Epinephrine

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Epinephrine®
Adult Indications and Dosage
Pediatric Indications and Dosage
Contraindications
Warnings
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration and Monitoring
IV Compatibility
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Drug Names
Drug Shortage Status
Price

For patient information regarding Epinephrine, click here.

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: Gerald Chi

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Overview

Epinephrine is a sympathomimetic, vasopressor, and bronchodilator that is FDA approved for the treatment of respiratory distress due to bronchospasm. It also provides rapid relief of hypersensitivity reactions to drugs and other allergens, prolongs the action of anesthetics, and may be used as a hemostatic agent. Its cardiac effects may be of use in restoring cardiac rhythm in cardiac arrest due to various causes, but it is not used in cardiac failure or in hemorrhagic, traumatic, or cardiogenic shock. Common adverse reactions include palpitations, pallor, sweating, nausea, vomiting, asthenia, dizziness, headache, tremor, anxiety, restlessness, and dyspnea.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Hypersensitivity Reactions
  • Dosing Information
Cardiac Resuscitation
  • Dosing Information
  • A dose of 0.5 mL (0.5 mg) diluted to 10 mL with sodium chloride injection can be administered intravenously or intracardially to restore myocardial contractility.
  • Intracardiac injection should only be administered by personnel well trained in the technique, if there has not been sufficient time to establish an intravenous route.
  • External cardiac massage should follow intracardial administration to permit the drug to enter coronary circulation. The drug should be used secondarily to unsuccessful attempts with physical or electromechanical methods.
Ophthalmologic Use
  • Dosing Information
  • Ophthalmologic use (for producing conjunctival decongestion, to control hemorrhage, produce mydriasis and reduce intraocular pressure) — use a concentration of 1:10,000 (0.1 mg/mL) to 1:1000 (1 mg/mL).
Regional Anesthesia
  • Dosing Information
  • A final concentration of 1:200,000 of epinephrine injection is recommended for infiltration injection, nerve block, caudal or other epidural blocks. From 0.3 to 0.4 mg of epinephrine (0.3 to 0.4 mL of 1:1000 solution) may be mixed with spinal anesthetic agents.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

Acute Symptomatic Bradyarrhythmia
  • Developed by: ACC/AHA
  • Class of Recommendation: Class IIb
  • Strength of Evidence: Category B

Non–Guideline-Supported Use

Gastrointestinal Hemorrhage

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding FDA-Labeled Use of Epinephrine in pediatric patients.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Epinephrine in pediatric patients.

Non–Guideline-Supported Use

Croup
  • Aerosolized levo-epinephrine (1:1000) is at least as effective as racemic epinephrine (2.25%) in the treatment of laryngotracheitis in children (6 months to 6 years of age) with moderate to severe croup.[5]
Wheezing
  • Subcutaneous epinephrine is effective in the treatment of acute wheezing in children less than 2 years of age.[6]

Contraindications

  • Epinephrine is contraindicated in patients with known hypersensitivity to sympathomimetic amines, in patients with angle closure glaucoma, and patients in shock (nonanaphylactic). It should not be used in patients anesthetized with agents such as cyclopropane or halothane as these may sensitize the heart to the arrhythmic action of sympathomimetic drugs.
  • Addition of epinephrine to local anesthetics for injection of certain areas (e.g., fingers, toes, ears, etc.) is contraindicated because of danger that vasoconstriction may result in sloughing of tissue.
  • Except as diluted for admixture with local anesthetics to reduce absorption and prolong action, epinephrine should not ordinarily be used in those cases where vasopressor drugs may be contraindicated, e.g., in thyrotoxicosis, diabetes, in obstetrics when maternal blood pressure is in excess of 130/80 and in hypertension and other cardiovascular disorders.

Warnings

  • Epinephrine may induce potentially serious cardiac arrhythmias in patients not suffering from heart disease and in patients with organic heart disease or who are receiving drugs that sensitize the myocardium.
  • Parenterally administered epinephrine initially may produce constriction of renal blood vessels and decrease urine formation.
  • Epinephrine Injection, USP is subject to oxidation and should be protected against exposure to light and stored in light-resistant containers.
  • Epinephrine is the preferred treatment for serious allergic or other emergency situations even though this product contains sodium metabisulfite, a sulfite that may in other products cause allergic-type reactions including anaphylactic symptoms or life-threatening or less severe asthmatic episodes in certain susceptible persons. The alternatives to using epinephrine in a life-threatening situation may not be satisfactory. The presence of a sulfite in this product should not deter administration of the drug for treatment of serious allergic or other emergency situations.

Precautions

  • Do not use the Injection if its color is pinkish or darker than slightly yellow or if it contains a precipitate.
  • Do not administer unless solution is clear and container is intact. Discard unused portion.
  • Although epinephrine can produce ventricular fibrillation, its actions in restoring electrical activity in asystole and in enhancing defibrillation of the fibrillating ventricle are well documented. The drug, however, should be used with caution in patients with ventricular fibrillation.
  • Epinephrine should be used cautiously in patients with hyperthyroidism, hypertension and cardiac arrhythmias. All vasopressors should be used cautiously in patients taking monoamine oxidase (MAO) inhibitors.

