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TRANSFORMAR COMO VOCÊ USA INFORMAÇÕES SOBRE DROGAS
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0.2 to 0.5 mg IM; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.[54255] [60589] [64934] [66054] [66106] [70421] [70422] [70423]
0.01 mg/kg/dose (Max: 0.5 mg/dose) IM; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.[54255] [60589] [64934] [66106] [70420] [70421] [70422] [70423]
0.01 mg/kg/dose (Max: 0.3 mg/dose) IM; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.[54255] [60589] [64934] [66106] [70420] [70421] [70422] [70423]
0.2 to 0.5 mg subcutaneously; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.[54255] [54322] [54323] [60589] [64934] [66054] [66106] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.01 mg/kg/dose (Max: 0.5 mg/dose) subcutaneously; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.[54255] [54322] [54323] [60589] [64934] [66106] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.01 mg/kg/dose (Max: 0.3 mg/dose) subcutaneously; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.[54255] [54322] [54323] [60589] [64934] [66106] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.3 mg/dose IM; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54257] [57081] [62025]
0.3 mg/dose IM; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54257] [57081] [62025]
0.15 mg/dose IM; may repeat the dose for severe persistent anaphylaxis.[54140] [54257] [57081] [62025] Some experts recommend 0.3 mg/dose.[54255] [54293] [64934] The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54257] [57081] [62025]
0.15 mg/dose IM; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54257] [57081] [62025]
0.1 mg/dose IM; may repeat the dose for severe persistent anaphylaxis.[54257] Some experts recommend 0.15 mg/dose.[54255] [54293] [64934] The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257]
0.1 mg/dose IM; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257]
0.3 mg/dose subcutaneously; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54257] [57081] [62025] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.3 mg/dose subcutaneously; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54257] [57081] [62025] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.15 mg/dose subcutaneously; may repeat the dose for severe persistent anaphylaxis.[54140] [54257] [57081] [62025] Some experts recommend 0.3 mg/dose.[54255] [54293] [64934] The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54257] [57081] [62025] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.15 mg/dose subcutaneously; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54257] [57081] [62025] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.1 mg/dose subcutaneously; may repeat the dose for severe persistent anaphylaxis.[54257] Some experts recommend 0.15 mg/dose.[54255] [54293] [64934] The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.1 mg/dose subcutaneously; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257] Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[66106]
0.05 to 0.1 mg (of a 0.1 mg/mL solution) IV every 5 to 15 minutes as needed. Intravenous epinephrine given by boluses may be considered for anaphylactic shock when an IV line is in place.[66054]
0.01 mg/kg/dose (0.1 mL/kg/dose of a 0.1 mg/mL solution) IV every 3 to 5 minutes as needed. Max: 1 mg/dose (10 mL/dose of a 0.1 mg/mL solution).[54254] [54255] [66053]
2 mcg/minute continuous IV infusion, initially. Titrate dose according to blood pressure, cardiac rate, and oxygenation. Max: 15 mcg/minute. Intravenous epinephrine given by continuous infusion may be considered if inadequate response to IM epinephrine and intravenous saline or as an alternative to IV boluses for anaphylactic shock in persons not in cardiac arrest.[66054] [66106]
0.1 to 1 mcg/kg/minute continuous IV infusion. Titrate dose according to blood pressure, cardiac rate, and oxygenation. Intravenous epinephrine given by continuous infusion may be considered if inadequate response to IM epinephrine and intravenous saline.[64934]
1 oral inhalation (0.125 mg); may repeat once after 1 minute if needed. Wait at least 4 hours between doses. Max: 2 inhalations (0.25 mg)/dose and 8 inhalations (1 mg)/day.[63740] Guidelines for asthma treatment do not recommend use; prescribe a selective short-acting beta-agonist (SABA).[33558] [64807]
