Generic Name: epinephrine

Uses

Bronchospasm

Has been used as as a quick-relief bronchodilator for symptomatic treatment of acute symptoms and exacerbations of bronchial asthma and reversible bronchospasm associated with chronic bronchitis, emphysema, and other obstructive pulmonary diseases. However, generally should be used only when selective β₂-agonists are not readily available, since excessive cardiac stimulation (e.g., increased heart rate, myocardial irritability, increased oxygen demand) can occur with nonselective agents, particularly at high doses.

Orally inhaled selective β₂-agonists currently are recommended for prehospital management of asthma exacerbations (e.g., in emergency medicine facilities and/or ambulances) and for acute asthma management in emergency rooms and hospitals. Reserve sub-Q epinephrine for severe exacerbations when selective agents are not readily available or are ineffective. No proven advantage of systemically administered (e.g., sub-Q) epinephrine therapy over orally inhaled therapy for the acute management of asthma exacerbations. Parenteral epinephrine may be particularly useful in treating anaphylaxis and angioedema coexisting with asthma.

Nebulized bronchodilator therapy generally should be reserved for patients who are unable to coordinate inhalation via an MDI because of their age, agitation, or exacerbation severity.

Regular, daily use of a short-acting, inhaled β-agonist generally is no longer recommended for maintenance therapy of asthma. Current asthma guidelines emphasize long-term control with anti-inflammatory agents (e.g., corticosteroids), and concomitant anti-inflammatory therapy with an inhaled corticosteroid is recommended whenever inhaled β-agonist bronchodilators are used for maintenance.

Sensitivity Reactions

Drug of choice in the emergency treatment of severe acute anaphylactic reactions, including anaphylactic shock, which can be profound and life-threatening.

May relieve anaphylactic symptoms (e.g., urticaria, pruritus, angioedema, wheezing, dyspnea, hypotension, swelling of the lips, eyelids, and tongue) caused by reactions to drugs, contrast media, sera, insect stings or bites, foods (e.g., milk, eggs, fish, shellfish, peanuts, tree nuts), latex, or other allergens as well as idiopathic or exercise-induced anaphylaxis.

Give to all patients with signs of shock, airway swelling, or definite breathing difficulty. Drug of choice for the treatment of both vasodilation/hypotension and cardiac arrest associated with anaphylaxis.

Parenteral administration (IM route favored) is preferred for the treatment of anaphylaxis. Administer IV if anaphylaxis appears to be severe with immediate life-threatening manifestations. Absorption and subsequent achievement of peak plasma concentrations after sub-Q injection is slower and may be substantially delayed in patients with shock.

High IV doses (i.e., rapid progression to high dose) should be used without hesitation in any patient in full cardiac arrest.

If necessary, institute other measures for management of cardiac arrhythmias, laryngeal edema, or bronchospasm. Once adequate ventilation is ensured, maintenance of BP in anaphylactic shock should be achieved with other pressor agents (e.g., norepinephrine, metaraminol).

Close monitoring critical; fatal overdose of epinephrine reported.

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. Increased incidence and severity of anaphylaxis in patients receiving β-adrenergic blocking agents.

CPR and Cardiac Arrhythmias

Used for its α-adrenergic stimulatory effects to increase blood flow in ACLS during CPR. The principal beneficial effects in patients with cardiac arrest result from increases in aortic diastolic blood pressure and in myocardial and cerebral blood flow during resuscitation. The value and safety of the β-adrenergic effects are controversial because they may increase myocardial work and reduce subendocardial perfusion.

A drug of choice and a high priority for ACLS in cardiac arrest to facilitate return of spontaneous circulation (ROSC); generally used after failure of artificial ventilation, external or internal cardiac compression, and initial defibrillation to restore effective circulation.

Cardiac arrest: May be administered IV, intraosseously, or intracardially or by direct instillation into the tracheobronchial tree via an endotracheal tube to restore cardiac rhythm as an adjunct in the management of cardiac arrest.

Asystole: Restores cardiac electrical activity in asystole and, in some cases, restores myocardial contractility in electromechanical dissociation.

Impending pulseless electrical activity: May produce beneficial vasopressor effects in patients who are not in cardiac arrest but who have other indications for vasopressor therapy (e.g., in those with severe bradycardia and hypotension who are close to pulseless electrical activity or even asystole).

Bradycardia: Treatment of symptomatic bradycardia unresponsive to atropine, as a temporizing measure while awaiting availability of a pacemaker (e.g., out-of-hospital setting) or if pacing ineffective.

Drug-induced cardiovascular emergencies or altered vital signs: May consider use in bradycardia or shock associated with β-adrenergic or calcium-channel blocking agent or tricyclic antidepressant toxicity.

