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Medication Safety Issues
Sound-alike/look-alike issues:
EPINEPHrine may be confused with ePHEDrine
Epifrin® may be confused with ephedrine, EpiPen®
EpiPen® may be confused with Epifrin®
High alert medication: The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.
Medication errors have occurred due to confusion with epinephrine products expressed as ratio strengths (eg, 1:1000 vs 1:10,000).
Epinephrine 1:1000 = 1 mg/mL and is most commonly used I.M.
Epinephrine 1:10,000 = 0.1 mg/mL and is used I.V.
Medication errors have occurred when topical epinephrine 1 mg/mL (1:1000) has been inadvertently injected. Vials of injectable and topical epinephrine look very similar. Epinephrine should always be appropriately labeled with the intended administration.
International issues:
EpiPen® may be confused with Epigen® which is a brand name for glycyrrhizinic acid in Mexico
EpiPen® may be confused with Epopen® which is a brand name for epoetin alfa in Spain
Pronunciation
(ep i NEF rin)
U.S. Brand Names
Index Terms
Generic Available
Yes: Solution for injection
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of bronchospasms, bronchial asthma, nasal congestion, viral croup, anaphylactic reactions, cardiac arrest; added to local anesthetics to decrease systemic absorption of intraspinal and local anesthetics and increase duration of action; decrease superficial hemorrhage
Use: Dental
Emergency drug for treatment of anaphylactic reactions; used as vasoconstrictor to prolong local anesthesia
Use: Unlabeled/Investigational
ACLS guidelines: Ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT) unresponsive to initial defibrillatory shocks; pulseless electrical activity; asystole; hypotension/shock unresponsive to volume resuscitation; symptomatic bradycardia unresponsive to atropine or pacing; inotropic support
Pregnancy Risk Factor
C
Pregnancy Considerations
Teratogenic effects have been observed in animal reproduction studies. Epinephrine crosses the placenta and may cause fetal anoxia. Use during pregnancy when the potential benefit to the mother outweighs the possible risk to the fetus.
Lactation
Excretion in breast milk unknown
Contraindications
There are no absolute contraindications to the use of injectable epinephrine (including EpiPen®, EpiPen® Jr, and Twinject®) in a life-threatening situation.
Injectable solution: Per the manufacturer, contraindicated in narrow-angle glaucoma; shock; during general anesthesia with halogenated hydrocarbons or cyclopropane (currently not available); individuals with organic brain damage; with local anesthesia of the digits; during labor; heart failure; coronary insufficiency
Primatene Mist®, S2®: concurrent use or within 2 weeks of MAO inhibitors
Raphon: Hypersensitivity to epinephrine or any component of the formulation
Warnings/Precautions
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.
• Parkinson's disease: Use with caution in patients with Parkinson's disease; may cause temporary worsening of symptoms.
• Thyroid disease: Use with caution in patients with thyroid disease.
Concurrent drug therapy issues:
• Monoamine oxidase inhibitors (MAO-I): Use with extreme caution in patients taking MAO inhibitors; effects of epinephrine may be potentiated. The concomitant use with some formulations (eg, Primatene Mist®, S2®) of epinephrine is contraindicated.
• Tricyclic antidepressants: Use with caution in patients taking tricyclic antidepressants; effects of epinephrine may be potentiated.
Special populations:
• Elderly: Use with caution in the elderly.
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.
• I.V. administration: Rapid I.V. administration may cause death from cerebrovascular hemorrhage or cardiac arrhythmias. However, rapid I.V. administration during pulseless arrest is necessary.
• Sulfites: Some products contain sulfites as preservatives. The presence of sulfites in some products (eg, EpiPen® and Twinject®) should not deter administration during a serious allergic or other emergency situation even if the patient is sulfite-sensitive.
• Topical: Avoid topical application where reduced perfusion could lead to ischemic tissue damage (eg, penis, ears, digits).
Adverse Reactions
Frequency not defined.