1 oral inhalation (0.125 mg); may repeat once after 1 minute if needed. Wait at least 4 hours between doses. Max: 2 inhalations (0.25 mg)/dose and 8 inhalations (1 mg)/day.[63740] Guidelines for asthma treatment do not recommend use; prescribe a selective short-acting beta-agonist (SABA).[33558] [64807]
0.3 to 0.5 mg subcutaneously every 20 minutes as needed for up to 3 doses. Guidelines state there is no proven advantage of systemic therapy over the use of inhaled short-acting beta-agonists.[33558] [64807]
0.3 to 0.5 mg subcutaneously every 20 minutes as needed for up to 3 doses. Guidelines state there is no proven advantage of systemic therapy over the use of inhaled short-acting beta-agonists.[33558] [64807]
0.01 mg/kg/dose (Max: 0.5 mg/dose) subcutaneously every 20 minutes as needed for up to 3 doses may be given if an inhaled short-acting beta-agonist (e.g., albuterol) is not available. Guidelines state there is no proven advantage of systemic therapy over the use of inhaled short-acting beta-agonists.[33558] [64807]
0.3 to 0.5 mg/dose IM every 5 to 15 minutes as needed for up to 3 doses. Reserved for patients with poor inspiratory flow, those who cannot cooperate with inhaled therapy, or those with severe asthma with suboptimal response to initial aerosolized therapy.[60589] [64934] Also, typically reserved for use in addition to standard therapy for asthma complicated by anaphylaxis or angioedema. Guidelines state there is no proven advantage of systemic therapy over inhaled short-acting beta-agonists.[33558] [64807]
0.01 mg/kg/dose (Max: 0.5 mg/dose) IM every 5 to 15 minutes as needed for up to 3 doses. Reserved for patients with poor inspiratory flow, those who cannot cooperate with inhaled therapy, or those with severe asthma with suboptimal response to initial aerosolized therapy.[64934] Also, typically reserved for use in addition to standard therapy for asthma complicated by anaphylaxis or angioedema. Guidelines state there is no proven advantage of systemic therapy over inhaled short-acting beta-agonists.[33558] [64807]
0.01 mg/kg/dose (Max: 0.3 mg/dose) IM every 5 to 15 minutes as needed for up to 3 doses. Reserved for patients with poor inspiratory flow, those who cannot cooperate with inhaled therapy, or those with severe asthma with suboptimal response to initial aerosolized therapy.[64934] Also, typically reserved for use in addition to standard therapy for asthma complicated by anaphylaxis or angioedema. Guidelines state there is no proven advantage of systemic therapy over inhaled short-acting beta-agonists.[33558] [64807]
0.5 mL/kg/dose (Max: 5 mL/dose) of 1 mg/mL solution diluted in 2 to 2.5 mL of saline inhaled by nebulizer every 20 minutes as needed as an alternative if racemic epinephrine is not available; 5 mL of L-epinephrine 1 mg/mL is equivalent to 0.5 mL of racemic epinephrine 2.25%. In general, improvement is seen within 10 to 30 minutes and lasts 2 hours after administration.[54245] [54247] [54249] [54250] [59632] [64934]
0.3 to 0.5 mL of 1 mg/mL solution subcutaneously or IM every 1 to 2 hours.
1 mg IV or IO every 3 to 5 minutes as needed. For a nonshockable rhythm, administer epinephrine as soon as possible. For a shockable rhythm, administer epinephrine after initial defibrillation attempts have failed. High-dose epinephrine is not recommended for routine use. Do not interrupt CPR to administer drug therapy.[66054]
0.01 mg/kg/dose (Max: 1 mg/dose) IV or IO every 3 to 5 minutes as needed. High-dose epinephrine is not recommended for routine use. Do not interrupt CPR to administer drug therapy.[43713] [63412] [66053]
0.01 to 0.03 mg/kg/dose IV or IO every 3 to 5 minutes as needed. High-dose epinephrine is not recommended for routine use. Do not interrupt CPR to administer drug therapy.[44520] [52326] [66055]
2 to 2.5 mg ET every 3 to 5 minutes as needed until vascular access is obtained. For a nonshockable rhythm, administer epinephrine as soon as possible. For a shockable rhythm, administer epinephrine after initial defibrillation attempts have failed.[45649] [66054]
0.1 mg/kg/dose (Max: 2.5 mg/dose) ET every 3 to 5 minutes as needed until vascular access obtained.[43713] [64934] [66053]
0.05 to 0.1 mg/kg/dose ET every 3 to 5 minutes as needed until vascular access is obtained.[44520] [52326] [64934] [66055]
0.3 to 0.5 mg intracardially. Follow administration with external cardiac massage to permit the drug to enter the coronary circulation.[45416] [49567]