Adverse Reactions

Clinical Trials Experience

There is limited information regarding Clinical Trial Experience of Epinephrine in the drug label.

Postmarketing Experience


Drug Interactions

  • Epinephrine should not be administered concomitantly with other sympathomimetic drugs (such as isoproterenol) because of possible additive effects and increased toxicity. Combined effects may induce serious cardiac arrhythmias. They may be administered alternately when the preceding effect of other such drugs has subsided.
  • Administration of epinephrine to patients receiving cyclopropane or halogenated hydrocarbon general anesthetics such as halothane which sensitize the myocardium, may induce cardiac arrhythmia. When encountered, such arrhythmias may respond to administration of a beta-adrenergic blocking drug. Epinephrine also should be used cautiously with other drugs (e.g., digitalis glycosides) that sensitize the myocardium to the actions of sympathomimetic agents.
  • Diuretic agents may decrease vascular response to pressor drugs such as epinephrine.
  • Epinephrine may antagonize the neuron blockade produced by guanethidine resulting in decreased antihypertensive effect and requiring increased dosage of the latter.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA):

  • Pregnancy Category C
  • Animal reproduction studies have not been conducted with epinephrine. It is also not known whether epinephrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Epinephrine should be given to a pregnant woman only if clearly needed.

Pregnancy Category (AUS):

  • Australian Drug Evaluation Committee (ADEC) Pregnancy Category

There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Epinephrine in women who are pregnant.

Labor and Delivery

  • Parenteral administration of epinephrine if used to support blood pressure during low or other spinal anesthesia for delivery can cause acceleration of fetal heart rate and should not be used in obstetrics when maternal blood pressure exceeds 130/80.

Nursing Mothers

There is no FDA guidance on the use of Epinephrine with respect to nursing mothers.

Pediatric Use

There is no FDA guidance on the use of Epinephrine with respect to pediatric patients.

Geriatic Use

There is no FDA guidance on the use of Epinephrine with respect to geriatric patients.

Gender

There is no FDA guidance on the use of Epinephrine with respect to specific gender populations.

Race

There is no FDA guidance on the use of Epinephrine with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Epinephrine in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Epinephrine in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Epinephrine in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Epinephrine in patients who are immunocompromised.


Administration and Monitoring

Administration

  • Intracardial
  • Intravenous
  • Subcutaneous

Monitoring

There is limited information regarding Monitoring of Epinephrine in the drug label.

IV Compatibility

There is limited information regarding IV Compatibility of Epinephrine in the drug label.

Overdosage

Acute Overdose

Signs and Symptoms

Management

  • Toxic effects of overdosage can be counteracted by injection of an alpha-adrenergic blocker and a beta-adrenergic blocker. In the event of a sharp rise in blood pressure, rapid-acting vasodilators such as the nitrites, or alpha-adrenergic blocking agents can be given to counteract the marked pressor effect of large doses of epinephrine.

Chronic Overdose

There is limited information regarding Chronic Overdose of Epinephrine in the drug label.

Pharmacology

Epinephrine.png
Epinephrine
Systematic (IUPAC) name
(R)-4-(1-Hydroxy-2-(methylamino)ethyl)benzene-1,2-diol
Identifiers
CAS number 51-43-4
ATC code A01AD01 B02BC09 C01CA24 R01AA14 R03AA01 S01EA01
PubChem 5816
DrugBank DB00668
Chemical data
Formula C9H13NO3 
Mol. mass 183.204 g/mol
SMILES eMolecules & PubChem
Pharmacokinetic data
Bioavailability  ?
Metabolism adrenergic synapse (MAO and COMT)
Half life 2 minutes
Excretion Urine
Therapeutic considerations
Pregnancy cat.

C(US)

Legal status

Prescription Only (S4)(AU) POM(UK) OTC(US)

Routes IV, IM, endotracheal, IC, Nasal Ophthalmic

Mechanism of Action

  • The actions of epinephrine resemble the effects of stimulation of adrenergic nerves. To a variable degree it acts on both alpha and beta receptor sites of sympathetic effector cells. Its most prominent actions are on the beta receptors of the heart, vascular and other smooth muscle. When given by rapid intravenous injection, it produces a rapid rise in blood pressure, mainly systolic, by (1) direct stimulation of cardiac muscle which increases the strength of ventricular contraction, (2) increasing the heart rate and (3) constriction of the arterioles in the skin, mucosa and splanchnic areas of the circulation.
  • When given by slow intravenous injection epinephrine usually produces only a moderate rise in systolic and a fall in diastolic pressure. Although some increase in pulse pressure occurs, there is usually no great elevation in mean blood pressure. Accordingly, the compensatory reflex mechanisms that come into play with a pronounced increase in blood pressure do not antagonize the direct cardiac actions of epinephrine as much as with catecholamines that have a predominant action on alpha receptors.
  • Total peripheral resistance decreases by action of epinephrine on beta receptors of the skeletal muscle vasculature and blood flow is thereby enhanced. Usually this vasodilator effect of the drug on the circulation predominates so that the modest rise in systolic pressure which follows slow injection or absorption is mainly the result of direct cardiac stimulation and increase in cardiac output. In some instances peripheral resistance is not altered or may even rise owing to a greater ratio of alpha to beta activity in different vascular areas.
  • Epinephrine relaxes the smooth muscles of the bronchi and iris and is a physiologic antagonist of histamine. The drug also produces an increase in blood sugar and glycogenolysis in the liver.
  • Intravenous injection produces an immediate and intensified response. Following intravenous injection epinephrine disappears rapidly from the blood stream.