Cardiovascular: Angina, cardiac arrhythmia, chest pain, flushing, hypertension, pallor, palpitation, sudden death, tachycardia (parenteral), vasoconstriction, ventricular ectopy
Central nervous system: Anxiety (transient), apprehensiveness, cerebral hemorrhage, dizziness, headache, insomnia, lightheadedness, nervousness, restlessness
Gastrointestinal: Dry throat, loss of appetite, nausea, vomiting, xerostomia
Genitourinary: Acute urinary retention in patients with bladder outflow obstruction
Neuromuscular & skeletal: Tremor, weakness
Ocular: Allergic lid reaction, burning, eye pain, ocular irritation, precipitation of or exacerbation of narrow-angle glaucoma, transient stinging
Respiratory: Dyspnea, pulmonary edema
Miscellaneous: Diaphoresis
Drug Interactions
Antacids: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Aluminum Hydroxide. Risk C: Monitor therapy
Atomoxetine: May enhance the hypertensive effect of Sympathomimetics. Atomoxetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
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. 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. Risk D: Consider therapy modification
Bromocriptine: Alpha-/Beta-Agonists may enhance the adverse/toxic effect of Bromocriptine. Including increased blood pressure, ventricular arrhythmias, and seizure. Risk C: Monitor therapy
Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy
Carbonic Anhydrase Inhibitors: May decrease the excretion of Alpha-/Beta-Agonists. Exceptions: Brinzolamide; Dorzolamide. Risk C: Monitor therapy
COMT Inhibitors: May decrease the metabolism of COMT Substrates. Risk C: Monitor therapy
Inhalational Anesthetics: May enhance the arrhythmogenic effect of EPINEPHrine. Risk D: Consider therapy modification
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination
MAO Inhibitors: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Primarily with oral administration of phenylephrine. Risk D: 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. Risk D: Consider therapy modification
Spironolactone: May diminish the vasoconstricting effect of Alpha-/Beta-Agonists. Risk C: Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Risk D: Consider therapy modification
Ethanol/Nutrition/Herb Interactions
Herb/Nutraceutical: Avoid ephedra, yohimbe (may cause CNS stimulation).
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.
Adrenalin®: Store between 15°C to 25°C (59°F to 77°F); do not freeze. Protect from light. The 1:1000 solution should be discarded 30 days after initial use.
EpiPen® and EpiPen® Jr: Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F); do not freeze or refrigerate. Protect from light by storing in carrier tube provided.
Primatene® Mist: Store between 20°C to 25°C (68°F to 77°F).
Raphon: Store between 2°C to 25°C (36°F to 77°F). Refrigerate after opening.
S2®: Store between 2°C to 20°C (36°F to 68°F). Protect from light.
Twinject®: 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.
Reconstitution
Standard I.V. diluent: 1 mg/250 mL NS.
Preparation of adult I.V. infusion: Dilute 1 mg in 250 mL of D5W or NS (4 mcg/mL).
S2®: Dilution not required when administered via hand-bulb nebulizer; dilute with NS 3-5 mL if using jet nebulizer.
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: Compatible: Amiodarone, anidulafungin, atracurium, bivalirudin, calcium chloride, calcium gluconate, ceftazidime, cisatracurium, clonidine, dexmedetomidine, diltiazem, dobutamine, dopamine, famotidine, fenoldopam, fentanyl, furosemide, heparin, hetastarch (Hextend®), hydrocortisone sodium succinate, hydromorphone, inamrinone, labetalol, levofloxacin, lorazepam, midazolam, milrinone, morphine, nicardipine, nitroglycerin, nitroprusside, norepinephrine, pancuronium, pantoprazole, phytonadione, potassium chloride, propofol, ranitidine, remifentanil, tigecycline, tirofiban, vasopressin, vecuronium, vitamin B complex with C, warfarin. Incompatible: Ampicillin, micafungin, sodium bicarbonate, thiopental. Variable (consult detailed reference): Drotrecogin alfa, nesiritide.
Compatibility in syringe: Compatible: Caffeine citrate, diatrizoate meglumine 52%, diatrizoate sodium 8%, diatrizoate sodium 60%, doxapram, heparin, iohexol, iopamidol, iothalamate meglumine 60%, ioxaglate meglumine 39.3%, ioxaglate sodium 19.6%, milrinone. Incompatible with pantoprazole, sodium bicarbonate. Variable (consult detailed reference): Sodium bicarbonate.