2 to 10 mcg/minute continuous IV or IO infusion; titrate to desired effect.[45649] [66054]
0.1 to 1 mcg/kg/minute continuous IV or IO infusion; titrate to desired effect.[43713] [66053]
0.1 to 1 mcg/kg/minute continuous IV or IO infusion; titrate to desired effect.[43713] [66053]
0.001 mg/kg/dose IV or IO (one-tenth the standard resuscitation dose); titrate to desired hemodynamic effect. A continuous infusion of 0.01 to 0.2 mcg/kg/minute IV or IO has also been recommended.[63412]
2 to 10 mcg/minute or 0.1 to 0.5 mcg/kg/minute continuous IV or IO infusion. Titrate to desired effect.[45649] [60266] [63867]
0.01 mg/kg/dose (0.1 mL/kg/dose of a 0.1 mg/mL solution) IV or IO; may repeat every 3 to 5 minutes. Max: 1 mg/dose (10 mL of a 0.1 mg/mL solution). Do not interrupt CPR to administer drug therapy. Higher doses of epinephrine are not recommended except when indicated for exceptional circumstances (e.g., beta-blocker overdosage).[43713] [60636]
0.01 to 0.03 mg/kg/dose (0.1 to 0.3 mL/kg/dose of a 0.1 mg/mL solution) IV; may repeat every 3 to 5 minutes. Do not interrupt CPR to administer drug therapy. After administration, flush the IV line with 0.5 to 1 mL of 0.9% Sodium Chloride Injection to ensure drug delivery. Higher doses of epinephrine are not recommended.[44520] [52326] [61541]
0.1 mg/kg/dose (0.1 mL/kg/dose of a 1 mg/mL solution) ET; may repeat every 3 to 5 minutes until vascular access obtained. Max: 2.5 mg/dose (2.5 mL/dose of a 1 mg/mL solution). If CPR is in progress, stop chest compressions briefly to administer medication. Follow ET administration with saline flush or dilute the drug in isotonic saline (5 mL or more) and deliver several consecutive positive-pressure ventilations.[43713] [60636] [64934]
0.05 to 0.1 mg/kg/dose (0.5 to 1 mL/kg/dose of a 0.1 mg/mL solution) ET; may repeat every 3 to 5 minutes until vascular access is obtained. Follow ET administration with saline flush or dilute the drug in isotonic saline (0.5 to 1 mL) and deliver several consecutive positive-pressure ventilations.[44520] [52326] [61541] [64934]
0.01 to 2 mcg/kg/minute continuous IV infusion. Titrate by 0.05 to 0.2 mcg/kg/minute every 10 to 15 minutes to clinical response.[56575] [60589] [65299] After hemodynamic stabilization, wean incrementally every 10 to 30 minutes over a 12- to 24-hour period.[56575] [60589] Guidelines consider epinephrine as an alternative to norepinephrine in settings where norepinephrine is not available and suggest adding epinephrine to norepinephrine and vasopressin if inadequate mean arterial pressure (MAP) for patients with septic shock. Epinephrine may be useful in refractory septic shock patients with myocardial dysfunction.[67037]
0.1 to 1 mcg/kg/minute continuous IV infusion. Titrate to clinical response. Doses up to 5 mcg/kg/minute may be necessary for shock.[43713] [44772] [64934] [66053]
0.1 to 1 mcg/kg/minute continuous IV infusion. Titrate to clinical response. Doses up to 5 mcg/kg/minute may be necessary for shock.[43713] [44772] [64934] [66053]
Apply 0.002% to 0.1% solutions topically.
NOTE: These products are discontinued in the U.S. Instill 1 to 2 drops of 0.5%, 1% or 2% ophthalmic solution into affected eye(s) once or twice daily.
Initially, 0.25 mcg/kg/minute and increase by 0.25 mcg/kg/minute to maintain a systolic blood pressure of 100 mmHg or more in combination with IV diazepam, general anesthesia with thiopental, and FiO2 40%. Diazepam was continued for 2 to 4 additional days. Other vasopressors and/or inotropic agents were used as necessary. Eleven cases of acute chloroquine overdose (total ingested dose ranged from 5 to 12 g) were treated with epinephrine; 10 patients were discharged alive from the hospital. The 1 patient who died ingested the largest total dose (15 g) of chloroquine.[23704]
Apply topically to nose as drops, spray, or with a sterile swab as needed.[46634]
Apply topically to nose as drops, spray, or with a sterile swab as needed.[46634]
Must dilute prior to intraocular use. Dilute 1 mL of epinephrine 1 mg/mL in 100 to 1,000 mL of an ophthalmic irrigation fluid to create an epinephrine concentration of 10 mcg/mL to 1 mcg/mL. Use the irrigating solution as needed for the surgical procedure. After dilution in an ophthalmic irrigating fluid, the solution may also be injected intracamerally as a bolus dose of 0.1 mL at a dilution of 10 mcg/mL to 2.5 mcg/mL.[60589] Check product specific labels; only use 1 mg/mL single-use products intended for ophthalmic administration.
