefilled auto-injector for emergency treatment of allergic reactions.^{163 219 221} When using the auto-injector, administer appropriate weight-based dose by IM or sub-Q injection into anterolateral aspect of thigh; may administer through clothing if necessary.^{163 164 219 221} Do not reuse auto-injectors.^{164 220 222} Consult manufacturer's prescribing information for additional instructions.^{163 164 219 220 221 222}

For self-medication, instruct patients and caregivers about proper administration techniques using the auto-injector provided by the manufacturer.^{163 164 219 221} First aid providers should be familiar with the auto-injector in order to assist patients experiencing an anaphylactic reaction, and they should be able to administer the auto-injector in the event that patient is unable to self-administer, provided that state law permits and valid prescription exists.²¹⁷

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

May administer by slow, direct IV injection or continuous IV infusion.^{193 195 197} Commercially available as a 0.1-mg/mL solution for IV administration.^{193 212} Must further dilute the commercially available 1-mg/mL solution prior to IV administration.^{101 195 238}

Extreme caution recommended when epinephrine is administered by direct IV injection since risk of overdosage and adverse cardiovascular effects is substantially higher; administer slowly and with close hemodynamic monitoring.^{193 196 198 228}

During cardiac resuscitation, may administer IV into a central or peripheral line.^{212 401} CPR should not be interrupted for placement of a central line.⁴⁰¹ After administration through a peripheral line, flush with 20 mL of IV fluid and elevate extremity to ensure drug delivery into central compartment.⁴⁰¹

To minimize risk of necrosis, administer continuous IV infusions into a large vein.¹⁹⁵ Avoid catheter tie-in technique to avoid stasis and increased local concentrations of the drug.¹⁹⁵ Take care to avoid extravasation because local necrosis may result.¹⁹⁵

Dilution

Must dilute the commercially available 1-mg/mL solution prior to IV administration.^{101 195 238}

Various methods have been described for diluting epinephrine solutions for IV administration; consult manufacturers' information for specific instructions.^{101 195 238}

Rate of Administration

Administer slowly (after appropriate dilution) by IV injection or continuous IV infusion.^{193 195 196 197 228}

Recommended rates of infusion vary based on indicated use.^{196 228 401 403 404} While low rates (e.g., <0.3 mcg/kg per minute) generally produce predominantly β-adrenergic effects and higher rates (e.g., >0.3 mcg/kg per minute) produce α-adrenergic vasoconstriction,⁴⁰³ there is substantial interindividual variability; titrate infusion rate based on clinical response.^{196 228 401 403 404} (See Dosage under Dosage and Administration.)

Topical Administration

Apply solutions topically as a spray or on cotton or gauze to the skin, mucous membranes, or other tissues.^a

Dosage

Dosage of epinephrine salts is expressed in terms of epinephrine.^a

Pediatric Patients

Sensitivity Reactions

Anaphylaxis

IM or Sub-Q

0.01 mg/kg (0.01 mL/kg of a 1-mg/mL solution) (up to 0.3–0.5 mg per dose depending on patient weight); repeat every 5–15 minutes as needed.^{169 195 197 212 218} Some clinicians state that doses may be repeated at 20-minute to 4-hour intervals depending on severity of the condition and patient response.²¹¹

For self-administration using a prefilled auto-injector, inject 0.15 or 0.3 mg, depending on body weight; 0.3 mg recommended for patients weighing ≥30 kg and 0.15 mg recommended for patients weighing 15–30 kg.^{163 219 221} Use alternative injectable forms if dose <0.15 mg considered more appropriate.^{163 219 221} For severe persistent anaphylaxis, repeat doses may be needed; if >2 sequential doses are required, administer subsequent doses only under direct medical supervision.^{163 219 221}

IV

If necessary, initial dose of 0.01 mg/kg (0.1 mL/kg of a 0.1-mg/mL solution) may be administered.¹⁰¹ If repeat doses are required, initiate a continuous IV infusion at a rate of 0.1 mcg/kg per minute; increase gradually to 1.5 mcg/kg per minute to maintain BP.¹⁰¹

Pediatric Advanced Life Support (PALS)