Anesthesia accidents: May be useful in treating cardiac arrest following anesthesia accidents, but should be used with extreme caution, if at all, in patients receiving cyclopropane or halogenated hydrocarbon general anesthetics. (See General Anesthetics under Interactions.)

Heart block: Has been used in the treatment of syncope and/or bradycardia resulting from AV nodal block, but has largely been replaced by isoproterenol. Electrical cardiac pacemakers have largely replaced drug therapy in third-degree AV nodal block (complete heart block).

Radiographic Uses

Has been given intra-arterially† as an adjunct to radiographic contrast media in arteriography†.

GI and Renal Hemorrhage

Has been administered intra-arterially† via the celiac artery, inferior mesenteric artery, or superior mesenteric artery to control hemorrhage in patients with severe GI bleeding†.

Has been administered intra-arterially† via the renal artery to control hemorrhage in patients with renal arterial bleeding†.

Radiation Nephritis

Has been injected into a renal artery prior to and during irradiation of the abdominal area to protect the kidney from radiation nephritis†.

Adjunct to Local Anesthesia

May be added to solutions of some local anesthetics to decrease the rate of their vascular absorption (to localize and prolong the duration of anesthesia and decrease the risk of systemic toxicity).

Superficial Bleeding

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

Cardiogenic, Hemorrhagic, and Traumatic Shock

Should not be used in cardiogenic shock (because it increases myocardial oxygen demand) or in hemorrhagic or traumatic shock.

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. (See Pregnancy under Cautions.) Other β-agonists (e.g., terbutaline) preferred.

Hypoglycemia

Has been used parenterally to correct hypoglycemia† in insulin shock; however, dextrose and/or glucagon is more effective.

Dosage and Administration

Administration

Administer by sub-Q, IM, or IV injection or by IV infusion. Also may be administered intra-arterially† (e.g., for radiography, for local control of bleeding).

In extreme cardiac emergencies, may be administered intracardially, via an endotracheal tube, or by intraosseous infusion†. Although endotracheal administration of epinephrine is possible, IV or intraosseous† administration is preferred because of more predictable drug delivery and pharmacologic effect.

Rapid IV injection (bolus dose) or endotracheal administration of epinephrine may cause failure of exhaled carbon dioxide detectors (used to confirm endotracheal tube placement in the trachea during cardiac arrest) despite adequate placement (i.e., false-negative reading). Use a second method to confirm tube placement.

For bronchodilation, administer by oral inhalation via a metered-dose inhaler (MDI), nebulization, or intermittent positive-pressure breathing (IPPB) apparatus or inject sub-Q or IM.

Apply topically to the skin and mucous membranes for local hemostasis.

Sub-Q Injection

Injections containing 1 mg/mL preferably are administered sub-Q. However, absorption and subsequent achievement of peak plasma concentrations is slower and may be substantially delayed if shock is present.

IM Injection

Injections containing 1 mg/mL also may be injected IM, but IM injection into the buttocks should be avoided.

For self-medication, instruct patients and their caregivers about proper administration techniques using the auto-injector provided by the manufacturer. First aid providers should be familiar with the auto-injector in order to assist patients having an anaphylactic reaction with self-medication, and they should be able to administer the auto-injector, if a patient is unable to self-administer, provided that state law permits it and valid prescription exists.

Technique for Using Auto-injector

Inject the age-appropriate dose IM only into the anterolateral aspect of the thigh.

The patient should grasp the prefilled auto-injector with the black tip pointed downward; the grey activation cap should be removed. Point the black tip toward the outer thigh, swing and jab it firmly into the outer thigh so that the auto-injector is perpendicular (90° angle) to the thigh, and hold firmly in the thigh for several seconds until the dose is delivered. Administer through clothing if necessary. Massage injection area for several seconds. If the needle is not exposed at the black tip, repeat administration.

Never put thumb, fingers, or hand over the black tip.

Do not remove the grey activation cap until ready to use.

The auto-injector is overfilled and most of the solution (90%) will remain after injection of the age-approriate dose and cannot be reused.

After use, bend the needle back against a hard surface. Then, deliver the used auto-injector to a health-care provider for proper disposal.

IV Administration

Emergency situations: Inject very slowly IV as a dilute solution or infuse slowly IV. When injected peripherally, 1–2 minutes generally are required to reach central circulation.

Severe asthma or anaphylaxis: IV therapy may be necessary (e.g., for severe anaphylactic shock with immediate life-threatening manifestations) when drug absorption from sub-Q or IM injection is likely to be impaired.

CPR: When a vein has not been cannulated prior to the arrest, a peripheral vein (antecubital or external jugular in adults and the largest most accessible vein that does not interrupt resuscitation in pediatric patients) is preferred since central venous access requires interruption of chest compressions, is technically more difficult, and is associated with an increased risk of complications. Venous access can be challenging in infants and children during an emergency, whereas intraosseous access can be easily achieved. Limit the time attempting venous access; if reliable access cannot be achieved quickly, establish intraosseous access.

