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EPINEPHrine (Systemic)

Pronunciation

Pronunciation

(ep i NEF rin)

Index Terms

  • Adrenaline
  • Adrenaline Acid Tartrate
  • Adrenaline Bitartrate
  • Adrenaline Hydrochloride
  • Adrenaline Tartrate
  • Epinephrine Bitartrate
  • Epinephrine HCl/D5W
  • Epinephrine Hydrochloride

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Device, Injection:

EpiPen 2-Pak: 0.3 mg/0.3 mL (2 ea) [latex free; contains sodium metabisulfite]

EpiPen Jr 2-Pak: 0.15 mg/0.3 mL (2 ea) [contains sodium metabisulfite]

Kit, Injection:

Adyphren: 1 mg/mL [contains sodium metabisulfite]

Adyphren II: 1 mg/mL [contains sodium metabisulfite]

EPIsnap: 1 mg/mL [contains sodium metabisulfite]

EPY: 1 mg/mL [DSC] [contains sodium metabisulfite]

EPY II: 1 mg/mL [DSC] [contains sodium metabisulfite]

Solution, Injection:

Adrenalin: 30 mg/30 mL (30 mL) [contains chlorobutanol (chlorobutol), disodium edta, sodium metabisulfite]

Generic: 0.1 mg/mL (10 mL); 1 mg/mL (1 mL)

Solution, Intravenous [preservative free]:

Generic: 1 mg/mL (1 mL)

Solution, Injection, as hydrochloride:

Adrenalin: 1 mg/mL (30 mL [DSC]) [contains chlorobutanol (chlorobutol), sodium bisulfite]

Adrenalin: 1 mg/mL (1 mL [DSC]) [contains sodium bisulfite]

Adrenalin: 1 mg/mL (1 mL) [contains sodium metabisulfite]

Generic: 1 mg/mL (1 mL, 30 mL)

Solution Auto-injector, Injection:

Adrenaclick: 0.15 mg/0.15 mL (2 ea); 0.3 mg/0.3 mL (2 ea) [latex free; contains chlorobutanol (chlorobutol), sodium bisulfite]

Auvi-Q: 0.15 mg/0.15 mL (2 ea [DSC]); 0.3 mg/0.3 mL (2 ea [DSC]) [contains sodium bisulfite]

Generic: 0.15 mg/0.15 mL (1 ea, 2 ea); 0.3 mg/0.3 mL (1 ea, 2 ea)

Solution Prefilled Syringe, Injection:

Generic: 0.1 mg/mL (10 mL)

Brand Names: U.S.

  • Adrenaclick
  • Adrenalin
  • Adyphren
  • Adyphren II
  • Auvi-Q [DSC]
  • EpiPen 2-Pak
  • EpiPen Jr 2-Pak
  • EPIsnap
  • EPY II [DSC]
  • EPY [DSC]

Pharmacologic Category

  • Alpha/Beta Agonist

Pharmacology

Stimulates alpha-, beta1-, and beta2-adrenergic receptors resulting in relaxation of smooth muscle of the bronchial tree, cardiac stimulation (increasing myocardial oxygen consumption), and dilation of skeletal muscle vasculature; small doses can cause vasodilation via beta2-vascular receptors; large doses may produce constriction of skeletal and vascular smooth muscle

Absorption

Orally ingested doses are rapidly metabolized in GI tract and liver; pharmacologically active concentrations are not achieved

Distribution

Does not cross blood-brain barrier

Metabolism

Taken up into the adrenergic neuron and metabolized by monoamine oxidase and catechol-o-methyltransferase; circulating drug hepatically metabolized

Excretion

Urine (as inactive metabolites, metanephrine, and sulfate and hydroxy derivatives of mandelic acid; small amounts as unchanged drug)

Onset of Action

Bronchodilation: SubQ: ~5 to 10 minutes

Half-Life Elimination

IV: <5 minutes

Use: Labeled Indications

Hypersensitivity: Treatment of type I allergic reactions including anaphylactic reactions.

Hypotension/shock: Treatment of hypotension associated with septic shock in adults (increase mean arterial blood pressure).