IV or IO

Neonates: Usual IV dose is 0.01–0.03 mg/kg (0.1–0.3 mL/kg of a 0.1-mg/mL solution).^{213 214} Higher doses not recommended because of risk of exaggerated hypertension, decreased myocardial function, and worsening neurologic function.²¹³

Pediatric patients: Usual IV/IO dose is 0.01 mg/kg (0.1 mL/kg of a 0.1-mg/mL solution), up to a maximum single dose of 1 mg, repeated every 3–5 minutes as needed.^{402 403} Lack of survival benefit and potential harm from routine use of higher doses, particularly in cases of asphyxia.^{181 403} However, may consider high-dose epinephrine in exceptional circumstances (e.g., β-adrenergic blocking agent overdose).⁴⁰³

For postresuscitation stabilization in pediatric patients, usual dosage is 0.1–1 mcg/kg per minute by IV/IO infusion; adjust based on patient response.⁴⁰³ Low-dose infusions (<0.3 mcg/kg per minute) generally produce predominantly β-adrenergic effects, while higher-dose infusions (>0.3 mcg/kg per minute) result in α-adrenergic vasoconstriction.⁴⁰³

For emergency treatment of infants and children with bradycardia and cardiopulmonary compromise (with a palpable pulse), may give 0.01 mg/kg (0.1 mL/kg of a 0.1-mg/mL solution) by IV/IO injection, repeated every 3–5 minutes as needed.⁴⁰³

Endotracheal

Optimum dose not established.⁴⁰³

Neonates: If endotracheal route is used, doses of 0.01 or 0.03 mg/kg will likely be ineffective.²¹³ Although safety and efficacy not established, consider endotracheal administration of a higher dose (0.05–0.1 mg/kg) while IV access is being obtained.^{213 214}

Pediatric patients: Usual dose is 0.1 mg/kg (0.1 mL/kg of a 1-mg/mL solution), up to a maximum single dose of 2.5 mg, for cardiac resuscitation; repeat every 3–5 minutes as needed.^{402 403} Flush with at least 5 mL of 0.9% sodium chloride injection after each dose.⁴⁰³

For emergency treatment of infants and children with bradycardia and cardiopulmonary compromise (with a palpable pulse), may administer endotracheally at a dose of 0.1 mg/kg (0.1 mL/kg of a 1-mg/mL solution) if IV/IO access not available.⁴⁰³

Septic Shock

IV

If epinephrine is used in pediatric patients, some clinicians have recommended an infusion rate of 0.05–0.3 mcg/kg per minute, titrated to effect.^{204 237}

When therapy is discontinued, decrease infusion rate gradually (e.g., by reducing every 30 minutes over a 12- to 24- hour period).¹⁹⁵

Bronchospasm

Sub-Q

Pediatric patients ≤12 years of age: For severe asthma, inject 0.01 mg/kg (0.01 mL/kg of a 1-mg/mL solution) every 20 minutes as needed for 3 doses; do not exceed 0.3–0.5 mg per dose.¹⁶⁰

Adolescents >12 years of age: 0.3–0.5 mg every 20 minutes as needed for 3 consecutive doses.^{160 162}

IV

Neonates: 0.01 mg/kg by slow IV injection has been recommended.^{193 211}

Infants: Initially, 0.05 mg by slow IV injection; may repeat every 20–30 minutes as needed.^{193 211}

Adults

Sensitivity Reactions

Anaphylaxis

IM or Sub-Q

Usual dose is 0.2–0.5 mg (0.2–0.5 mL of a 1-mg/mL solution); repeat every 5–15 minutes as needed.^{163 169 195 196 197 200 212 228}

For self-administration using a prefilled auto-injector, inject 0.3 mg.^{163 219 221} For severe persistent anaphylaxis, repeat doses may be needed; if >2 sequential doses are needed, administer subsequent doses only under direct medical supervision.^{163 219 221}

IV

In extreme circumstances (e.g., anaphylactic shock, cardiac arrest, or no response to initial IM injections), IV administration may be necessary.^{175 196 198 200 201 228}

Usual IV dose is 0.1–0.25 mg (1–2.5 mL of a 0.1-mg/mL solution); repeat every 5–15 minutes as necessary.^{193 212}

Alternatively, may administer as a continuous infusion at a rate of 2–15 mcg/minute; titrate based on severity of the reaction and clinical response.^{196 228}