If a central venous catheter is already in place at the time of arrest, it can be used because of more rapid onset (in adults), more secure access to circulation, and avoidance of tissue infiltration. Tissue infiltration may lead to local ischemia, tissue injury, and ulceration. Avoid central venous line placement in patients who are candidates for pharmacologic reperfusion (e.g., with thrombolytic therapy).

Dilution

Prepare infusion solutions containing 2 or 4 mcg/mL by adding 1 mg to 500 or 250 mL of a compatible IV solution, respectively.

Prepare solutions containing 0.05 mg/mL by adding 0.5 mg (0.5 mL of a 1:1000 injection) to 10 mL of 0.9% sodium chloride injetion.

Prepare a 1:10,000 solution (0.1 mg/mL) by diluting 1 mL of a commercially available 1:1000 injection (1 mg/mL) with 10 mL of water for injection or 0.9% sodium chloride injection. Alternatively, a commercially available 1:10,000 (0.1 mg/mL) injection can be used.

Prepare a 1:100,000 solution (0.01 mg/mL) by diluting 0.1 mL of a commercially available 1:1000 injection (1 mg/mL) with 10 mL of 0.9% sodium chloride injection.

Rate of Administration

Severe asthma or anaphylaxis: Inject IV slowly (e.g., over 5–10 minutes) or administer by rapid IV injection (i.e., bolus).

Alternatively in adults, infuse IV at an initial rate of 1 mcg/minute, increasing to 4 mcg/minute as needed.

In children after an initial 1-mcg/kg IV bolus, infuse IV at an initial rate of 0.1 mcg/kg per minute, increasing gradually up to 1.5 mcg/kg per minute as needed.

CPR: Inject doses by IV push in adults, repeating at 3- to 5-minute intervals as needed; follow each dose injected peripherally with a 20-mL flush of IV fluid to ensure distribution into the central compartment; if injected IV in an extremity, elevate the extremity for 10–20 seconds.

In children, infuse IV at an initial rate of 0.1 mcg/kg per minute, increasing gradually to a maximum of 1 mcg/kg per minute as needed for CPR.

Bradycardia or hypotension (i.e., nonarrest rate): In adults, infuse IV at an initial rate of 1 mcg/minute, titrating to hemodynamic response at rates ranging from 2–10 mcg/minute. Assess intravascular volume and support as needed.

In children, infuse IV at a rate of 0.1–0.2 mcg/kg per minute for refractory bradycardia.

Intra-arterial Administration

Injections have been administered intra-arterially† for local effects (e.g., to control local bleeding, prevent radiation nephritis, as an adjunct to arteriography).

Rate of Administration

GI hemorrhage: 8–20 mcg/minute infused into the celiac or inferior or superior mesenteric artery†.

Renal hemorrhage: 10 mcg/minute infused into the renal artery†.

Radiation nephritis: 3–7.6 mcg/minute infused into the renal artery†.

Adjunct to arteriography: 8–12 mcg/minute infused into the celiac or superior mesenteric artery†.

Intracardiac Injection

Limit intracardiac injection to personnel well trained in the technique and generally use only during open cardiac massage or when other routes of administration are persistently inaccessible.

Inject into the left ventricular chamber.

Follow intracardiac administration by external cardiac massage to ensure entry of the drug into the coronary circulation.

Suspensions must not be administered intracardially.

Administration Risks

Hazards include coronary artery laceration, cardiac tamponade, pneumothorax, and the need to interrupt external chest compressions and ventilation during the period of administration.

Endotracheal Administration

Limit endotracheal administration to personnel well trained in the technique.

In intubated patients, doses can be instilled directly into the bronchial tree via the endotracheal tube.

Pass a catheter beyond the tip of the tracheal tube, stop chest compressions, inject the drug solution directly into the tracheal tube, follow immediately with several quick insufflations to create a rapidly absorbed aerosol, and then resume compressions.

For pediatric patients, flush with a minimum of 5 mL of 0.9% sodium chloride injection after each dose.

For pediatric patients, administration via a tracheal tube is preferred to a catheter or feeding tube because these latter 2 methods often are cumbersome and depend on finding the correct-size catheter to place through the tracheal tube.

Dilution

Adults: Dilute dose in 5–10 mL of 0.9% sodium chloride or sterile water. Systemic absorption may be increased by diluting in sterile water instead of 0.9% sodium chloride; however, sterile water may have a more negative effect on arterial oxygen pressure (PaO₂) than sodium chloride. Alternatively, a commercially available 1:10,000 (0.1 mg/mL) injection may be administered undiluted via the endotracheal tube.