Mydriasis during intraocular surgery: Induction and maintenance of mydriasis during intraocular surgery.

Contraindications

There are no absolute contraindications to the use of injectable epinephrine (including Adrenaclick, Auvi-Q, EpiPen, EpiPen Jr, Allerject [Canadian product], and Twinject [Canadian product]) in a life-threatening situation. Some products include the following contraindications: Hypersensitivity to sympathomimetic amines; general anesthesia with halogenated hydrocarbons (eg, halothane) or cyclopropane; narrow angle glaucoma; nonanaphylactic shock; in combination with local anesthesia of certain areas such as fingers, toes, and ears; use in situations where vasopressors may be contraindicated (eg, thyrotoxicosis, diabetes, in obstetrics when maternal blood pressure is in excess of 130/80 mm Hg and in hypertension and other cardiovascular disorders)

Injectable solution (Adrenalin, Epinephrine injection, USP): There are no contraindications listed in the manufacturer’s labeling.

Dosing: Adult

Note: As of May 1, 2016, ratio expressions of epinephrine concentrations are prohibited on drug labels. Ampules, vials, and syringes of epinephrine with ratio expressions may however remain in inventory until replaced by products with revised labeling. Therefore, the ratio expression of 1:1000 is equivalent to 1 mg/mL and 1:10,000 is equivalent to 0.1 mg/mL (ISMP 2015).

Asystole/pulseless arrest, pulseless VT/VF (ACLS [Neumar 2010]):

IV, I.O.: 1 mg every 3 to 5 minutes until return of spontaneous circulation; if this approach fails, higher doses of epinephrine (up to 0.2 mg/kg) have been used for treatment of specific problems (eg, beta-blocker or calcium channel blocker overdose)

Note: High IV dose epinephrine (ie, >1 mg per dose) has not been shown to improve survival or neurological outcomes as compared to standard dose epinephrine and is not recommended (ACLS [Neumar, 2010]; ACLS [Neumar 2015]).

Endotracheal: 2 to 2.5 mg every 3 to 5 minutes until IV/I.O. access established or return of spontaneous circulation; dilute in 5 to 10 mL NS or sterile water. Note: Absorption may be greater with sterile water (Naganobu 2000). May cause false-negative reading with exhaled CO2 detectors; use second method to confirm tube placement if CO2 is not detected (ACLS [Neumar 2010]).

Bradycardia (symptomatic; unresponsive to atropine or pacing): IV infusion: 2 to 10 mcg/minute or 0.1 to 0.5 mcg/kg/minute (7 to 35 mcg/minute in a 70 kg patient); titrate to desired effect (ACLS [Neumar 2010]; AHA [Peberdy 2010]).

Bronchodilator: SubQ: Acute severe asthma unresponsive to inhaled beta-agonist (off-label use): 0.01 mg/kg divided into 3 doses of approximately 0.3 mg every 20 minutes. Note: The 1 mg/mL concentration is recommended (AHA [Vanden Hoek 2010]).

Hypersensitivity reaction (eg, anaphylaxis): Note: SubQ administration results in slower absorption and is less reliable. IM administration in the anterolateral aspect of the middle third of the thigh is preferred in the setting of anaphylaxis (AHA [Vanden Hoek 2010]; WAO [Kemp 2008]).

IM (preferred), SubQ: 0.2 to 0.5 mg using the 1 mg/mL solution every 5 to 15 minutes in the absence of clinical improvement (AAAAI [Lieberman 2015]; AHA [Vanden Hoek 2010]; WAO [Kemp 2008]).

IV:

Slow IV bolus: 0.1 mg using the 0.1 mg/mL solution (further diluted in 10 mL of NS) administered over 5 to 10 minutes (Barach 1984)

Continuous infusion: May initiate with an infusion at 2 to 15 mcg/minute (with crystalloid administration) (AAAAI [Lieberman 2015]; AHA [Vanden Hoek 2010]; Brown 2004).

Note: In general, IV administration should only be done in patients who are unresponsive or profoundly hypotensive who have failed to respond to IV fluid replacement and several epinephrine injections (WAO [Kemp, 2008]). If the patient is in cardiopulmonary arrest, use of higher IV/IO push doses (ie, 1 mg every 3 to 5 minutes) should be employed or appropriate endotracheal doses administered if an advanced airway is in place (AAAAI [Lieberman 2015]; AHA [Neumar 2010]).