ACLS and Cardiac Arrhythmias

Cardiac Arrest

IV or IO

ACLS guidelines recommend 1 mg every 3–5 minutes by IV/IO injection.^{400 401}

Higher doses (e.g., 0.1–0.2 mg/kg) do not provide any benefits in terms of survival or neurologic outcomes compared with the standard dose (1 mg) and may be harmful.^{115 118 175 400}

Optimal timing of administration, particularly in relation to defibrillation, not known and may vary based on patient-specific factors and resuscitation conditions.⁴⁰⁰ In adults with asystole or PEA, may administer as soon as feasible after onset of cardiac arrest based on studies demonstrating improved survival to hospital discharge and increased ROSC when the drug is administered early during course of treatment for a nonshockable rhythm.^{400 401}

For postresuscitation stabilization, usual IV dosage is 0.1–0.5 mcg/kg per minute; adjust based on patient response.⁴⁰⁴

Endotracheal

Optimal dose not established, but typical doses are 2–2.5 times those administered IV.⁴⁰¹

Bradycardia:

IV

For symptomatic bradycardia, initial IV infusion rate of 2–10 mcg/minute has been recommended; adjust according to patient response.⁴⁰¹

Adjunct to Local Anesthesia

Local Injection

In conjunction with local anesthetics, has been used in concentrations of 0.002–0.02 mg/mL; most frequently used concentration is 0.005 mg/mL.^a

Superficial Bleeding

Topical

As a topical hemostatic, solution concentrations of 0.002–0.1% have been sprayed or applied with cotton or gauze to the skin, mucous membranes, or other tissues.^a

Septic Shock

IV

Manufacturer suggests IV infusion of 0.05–2 mcg/kg per minute.¹⁹⁵ May increase infusion rate by 0.05–0.2 mcg/kg per minute every 10–15 minutes to achieve desired BP goal.¹⁹⁵ Duration of therapy or total dose required not known; treatment may be necessary for several hours or days until the patient's hemodynamic status improves.¹⁹⁵

When therapy is discontinued, decrease infusion rate gradually (e.g., by reducing every 30 minutes over a 12- to 24-hour period).¹⁹⁵

Bronchospasm

Sub-Q

For severe asthma, 0.3–0.5 mg (0.3–0.5 mL of a 1-mg/mL solution) may be administered every 20 minutes for 3 doses.¹⁶⁰

Alternatively, may administer 0.01 mg/kg (using a 1-mg/mL solution) divided into 3 doses of approximately 0.3 mg each, given at 20-minute intervals.¹⁹⁶

IV

0.1–0.25 mg (1–2.5 mL of a 0.1-mg/mL solution) injected slowly.¹⁹³

Prescribing Limits

Pediatric Patients

Sensitivity Reactions

Anaphylaxis

IM or Sub-Q

Maximum for pediatric patients: 0.3–0.5 mg of epinephrine per dose depending on weight.^{169 195 197 211 212 218}

Pediatric Resuscitation

IV/IO

Maximum single dose of 1 mg.^{402 403}

Endotracheal

Maximum single dose of 2.5 mg.⁴⁰³

Bronchospasm

Sub-Q

Maximum for pediatric patients ≤12 years of age: 0.3–0.5 mg per dose.^{a 160 162}

Adults

Sensitivity Reactions

Anaphylaxis

IM or Sub-Q

Single doses should not exceed 0.5 mg.^{169 195 197}

Cautions for Epinephrine

Contraindications

• No absolute contraindications to use in life-threatening conditions.²⁰⁰

• Relative contraindications include shock (other than anaphylactic and septic shock), known hypersensitivity to sympathomimetic amines, coronary insufficiency, or cardiac dilatation, as well as use in most patients with angle-closure glaucoma, or organic brain damage.^{193 195 212} Contraindicated for use during general anesthesia with agents such as cyclopropane and halogenated hydrocarbon anesthetics (e.g., halothane).^{193 212}

• Contraindicated in conjunction with local anesthetics for use in certain areas (e.g.,fingers, toes, ears).^{172 212}

Warnings/Precautions

Warnings

High BP Induction

Inadvertent induction of high arterial BP with epinephrine can cause angina pectoris, aortic rupture, or cerebral hemorrhage.^{172 193}