Compatibility when admixed: Compatible: Amikacin, bupivacaine, cimetidine, dobutamine, fentanyl, furosemide, ranitidine, sufentanil, verapamil. Incompatible: Aminophylline, hyaluronidase, sodium bicarbonate.
Mechanism of Action
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
Pharmacodynamics/Kinetics
Onset of action: Bronchodilation: SubQ: ~5-10 minutes; Inhalation: ~1 minute
Distribution: Crosses placenta
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)
Dosage
Neonates: Cardiac arrest:
I.V.: 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) every 3-5 minutes until return of spontaneous circulation
Intratracheal: Although I.V. route is preferred, may consider administration of doses up to 0.1 mg/kg (1 mL/kg of 1:10,000 solution) every 3-5 minutes until I.V. access established or return of spontaneous circulation
Infants and Children:
Asystole/pulseless arrest, pulseless VT/VF (after failed defibrillations):
I.V., I.O.: 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution) (maximum single dose: 1 mg) every 3-5 minutes until return of spontaneous circulation
Intratracheal: 0.1 mg/kg (0.1 mL/kg of 1:1000 solution) (maximum single dose: 10 mg) every 3-5 minutes until I.V./I.O access established or return of spontaneous circulation
Bradycardia (symptomatic; unresponsive to atropine or pacing):
I.V., I.O.: 0.01 mg/kg (0.1 mL/kg of 1:10,000 solution) (maximum single dose: 1 mg) every 3-5 minutes as needed
Intratracheal: 0.1 mg/kg or (0.1 mL/kg of 1:1000 solution) (maximum single dose: 10 mg) every 3-5 minutes as needed until I.V./I.O access established
Continuous I.V. infusion: 0.1-1 mcg/kg/minute; doses <0.3 mcg/kg/minute generally produce beta-adrenergic effects and higher doses generally produce alpha-adrenergic vasoconstriction; titrate dosage to desired effect
Bronchodilator:
SubQ: 0.01 mg/kg (0.01 mL/kg of 1:1000 solution) (maximum single dose: 0.5 mg) every 20 minutes for 3 doses
Nebulization: S2® (racepinephrine, OTC labeling):
Children <4 years: Jet nebulizer: Croup: 0.05 mL/kg (maximum dose: 0.5 mL); dilute in 3 mL of NS. Administer over ~15 minutes; do not administer more frequently than every 2 hours
Children ?4 years: Refer to adult dosing.
Inhalation: Children ?4 years: Primatene® Mist: Refer to adult dosing.
Decongestant: Children ?6 years: Refer to adult dosing
Hypersensitivity reaction: Note: SubQ administration results in slower absorption and is less reliable. I.M. administration in the anterolateral aspect of the thigh is preferred in the setting of anaphylaxis (ACLS guidelines, 2005; Kemp, 2008).
I.M., SubQ: 0.01 mg/kg (0.01 mL/kg of 1:1000 solution) (maximum single dose: 0.5 mg) every 5-20 minutes; larger I.M. or SubQ doses, use of I.V. route, or continuous infusion may be needed for severe anaphylactic reactions
Self-administration following severe allergic reactions (eg, insect stings, food): Note: World Health Organization (WHO) and Anaphylaxis Canada recommend the availability of 1 dose for every 10-20 minutes of travel time to a medical emergency facility:
EpiPen® Jr: I.M., SubQ: Children 15-29 kg: 0.15 mg; if anaphylactic symptoms persist, dose may be repeated in 5-15 minutes using an additional EpiPen® Jr
EpiPen®: I.M., SubQ: Children ?30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated in 5-15 minutes using an additional EpiPen®
Twinject®: I.M. SubQ:
Children 15-29 kg: 0.15 mg; if anaphylactic symptoms persist, dose may be repeated in 5-15 minutes using the same device after partial disassembly
Children ?30 kg: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated in 5-15 minutes using the same device after partial disassembly
Hypotension/shock, fluid-resistant (unlabeled use): Continuous I.V. infusion: 0.1-1 mcg/kg/minute; doses up to 5 mcg/kg/minute may rarely be necessary (Hegenbarth, 2008)
Adults:
Asystole/pulseless arrest, pulseless VT/VF:
I.V., I.O.: 1 mg every 3-5 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)
Intratracheal: 2-2.5 mg every 3-5 minutes until I.V./I.O access established or return of spontaneous circulation; dilute in 5-10 mL NS or distilled water. Note: Absorption is greater with distilled water, but causes more adverse effects on PaO2.