Self-administration following severe allergic reactions (eg, insect stings, food): Note: The World Health Organization (WHO) and Anaphylaxis Canada recommend the availability of one dose for every 10 to 20 minutes of travel time to a medical emergency facility. If anaphylactic symptoms persist after first dose, may repeat dose in 5 to 15 minutes (AHA [Vanden Hoek 2010]); more than 2 sequential doses should only be administered under direct medical supervision.

Adrenaclick: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Adrenaclick injector

Allerject [Canadian product]: IM: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Allerject injector

Auvi-Q: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated

EpiPen: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional EpiPen

Twinject [Canadian product]: IM, SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated in 5 to 15 minutes using the same device after partial disassembly

Hypotension/septic shock:

Manufacturer's labeling: Septic shock: IV infusion: Initial: 0.05 to 2 mcg/kg/minute (3.5 to 140 mcg/minute in a 70 kg patient); titrate to desired mean arterial pressure (MAP). May adjust dose every 10 to 15 minutes by 0.05 to 0.2 mcg/kg/minute to achieve desired blood pressure goal. After hemodynamic stabilization, may wean incrementally every 30 minutes over 12 to 24 hours.

American Heart Association recommendation: Severe and fluid resistant (off-label dosing): IV infusion: Initial: 0.1 to 0.5 mcg/kg/minute (7 to 35 mcg/minute in a 70 kg patient); titrate to desired response (AHA [Peberdy 2010]).

Mydriasis during intraocular surgery, induction and maintenance: Intraocular: Must dilute 1 mg/mL solution to a concentration of 1 to 10 mcg/mL prior to intraocular use: May use as an irrigation solution as needed during the procedure or may administer intracamerally (ie, directly into the anterior chamber of the eye) with a bolus dose of 0.1 mL of a 2.5 to 10 mcg/mL dilution.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: As of May 1, 2016, ratio expressions of epinephrine concentrations are prohibited on drug labels. Ampules, vials, and syringes of epinephrine with ratio expressions may however remain in inventory until replaced by products with revised labeling. Therefore, the ratio expression of 1:1000 is equivalent to 1 mg/mL and 1:10,000 is equivalent to 0.1 mg/mL (ISMP 2015).

Asystole/pulseless arrest, pulseless VT/VF (after failed defibrillation attempts) (PALS [Kleinman 2010]): Infants, Children, and Adolescents:

IV, I.O.: 0.01 mg/kg (0.1 mL/kg of 0.1 mg/mL solution) (maximum single dose: 1 mg) every 3 to 5 minutes until return of spontaneous circulation

Endotracheal: 0.1 mg/kg (0.1 mL/kg of 1 mg/mL solution) (maximum single dose: 2.5 mg) every 3 to 5 minutes until IV/I.O. access established or return of spontaneous circulation. Note: Recent clinical studies suggest that lower epinephrine concentrations delivered by endotracheal administration may produce transient beta2-adrenergic effects which may be detrimental (eg, hypotension, lower coronary artery perfusion pressure). IV or I.O. are the preferred methods of administration.

Bradycardia (symptomatic; unresponsive to atropine or pacing) (PALS [Kleinman 2010]): Infants, Children, and Adolescents:

IV, I.O.: 0.01 mg/kg (0.1 mL/kg of 0.1 mg/mL solution) (maximum single dose: 1 mg) every 3 to 5 minutes as needed

Endotracheal: 0.1 mg/kg (0.1 mL/kg of 1 mg/mL solution) (maximum single dose: 2.5 mg) every 3 to 5 minutes as needed until IV/I.O. access established. Note: Recent clinical studies suggest that lower epinephrine concentrations delivered by endotracheal administration may produce transient beta2-adrenergic effects which may be detrimental (eg, hypotension, lower coronary artery perfusion pressure). IV or I.O. are the preferred methods of administration.