Intraosseous Administration

When IV administration is not possible, epinephrine may be given by intraosseous administration for emergency uses such as CPR.

Limit intraosseous administration to personnel well trained in the technique.

Place a cannula in a noncollapsible marrow venous plexus; such access often can be achieved in 30–60 seconds.

Use a rigid needle, preferably a specially designed intraosseous or Jamshidi-type bone marrow needle; a styleted needle is preferred to prevent obstruction of the needle with cortical bone.

Insert the intraosseous needle into the anterior tibial bone marrow; alternatively, the distal femur, medial malleolus, or anterior superior iliac spine can be used.

In older children and adults, intraosseous cannulas also have been inserted successfully into the distal radius or ulna as well as the proximal tibia.

Successful intraosseous placement outside the hospital (e.g., by emergency medical services) generally is more difficult in older than in younger children.

Onset of action and systemic concentrations are comparable to those achieved with central venous administration.

Administration Risks

Complications are uncommon (less than 1% of patients), and include tibial fracture, lower-extremity compartment syndrome, extravasation, and osteomyelitis; careful technique can minimize the risk. Local effects on bone marrow and bone growth appear to be minimal. Risk of microscopic pulmonary fat and bone marrow emboli does not appear to be increased.

Oral Inhalation

Epinephrine base or hydrochloride may be administered via oral inhalation using a nebulizer, aerosol (metered-dose inhaler [MDI]), or intermittent positive-pressure breathing (IPPB) apparatus.

For nebulization, use a glass or plastic nebulizer capable of delivering a very fine mist and that works effectively with a very small volume of solution. Place the dose in the nebulizer reservoir and then place the nozzle just inside the partially opened mouth. Squeeze the bulb once or twice, inhaling deeply to draw the vaporized solution into the lungs. Rinse mouth with water immediately to prevent oropharyngeal dryness.

Solutions intended for oral inhalation are more concentrated than those intended for injection and must not be administered parenterally.

Do not administer oral inhalation solutions intranasally.

Topical Administration

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

Dosage

Available as epinephrine and epinephrine hydrochloride; dosage expressed in terms of epinephrine.

Pediatric Patients

Bronchospasm

Treatment of Acute Exacerbations of Asthma

Oral Inhalation

Children ≥4 years of age: 220 mcg (1 inhalation) of epinephrine via an MDI, repeated once if necessary after at least 1 minute; do not administer subsequent doses for at least 3 hours.

Children ≥4 years of age: After placing approximately 10 drops of 1% (1:100) epinephrine in the nebulizer reservoir, administer 1–3 deep inhalations via the hand-bulb. Do not repeat more often than every 3 hours; use the least number of inhalations producing relief.

Sub-Q

For severe asthma, inject 0.01 mg/kg (0.01 mL/kg of a 1:1000 injection) or 0.3 mg/m² (0.3 mL/m² of a 1:1000 injection) sub-Q.

Single pediatric doses should not exceed 0.3–0.5 mg every 20 minutes as needed for up to 3 consecutive doses.

IV

Neonates: Inject 0.01 mg/kg IV.

Infants: Inject 0.05 mg IV initially, repeated at 20- to 30-minute intervals as needed.

Sensitivity Reactions

Anaphylaxis

IM

Inject 0.01 mg/kg (0.01 mL/kg of a 1:1000 injection) (up to 0.5 mg/dose), repeated every 10–20 minutes as needed for up to 3 consecutive doses.

For self-administration using a prefilled auto-injector (e.g., EpiPen^®), inject 0.15 or 0.3 mg, depending on body weight; a dose of 0.01 mg/kg generally is recommended. Clinicians may recommend higher or lower doses depending on individual patient needs and considering the life-threatening nature of anaphylaxis. The 0.15-mg dose may be more approriate for children <30 kg. If doses <0.15 mg are considered more appropriate, alternative injectable forms of the drug should be used. For severe persistent anaphylaxis, repeated doses may be needed.

Sub-Q

Inject 0.01 mg/kg (0.01 mL/kg of a 1:1000 injection) or 0.3 mg/m² (0.3 mL/m² of a 1:1000 injection) sub-Q. Single pediatric doses should not exceed 0.5 mg, repeated as needed at 20-minute to 4-hour intervals depending on the severity of the condition and the response of the patient.

IV

In severe anaphylactic shock, IV administration may be necessary since absorption may be impaired with sub-Q or IM administration.

If necessary, inject an initial dose of 10 mcg/kg (0.1 mL/kg of a 1:10,000 dilution), followed by a continuous IV infusion at an initial rate of 0.1 mcg/kg per minute (using a diluted solution containing 4 mcg/mL); the infusion may be increased as necessary to a maximum of 1.5 mcg/kg per minute to maintain BP.