Must dilute prior to intraocular use. Dilute 1 mL of epinephrine 1 mg/mL in 100 to 1,000 mL of an ophthalmic irrigation fluid to create an epinephrine concentration of 10 mcg/mL to 1 mcg/mL. Use the irrigating solution as needed for the surgical procedure. After dilution in an ophthalmic irrigating fluid, the solution may also be injected intracamerally as a bolus dose of 0.1 mL at a dilution of 10 mcg/mL to 2.5 mcg/mL.[60589] Check product specific labels; only use 1 mg/mL single-use products intended for ophthalmic administration.
Soak gauze or a cotton pledget in 0.1 to 1 mg/mL solution and place in the affected nostril(s) for 30 minutes.[65040] [65041] [65042]
Dependent on route of administration and indication for therapy.
Dependent on route of administration and indication for therapy.
Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.5 mg/dose IM/subcutaneously and 1 mg/dose IV). For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM/subcutaneously or 8 oral inhalations/24 hours of epinephrine 0.125 mg oral inhalation (e.g., Primatene Mist inhaler, non-prescription).
12 years: Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.5 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM/subcutaneously or 8 oral inhalations/24 hours of epinephrine 0.125 mg oral inhalation (e.g., Primatene Mist inhaler, non-prescription).
4 to 11 years weighing more than 30 kg: Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.5 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM/subcutaneously.
4 to 11 years weighing 30 kg or less: Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.3 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose subcutaneously and 0.3 mg/dose IM).
1 to 3 years: Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.3 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose subcutaneously and 0.3 mg/dose IM).
Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.3 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose subcutaneously and 0.3 mg/dose IM).
Dependent on route of administration and indication for therapy. For CPR, 0.03 mg/kg/dose IV and 0.1 mg/kg/dose ET.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
† Off-label indication
Epinephrine is a nonselective adrenergic agonist with a high affinity for beta1-, beta2-, and alpha1-receptors. Exogenous epinephrine is a sympathomimetic catecholamine with dose-dependent effects; beta-adrenergic effects (e.g., inotropy, vasodilation) are more pronounced at low doses and alpha-adrenergic effects (e.g., vasoconstriction) at high doses.[43713][54334][54335] Epinephrine has many therapeutic applications. Intramuscular epinephrine is the drug of choice for anaphylaxis.[66106] Intravenous epinephrine is recommended during cardiopulmonary resuscitation, specifically for the treatment of symptomatic bradycardia, cardiac arrest, and as an adjunct to electrical defibrillation in ventricular fibrillation/pulseless ventricular tachycardia. Additionally, epinephrine is used for hypotension, fluid-resistant shock, and inotropic support in a variety of settings (e.g., postresuscitation and postoperative).[43713][45649][66053][66054][67037] Intravenous epinephrine is the vasopressor of choice in anaphylactic shock, as it provides beta2 stimulation.[65559] In patients with sinus node dysfunction or second- or third-degree atrioventricular block associated with symptoms of hemodynamic compromise who are at a low likelihood of coronary ischemia, epinephrine may be considered to increase heart rate, improve atrioventricular conduction, increase ventricular rate, and improve symptoms.[63867] Inhaled epinephrine is used as a bronchodilator for the treatment of severe croup symptoms in young children.[59632] However, clinical guidelines do not recommend inhaled epinephrine in asthma or bronchiolitis.[58442][64807][66299] Additionally, injectable epinephrine is only recommended as an adjunct to standard asthma therapy for an acute exacerbation associated with anaphylaxis and angioedema or for an exacerbation unresponsive to standard therapy.[64807][64934]
For storage information, see the specific product information within the How Supplied section.
IV Push
Continuous IV infusion
Dilution
Administration
Extravasation Management
Intraosseous Administration
NOTE: Epinephrine is not FDA-approved for intraosseous administration.
Intracardiac Administration
Topical Nasal Administration
Inhalation Solution (Primatene Mist Aerosol Spray, nonprescription product)
Irrigation for intraocular use
Intracameral injection for intraocular use
Endotracheal Administration
NOTE: Epinephrine is not FDA-approved for endotracheal (ET) administration.