Cardiac output maintenance/stabilization, postresuscitation (PALS [Kleinman 2010]): Infants, Children, and Adolescents: Continuous IV/I.O. infusion: 0.1 to 1 mcg/kg/minute; doses <0.3 mcg/kg/minute generally produce beta-adrenergic effects and higher doses (>0.3 mcg/kg/minute) generally produce alpha-adrenergic vasoconstriction; titrate dosage to desired effect.

Hypersensitivity reaction (eg, anaphylaxis): Infants, Children, and Adolescents: Note: SubQ administration results in slower absorption and is less reliable. IM administration in the anterolateral aspect of the middle third of the thigh is preferred in the setting of anaphylaxis (AAAAI [Lieberman 2015]; Campbell 2014; Simons 2011).

IM (preferred), SubQ: 0.01 mg/kg (0.01 mL/kg of 1 mg/mL solution) not to exceed 0.3 to 0.5 mg every 5 to 15 minutes (Hegenbarth 2008; Simons 2011; Simons 2015).

Self-administration following severe allergic reactions (eg, insect stings, food): Note: If anaphylactic symptoms persist after first dose, may repeat dose in 5 to 15 minutes (Simons 2011); more than 2 sequential doses should only be administered under direct medical supervision.

Adrenaclick: IM, SubQ:

Children 15 to 29 kg: 0.15 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Adrenaclick injector

Children ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Adrenaclick injector

Allerject [Canadian product]: IM:

Children 15 to 29 kg: 0.15 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Allerject injector

Children ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional Allerject injector

Auvi-Q: IM, SubQ:

Children 15 to 29 kg: 0.15 mg; if anaphylactic symptoms persist, dose may be repeated

Children ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated

EpiPen Jr: IM, SubQ: Children 15 to 29 kg: 0.15 mg; if anaphylactic symptoms persist, dose may be repeated using an additional EpiPen Jr

EpiPen: IM, SubQ: Children ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated using an additional EpiPen

Twinject [Canadian product]: IM, SubQ:

Children 15 to 29 kg: 0.15 mg; if anaphylactic symptoms persist, dose may be repeated in 5 to 15 minutes using the same device after partial disassembly

Children ≥30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated in 5 to 15 minutes using the same device after partial disassembly

Alternate auto-injector dose: IM (Sicherer 2007):

Children 10 to 25 kg: 0.15 mg

Children >25 kg: 0.3 mg

Hypotension/shock, fluid-resistant (off-label use): Continuous IV infusion: 0.1 to 1 mcg/kg/minute; doses up to 5 mcg/kg/minute may rarely be necessary (Hegenbarth 2008)

Mydriasis during intraocular surgery, induction and maintenance: Infants, Children, and Adolescents: Intraocular: Refer to adult dosing.

Dosing: Renal Impairment

There are no dosage adjustment provided in manufacturer's labeling.

Dosing: Hepatic Impairment

There are no dosage adjustment provided in manufacturer's labeling.

Reconstitution

Endotracheal (off-label route): Dilute in NS or sterile water.

Intraocular: Dilute 1 mL of 1 mg/mL solution in 100 mL to 1,000 mL of an ophthalmic irrigation fluid for a final concentration of 1 to 10 mcg/mL); may use this solution as an irrigation as needed during the procedure. May also prepare a dilution of 2.5 to 10 mcg/mL for intracameral administration.

Intravenous: Although the manufacturer recommends dilution in dextrose containing solutions (provides protection against significant loss of potency by oxidation) and does not recommend dilution in NS alone, dilution in NS has been reported to be physically compatible (Trissel 2014).

Administration

Epinephrine solutions for injection can be administered IM, I.O., endotracheally, IV, or SubQ. Note: Adrenaclick, Allerject [Canadian product], Auvi-Q, EpiPen and EpiPen Jr Auto-Injectors contain a single, fixed-dose of epinephrine and may only be administered IM (preferred) or SubQ. Twinject Auto-Injectors [Canadian product] contain two doses; the first fixed-dose is available for auto-injection; the second dose is available for manual injection following partial disassembly of device.

