General

High Alert Medication: This medication bears a heightened risk of causing significant patient harm when it is used in error.

Pronunciation:
ep-i-nef-rin


Trade Name(s)

  • Adrenalin
  • Allerject [Canada]
  • Anapen [Canada]
  • AsthmaNefrin
  • EpiPen
  • racepinephrine
  • S-2 (racepinephrine) [Canada]

Pregnancy Category
Category C

Ther. Class.
antiasthmatics
bronchodilators
vasopressors

Pharm. Class.
adrenergics

See ophthalmic medications for ophthalmic use

Indications

  • SC: IV: Inhaln: Management of reversible airway disease due to asthma or COPD.
  • SC: IM: IV: Management of severe allergic reactions.
  • IV, Intracardiac, Intratracheal, Intraosseous (part of advanced cardiac life support [ACLS] and pediatric advanced life support [PALS] guidelines): Management of cardiac arrest (unlabeled).
  • Inhaln: Management of upper airway obstruction and croup (racemic epinephrine).
  • Local/Spinal: Adjunct in the localization/prolongation of anesthesia.

Action

  • Results in the accumulation of cyclic adenosine monophosphate (cAMP) at beta-adrenergic receptors.
  • Affects both beta1(cardiac)-adrenergic receptors and beta2(pulmonary)-adrenergic receptor sites.
  • Produces bronchodilation.
  • Also has alpha-adrenergic agonist properties, which result in vasoconstriction.
  • Inhibits the release of mediators of immediate hypersensitivity reactions from mast cells.

Therapeutic Effect(s):

  • Bronchodilation.
  • Maintenance of heart rate and BP.
  • Localization/prolongation of local/spinal anesthetic.

Pharmacokinetics

Absorption: Well absorbed following subcut administration; some absorption may occur following repeated inhalation of large doses.

Distribution: Does not cross the blood-brain barrier; crosses the placenta and enters breast milk.

Metabolism and Excretion: Action is rapidly terminated by metabolism and uptake by nerve endings.

Half-life: Unknown.

TIME/ACTION PROFILE (bronchodilation)

ROUTEONSETPEAKDURATION
Inhaln1 minunknown1–3 hr
Subcut5–10 min20 min<1–4 hr
IM6–12 minunknown<1–4 hr
IVrapid20 min20–30 min

Contraindication/Precautions

Contraindicated in:

  • Hypersensitivity to adrenergic amines;
  • Some products may contain bisulfites or fluorocarbons (in some inhalers) and should be avoided in patients with known hypersensitivity or intolerance.

Use Cautiously in:

  • Cardiac disease (angina, tachycardia, MI);
  • Hypertension;
  • Hyperthyroidism;
  • Diabetes;
  • Cerebral arteriosclerosis;
  • Glaucoma (except for ophthalmic use);
  • Excessive use may lead to tolerance and paradoxical bronchospasm (inhaler);
  • OB: Use only if potential maternal benefit outweighs potential risks to fetus;
  • Lactation: High intravenous doses of epinephrine might ↓ milk production or letdown. Low-dose epidural, topical, inhaled, or ophthalmic epinephrine are unlikely to interfere with breast feeding (NIH);
  • Geri: More susceptible to adverse reactions; may require ↓ dose.

Adverse Reactions/Side Effects

CNS: nervousness, restlessness, tremor, headache, insomnia

Resp: PARADOXICAL BRONCHOSPASM (EXCESSIVE USE OF INHALERS)

CV: angina, arrhythmias, hypertension, tachycardia

GI: nausea, vomiting

Endo: hyperglycemia

* CAPITALS indicate life-threatening.
Italics indicate most frequent.

Interactions

Drug-Drug

  • Concurrent use with other adrenergic agents will have additive adrenergic side effects.
  • Use with MAO inhibitors may lead to hypertensive crisis.
  • Beta blockers may negate therapeutic effect.
  • Tricyclic antidepressants enhance pressor response to epinephrine.

Drug-Natural Products:

Use with caffeine-containing herbs ( cola nut, guarana, mate , tea, coffee) ↑ stimulant effect.

Route/Dosage

SC: IM: (Adults) Anaphylactic reactions/asthma– 0.1–0.5 mg (single dose not to exceed 1 mg); may repeat q 10–15 min for anaphylactic shock or q 20 min–4 hr for asthma.

SC: (Children > 1 mo): Anaphylactic reactions/asthma– 0.01 mg/kg (not to exceed 0.5 mg/dose) q 15 min for 2 doses, then q 4 hr.

IV: (Adults) Severe anaphylaxis– 0.1–0.25 mg q 5–15 min; may be followed by 1–4 mcg/min continuous infusion; cardiopulmonary resuscitation (ACLS guidelines)– 1 mg q 3–5 min; bradycardia (ACLS guidelines)– 2–10 mcg/min).