Bradycardia (symptomatic; unresponsive to atropine or pacing): I.V. infusion: 1-10 mcg/minute; titrate to desired effect
Bronchodilator:
SubQ: 0.3-0.5 mg (1:1000 solution) every 20 minutes for 3 doses
Nebulization: S2® (racepinephrine, OTC labeling):
Hand-bulb nebulizer: Add 0.5 mL (~10 drops) to nebulizer; 1-3 inhalations up to every 3 hours if needed
Jet nebulizer: Add 0.5 mL (~10 drops) to nebulizer and dilute with 3 mL of NS; administer over ~15 minutes every 3-4 hours as needed
Inhalation: Primatene® Mist (OTC labeling): One inhalation, wait at least 1 minute; if not relieved, may use once more. Do not use again for at least 3 hours.
Decongestant: Intranasal: Apply 1:1000 solution locally as drops or spray or with sterile swab
Hypersensitivity reaction: Note: SubQ administration results in slower absorption and is less reliable. I.M. administration in the anterolateral aspect of the thigh is preferred in the setting of anaphylaxis (ACLS guidelines, 2005; Kemp, 2008).
I.M., SubQ: 0.3-0.5 mg (1:1000 solution) every 15-20 minutes if condition requires
I.V.: 0.1 mg (1:10,000 solution) over 5 minutes; may infuse at 1-4 mcg/minute to prevent the need to repeat injections frequently
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 10-20 minutes of travel time to a medical emergency facility. More than 2 doses should only be administered under direct medical supervision.
Twinject®: I.M., SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated in 5-15 minutes using the same device after partial disassembly
EpiPen®: I.M., SubQ: 0.3 mg; if anaphylactic symptoms persist, dose may be repeated in 5-15 minutes using an additional EpiPen®
Hypotension/shock, severe and fluid resistant (unlabeled use): I.V. infusion: Initial: 1 mcg/minute; titrate to desired response; usual range: 2-10 mcg/minute (AHA, 2005)
Dental Usual Dosing
Hypersensitivity reaction:
Infants and Children:
SubQ, I.V.: 0.01 mg/kg every 20 minutes; larger doses or continuous infusion may be needed for some anaphylactic reactions
SubQ, I.M.:
15-30 kg: Twinject®: 0.15 mg (for self-administration following severe allergic reactions to insect stings, food, etc)
>30 kg: Refer to adult dosing
I.M.:
<30 kg: EpiPen® Jr: 0.15 mg (for self-administration following severe allergic reactions to insect stings, food, etc)
>30 kg: Refer to adult dosing
Adults:
I.M., SubQ: 0.3-0.5 mg (1:1000) every 15-20 minutes if condition requires (I.M route is preferred)
>30 kg: Twinject®: 0.3 mg (for self-administration following severe allergic reactions to insect stings, food, etc)
I.M.: >30 kg: EpiPen®: 0.3 mg (for self-administration following severe allergic reactions to insect stings, food, etc)
I.V.: 0.1 mg (1:10,000) over 5 minutes. May infuse at 1-4 mcg/minute to prevent the need to repeat injections frequently.
Administration: I.M.
I.M. administration into the buttocks should be avoided. I.M. administration in the anterolateral aspect of the thigh is preferred in the setting of anaphylaxis (ACLS guidelines, 2005; Kemp, 2008). EpiPen®, EpiPen® Jr, and Twinject® Auto-Injectors should only be injected into the anterolateral aspect of the thigh, through clothing if necessary.
Note: EpiPen® and EpiPen® Jr Auto-Injectors contain a single, fixed-dose of epinephrine. Twinject® Auto-Injectors 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.