IV: When administering as a continuous infusion, central line administration is preferred. IV infusions require an infusion pump. If central line not available, as a temporary measure, may administer through a large vein. Avoid use of ankle veins (due to potential for gangrene), leg veins in elderly patients, or leg veins in those suffering from occlusive vascular diseases (eg, diabetic endarteritis, Buerger disease, arteriosclerosis, atherosclerosis).

Vesicant; ensure proper needle or catheter placement prior to and during infusion; avoid extravasation.

Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Initiate phentolamine (or alternative antidote). Apply dry warm compresses (Hurst 2004).

Phentolamine: Dilute 5 to 10 mg in 10 to 15 mL NS and administer into extravasation site as soon as possible after extravasation (Peberdy 2010).

Alternatives to phentolamine:

Nitroglycerin topical 2% ointment (based on limited case reports in neonates/infants): Apply 4 mm/kg as a thin ribbon to the affected areas; may repeat after 8 hours if needed (Wong 1992) or apply a 1-inch strip on the affected site (Denkler 1989).

Terbutaline (based on limited case reports): Infiltrate extravasation area using a solution of terbutaline 1 mg diluted to 10 mL in NS (large extravasation site; administration volume varied from 3 to 10 mL) or 1 mg diluted in 1 mL NS (small/distal extravasation site; administration volume varied from 0.5 to 1 mL) (Stier 1999).

Subcutaneous: SubQ administration results in slower absorption and is less reliable.

IM: IM administration in the anterolateral aspect of the middle third of the thigh is preferred in the setting of anaphylaxis (AHA [Vanden Hoek 2010]; WAO [Kemp 2008]). Do not administer repeated injections at the same site. Do not inject into the buttocks. Adrenaclick, Allerject [Canadian product], Auvi-Q, EpiPen, EpiPen Jr, and Twinject Auto-Injectors [Canadian product] should only be injected into the anterolateral aspect of the thigh, through clothing if necessary.

Obesity: In overweight or obese children, because skin surface to muscle depth is greater in the upper half of the thigh, administration into the lower half of the thigh may be preferred. In very obese children, injection into the calf will provide an even greater chance of intramuscular administration (Arkwright 2013).

Intraocular: May administer as an irrigation solution as needed during the procedure or may administer intracamerally (ie, directly into the anterior chamber of the eye).

Endotracheal (cardiac arrest): Dilute in NS or sterile water. Absorption may be greater with sterile water (Naganobu 2000). Stop compressions, spray drug quickly down tube. Follow immediately with several quick insufflations and continue chest compressions. May cause false-negative reading with exhaled CO2 detectors; use second method to confirm tube placement if CO2 is not detected (ACLS [Neumar 2010]).

Compatibility

Stable in dextran 6% in dextrose, dextran 6% in NS, D5LR, D51/4NS, D51/2NS, D5NS, D5R, D2.5W, D5W, D10W, D10NS, LR, NS, Ringer's injection; incompatible with sodium bicarbonate.

Y-site administration: Incompatible with ampicillin, micafungin, sodium bicarbonate, thiopental.

Storage

Epinephrine is sensitive to light and air. Protection from light is recommended. Oxidation turns drug pink, then a brown color. Solutions should not be used if they are discolored or contain a precipitate.

Adrenaclick: Store between 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze or refrigerate.

Adrenalin: Store between 20°C to 25°C (68°F to 77°F); do not freeze.

Allerject [Canadian product]: Store between 15°C to 30°C (59°F to 86°F); do not refrigerate.

Auvi-Q: Store between 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not refrigerate.

Epinephrine injection, USP: Store between 20°C to 25°C (68°F to 77°F); do not refrigerate; protect from freezing.

EpiPen and EpiPen Jr: Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze or refrigerate.

Twinject [Canadian product]: Store between 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze or refrigerate. Protect from light.

Stability of injection of parenteral admixture at room temperature (25°C) or refrigeration (4°C) is 24 hours.