Hypovolemia

Vasopressor therapy is not a substitute for replacement of blood, plasma, fluids, and/or electrolytes.²¹² Correct blood volume depletion as fully as possible before epinephrine administration.¹⁹⁵

Extravasation

Avoid extravasation; severe local adverse effects (e.g., tissue necrosis) may occur as a result of local vasoconstriction.¹⁹⁵

Check site of infusion frequently for free flow and observe infused vein for blanching.¹⁹⁵

Avoid injection into leg veins, especially in geriatric patients or those with occlusive vascular diseases (e.g., arteriosclerosis, atherosclerosis, Buerger’s disease, diabetic endarteritis).¹⁹⁵

If blanching is observed in the infused vein, changing the injection site periodically may be advisable.¹⁹⁵

If extravasation occurs, infiltrate affected area liberally with 10–15 mL of sodium chloride solution containing 5–10 mg of phentolamine mesylate.¹⁹⁵ Immediate and conspicuous local hyperemic changes occur if area is infiltrated within 12 hours; therefore, administer phentolamine as soon as possible after extravasation noted.¹⁹⁵

Concomitant Diseases

Adverse reactions most likely to occur in hypertensive or hyperthyroid patients; use with extreme caution, if at all.^a

Use with caution in patients with Parkinson's disease, diabetes mellitus, pheochromocytoma, cardiovascular disease, or psychoneurotic disorders.^{195 212}

Cardiac Arrhythmias

Can induce serious cardiac arrhythmias in patients without heart disease, in those with organic heart disease, and in those with drug-induced myocardial sensitization.^{172 193}

General Anesthetics

Can convert asystole to VF in anesthetic cardiac accidents since many anesthetics sensitize the myocardium to epinephrine.²¹²

Cyclopropane or halogenated hydrocarbon general anesthetics that increase cardiac irritability and seem to sensitize the myocardium to epinephrine may cause arrhythmias including VPC, VT, or VF.^{a 172 193} (See Contraindications under Cautions.)

Sensitivity Reactions

Sulfites

Some formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.¹⁰²

Presence of sulfites in a parenteral epinephrine preparation and the possibility of allergic-type reactions should not deter use of the drug when indicated for the treatment of serious allergic reactions or for other emergency situations.¹⁰² Epinephrine is the preferred treatment for such conditions, and currently available alternatives to epinephrine may not be optimally effective.¹⁰²

Consider that sulfites may be responsible for paradoxical worsening of respiratory function in asthmatics or for worsening symptoms or decreased bronchodilatory response with increasing use of the drug.^a

Sympathomimetic Amines

Caution in those with a history of sensitivity to sympathomimetic amines.^a

General Precautions

Cardiovascular Effects

Can cause VF, but beneficial effects in restoring electrical activity and enhancing defibrillation are well documented.^{172 193}

May cause tachycardia, ventricular ectopy, tachyarrhythmias, hypertension, and vasoconstriction in patients with a perfusing rhythm.¹⁷⁵

Caution in patients with underlying cardiovascular disease (e.g., cardiac arrhythmias, coronary artery disease, organic heart disease).¹⁶³

Extreme caution in patients with prefibrillatory rhythm because of excitatory cardiac activity.¹⁹³

Overdosage or inadvertent IV administration may cause cerebrovascular hemorrhage secondary to a marked increase in BP.²¹²

Respiratory Disease and Effects

Caution in patients with long-standing bronchial asthma and substantial emphysema who may also have degenerative heart disease.^a

Can cause pulmonary edema secondary to peripheral vasoconstriction and cardiac stimulation.¹⁹⁵

Diuretics

May decrease vascular vasopressor response.^{172 193}

MAO Inhibitors

Use vasopressors cautiously with MAO inhibitors.^{172 193}

Specific Populations

Pregnancy

Category C.^{163 172 193}

Use during pregnancy only if clearly indicated.^{195 212}

Some manufacturers state that epinephrine injection should be avoided during the second stage of labor or when maternal BP is >130/80 mm Hg.^{195 212}

When administered in ACLS, may decrease blood flow to the uterus; however, the woman must be resuscitated for survival of the fetus.^{195 196}