Administration: I.V.
When administering as a continuous infusion, central line administration is preferred. I.V. infusions require an infusion pump.
Administration: Inhalation
S2®: If using jet nebulizer: Administer over ~15 minutes; must be diluted.
Administration: Other
Intratracheal: Dilute in NS or distilled water. Absorption is greater with distilled water, but causes more adverse effects on PaO2. Pass catheter beyond tip of tracheal tube, stop compressions, spray drug quickly down tube. Follow immediately with several quick insufflations and continue chest compressions.
Subcutaneous: SubQ administration results in slower absorption and is less reliable. I.M. administration into the buttocks should be avoided. I.M. administration in the anterolateral aspect of the thigh is preferred in the setting of anaphylaxis (ACLS guidelines, 2005; Kemp, 2008). EpiPen®, EpiPen® Jr, and Twinject® Auto-Injectors should only be injected into the anterolateral aspect of the thigh, through clothing if necessary.
Note: EpiPen® and EpiPen® Jr Auto-Injectors contain a single, fixed-dose of epinephrine. Twinject® Auto-Injectors 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.
Administration: I.V. Detail
Extravasation management: Use phentolamine as antidote. Mix 5 mg with 9 mL of NS. Inject a small amount of this dilution into extravasated area. Blanching should reverse immediately. Monitor site. If blanching should recur, additional injections of phentolamine may be needed.
pH: 2.5-5.0
Monitoring Parameters
Pulmonary function, heart rate, blood pressure, site of infusion for blanching, extravasation; cardiac monitor and blood pressure monitor required during continuous infusion. If using to treat hypotension, assess intravascular volume and support as needed.
Patient Education
Use this medication exactly as directed; do not take more than recommended dosage. Avoid other stimulant prescriptive or OTC medications to avoid serious overdose reactions. You may experience dizziness, blurred vision, restlessness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or difficulty urinating (empty bladder immediately before taking this medication). Report excessive nervousness or excitation, inability to sleep, facial flushing, pounding heartbeat, muscle tremors or weakness, chest pain or palpitations, bronchial irritation or coughing, or increased sweating.
Aerosol: Use aerosol or nebulizer as per instructions. Clear as much mucus as possible before use. Rinse mouth following each use. If more than one inhalation is necessary, wait 1 minute between inhalations. May cause restlessness or nervousness; use caution when driving or engaging in hazardous activities until response to medication is known. Report persistent nervousness, restlessness, sleeplessness, palpitations, tachycardia, chest pain, muscle tremors, dizziness, flushing, or if breathing difficulty persists.
Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. Consult prescriber if breast-feeding.
Geriatric Considerations
The use of epinephrine in the treatment of acute exacerbations of asthma was studied in the elderly. A dose of 0.3 mg SubQ every 20 minutes for three doses was well tolerated in elderly patients with no history of angina or recent myocardial infarction. There was no significant difference in the incidence of ventricular arrhythmias in elderly versus younger adults.
Additional Information
Twinject® and EpiPen® are not interchangeable due to packaging considerations.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments:
Extravasation Management: Antidote for peripheral ischemia caused by epinephrine extravasation: To prevent sloughing and necrosis in ischemic areas, the area should be infiltrated as soon as possible with 5-10 mg of Regitine® (phentolamine), an adrenergic blocking agent, diluted in 10-15 mL of saline. A syringe with a fine hypodermic needle should be used, and the solution liberally infiltrated throughout the ischemic area. Sympathetic blockade with phentolamine causes immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. Therefore, phentolamine should be given as soon as possible after the extravasation is noted, as phentolamine may be ineffective if given >12 hours after extravasation.
Evidence Based Information:
Septic Shock: Epinephrine's use may be limited by its effects on renal and gastric blood flow and its propensity to increase lactic acid concentrations.
The 2008 Surviving Sepsis Campaign Guidelines (Dellinger, 2008) state that epinephrine should not be administered as the initial vasopressor in septic shock (Grade 2C) and should only be used as an alternative when blood pressure is poorly responsive to norepinephrine or dopamine (Grade 2B).