Drug Interactions

Alpha1-Blockers: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Similarly, Alpha-/Beta-Agonists may antagonize Alpha1-Blocker vasodilation. Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Monitor therapy

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Benperidol: May diminish the therapeutic effect of EPINEPHrine (Systemic). Monitor therapy

Benzylpenicilloyl Polylysine: Alpha-/Beta-Agonists may diminish the diagnostic effect of Benzylpenicilloyl Polylysine. Management: Consider use of a histamine skin test as a positive control to assess a patient's ability to mount a wheal and flare response. Consider therapy modification

Beta-Blockers: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Epinephrine used as a local anesthetic for dental procedures will not likely cause clinically relevant problems. Some beta-adrenoceptor mediated effects of Alpha-/Beta-Agonists (Direct-Acting), including anti-anaphylactic effects of epinephrine, may be diminished by Beta-Blockers. Management: Cardioselective beta-blockers and lower doses of epinephrine may confer a more limited risk. Patients who may require acute subcutaneous epinephrine (e.g., bee sting kits) should probably avoid beta blockers. Consider therapy modification

Blonanserin: May diminish the therapeutic effect of EPINEPHrine (Systemic). Avoid combination

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy

Cocaine: May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Consider therapy modification

COMT Inhibitors: May decrease the metabolism of COMT Substrates. Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy

Ergot Derivatives: May enhance the hypertensive effect of Alpha-/Beta-Agonists. Ergot Derivatives may enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Exceptions: Ergoloid Mesylates; Nicergoline. Avoid combination

Hyaluronidase: May enhance the vasoconstricting effect of Alpha-/Beta-Agonists. Management: Avoid the use of hyaluronidase to enhance dispersion or absorption of alpha-/beta-agonists. Use of hyaluronidase for other purposes in patients receiving alpha-/beta-agonists may be considered as clinically indicated. Consider therapy modification

Inhalational Anesthetics: May enhance the arrhythmogenic effect of EPINEPHrine (Systemic). Management: Administer epinephrine with added caution in patients receiving, or who have recently received, inhalational anesthetics. Use lower than normal doses of epinephrine and monitor for the development of cardiac arrhythmias. Consider therapy modification

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification

Lurasidone: EPINEPHrine (Systemic) may enhance the hypotensive effect of Lurasidone. Avoid combination

MAO Inhibitors: May enhance the hypertensive effect of EPINEPHrine (Systemic). Monitor therapy

Promethazine: May diminish the vasoconstricting effect of EPINEPHrine (Systemic). Management: When vasoconstrictive effects are desired in patients receiving promethazine, consider alternatives to epinephrine. Consider use of norepinephrine or phenylephrine, and avoid epinephrine, when treating hypotension associated with promethazine overdose. Consider therapy modification

Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the tachycardic effect of Alpha-/Beta-Agonists. Serotonin/Norepinephrine Reuptake Inhibitors may enhance the vasopressor effect of Alpha-/Beta-Agonists. Consider therapy modification

Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy

Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Management: Avoid, if possible, the use of direct-acting alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Consider therapy modification

Adverse Reactions

Frequency not defined.

Cardiovascular: Angina pectoris, cardiac arrhythmia, cerebrovascular accident, chest pain, hypertension, ischemic heart disease, limb ischemia, localized blanching, myocardial infarction, palpitations, supraventricular tachycardia, tachyarrhythmia, tachycardia, vasoconstriction, ventricular arrhythmia, ventricular ectopy, ventricular fibrillation

Central nervous system: Anxiety, apprehension, disorientation, dizziness, drowsiness, exacerbation of Parkinson's disease, excitability, headache, memory impairment, nervousness, panic, paresthesia, psychomotor agitation, restlessness, tingling sensation

Dermatologic: Diaphoresis, gangrene of skin or other tissue (at injection site), pallor, piloerection, skin necrosis (with extravasation)

Endocrine & metabolic: Hyperglycemia, hypoglycemia, hypokalemia, increased serum glucose (transient), insulin resistance, lactic acidosis

Gastrointestinal: Nausea, vomiting

Hematologic & oncologic: Hemorrhage (CNS)

Local: Injection site tissue necrosis (including necrotizing fasciitis and myonecrosis)

Neuromuscular & skeletal: Tremor, weakness

Renal: Renal insufficiency

Respiratory: Dyspnea, pulmonary edema, rales

Warnings/Precautions

Concerns related to adverse effects:

• Arrhythmias: May induce cardiac arrhythmias; use with caution especially in patients with cardiac disease or those receiving drugs that sensitize the myocardium.