Transient and moderate anxiety, disorientation, hyperactivity, restlessness, apprehension, excitability, memory impairment, nervousness, panic, psychomotor agitation, weakness, dizziness, drowsiness, lightheadedness, headache, tingling, and tremor may occur with therapeutic doses of systemic epinephrine and are more likely in patients with hypertension or hyperthyroidism. Paresthesias, stroke, and central nervous system bleeding have been reported with intravenous epinephrine infusion.[45416] [49567] [54140] [56575] [60589]
Adrenergically modulated vasoactive and smooth muscle responses to epinephrine can result in nausea, vomiting, diaphoresis, pallor, respiratory distress, respiratory weakness, dyspnea, or apnea. These reactions can occur with therapeutic doses of epinephrine and are more likely to occur in patients with heart disease, hypertension, or hyperthyroidism.[45416] [49567] [54140] [60589]
Cardiac arrhythmias (or arrhythmia exacerbation), including palpitations, premature ventricular contractions (PVCs), sinus tachycardia, supraventricular tachycardia (SVT), and severe ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia), are well described potential adverse effects of epinephrine due to beta-stimulation of the myocardium and conduction system. Myocardial ischemia and myocardial infarction have also been associated with epinephrine infusion. Chest pain (unspecified) and angina may occur, the latter occurring more frequently in adult patients with coronary artery disease. Stress cardiomyopathy has been reported rarely in patients treated with systemic epinephrine. Patients at risk for epinephrine-induced arrhythmias and ischemia include those with organic heart disease, coronary artery disease, cerebrovascular disease, high blood pressure, and those receiving drugs that sensitize the myocardium. Severe hypertension may occur in patients receiving intravenous epinephrine. Hypertension occurring quickly has resulted in cerebral hemorrhage, especially in patients with cardiovascular disease. When epinephrine is administered as a continuous intravenous infusion, vital signs should be monitored during titration; invasive arterial blood pressure monitoring and central venous pressure monitoring are recommended. Peripheral constriction and cardiac stimulation produced by intravenous administration of epinephrine may result in pulmonary edema. If pulmonary edema occurs, administer a rapid acting alpha-adrenergic blocking drug (e.g., phentolamine) and provide respiratory support. Rales have also been reported. The potential for these serious cardiovascular risks should not outweigh the beneficial effects of the use of epinephrine for acute, life-threatening conditions.[45416] [49567] [54140] [60589]
Epinephrine administration may lead to local and/or peripheral vasoconstriction depending on the route of administration. Accidental injection into the fingers, hands, or feet may result in loss of blood flow to those areas which may present as site pallor, coldness, or hypoesthesia.[45416] [57081] Extravasation of epinephrine, especially with repeated injections or high infusion rates, can result in an injection site reaction leading to severe tissue damage and tissue necrosis. When epinephrine is administered intravenously, the infusion site should be checked frequently for free flow. If skin blanching along the course of the infused vein occurs, consider changing the infusion site at intervals to allow the effects of local vasoconstriction to subside. If extravasation of intravenous drug or accidental digital injection occurs, infiltrate a diluted phentolamine solution into the area as soon as possible to antagonize vasoconstriction and reduce and/or prevent devastating sloughing and tissue necrosis. Phentolamine causes sympathetic blockage resulting in immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours.[52618] [54685] [60589] Skin laceration and bent or embedded needles have been reported when epinephrine has been injected into the thigh of young children who are uncooperative; caregivers should be instructed to hold the child's leg firmly to limit movement prior to and during injection. Rare cases of serious skin and soft tissue infection, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene) have been reported at the epinephrine injection site when used for anaphylaxis. Cleansing with alcohol does not kill bacterial spores and does not lower the risk; intramuscular and subcutaneous epinephrine for anaphylaxis should only be administered into the anterolateral aspect of the thigh (not the buttock). Patients should seek medical care if they develop signs and symptoms of infection at the injection site (e.g., persistent redness, warmth, swelling, tenderness). Injection site ecchymosis, bleeding, skin discoloration, erythema, and skeletal injury have also been associated with intramuscular and subcutaneous use.[57081] Piloerection, a common sympathetic reflex, has been associated with intravenous administration.[60589]
Transient increases in blood sugar or hyperglycemia may occur in diabetic patients administered inhaled or systemic epinephrine. Hypoglycemia and insulin resistance also has been reported with the intravenous use of epinephrine. Hypokalemia has been reported. Metabolic acidosis secondary to lactic acidosis has been associated with long-term administration or overdose of epinephrine.[56575] [60589]