Neonates, alternatively: Inject 0.01 mg (10 mcg)/kg.

Infants, alternatively: Inject 0.05 mg (50 mcg) initially, repeated at 20- to 30-minute intervals as needed.

CPR and Cardiac Arrhythmias

Bradycardia and Pediatric Advanced Life Support

IV

Neonates: The usual dose is 0.01–0.03 mg/kg (0.1–0.3 mL/kg of a 1:10,000 injection), repeated every 3–5 minutes if necessary for CPR or bradycardia. Higher IV doses are not recommended because of risk of exaggerated hypertension, decreased myocardial function, and worsening neurologic function.

Pediatric Patients: The usual initial dose is 0.01 mg/kg (0.1 mL/kg of a 1:10,000 injection), up to a maximum single dose of 1 mg, for CPR or bradycardia, repeated every 3–5 minutes as needed. Higher IV doses not recommended; use a standard dose for the first and subsequent doses. No survival benefit from routine use of high-dose epinephrine; may be harmful, particularly in asphyxia. Risk of exaggerated hypertension, decreased myocardial function, and worsening neurologic function with high doses. May consider high-dose epinephrine in certain circumstances (e.g., β-adrenergic blocking agent overdose).

Pediatric Patients: Alternatively, infuse at an initial rate of 0.1 mcg/kg per minute; increase the rate in increments of 0.1 mcg/kg per minute, if necessary, to a maximum of 1 mcg/kg per minute. 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) generally result in α-adrenergic vasoconstriction, but there is substantial interindividual variation in catecholamine response, and infusion dosage should be titrated to the desired effect.

Pediatric patients: For refractory bradycardia, consider continuous infusion at a rate of 0.1–0.2 mcg/kg per minute.

Intraosseous

Pediatric patients: The usual initial dose is 0.01 mg/kg (0.1 mL/kg of a 1:10,000 injection), up to a maximum single dose of 1 mg, for CPR or bradycardia, repeated every 3–5 minutes as needed. Higher intraosseous doses are not recommended; use a standard dose for the first and subsequent doses. No survival benefit from routine use of high-dose epinephrine; may be harmful, particularly in asphyxia. Risk of exaggerated hypertension, decreased myocardial function, and worsening neurologic function with high doses. May consider high-dose epinephrine in certain circumstances (e.g., β-adrenergic blocking agent overdose).

Endotracheal

Optimum dose not established.

Neonates: IV administration (of 0.01–0.03 mg/kg per dose [0.1–0.3 mL/kg of a 1:10,000 injection]) is the preferred route. If the endotracheal route is used, doses of 0.01 or 0.03 mg/kg will likely be ineffective. Although safety and efficacy have not been established, consider endotracheal administration of a higher dose (up to 0.1 mg/kg) while access is being obtained.

Pediatric patients: The usual initial dose is 0.1 mg/kg (0.1 mL/kg of a 1:1000 injection), up to a maximum single dose of 10 mg, for CPR or bradycardia, repeated every 3–5 minutes as needed.

Generally flush the dose with a minimum of 5 mL of 0.9% sodium chloride injection followed by 5 assisted manual ventilations to promote absorption.

Intracardiac

Pediatric patients: 0.005–0.01 mg/kg (0.05–0.1 mL/kg of a 1:10,000 injection).

Adults

Bronchospasm

Treatment of Acute Exacerbations of Asthma

Oral Inhalation

220 mcg (1 inhalation) of epinephrine via an MDI, repeated once if necessary after at least 1 minute; do not administer subsequent doses for at least 3 hours.

After placing approximately 10 drops of 1% (1:100) epinephrine in the nebulizer reservoir, administer 1–3 deep inhalations via the hand-bulb. Do not repeat more often than every 3 hours; the least number of inhalations producing relief should be used.

Sub-Q

For severe asthma, the usual initial dose is 0.1–0.5 mg (0.1–0.5 mL of a 1:1000 injection). Initial doses should be small and may be increased if necessary, but single doses should not exceed 1 mg.

May give at 20-minute to 4-hours intervals depending on the severity of the condition and patient response.

Alternatively, may administer 0.01 mg/kg (concentration of 1:1000) divided into 3 doses of approximately 0.3 mg, given at 20-minute intervals.

IM

For severe asthma, the usual initial dose is 0.1–0.5 mg (0.1–0.5 mL of a 1:1000 injection). Initial doses should be small and may be increased if necessary, but single doses should not exceed 1 mg.

IV

0.1–0.25 mg injected slowly.

Sensitivity Reactions

Anaphylaxis

IM

The usual initial dose is 0.1–0.5 mg (0.1–0.5 mL of a 1:1000 injection).

For the treatment of reactions caused by drugs that were given IM, epinephrine may be administered at the site of injection of the other drug to minimize further absorption.