IV: Children Severe anaphylaxis– 0.1 mg (less in younger children); may be followed by 0.1 mcg/kg/min continuous infusion (may be ↑ up to 1.5 mcg/kg/min); symptomatic bradycardia/pulseless arrest (PALS guidelines)– 0.01 mg/kg, may be repeated q 3–5 min, higher doses (up to 0.1–0.2 mg/kg) may be considered; may also be given by the intraosseous route. May also be given by the endotracheal route in doses of 0.1–0.2 mg/kg diluted to a volume of 3–5 mL with normal saline followed by several positive pressure ventilations.

Inhaln: (Adults) Inhalation solution– 1 inhalation of 1% solution; may be repeated after 1–2 min; additional doses may be given q 3 hr; racepinephrine– Via hand nebulizer, 2–3 inhalations of 2.25% solution; may repeat in 5 min with 2–3 more inhalations, up to 4–6 times daily.

Inhaln: (Children > 1 mo): 0.25–0.5 mL of 2.25% racemic epinephrine solution diluted in 3 mL normal saline.

IV: Intratracheal: Neonates 0.01–0.03 mg/kg q 3–5 min as needed.

IM: (Children > 1 mo <30 kg): 0.15 mg (EpiPen Jr); > 30 kg: 0.3 mg (EpiPen).

Intracardiac: (Adults) 0.3–0.5 mg.

Endotracheal: (Adults) Cardiopulmonary resuscitation (ACLS guidelines)– 2–2.5 mg.

Topical: (Adults and Children ≥6 yr): Nasal decongestant– Apply 1% solution as drops, spray, or with a swab.

Intraspinal: (Adults and Children) 0.2–0.4 mL of 1:1000 solution.

With Local Anesthetics: (Adults and Children) Use 1:200,000 solution with local anesthetic.

Availability (generic available)

Inhalation solution (racepinephrine): 2.25% [Canada]

Intranasal solution: 1 mg/mL (1:1000)

Solution for injection: 0.1 mg/mL (1:10,000), 1 mg/mL (1:1000)

Autoinjector (EpiPen): 0.15 mg/0.15 mL (1:1000), 0.15 mg/0.3 mL (1:2000), 0.3 mg/0.3 mL (1:1000)

Assessment

  • Bronchodilator: Assess lung sounds, respiratory pattern, pulse, and BP before administration and during peak of medication. Note amount, color, and character of sputum produced, and notify health care professional of abnormal findings.
  • Monitor pulmonary function tests before and periodically during therapy.
  • Observe for paradoxical bronchospasm (wheezing). If condition occurs, withhold medication and notify health care professional immediately.
    • Observe patient for drug tolerance and rebound bronchospasm. Patients requiring more than 3 inhalation treatments in 24 hr should be under close supervision. If minimal or no relief is seen after 3–5 inhalation treatments within 6–12 hr, further treatment with aerosol alone is not recommended.
    • Assess for hypersensitivity reaction (rash; urticaria; swelling of the face, lips, or eyelids). If condition occurs, withhold medication and notify health care professional immediately.
  • Vasopressor: Monitor BP, pulse, ECG, and respiratory rate frequently during IV administration. Continuous ECG, hemodynamic parameters, and urine output should be monitored continuously during IV administration.
    • Monitor for chest pain, arrhythmias, heart rate >110 bpm, and hypertension. Consult physician for parameters of pulse, BP, and ECG changes for adjusting dose or discontinuing medication.
  • Shock: Assess volume status. Correct hypovolemia prior to administering epinephrine IV.
  • Nasal Decongestant: Assess patient for nasal and sinus congestion prior to and periodically during therapy.

Lab Test Considerations: May cause transient ↓ in serum potassium concentrations with nebulization or at higher than recommended doses.

  • May cause an ↑ in blood glucose and serum lactic acid concentrations.

Toxicity Overdose: Symptoms of overdose include persistent agitation, chest pain or discomfort, decreased BP, dizziness, hyperglycemia, hypokalemia, seizures, tachyarrhythmias, persistent trembling, and vomiting.
  • Treatment includes discontinuing adrenergic bronchodilator and other beta-adrenergic agonists and symptomatic, supportive therapy. Cardioselective beta blockers are used cautiously because they may induce bronchospasm.