Intravenously administered epinephrine may initially produce constriction of renal blood vessels, resulting in oliguria. Renal insufficiency has been associated with intravenous infusion.[60589]
Appropriate product selection and proper dilution with the intraocular use of epinephrine are imperative. Certain excipients may be harmful to the eye when used ophthalmically. For example, epinephrine products containing sodium bisulfite have been associated with corneal endothelial damage and corneal edema when used in the eye at undiluted concentrations (1 mg/mL).[60589]
Although there are no absolute contraindications to the use of parenteral epinephrine when used in acute, life-threatening situations, some product labeling describe epinephrine as contraindicated in persons with known hypersensitivity to sympathomimetic amines, such as epinephrine.[45416]
Epinephrine may induce cardiac arrhythmias, myocardial ischemia, and angina pectoris in patients, especially patients with coronary artery disease, cardiomyopathy, organic cardiac disease, high blood pressure, or patients receiving drugs that sensitize the myocardium.[56575] [60589] Certain epinephrine formulations that are intended only for hypersensitivity reactions, cardiac resuscitation, ophthalmological use, or regional anesthesia are contraindicated in nonanaphylactic shock.[45416] [49567] However, other epinephrine formulations are indicated for hypotension associated with septic shock. Correct hypovolemia as fully as possible before any vasopressor is administered. When, as an emergency measure, intraaortic pressures must be maintained to prevent cerebral or coronary artery ischemia, epinephrine can be administered before and concurrently with blood volume replacement.[60589]
Some epinephrine preparations contain sodium metabisulfite and should not be used in patients with sulfite hypersensitivity unless the patient is being treated for an emergent condition such as anaphylaxis or cardiac arrest. Epinephrine is the preferred treatment for anaphylaxis, and the alternatives to using epinephrine in anaphylaxis may not be satisfactory. The presence of sulfite in epinephrine emergency kits or syringes should not deter administration of the drug for emergent treatment of anaphylaxis, even if the patient is sulfite-sensitive.[45416] [49567] [54140] [56575]
Although there are no absolute contraindications to the use of parenteral epinephrine when used in acute, life-threatening situations, some product labeling states epinephrine is contraindicated in closed-angle glaucoma because it can exacerbate this condition.[45416] [49567]
Epinephrine is a potent vasoconstrictor; inadvertent digital or intraarterial administration can lead to vasoconstriction, vasospasm, thrombosis, and subsequent tissue necrosis. Epinephrine and epinephrine-containing products (e.g., local anesthetics with epinephrine) should never be injected into extremities such as fingers, toes, ears, nose, and genitalia. Do not administer repeated injections at the same site. In addition, caution should be observed to avoid extravasation during intravenous administration as peripheral ischemia, tissue necrosis, and/or gangrene in the surrounding area can occur. Infusion sites should be checked frequently for free flow. If blanching along the course of the infused vein occurs, consider changing the infusion site at intervals to allow the effects of local vasoconstriction to subside. If inadvertent digital injection or extravasation occurs, the affected area should be infiltrated as soon as possible with a 0.9% Sodium Chloride Injection solution containing phentolamine; inject liberally throughout the ischemic area using a fine hypodermic needle. The ischemic area may be identified by a cool, hard, and pallid appearance. Sympathetic blockade with phentolamine causes immediate and noticeable local hyperemic changes if the area is infiltrated within 12 hours of extravasation. When used for anaphylaxis, epinephrine should be administered into the anterolateral aspect of the thigh (vastus lateralis muscle) because of its location, size, and available blood flow. Injection into the buttock may not be effective for anaphylaxis and has been associated with the development of gas gangrene; cleansing with alcohol does not kill bacterial spores and does not lower the risk. Advise patients to seek medical care if they develop signs or symptoms of infection at the injection site (e.g., persistent redness, warmth, swelling, tenderness).[45416] [49567] [53965] [54140] [54685] [54686] [54687] [60589]
Avoid the use of epinephrine, if possible, in patients with organic brain syndrome or cerebrovascular disease due to the risk of cerebral hemorrhage caused by a sharp rise in blood pressure associated with the intravenous administration of epinephrine. Patients with cerebrovascular disease are at risk for epinephrine-induced cardiac arrhythmias and angina.[49567] [54140] [60589]
Use epinephrine with great caution in patients with hypertension, as dangerously high blood pressure may occur. Increases in blood pressure can put patients with hypertension at risk for cardiac arrhythmias. When administered intravenously, monitor vital signs during infusion titration; invasive arterial blood pressure and central venous pressure monitoring are recommended. Patients receiving monoamine oxidase inhibitors (MAOI) or antidepressants of the triptyline or imipramine types may experience severe, prolonged hypertension when given epinephrine.[45416] [49567] [54140] [60589]