• Injection site infection: Serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), have been reported rarely at the injection site. Cleansing skin with alcohol may reduce bacteria at the injection site, but alcohol cleansing does not kill Clostridium spores; avoid injection into the buttock to decrease risk of Clostridium infections. Monitor for signs/symptoms of injection site infection.

• Pulmonary edema: Due to peripheral constriction and cardiac stimulation, pulmonary edema may occur.

• Renal effects: Due to renal blood vessel constriction, decreased urine output may occur.

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular diseases (eg, coronary artery disease, hypertension).

• Cerebrovascular disease: Use with caution in patients with cerebrovascular disease.

• Diabetes: Use with caution in patients with diabetes mellitus; may transiently increase blood glucose levels.

• Extravasation: IV administration: Vesicant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.

• Hypovolemia: Correct blood volume depletion before administering any vasopressor.

• Parkinson disease: Use with caution in patients with Parkinson disease; may cause temporary worsening of symptoms.

• Pheochromocytoma: Use with caution in patients with pheochromocytoma.

• Thyroid disease: Use with caution in patients with thyroid disease.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Elderly: Use with caution in the elderly.

• Pediatric: Lacerations, bent needles, and embedded needles have been reported in young children who are uncooperative during injection for hypersensitivity reaction. To minimize risk, hold the child’s leg firmly in place and limit movement prior to and during injection.

Dosage form specific issues:

• Accidental injection: Accidental injection into digits, hands, or feet may result in local reactions including injection site pallor, coldness and hypoesthesia or injury resulting in bruising, bleeding, discoloration, erythema or skeletal injury. Patient should seek immediate medical attention if this occurs.

• IV administration: Rapid IV administration may cause death from cerebrovascular hemorrhage or cardiac arrhythmias. However, rapid IV administration during pulseless arrest is necessary.

• Sulfites: Some products contain sulfites as preservatives. The presence of sulfites in some products should not deter administration during a serious allergic or other emergency situation even if the patient is sulfite-sensitive.

Other warnings/precautions:

• Appropriate use: For treatment of hypersensitivity reactions, do not inject into the buttock; may not effectively treat anaphylaxis and has been associated with Clostridial infections (gas gangrene). Preferred injection site is anterolateral aspect of the thigh. Do not administer repeated injections at the same site (tissue necrosis may occur).

• Intraocular use: Must dilute 1 mg/mL solution to a concentration of 1 mcg/mL to 10 mcg/mL prior to intraocular use. When used undiluted, has been associated with corneal endothelial damage. Also, products containing chlorobutanol must not be used intraocularly (may be harmful to corneal endothelium).

Monitoring Parameters

Heart rate, blood pressure (invasive blood pressure monitoring and central venous pressure monitoring recommended while receiving continuous infusion); monitor site of infusion for blanching/extravasation; continuous cardiac monitoring required during continuous infusion. If using to treat hypotension, assess intravascular volume prior to and during therapy; support as needed.

Consult individual institutional policies and procedures.

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have been observed in animal reproduction studies. Epinephrine crosses the placenta (Sandler 1964). Uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia may occur. Epinephrine is recommended for the treatment of anaphylaxis in pregnant women. Specific dosing is not available; use with caution and monitor hemodynamic response (Hepner 2013). Medications used for the treatment of cardiac arrest in pregnancy are the same as in the non-pregnant woman. Doses and indications should follow current Advanced Cardiovascular Life Support guidelines. Appropriate medications should not be withheld due to concerns of fetal teratogenicity (Jeejeebhoy [AHA] 2015). Although epinephrine injection may be used for asthma exacerbations in pregnancy, systemic therapy has not been proven to be better than use of preferred inhaled agents (NAEPP 2005).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience dizziness, anxiety, tremors, nausea, vomiting, agitation, sweating a lot, pale skin, or headache. Have patient report immediately to prescriber angina, tachycardia, abnormal heartbeat, shortness of breath, severe loss of strength and energy, signs of infection at injection site, or severe injection site redness, burning, edema, pain, or irritation (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

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