Potential Diagnoses

Implementation

  • Do not confuse epinephrine with ephedrine.
  • High Alert: Patient harm or fatalities have occurred from medication errors with epinephrine. Epinephrine is available in various concentrations, strengths, and percentages and used for different purposes. Packaging labels may be easily confused or products incorrectly diluted. Dilutions should be prepared by a pharmacist. IV doses should be expressed in milligrams not ampules, concentration, or volume. Prior to administration, have second practitioner independently check original order, dose calculations, concentration, route of administration, and infusion pump settings.
  • Medication should be administered promptly at the onset of bronchospasm.
    • Use a tuberculin syringe with a 26-gauge ½-in. needle for subcut injection to ensure that correct amount of medication is administered.
    • Tolerance may develop with prolonged or excessive use. Effectiveness may be restored by discontinuing for a few days and then readministering.
    • Do not use solutions that are pinkish or brownish or that contain a precipitate.
    • For anaphylactic shock, volume replacement should be administered concurrently with epinephrine. Antihistamines and corticosteroids may be used in conjunction with epinephrine.
  • IM: SC: Medication can cause irritation of tissue. Rotate injection sites to prevent tissue necrosis. Massage injection sites well after administration to enhance absorption and to decrease local vasoconstriction. Avoid IM administration in gluteal muscle.
  • Endotracheal: Epinephrine can be injected directly into the bronchial tree via the endotracheal tube if the patient has been intubated. Perform 5 rapid insufflations; forcefully administer 10 mL containing 2–2.5 mg epinephrine (1 mg/mL) directly into tube; follow with 5 quick insufflations.
  • Inhaln: When using epinephrine inhalation solution, 10 drops of 1% base solution should be placed in the reservoir of the nebulizer.
    • The 2.25% inhalation solution of racepinephrine must be diluted for use in the combination nebulizer/respirator.
    • Allow 1–2 min to elapse between inhalations of epinephrine inhalation solution to make certain the second inhalation is necessary.
    • When epinephrine is used concurrently with corticosteroid or ipratropium inhalations, administer bronchodilator first and other medications 5 min apart to prevent toxicity from inhaled fluorocarbon propellants.
  • Endotracheal: Epinephrine can be injected directly into the bronchial tree via the endotracheal tube if the patient has been intubated. Perform 5 rapid insufflations; forcefully administer 10 mL containing 2–2.5 mg epinephrine (1 mg/mL) directly into tube; follow with 5 quick insufflations.

IV Administration

  • Direct IV: Diluent: The 1:10,000 solution can be administered undiluted. Dilute 1 mg (1 mL) of a 1:1000 solution in 9 mL of 0.9% NaCl to prepare a 1:10,000 solution. Concentration: 0.1 mg/mL (1:10,000).
  • Rate: Administer each 1 mg (10 mL) of a 1:10,000 solution over at least 1 min; more rapid administration may be used during cardiac resuscitation. Follow each dose with 20 mL IV saline flush.
  • Continuous Infusion: Diluent: Dilute 1 mg (1 mL) of a 1:1000 solution in 250 mL of D5W or 0.9% NaCl. Protect from light. Infusion stable for 24 hr. Concentration: 4 mcg/mL.
  • Rate: See Route/Dosage section. Titrate to response (BP, heart rate, respiratory rate).
  • Y-Site Compatibility
    • alfentanil
    • amikacin
    • aminocaproic acid
    • amiodarone
    • amphotericin B lipid complex
    • amphotericin B liposome
    • anidulafungin
    • argatroban
    • ascorbic acid
    • atracurium
    • atropine
    • aztreonam
    • benztropine
    • bivalirudin
    • bleomycin
    • bumetanide
    • buprenorphine
    • butorphanol
    • calcium chloride
    • calcium gluconate
    • carboplatin
    • caspofungin
    • cefazolin
    • cefoperazone
    • cefotaxime
    • cefotetan
    • cefoxitin
    • ceftazidime
    • ceftriaxone
    • cefuroxime
    • chloramphenicol
    • chlorpromazine
    • cisatracurium
    • cisplatin
    • clindamycin
    • cyanocobalamin
    • cyclophosphamide
    • cyclosporine
    • cytarabine
    • dactinomycin
    • daptomycin
    • dexamethasone sodium phosphate
    • dexmedetomidine
    • dexrazoxane
    • digoxin
    • diltiazem
    • diphenhydramine
    • dobutamine
    • docetaxel
    • dopamine
    • doxorubicin
    • doxycycline
    • enalaprilat
    • ephedrine
    • epirubicin
    • epoetin alfa
    • eptifibatide
    • ertapenem
    • erythromycin
    • esmolol
    • etoposide
    • etoposide phosphate
    • famotidine
    • fenoldopam
    • fentanyl
    • fluconazole
    • fludarabine
    • folic acid
    • foscarnet
    • furosemide
    • gemcitabine
    • gentamicin
    • glycopyrrolate
    • granisetron
    • heparin
    • hetastarch
    • hydrocortisone sodium succinate
    • hydromorphone
    • ibuprofen
    • idarubicin
    • ifosfamide
    • imipenem/cilastatin
    • irinotecan
    • isoproterenol
    • ketamine
    • ketorolac
    • labetalol
    • levofloxacin
    • leucovorin caclium
    • lidocaine
    • linezolid
    • lorazepam
    • magnesium sulfate
    • mannitol
    • mechlorethamine
    • meperidine
    • metaraminol
    • methotrexate
    • methoxamine
    • methyldopa
    • methylprednisolone sodium succinate
    • metoclopramide
    • metoprolol
    • metronidazole
    • midazolam
    • milrinone
    • mitoxantrone
    • morphine
    • moxifloxacin
    • multiple vitamins
    • mycophenolate
    • nafcillin
    • nalbuphine
    • naloxone
    • nicardipine
    • nitroglycerin
    • nitroprusside
    • norepinephrine
    • octreotide
    • ondansetron
    • oxacillin
    • oxaliplatin
    • oxytocin
    • paclitaxel
    • palonosetron
    • pamidronate
    • pancuronium
    • pantoprazole
    • pemetrexed
    • penicillin G potassium
    • pentamidine
    • pentazocine
    • phentolamine
    • phenylephrine
    • phytonadione
    • piperacillin/tazobactam
    • potassium acetate
    • potassium chloride
    • procainamide
    • prochlorperazine
    • promethazine
    • propofol
    • propranolol
    • protamine
    • pyridoxime
    • quinupristin/dalfopristin
    • ranitidine
    • remifentanil
    • rocuronium
    • sodium acetate
    • streptokinase
    • succinylcholine
    • sufentanil
    • tacrolimus
    • teniposide
    • theophylline
    • thiamine
    • thiotepa
    • ticarcillin/clavulanate
    • tigecycline
    • tirofiban
    • tobramycin
    • tolazoline
    • trimetaphan
    • vancomycin
    • vasopressin
    • vecuronium
    • verapamil
    • vinblastine
    • vincristine
    • vinorelbine
    • vitamin B complex with C
    • voriconazole
    • warfarin
    • zoledronic acid
  • Y-Site Incompatibility
    • acyclovir
    • alemtuzumab
    • aminophylline
    • azathioprine
    • carmustine
    • dantrolene
    • diazepam
    • diazoxide
    • fluorouracil
    • ganciclovir
    • indomethacin
    • micafungin
    • pentobarbital
    • phenobarbital
    • phenytoin
    • sodium bicarbonate
    • thiopental
    • trimethoprim/sulfamethoxazole