Cardiac Arrest: Epinephrine can be given by endotracheal route during cardiac resuscitation. High-intravenous dose epinephrine (0.1 mg/kg) has not shown to improve survival or neurological outcomes. May have more postresuscitation complications than survivors who receive standard dose epinephrine. Eight randomized clinical studies (>9000 patients) have found no improvement in survival to hospital discharge or neurological outcomes compared with standard epinephrine.
Out-of-hospital cardiac arrest: A prospective, multicenter, double-blind randomized, controlled trial evaluated the efficacy of vasopressin or epinephrine when administered to adult patients who suffered an out-of-hospital cardiac arrest (Wenzel, 2004). For inclusions, patients presented with ventricular fibrillation, pulseless electrical activity, or asystole. They were excluded if they were successfully defibrillated without the administration of a vasopressor, had a terminal illness or had a "do not resuscitate" (DNR) order, a lack of intravenous access, hemorrhagic shock, pregnancy, cardiac arrest due to trauma, or were <18 years of age. Eligible patients were randomized to intravenous vasopressin (40 units, n=589) or epinephrine (1 mg, n=597). Each patient received an injection of the study drug, if spontaneous circulation was not restored in 3 minutes they received a second dose (same amount) of the same study drug. If there was no response, the managing physician had the option of giving epinephrine. Patients with ventricular fibrillation were randomized after the first three attempts at defibrillation failed; all others were randomized immediately. The primary endpoint was survival to hospital admission; the secondary endpoint was survival to hospital discharge. Five hundred and eighty-nine patients were randomized to vasopressin and five hundred and ninety-seven patients were randomized to epinephrine. There was no significant difference in the rate of hospital admission between the vasopressin group and the epinephrine group if they had ventricular fibrillation (46.2% vs 43% respectively, p: 0.48) or pulseless electrical activity (33.7% vs 30.5% respectively, p: 0.65). Patients with asystole responded significantly better to vasopressin; having higher rates of hospital admission (29% vs 20.3% in the epinephrine group, p: 0.02) and hospital discharge (4.7% vs 1.5% in the epinephrine group, p: 0.04). Patients who failed vasopressin therapy and received additional epinephrine had significant improvement in survival to hospital admission (25.7% vs 16.4% in the epinephrine group, p: 0.002) and discharge (6.2% vs 1.7%, p: 0.002). Similar patients who were randomized to epinephrine and failed to respond did not improve with additional epinephrine. Cerebral performance among all patients who survived to discharge was similar in both groups. In this trial, vasopressin was superior to epinephrine in patients with asystole. Vasopressin followed by epinephrine may be more effective than epinephrine alone in refractory out-of-hospital cardiac arrest.
More recently, Gueugniaud, et al evaluated the combination of vasopressin and epinephrine compared to epinephrine alone in the treatment of out-of-hospital cardiac arrest (Gueugniaud, 2008). This multicenter, double-blind, randomized, controlled trial enrolled 2894 adult patients with out-of-hosptial cardiac arrest with either ventricular fibrillation, pulseless electrical activity, or asystole. Patients were exluded if <18 years of age, successfully defibrillated without vasopressors, traumatic cardiac arrest, pregnant, documented terminal illness, and DNR orders or irreversible cardiac arrest. Patients were randomized to either intravenous vasopressin (40 units) and epinephrine (1 mg) or epinephrine (1 mg) and a placebo. The medications/placebo were given within 10 seconds of each other and followed by a saline flush. Patients with ventricular fibrillation received defibrillation before the administration of study drug. The primary endpoint was survival to hospital admission; secondary endpoints were return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and 1-year survival. Similar to the previous study, there was no significant difference in the rate of hospital admission between the two groups (20.7% vs 21.3%, p=0.69). Also, return of spontaneous circulation, survival to hospital discharge, good neurologic recovery, and 1-year survival were all similar between groups. In contrast to the previous study, patients with asystole had no benefit from the combination of vasopressin and epinephrine when compared to epinephrine/placebo. In this study, asystole was the most common initial cardiac rhythm, presenting in 82.8% of the patients. Based on the results of the most recent study, it appears that vasopressin plus epinephrine has no benefit over epinephrine in out-of-hospital cardiac arrest.