Epinephrine should be used with caution in patients with thyroid disease such as hyperthyroidism or thyrotoxicosis as well as those with pheochromocytoma; these patients may experience a greater sensitivity to the adverse effects of epinephrine. This is typically not of concern in acute, life-threatening situations.[45416] [49567] [54140] [60589]
Epinephrine should be administered with caution to patients with diabetes mellitus. Diabetic patients may experience transient increases in blood glucose. Epinephrine can cause hyperglycemia due to increased glycogenolysis in the liver, decreased tissue uptake of glucose, and decreased insulin release from the pancreas. This is typically not of concern when diluted for admixture with local anesthetics to reduce absorption and prolong the action of the anesthetic or in acute, life-threatening situations.[49567] [54140] [60589]
Use systemic epinephrine cautiously in persons with renal impairment. When administered intravenously, epinephrine may produce constriction of renal blood vessels and a decrease in urine formation.[56575] [60589]
Dilute epinephrine injection prior to intraocular use. Use only the 1 mg/mL single use vial or ampule specifically intended for ophthalmic administration; concentration and formulation affect the safety of ophthalmic administration. Epinephrine products containing sodium bisulfite have been associated with corneal endothelial damage when used in the eye at undiluted concentrations (1 mg/mL).[60589]
Use epinephrine with caution in persons with Parkinson's disease. Persons with Parkinson's disease may experience psychomotor agitation or a temporary worsening of symptoms.[56575] [60589]
Geriatric persons may be particularly sensitive to the effects of epinephrine at greater risk of developing adverse reactions when epinephrine is administered parenterally. In general, use caution in selecting the epinephrine dose for older adults, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Avoid administration in the veins of the leg in older adults.[56575] [60589]
Lacerations, bent needles, and embedded needles have been reported when epinephrine has been injected into the thigh of infants and young children who are uncooperative and kick or move during an injection. To minimize the risk of injury, instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during injection.[57081]
Do not withhold or delay life-sustaining therapy during pregnancy due to potential concerns regarding the effects of epinephrine on the fetus. Limited published data on epinephrine use in human pregnancy are not sufficient to determine a drug-associated risk of major birth defects or miscarriage. In animal reproduction studies, epinephrine demonstrated adverse developmental effects (e.g., gastroschisis, embryonic lethality, delayed skeletal ossification) when administered during organogenesis at doses approximately 2 to 15 times the maximum recommended daily dose. Avoid epinephrine during the second stage of labor or during obstetric delivery when the maternal blood pressure exceeds 130/80 mmHg. Epinephrine usually inhibits spontaneous or oxytocin-induced uterine contractions and may delay the second stage of labor, potentially resulting in a prolonged period of uterine atony with hemorrhage. Although epinephrine may improve maternal hypotension associated with septic shock and anaphylaxis, it can cause uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia.[56575] Although there are no absolute contraindications to the use of parenteral epinephrine when used in acute, life-threatening situations, some product labeling describe epinephrine as contraindicated during labor or in obstetrics when the maternal blood pressure exceeds 130/80 mmHg.[45416] [49567]
Parenteral epinephrine is the first-line medication for acute, life-threatening situations; it should be used in the same manner for breast-feeding and non-breast-feeding persons. There is no information regarding the presence of epinephrine in human milk or its effects on the breast-fed infant or milk production. Epinephrine exposure is expected to be very low in the breast-fed infant due to poor bioavailability and short half-life. The lack of clinical data during lactation precludes a clear determination of the risk of epinephrine to a breast-fed infant.[56575] [60589]
Epinephrine has complex target organ effects. It is a potent agonist at both alpha- and beta- receptors throughout the body except for the sweat glands and facial arteries. Epinephrine is a nonselective adrenergic agonist; it stimulates alpha1-, alpha2-, beta1-, and beta2-adrenergic receptors, although the degree of stimulation at these receptors may vary depending on the dose administered (i.e., the circulating concentration of epinephrine at the receptor). Stimulation of alpha1-receptors by epinephrine leads to arteriolar vasoconstriction. Stimulation of presynaptic alpha2-receptors inhibits norepinephrine release via negative feedback while stimulation of post-synaptic alpha2-receptors also leads to arteriolar vasoconstriction. Stimulation of beta1-receptors induces a positive chronotropic and inotropic response. Stimulation of beta2-receptors by epinephrine leads to arteriolar vasodilation, bronchial smooth muscle relaxation, and increased glycogenolysis. Subsequent to binding at the adrenergic receptor, the intracellular actions of epinephrine are mediated by cyclic adenosine monophosphate (cAMP). The production of cAMP is augmented by beta-stimulation and attenuated by alpha-stimulation.