Initial doses should be small and may be increased if necessary, but single doses should not exceed 1 mg.

Alternatively, inject 0.3–0.5 mg (0.3–0.5 mL of a 1:1000 injection), repeated every 15–20 minutes, as needed.

For self-administration using a prefilled auto-injector (e.g., EpiPen^®), inject 0.3 mg. Clinicians may recommend higher or lower doses depending on individual patient needs and considering the life-threatening nature of anaphylaxis.

For severe persistent anaphylaxis, repeated doses may be needed.

Sub-Q

Consider the possibility that drug absorption from sub-Q injection may be inadequate in anaphylaxis, particularly with shock.

The usual initial dose is 0.1–0.5 mg (0.1–0.5 mL of a 1:1000 injection). For the treatment of reactions caused by drugs that were given sub-Q, epinephrine may be administered at the site of injection of the other drug to minimize further absorption.

Initial doses should be small and may be increased if necessary, but single doses should not exceed 1 mg.

May be given at 20-minute to 4-hours intervals depending on the severity of the condition and patient response.

Alternatively, inject 0.3–0.5 mg every 20 minutes as needed for up to 3 doses.

IV

In severe or life-threatening anaphylaxis, IV administration may be necessary since absorption may be impaired with sub-Q or IM administration.

If necessary, inject 0.1–0.25 mg(e.g., 1–2.5 mL of a 1:10,000 injection or dilution) slowly and cautiously (e.g., over 5–10 minutes), and repeat every 5–15 minutes as necessary or follow by a continuous infusion at an initial rate of 1 mcg/minute, increasing the rate to up to 4 mcg/minute as necessary. Individual doses up to 0.5 mg also have been used.

To optimally control administration, some clinicians recommend an initial dose of 0.1 mg (10 mL of a 1:100,000 injection or dilution) given over 5–10 minutes, followed by a continuous infusion as necessary.

Alternatively, 0.025–0.05 mg (0.25–0.5 mL of a 1:10,000 injection) be given every 5–15 minutes following initial sub-Q or IM administration of 0.5 mg.

CPR and Cardiac Arrhythmias

The optimum dose of epinephrine during CPR remains controversial. The usual dose of 0.5–1 mg has been questioned since it is not based on body weight and may be lower than necessary for optimum cardiovascular effects.

CPR (Cardiac Arrest)

IV

Inject 1 mg every 3–5 minutes.

Has been infused at an initial rate of 1 mcg/minute and, increased to 3–4 mcg/minute as needed, via a central line to reduce the risk of extravasation and ensure good bioavailability.

Higher (>1-mg) doses may be indicated in certain circumstances, (e.g., β-adrenergic or calcium-channel blocking agent overdose).

Intraosseous

Intraosseous doses generally are the same as those administered IV.

Usually, 1 mg every 3–5 minutes.

Endotracheal

Optimum dose not established.

If IV or intraosseous access is delayed or cannot be established, endotracheal doses 2–2.5 times those administered IV (i.e., 2–2.5 mg) are recommended.

Intracardiac

Inject 0.1–1 mg (usually as 1–10 mL of a 1:10,000 injection) into the left ventricular chamber.

Sub-Q

Following initial IV administration, 0.3 mg may be injected sub-Q.

Persistent or Recurrent Ventricular Fibrillation/Tachycardia

IV

Inject 1 mg by rapid injection (IV push) every 3–5 minutes.

Pulseless Electrical Activity

IV

Inject 1 mg by rapid injection (IV push) every 3–5 minutes.

Asystole

IV

Inject 1 mg by rapid injection (IV push) every 3–5 minutes.

Bradycardia:

IV

For symptomatic bradycardia without cardiac arrest, infuse at an initial rate of 1 mcg/minute; subsequent dosage is adjusted according to the patient’s response and generally ranges from 2–10 mcg/minute.

Radiographic Use

Arteriography

IV

As an adjunct in arteriography†, 16–24 mL of sodium chloride injection containing 1 mcg of epinephrine per mL has been infused into the celiac or superior mesenteric artery† over 2 minutes; the radiographic contrast medium was administered 7–10 minutes later.

Hemorrhage

GI

Intra-arterial

To control GI bleeding†, infuse into the celiac artery†, inferior mesenteric artery†, or superior mesenteric artery† at a rate of 8–20 mcg/minute for 4 minutes to 3 hours.

Renal

Intra-arterial

To control bleeding from the kidney†, infuse into the renal artery† at a rate of 10 mcg/minute for 10 minutes.

Radiation Nephritis

Abdominal Irradiation

Intra-arterial

To prevent radiation nephritis†, infuse into the renal artery† at a rate of 3–7.6 mcg/minute for 4–10 minutes prior to and continued during the period of abdominal irradiation.