Lactation

Risk unknown.¹⁷¹

Pediatric Use

Used in pediatric patients of all ages, dosing according to body weight.^{101 160 162 163 172 193 403}

Geriatric Use

Use with caution.^{a 195}

Common Adverse Effects

Fear, anxiety, tenseness, restlessness, headache, tremor, dizziness, lightheadedness, nervousness, sleeplessness, excitability, and weakness.^a Increased rigidity and tremor in patients with parkinsonian syndrome. May aggravate or induce psychomotor agitation, disorientation, impaired memory, assaultive behavior, panic, hallucinations, suicidal or homicidal tendencies, and psychosis characterized by clear consciousness with schizophrenic-like thought disorder and paranoid delusions.^a Nausea, vomiting, sweating, pallor, respiratory difficulty, or respiratory weakness and apnea.^a

ECG changes including a decrease in T-wave amplitude in all leads in normal individuals.^a Disturbances of cardiac rhythm and rate may result in palpitation and tachycardia.^a Aggravation or precipitation of angina pectoris by increasing cardiac work and accentuating the insufficiency of the coronary circulation.^a Potentially fatal ventricular arrhythmias including fibrillation, especially in patients with organic heart disease or those receiving other drugs that sensitize the heart to arrhythmias.^a

Hypertension secondary to overdosage or inadvertent IV injection of usual sub-Q doses.^a Subarachnoid hemorrhage and hemiplegia have resulted from hypertension, even following usual sub-Q doses.^a

Necrosis from repeated injections because of vascular constriction at the injection site.^a Tissue necrosis in the extremities, kidneys, and liver.^a

Severe metabolic acidosis from prolonged use or overdosage because of elevated blood concentrations of lactic acid.^a

Absorption from the respiratory tract following large orally inhaled doses may result in adverse effects similar to those occurring after parenteral administration.^a Rebound bronchospasm may occur when the effects of epinephrine end.^a Further reductions in arterial oxygen tension.^a Dryness of pharyngeal membranes may follow oral inhalation.^a

Drug Interactions

Specific Drugs

Epinephrine Pharmacokinetics

Absorption

Bioavailability

Rapidly metabolized in the GI tract and liver after oral ingestion; pharmacologically active concentrations are not reached when given orally.^a

Well absorbed after sub-Q or IM injection; absorption can be hastened by massaging the injection site.^a

Absorbed rapidly through the lung capillary bed following endotracheal administration;¹⁹³ serum concentrations achieved only 10% of those with an equivalent IV dose.¹⁶¹

Absorption is slight and the effects are restricted mainly to the respiratory tract after usual orally inhaled doses; absorption somewhat increased when larger doses are inhaled, and systemic effects may occur.^a

Onset

Rapid onset of action when solutions are administered parenterally or by oral inhalation.^{a 163}

Sub-Q injection in asthmatic attacks may produce bronchodilation within 5–10 minutes and maximal effects in about 20 minutes.^a

After oral inhalation, bronchodilation usually occurs within 1 minute.^a

Duration

Short duration of action when solutions are administered parenterally or by oral inhalation.^{a 163}

Distribution

Extent

Epinephrine crosses the placenta but not the blood-brain barrier.^a

Distributed into milk.^a

Elimination

Metabolism

Pharmacologic actions are terminated mainly by uptake and metabolism in sympathetic nerve endings.^a

Circulating drug is metabolized in the liver and other tissues by a combination of reactions involving the enzymes catechol-O-methyltransferase (COMT) and MAO.^a

Elimination Route

40% excreted in urine, mainly as inactive metabolites.^a

Stability

Storage

Epinephrine, epinephrine salts, and preparations containing the drug gradually darken on exposure to light and air and must be stored in tight, light-resistant containers.^{a 167}

Discard solutions with a color that is pinkish or darker than slightly yellow or that contain a precipitate.^{a 167}

Commercially available preparations vary in stability, depending on the form in which epinephrine is present and on the preservatives used.^a Follow the manufacturer’s directions with respect to storage requirements for each product.^a

Parenteral

Injection

Epinephrine: 20–25°C; protect from light and freezing.^{169 172 193 195 238}

In some commercially available injections, air has been replaced with nitrogen to avoid oxidation.^a