In-hospital cardiac arrest: A small in-hospital cardiac arrest study evaluated the efficacy of vasopressin or epinephrine in 200 patients. The investigators did not find any differences between the two treatment groups with regard to survival, hospital discharge, or cerebral performance (Stiell, 2001).
Dental Health: Effects on Dental Treatment
Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation) and dry throat.
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
Nervousness and restlessness are common; may cause insomnia
Mental Health: Effects on Psychiatric Treatment
None reported; however, use cautiously with psychotropics that block alpha-receptors (phenothiazines); may produce paradoxical hypotension
Nursing: Physical Assessment/Monitoring
Assess other medications patient may be taking for effectiveness and interactions. Monitor therapeutic effectiveness (according to purpose for use) and adverse reactions. Monitor vital signs. Assess knowledge/teach patient appropriate use, interventions to reduce side effects, and adverse symptoms to report. I.V. central line with infusion pump and continuous cardiac/hemodynamic monitoring is necessary.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Aerosol for oral inhalation:
Primatene® Mist: 0.22 mg/inhalation (15 mL, 22.5 mL [DSC]) [contains CFCs]
Injection, solution [prefilled auto injector]:
EpiPen®: 0.3 mg/0.3 mL (2 mL) [1:1000 solution; delivers 0.3 mg per injection; contains sodium metabisulfite; available as single unit or in double-unit pack with training unit]
EpiPen® Jr: 0.15 mg/0.3 mL (2 mL) [1:2000 solution; delivers 0.15 mg per injection; contains sodium metabisulfite; available as single unit or in double-unit pack with training unit]
Twinject®: 0.15 mg/0.15 mL (1.1 mL) [1:1000 solution; delivers 0.15 mg per injection; contains sodium bisulfite; two 0.15 mg doses per injector]; 0.3 mg/0.3 mL (1.1 mL) [1:1000 solution; delivers 0.3 mg per injection; contains sodium bisulfite; two 0.3 mg doses per injector]
Injection, solution, as hydrochloride: 0.1 mg/mL (10 mL) [1:10,000 solution]; 1 mg/mL (1 mL) [1:1000 solution]
Adrenalin®: 1 mg/mL (1 mL) [1:1000 solution; contains sodium bisulfite]
Adrenalin®: 1 mg/mL (30 mL) [1:1000 solution; contains chlorobutanol, sodium bisulfite]
Solution for oral inhalation [racepinephrine; preservative free]:
S2®: 2.25% (0.5 mL) [as d-epinephrine 1.125% and l-epinephrine 1.125%]
Solution, intranasal, as hydrochloride [drops, spray]:
Adrenalin®: 1 mg/mL (30 mL) [1:1000 solution; contains sodium bisulfite]
Solution, topical [racepinephrine]:
Raphon: 2.25% (15 mL) [as d-epinephrine 1.125% and l-epinephrine 1.125%; contains benzoic acid, metabisulfites] [DSC]
Pricing: U.S. (www.drugstore.com)
Device (EpiPen)
0.3 MG/0.3ML (1:1000) (1): $65.04
Device (EpiPen 2-Pak)
0.3 MG/0.3ML (1:1000) (2): $121.80
Device (EpiPen Jr)
0.15 MG/0.3ML (1:2000) (1): $64.99
Device (EpiPen Jr 2-Pak)
0.15 MG/0.3ML (1:2000) (2): $115.49
Device (Twinject)
0.15 mg/dose (1): $86.63
Nebulization (S-2)
2.25% (30): $54.99
Solution (EPINEPHrine HCl)
1 mg/mL (3): $13.99
References
“2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2005, 112(24 Suppl): 1-211.
Annane D, Vignon P, Renault A, et al, “Norepinephrine Plus Dobutamine Versus Epinephrine Alone for Management of Septic Shock: A Randomized Trial,” Lancet, 2007, 370(9588):676-84.
Cydulka R, Davison R, Grammer L, et al, “The Use of Epinephrine in the Treatment of Older Adult Asthmatics,” Ann Emerg Med, 1988, 17(4):322-6.