Adjunct to Local Anesthesia

Local Injection

To localize and prolong the duration of local anesthesia, epinephrine may be used in concentrations of 1:500,000 to 1:50,000; 1:200,000 is used most commonly.

Superficial Bleeding

Topical

As a topical hemostatic, solutions concentrations of 1:50,000 (0.002%) to 1:1000 (0.1%) may be sprayed or applied with cotton or gauze to the skin, mucous membranes, or other tissues.

Prescribing Limits

Pediatric Patients

Bronchospasm

Treatment of Acute Exacerbations of Asthma

Oral Inhalation

Maximum for children ≥4 years of age: 1 or 2 doses 1 minute apart, repeated no more frequently than every 3 hours.

Sub-Q

Maximum for pediatric patients: 0.5 mg repeated no more frequently than every 20 minutes up to 3 times.

Sensitivity Reactions

Anaphylaxis

IM or Sub-Q

Maximum for pediatric patients: 0.5 mg repeated no more frequently than every 10 minutes up to 3 times.

IV

Up to 1.5 mcg/kg per minute.

CPR and Cardiac Arrhythmias

Bradycardia and Pediatric Advanced Life Support

IV

Maximum for neonates: 0.03 mg/kg repeated no more frequently than every 3–5 minutes. Higher IV doses are not recommended. (See Bradycardia and Pediatric Advanced Life Support under Dosage and Administration.)

Pediatric patients: Maximum 1 mg, as a single dose.

Intraosseous

Pediatric patients: Maximum 1 mg, as a single dose.

Endotracheal

Neonates: IV administration is the preferred route. Although safety and efficacy have not been established, consider an endotracheal dose up to 0.1 mg/kg, while access is being obtained.

Pediatric patients: Maximum 10 mg as a single dose.

Adults

Bronchospasm

Treatment of Acute Exacerbations of Asthma

Oral Inhalation

Maximum 1 or 2 doses 1 minute apart, repeated no more frequently than every 3 hours.

Sub-Q

Single doses should not exceed 1 mg.

Sensitivity Reactions

Anaphylaxis

IM

Single doses should not exceed 1 mg.

Sub-Q

Single doses should not exceed 1 mg.

Cautions

Contraindications

• No absolute contraindications to use in life-threatening conditions.
• Relative contraindications include shock (other than anaphylactic shock), organic heart disease, coronary insufficiency, or cardiac dilatation, as well as use in most patients with angle-closure glaucoma, arrhythmias, organic brain damage, or cerebral arteriosclerosis. Contraindicated for use during general anesthesia with chloroform, trichloroethylene, or cyclopropane, and should be used cautiously, if at all, with other halogenated hydrocarbon anesthetics such as halothane.
• Contraindicated in conjunction with local anesthetics for use in fingers, toes, ears, nose, or genitalia.

Warnings/Precautions

Warnings

High BP Induction

Inadvertent induction of high arterial BP can cause angina pectoris, aortic rupture, or cerebral hemorrhage.

Hypertension and Hyperthyroidism

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

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.

General Anesthetics

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

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. (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.

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. Epinephrine is the preferred treatment for such conditions, and currently available alternatives to epinephrine may not be optimally effective.

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.

Sympathomimetic Amines

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

General Precautions

Regular Inhalation Therapy

Concerns about the safety of regular use of inhaled β-agonist bronchodilators have been raised. Therefore, regular, daily use of a short-acting, inhaled β-agonist generally is no longer recommended for maintenance therapy of asthma, and use more than twice weekly or more than one canister monthly may indicate the need to initiate or increase long-term control therapy for asthma.

Cardiovascular Effects

Can cause VF, but beneficial effects in restoring electrical activity and enhancing defibrillation are well documented.

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

Caution in patients with underlying cardiovascular disease (e.g., angina pectoris, tachycardia, MI).

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

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

Respiratory Disease and Effects

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

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

Diuretics

May decrease vascular vasopressor response.

MAO Inhibitors

Use vasopressors cautiously with MAO inhibitors according to one manufacturer.

Specific Populations

Pregnancy

Category C.

Some manufacturers state that epinephrine injection is contraindicated during the second stage of labor or when maternal BP is >130/80 mm Hg.

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

Lactation

Risk unknown.

Pediatric Use

Used in pediatric patients of all ages, dosing according to body weight or surface area.

Oral inhalation aerosols are not recommended for children <4 years of age.

Geriatric Use

Use with caution.

Common Adverse Effects

Fear, anxiety, tenseness, restlessness, headache, tremor, dizziness, lightheadedness, nervousness, sleeplessness, excitability, and weakness. 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. Nausea, vomiting, sweating, pallor, respiratory difficulty, or respiratory weakness and apnea.

