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Epinephrine

Pronunciation

Class: alpha- and beta-Adrenergic Agonists
VA Class: AU100
CAS Number: 51-43-4
Brands: Adrenaclick, Adrenalin, Auvi-Q, EpiPen

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

Norepinephrine is considered drug of choice when a vasopressor is indicated in patients with septic shock; if adequate BP not achieved, epinephrine may be added or used as an alternative.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 (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.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

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 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

Interactions for Epinephrine

Specific Drugs

Drug

Interaction

Comments

α-Adrenergic blocking agents (e.g., phentolamine)

High-dose epinephrine vasoconstriction and hypertension antagonizeda

β-Adrenergic blocking agents (e.g., propranolol)

Antagonism of cardiac and bronchodilating effectsa

May potentiate pressor effects of epinephrine195

Anesthetics, general (e.g., halogenated hydrocarbons [e.g., halothane], cyclopropane)

Increased cardiosensitivity to epinephrinea

Use with caution, if at all; increased risk of ventricular arrhythmias such as VPCs, VT, or VF; contraindicated with chloroform, trichloroethylene, or cyclopropanea

May not be absorbed rapidly enough with topical hemostatic use to present a problem in short proceduresa

Prophylactic lidocaine or procainamide may provide some protectiona

IV propranolol may reverse arrhythmiasa

Antidepressants, MAO inhibitors

MAO is one enzyme involved in epinephrine metabolisma

May cause severe, prolonged hypertension195

Use with caution172 193

Antidepressants, tricyclic

Potentiation of epinephrine effects (especially on heart rate and rhythm)a

Antidiabetic agents (e.g., insulin, oral hypoglycemics)

Epinephrine-induced hyperglycemiaa

May require increased antidiabetic dosagea

Antihistamines, first generation (especially diphenhydramine, dexchlorpheniramine, tripelennamine)

Potentiation of epinephrine effects (especially on heart rate and rhythm)a

Antihypertensives

Antagonism of pressor effects of epinephrine195 212

Catechol-O-methyltransferase (COMT) inhibitors (e.g., entacapone)

Potentiation of pressor effects of epinephrine195

Clonidine

Potentiation of pressor effects of epinephrine195

Corticosteroids

Potentiation of hypokalemic effects of epinephrine195

Digoxin

Increased cardiosensitivity to epinephrinea

Avoid epinephrine with excessive digoxin dosages212

Diuretics

Antagonism of pressor effects and potentiation of arrhythmogenic effects of epinephrine195 212

Some diuretics may potentiate the hypokalemic effects of epinephrine195

Doxapram

Potentiation of pressor effects of epinephrine195

Ergot alkaloids

α-Adrenergic antagonisma

Possible reversal of pressor responsea

Nitrates

Antagonism of pressor effects of epinephrine195

Oxytocics

Severe, persistent, hypertension possible212

Phenothiazines

Reversal of epinephrine's vasopressor effect195

Do not use to treat phenothiazine-induced hypotension195

Quinidine

May potentiate arrhythmogenic effects of epinephrine195

Sympathomimetic amines

Additive effects and toxicitya

Avoid concomitant usea

Theophylline

Potentiation of hypokalemic effects of epinephrine195

Thyroid hormones

Potentiation of epinephrine effects (especially on heart rate and rhythm)a

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

For information on systemic interactions resulting from concomitant use, see Interactions.

Parenteral

Incompatible with sodium bicarbonate and other alkaline solutions.175

Solution CompatibilityHID

Compatibility studies conducted using epinephrine hydrochloride.HID

Compatible

Dextrose–Ringer’s injection combinations

Dextrose–Ringer’s injection, lactated, combinations

Dextrose 5% in Ringer’s injection, lactated

Dextrose–saline combinations

Dextrose 5% in sodium chloride 0.9%

Dextrose 2.5, 5, or 10% in water

Ionosol products (except as noted below)

Ringer’s injection

Ringer’s injection, lactated

Sodium chloride 0.9%

Sodium lactate (1/6) M

Incompatible

Ionosol T in dextrose 5%

Sodium bicarbonate 5%

Drug Compatibility

Compatibility studies conducted using epinephrine hydrochloride.HID

Admixture CompatibilityHID

Compatible

Amikacin sulfate

Bupivacaine HCl

Dobutamine HCl

Fentanyl citrate

Floxacillin sodium

Furosemide

Ranitidine HCl

Verapamil HCl

Incompatible

Aminophylline

Y-Site CompatibilityHID

Compatible

Amiodarone HCl

Anidulafungin

Atracurium besylate

Bivalirudin

Calcium chloride

Calcium gluconate

Caspofungin acetate

Ceftazidime

Cisatracurium besylate

Clonidine HCl

Dexmedetomidine HCl

Diltiazem HCl

Dobutamine HCl

Dopamine HCl

Famotidine

Fenoldopam mesylate

Fentanyl citrate

Furosemide

Heparin sodium

Hetastarch in lactated electrolyte injection (Hextend)

Hydrocortisone sodium succinate

Hydromorphone HCl

Labetalol HCl

Levofloxacin

Lorazepam

Midazolam HCl

Milrinone lactate

Morphine sulfate

Nicardipine HCl

Nitroglycerin

Norepinephrine bitartrate

Pancuronium bromide

Pantoprazole sodium

Phytonadione

Potassium chloride

Propofol

Ranitidine HCl

Remifentanil HCl

Sodium nitroprusside

Tigecycline

Tirofiban HCl

Vasopressin

Vecuronium bromide

Warfarin sodium

Incompatible

Ampicillin sodium

Hydroxyethyl starch 130/0.4 in sodium chloride 0.9%

Micafungin sodium

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

Advice to Patients

  • 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.

Effective May 1, 2016, a new USP labeling standard for Epinephrine Injection, USP has been implemented.227 Concentrations of single-entity preparations of epinephrine injection will be expressed only in terms of strength per mL; use of ratios (e.g., 1:1000 or 1:10,000) to express concentrations is no longer acceptable.226 227 Epinephrine injection 1:1000 is equivalent to 1 mg/mL and epinephrine injection 1:10,000 is equivalent to 0.1 mg/mL.226 227

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

Epinephrine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection

0.1 mg/mL*

Epinephrine Injection (available in prefilled syringes)

0.5 mg/mL

EpiPen Jr. Auto-Injector (delivers a single 0.15-mg [0.3 mL] dose)

Meridian

1 mg/mL*

Adrenaclick Auto-Injector (available in dose of 0.15 mg [0.15 mL] or 0.3 mg [0.3 mL])

Amedra

Adrenalin

Par

Auvi-Q Auto-Injector (available in dose of 0.15 mg [0.15 mL] or 0.3 mg [0.3 mL])

Sanofi-Aventis

Epinephrine Injection

EpiPen Auto-Injector (delivers a single 0.3-mg [0.3 mL] dose)

Meridian

AHFS DI Essentials. © Copyright 2016, Selected Revisions January 1, 2017. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

Only references cited for selected revisions after 1984 are available electronically.

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