Patient/Family Teaching

  • Instruct patient to take medication exactly as directed. If on a scheduled dosing regimen, take a missed dose as soon as possible; space remaining doses at regular intervals. Do not double doses. Caution patient not to exceed recommended dose; may cause adverse effects, paradoxical bronchospasm, or loss of effectiveness of medication.
    • Instruct patient to contact health care professional immediately if shortness of breath is not relieved by medication or is accompanied by diaphoresis, dizziness, palpitations, or chest pain.
    • Advise patient to consult health care professional before taking any OTC medications or alcoholic beverages concurrently with this therapy. Caution patient also to avoid smoking and other respiratory irritants.
  • Inhaln: Review correct administration technique (aerosolization, IPPB) with patient.
    • Do not spray inhaler near eyes.
    • Advise patients to use bronchodilator first if using other inhalation medications, and allow 5 min to elapse before administering other inhalant medications, unless otherwise directed.
    • Advise patient to rinse mouth with water after each inhalation dose to minimize dry mouth.
    • Advise patient to maintain adequate fluid intake (2000–3000 mL/day) to help liquefy tenacious secretions.
    • Advise patient to consult health care professional if respiratory symptoms are not relieved or worsen after treatment or if chest pain, headache, severe dizziness, palpitations, nervousness, or weakness occurs.
    • Advise patient to notify health care professional if pregnancy is planned or suspected or if breast feeding.
  • Autoinjector: Instruct patients using auto-injector for anaphylactic reactions to remove gray safety cap, placing black tip on thigh at right angle to leg. Press hard into thigh until auto-injector functions, hold in place for 10 seconds, remove, and discard properly. Massage injected area for 10 sec. Pedi: Teach parents or caregivers signs and symptoms of anaphlyaxis, how to use auto-injector safely, and to get the child to a hospital as soon as possible. Instruct parents or caregivers to teach child how to manage his or her allergy, how to self-inject, and what to do in an emergency. For children too young to self-inject and who will be separated from parent, tell parents to always discuss allergy and use of auto-injector with responsible adult.

Evaluation/Desired Outcomes

  • Prevention or relief of bronchospasm.
    • Increase in ease of breathing.
    • Prevention of bronchospasm or reduction of frequency of acute asthma attacks in patients with chronic asthma.
    • Prevention of exercise-induced asthma.
  • Reversal of signs and symptoms of anaphylaxis.
  • Increase in cardiac rate and output, when used in cardiac resuscitation.
  • Increase in BP, when used as a vasopressor.
  • Localization of local anesthetic.
  • Decrease in sinus and nasal congestion.