Davis C and Wax P, “Subcutaneous Epinephrine O.D. in a Child Resulting in Dysrhythmias and Myocardial Ischemia,” Vet Hum Toxicol, 1994, 36:367.
Dellinger RP, Levy MM, Carlet JM, et al, “Surviving Sepsis Campaign: International Guidelines for Management of Severe Sepsis and Septic Shock: 2008,” Intensive Care Med, 2008, 34(1):17-60. Available at http://www.survivingsepsis.org/system/files/images/2008_20International_20SSC_20Guidelines_1_.pdf
Expert Panel Report 3, “Guidelines for the Diagnosis and Management of Asthma,” Clinical Practice Guidelines, National Institutes of Health, National Heart, Lung, and Blood Institute, NIH Publication No. 08-4051, prepublication 2007. Available at http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
Goring-Morris J and Russell IF, “A Randomized Comparison of 0.5% Bupivacaine With a Lidocaine/Epinephrine/Fentanyl Mixture for Epidural Top-up for Emergency Caesarean Section After “Low Dose” Epidural for Labour,” Int J Obstet Anesth, 2006, 15(2):109-14.
Gueugniaud PY, David JS, Chanzy E, et al, “Vasopressin and Epinephrine vs. Epinephrine Alone in Cardiopulmonary Resuscitation,” N Engl J Med, 2008, 359(1):21-30.
Hegenbarth MA and the American Academy of Pediatrics Committee on Drugs, “Preparing for Pediatric Emergencies: Drugs to Consider,” Pediatrics, 2008, 121(2):433-43.
Illi A, Sundberg S, Ojala-Karlsson P, et al, “The Effect of Entacapone on the Disposition and Hemodynamic Effects of Intravenous Isoproterenol and Epinephrine,” Clin Pharmacol Ther, 1995, 58(2):221-7.
Kartawiadi L, Vercauteren MP, Van Steenberge AL, et al, “Spinal Analgesia During Labor With Low-dose Bupivacaine, Sufentanil, and Epinephrine. A Comparison with Epidural Analgesia,” Reg Anesth, 1996, 21(3):191-6.
Kemp SF, Lockey RF, Simons FE, et al, “Epinephrine: The Drug of Choice for Anaphylaxis. A Statement of the World Allergy Organization,” Allergy, 2008, 63(8):1061-70.
Klein JS, Rich MR, and Yunginger JW, “Myocardial Ischemia Without Coronary Artery Disease After Epinephrine Overdose for Insect Sting Reaction,” J Allergy Clin Immunol, 1995, 95(2):371.
Kuracheck SC and Rockoff MA, “Inadvertent Intravenous Administration of Racemic Epinephrine,” JAMA, 1984, 253(10):1441-2.
Murphy FT, Manown TJ, Knutson SW, et al, “Epinephrine-Induced Lactic Acidosis in the Setting of Status Asthmaticus,” South Med J, 1995, 88(5):577-9.
Russell JA, Walley KR, Singer J, et al, “Vasopressin Versus Norepinephrine Infusion in Patients With Septic Shock,” N Engl J Med, 2008, 358(9):877-87.
Stiell IG, Hebert PC, Wells GA, et al, “Vasopressin Versus Epinephrine for Inhospital Cardiac Arrest: A Randomised Controlled Trial,” Lancet, 2001, 358(9276):105-9.
Waisman Y, Klein BL, Boenning DA, et al, “Prospective Randomized Double-Blind Study Comparing L-Epinephrine and Racemic Epinephrine Aerosols in the Treatment of Laryngotracheitis (Croup),” Pediatrics, 1992, 89(2):302-6.
Wenzel V, Krismer AC, Arntz HR, et al, “A Comparison of Vasopressin and Epinephrine for Out-of-Hospital Cardiopulmonary Resuscitation. European Resuscitation Council Vasopressor during Cardiopulmonary Resuscitation Study Group,” N Engl J Med, 2004, 350(2):105-13.
International Brand Names
Lexi-Comp.com
Last full review/revision August 2009
Content last modified August 2009
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