Withdrawal of doses from multiple-dose vials introduces air into the vials, subjecting the remaining epinephrine to oxidation.^a Oxidation of epinephrine imparts first a pink, then a brown color.^a

Auto-injector (e.g., EpiPen): 20–25°C (may be exposed to 15–30°C); protect from light and do not refrigerate or freeze.^{163 164} Manufacturer's plastic carrying case provides added UV light protection.^{164 220 222} Avoid exposure to extreme heat or cold.¹⁶⁴

Compatibility

Parenteral

Incompatible with sodium bicarbonate and other alkaline solutions.¹⁷⁵

Solution CompatibilityHID

Compatibility studies conducted using epinephrine hydrochloride.^HID

Drug Compatibility

Compatibility studies conducted using epinephrine hydrochloride.^HID

Actions

• An endogenous catecholamine.^a

• Acts directly on both α- and β-adrenergic receptors of tissues innervated by sympathetic nerves except the sweat glands and arteries of the face.^a

• Main effects of therapeutic parenteral doses are relaxation of smooth muscle of the bronchial tree, cardiac stimulation, and dilation of skeletal muscle vasculature.^a

• Relaxes bronchial smooth muscle by stimulation of β₂-adrenergic receptors and constricts bronchial arterioles by stimulation of α-adrenergic receptors.^a Relieves bronchospasm, reduces congestion and edema, and increases tidal volume and vital capacity.^a

• Inhibits histamine release and antagonizes the effect of the mediator on end organs.^a As a result, may reverse histamine-induced bronchiolar constriction, vasodilation, and edema.^a

• Acts on β₁-adrenergic receptors in the heart, producing a positive chronotropic effect through the SA node and a positive inotropic effect on the myocardium.^{a 175} Cardiac output, oxygen consumption, and the work of the heart are increased.^a

• Constricts arterioles in the skin, mucous membranes, and viscera by its effect on α-adrenergic receptors and reduces cutaneous blood flow, especially in the hands and feet.^a Produces local vasoconstriction and hemostasis in bleeding from small vessels when applied topically but does not control bleeding from larger vessels.^a

• Increases glycogenolysis in the liver, reduces glucose uptake by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia.^a

• Importance of advising patients or their caregivers about common adverse effects with epinephrine including tachycardia, palpitations, sweating, nausea, vomiting, difficulty breathing, pallor, dizziness, weakness, shakiness, headache, apprehension, nervousness, or anxiety.^{163 195} These effects may be more persistent or severe in patients with hypertension or hyperthyroidism, and patients with coronary artery disease could experience angina.^{163 195}

• Importance of advising patients with diabetes mellitus that epinephrine may increase blood glucose and advising patients with Parkinson's disease that the drug may cause a temporary worsening of symptoms.^{163 195}

• For self-administration in anaphylaxis, instruct patients on proper techniques for storage, expiration dating (replacing before expiration), use, and disposal of prefilled auto-injectors (e.g., EpiPen).^{163 164 219 220 221 222}

• Importance of advising patients to go to the nearest emergency room after self-administration for anaphylaxis since further medical attention may be needed.¹⁶⁴ Instruct patient to inform clinician that epinephrine was self-administered (show injection site) and to bring used auto-injector for proper disposal.¹⁶⁴

• Give patients a copy of the manufacturer’s patient instructions.^{163 164}

• Importance of not injecting the dose via the auto-injector into the thumb, finger, or hand since loss of blood flow may occur in these areas.¹⁶⁴ Importance of seeking immediate medical attention if this occurs.¹⁶⁴

• For anaphylaxis, importance of remaining vigilant for possible recurrence despite an asymptomatic period;^{161 175} length of observation time not established.¹⁷⁵ Symptoms may recur within 1–36 hours after initial reaction.¹⁷⁵ Some experts suggest that patients with moderate to severe anaphylaxis should be observed for a minimum of 4–8 hours after treatment.²²⁸

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.^a

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^a

• Importance of informing patients of other important precautionary information.^a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Frequently asked questions

• Can you use an expired EpiPen in an emergency?
• Norepinephrine vs epinephrine: what's the difference?
• Can you bring an EpiPen on a plane?
• What's the mechanism of action for epinephrine?
• What is Neffy (nasal epinephrine)?

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