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

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

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

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

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

Interactions

Specific Drugs

Pharmacokinetics

Absorption

Bioavailability

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

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

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

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.

Onset

Rapid onset of action when solutions are administered parenterally or by oral inhalation.

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

After oral inhalation, bronchodilation usually occurs within 1 minute.

Duration

Short duration of action when solutions are administered parenterally or by oral inhalation.

Distribution

Extent

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

Distributed into milk.

Elimination

Metabolism

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

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

Elimination Route

40% excreted in urine, mainly as inactive metabolites.

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.

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

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

Oral Inhalation

Aerosol

20–25°C.

Contents under pressure; do not puncture or throw into an incinerator.

Use or storage near an open flame or temperature >49°C can cause the canister to burst.

Inhalation Solution

15–25°C in small, well-filled, tight containers; protect from light and freezing.

Parenteral

Injection

15–25°C; protect from light and freezing.

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

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

Auto-injector (e.g., EpiPen^®): 15–30°C; protect from light (dark place) and do not refrigerate or freeze. Manufacturer's plastic carrying case provides added UV light protection. Avoid exposure to extreme heat or cold.

Compatibility

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

Parenteral

Incompatible with sodium bicarbonate and other alkaline solutions.

Solution Compatibility

Drug Compatibility

Actions

• An endogenous catecholamine.
• Acts directly on both α- and β-adrenergic receptors of tissues innervated by sympathetic nerves except the sweat glands and arteries of the face.
• Main effects of therapeutic parenteral doses are relaxation of smooth muscle of the bronchial tree, cardiac stimulation, and dilation of skeletal muscle vasculature.
• Relaxes bronchial smooth muscle by stimulation of β₂-adrenergic receptors and constricts bronchial arterioles by stimulation of α-adrenergic receptors. Relieves bronchospasm, reduces congestion and edema, and increases tidal volume and vital capacity.
• Inhibits histamine release and antagonizes the effect of the mediator on end organs. As a result, may reverse histamine-induced bronchiolar constriction, vasodilation, and edema.
• 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. Cardiac output, oxygen consumption, and the work of the heart are increased.
• 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. Produces local vasoconstriction and hemostasis in bleeding from small vessels when applied topically but does not control bleeding from larger vessels.
• Increases glycogenolysis in the liver, reduces glucose uptake by tissues, and inhibits insulin release in the pancreas, resulting in hyperglycemia.

Advice to Patients

• Do not use solutions that are pinkish or darker than slightly yellow or if they contain a precipitate.
• For asthma, proper techniques for storage, use, care, and disposal of the metered-dose inhaler (MDI). Give patients a copy of the manufacturer’s patient instructions.
• For asthma, importance of discontinuing oral inhalation therapy and contacting a clinician if symptoms are not relieved within 20 minutes or they become worse.
• For asthma, importance of allowing at least 3 hours to elapse between orally inhaled doses.
• For asthma, importance of advising clinician if quick-relief use is more frequent than twice weekly or one canister monthly.
• For asthma, advise that oral inhalation therapy should be self-administered (OTC use) only if asthma was previously diagnosed by a clinician. Before considering self-administration therapy, inform clinician of any history of hospitalization for asthma.
• For asthma, importance of advising parents and caregivers to supervise children during oral inhalation therapy.
• Importance of not exceeding recommended dosages or frequency of administration because of the risk of adverse systemic effects (e.g., nervousness, tachycardia, other cardiac problems).
• Advise that certain oral inhalation aerosols contain chlorofluorocarbons, which may harm public health and environment by destroying ozone in the upper atmosphere.
• For self-administration in anaphylaxis, proper techniques for storage, attention to expiration dating (replacing before expiration), use, and disposal of the prefilled auto-injector (e.g., EpiPen^®) and for IM administration of the dose.
• Importance of going to the nearest emergency room after self-administration for anaphylaxis since further medical attention may be needed. Advise clinician that epinephrine was self-administered (show injection site) and give them the used auto-injector for proper disposal.
• Give patients a copy of the manufacturer’s patient instructions.
• 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. Importance of seeking immediate medical attention if this occurs.
• For anaphylaxis, importance of remaining vigilant for possible recurrence despite an asymptomatic period; length of observation time not established. Symptoms may recur within 1–36 hours after initial reaction. May discharge patient if asymptomatic for 4 hours after therapy; severity of reaction or other problems may require longer periods of observation.
• Importance of informing clinicians of underlying heart disease, hypertension, thyroid disease, diabetes mellitus, or prostatic enlargement that causes difficulty urinating.
• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs. Importance of avoiding MAO inhibitors and allowing at least 2 weeks to elapse after discontinuing these antidepressants.
• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.
• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

AHFS Drug Information. © Copyright, 1959-2009, Selected Revisions August 2007. 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.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.