Structure

  • Epinephrine Injection, USP 1:1000 is a sterile, nonpyrogenic solution. Each mL contains epinephrine 1 mg; sodium chloride 9 mg; sodium metabisulfite 0.9 mg added. May contain hydrochloric acid for pH adjustment.
  • The solution contains no bacteriostat or antimicrobial agent. It is administered by the following routes: intravenous, intracardiac (left ventricular chamber), via endotracheal tube into the bronchial tree, subcutaneous or intramuscular.
  • Epinephrine, USP is a sympathomimetic (adrenergic) agent designated chemically as 4-[1-hydroxy-2 (methylamino) ethyl]-1,2 benzenediol, a white, microcrystalline powder. It has the following structural formula:
This image is provided by the National Library of Medicine.
  • Sodium Chloride, USP is chemically designated NaCl, a white, crystalline compound freely soluble in water.

Pharmacodynamics

There is limited information regarding Pharmacodynamics of Epinephrine in the drug label.

Pharmacokinetics

  • Epinephrine is rapidly inactivated in the body and is degraded by enzymes in the liver and other tissues.

The large portion of injection doses is excreted in the urine as inactivated compounds. The remainder is excreted in the urine as unchanged or conjugated compounds.

Nonclinical Toxicology

There is limited information regarding Nonclinical Toxicology of Epinephrine in the drug label.

Clinical Studies

There is limited information regarding Clinical Studies of Epinephrine in the drug label.

How Supplied

  • Epinephrine Injection, USP 1:1000 (1 mg/mL) is supplied in a 1 mL ampul single-dose container (NDC 0409-7241-25).
  • Store at 20 to 25°C (68 to 77°F). [See USP Controlled Room Temperature.]
  • Protect from light.


Images

Drug Images

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Package and Label Display Panel

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This image of the FDA label is provided by the National Library of Medicine.
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This image of the FDA label is provided by the National Library of Medicine.
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This image of the FDA label is provided by the National Library of Medicine.

Patient Counseling Information

There is limited information regarding Patient Counseling Information of Epinephrine in the drug label.

Precautions with Alcohol

  • Alcohol-Epinephrine interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

  • Epinephrine®[7]

Look-Alike Drug Names

  • EPINEPHrine® — ePHEDrine®[8]

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

  1. Neumar, Robert W.; Charles W. Otto, Mark S. Link, Steven L. Kronick, Michael Shuster, Clifton W. Callaway, Peter J. Kudenchuk, Joseph P. Ornato, Bryan McNally, Scott M. Silvers, Rod S. Passman, Roger D. White, Erik P. Hess, Wanchun Tang, Daniel Davis, Elizabeth Sinz, Laurie J. Morrison (2010-11-02). "Part 8: adult advanced cardiovascular life support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care". Circulation 122 (18 Suppl 3): –729-767. doi:10.1161/CIRCULATIONAHA.110.970988. ISSN 1524-4539. PMID 20956224.
  2. Chung, S. C.; J. W. Leung, R. J. Steele, T. J. Crofts, A. K. Li (1988-06-11). "Endoscopic injection of adrenaline for actively bleeding ulcers: a randomised trial". British Medical Journal (Clinical Research Ed.) 296 (6637): 1631–1633. ISSN 0267-0623. PMID 3135047.
  3. Hirao, M.; K. Masuda, T. Asanuma, H. Naka, K. Noda, K. Matsuura, O. Yamaguchi, N. Ueda (1988-06). "Endoscopic resection of early gastric cancer and other tumors with local injection of hypertonic saline-epinephrine". Gastrointestinal Endoscopy 34 (3): 264–269. ISSN 0016-5107. PMID 3391382.
  4. Folwaczny, C.; W. Heldwein, G. Obermaier, N. Schindlbeck (1997-01). "Influence of prophylactic local administration of epinephrine on bleeding complications after polypectomy". Endoscopy 29 (1): 31–33. doi:10.1055/s-2007-1004058. ISSN 0013-726X. PMID 9083734.
  5. Waisman, Y.; B. L. Klein, D. A. Boenning, G. M. Young, J. M. Chamberlain, R. O'Donnell, D. W. Ochsenschlager (1992-02). "Prospective randomized double-blind study comparing L-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup)". Pediatrics 89 (2): 302–306. ISSN 0031-4005. PMID 1734400.
  6. Lowell, D. I.; G. Lister, H. Von Koss, P. McCarthy (1987-06). "Wheezing in infants: the response to epinephrine". Pediatrics 79 (6): 939–945. ISSN 0031-4005. PMID 3295741.
  7. EPINEPHRINE injection, solution.
  8. http://www.ismp.org.

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