EPINEPHrine (Systemic)

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

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 Amp: 1 mg/mL [contains sodium metabisulfite]

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

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

Epinephrinesnap-v: 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: 1 mg/mL (1 mL, 30 mL)

Solution, Intravenous [preservative free]:

Generic: 1 mg/mL (1 mL)

Solution, Injection, as hydrochloride:

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

Solution Auto-injector, Injection:

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

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

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

Solution Prefilled Syringe, Injection:

Generic: 0.1 mg/mL (10 mL)

Solution Prefilled Syringe, Injection, as hydrochloride:

Generic: 0.1 mg/mL (10 mL)

Bronchodilation: SubQ: ~5 to 10 minutes

Half-Life Elimination

IV: <5 minutes

Acute severe asthma unresponsive to inhaled beta-agonist

Based on the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, subcutaneous epinephrine is an effective and recommended treatment option for acute severe asthma with respiratory failure unresponsive to an inhaled beta-agonist.

Asystole/pulseless arrest, ventricular fibrillation, or pulseless ventricular tachycardia

Based on the American Heart Association (AHA) guidelines for cardiopulmonary resuscitation and emergency cardiovascular care (Adult Advanced Cardiovascular Life Support) and the AHA Pediatric Advanced Life Support guidelines, epinephrine may be used for asystole/pulseless arrest and ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) unresponsive to initial defibrillatory shocks.

Bradycardia unresponsive to atropine or pacing

Based on the American Heart Association (AHA) guidelines for cardiopulmonary resuscitation and emergency cardiovascular care (Adult Advanced Cardiovascular Life Support) and the AHA Pediatric Advanced Life Support guidelines, epinephrine may be used for bradycardia unresponsive to atropine or pacing.

Hypotension/shock unresponsive to volume resuscitation

Based on the American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care, epinephrine may be used for hypotension/shock unresponsive to volume resuscitation. Recommendations from the American Academy of Pediatrics also support use of epinephrine in pediatric patients with hypotension/shock unresponsive to volume resuscitation [AAP [Hegenbarth 2008]].

Additional Off-Label Uses

Inotropic support

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.

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 1:1,000 is equivalent to 1 mg/mL and 1:10,000 is equivalent to 0.1 mg/mL (ISMP 2015).

Acute severe asthma unresponsive to inhaled beta-agonist (off-label use): IM, SubQ: 0.01 mg/kg divided into 3 doses of approximately 0.3 to 0.5 mg every 20 minutes; the 1 mg/mL concentration is recommended (AHA [Vanden Hoek 2010]; Cydulka 2016; Shah 2012).

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

IV, Intraosseous: 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/intraosseous 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]).

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 (product specific): Intraocular: Must dilute 1 mL of a 1 mg/mL single-use 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. Note: Not all formulations of epinephrine injection are suitable for intraocular use; consult the prescribing information (ISMP 2017).

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

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

CloZAPine: May diminish the therapeutic effect of Alpha-/Beta-Agonists. 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

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Monitor therapy

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