The major therapeutic effects of systemic epinephrine include: bronchial smooth muscle relaxation, cardiac stimulation, vasodilation in skeletal muscle, and stimulation of glycogenolysis in the liver and other calorigenic mechanisms. The effects of epinephrine on smooth muscle are varied and determined by relative receptor density and hormonal effects. When used topically in the eye in patients with open-angle glaucoma, epinephrine lowers intraocular pressure, produces a brief mydriasis, and may improve the coefficient of aqueous outflow. When used topically on the skin or mucosal surfaces, epinephrine constricts arterioles, thus producing local vasoconstriction and hemostasis in small blood vessels.
Epinephrine primarily exerts its relaxant effect on bronchial smooth muscle via stimulation of beta2-receptors. Beta2-stimulation also prevents mast cell secretion of histamine and other autocoids, thus antagonizing its effect on end organs and reversing bronchoconstriction and edema. Furthermore, alpha-stimulation may decrease secretions from the bronchial mucosa, attenuating the development of edema. There is some evidence that epinephrine's alpha properties make it more effective than pure beta-agonists for the treatment of some pulmonary conditions such as bronchiolitis in children.[24251]
The potent cardiac effects of epinephrine are primarily mediated via stimulation of beta1-receptors on the myocardium and conducting system of the heart. The stimulation of these receptors results in both increased inotropic and chronotropic effects. Systolic blood pressure is usually elevated as a result of increased inotropy, although diastolic blood pressure is decreased secondary to epinephrine-induced vasodilation. As a result, pulse pressure is increased. Epinephrine indirectly causes coronary artery vasodilation, particularly during cardiac arrest. Epinephrine can simultaneously increase myocardial oxygen supply (secondary to coronary vasodilation) and increase oxygen demand (secondary to a positive inotropic and chronotropic effect on the heart). Increased myocardial excitability and automaticity markedly increase the potential for developing dysrhythmias. Nonspecific beta-stimulation by epinephrine, combined with moderate alpha agonism, results in inotropic effects equal to those of dopamine and dobutamine but greater chronotropic effects than either agent.
Blood flow to skeletal muscles is augmented by epinephrine via beta2-stimulation, resulting in vasodilation. Stimulation of alpha1-receptors by epinephrine leads to arteriolar vasoconstriction while stimulation of beta2-receptors by epinephrine leads to arteriolar vasodilation. At normal therapeutic doses, this effect is only mildly countered by the vasoconstriction caused by alpha-stimulation. At higher doses, however, vasoconstriction and elevation of both peripheral vascular resistance and blood pressure can occur.
The metabolic effects of epinephrine relate primarily to the regulatory processes that control glucose concentration in the plasma. Beta2-stimulation of the skeletal muscle and liver increases glycogenolysis. Alpha-stimulation of the liver increases gluconeogenesis and inhibits insulin release by the pancreatic islet cells. Furthermore, in adipose cells, beta-stimulation will induce the catabolism of triglycerides, therefore increasing plasma free fatty acids. Serum potassium concentrations fluctuate after administration of epinephrine. Initially, hyperkalemia occurs secondary to release of potassium ions from hepatocytes. Hypokalemia quickly follows as potassium ions are taken up by the skeletal muscle.
Revision Date: 04/18/2024, 08:37:45 AMEpinephrine is administered by intravenous, intramuscular, and subcutaneous injection, by inhalation, or topically to the eye. Epinephrine crosses the placenta but does not penetrate the blood-brain barrier to a great extent. The pharmacologic activity of epinephrine is rapidly inactivated in the liver. Circulating drug is metabolized by the enzymes catechol-O-methyltransferase and monoamine oxidase in the liver, kidney, and in other extraneuronal tissues. These inactive metabolites are then conjugated to either sulfates or glucuronides and renally excreted. Minimal amounts of the drug are excreted unchanged in the urine.[45416] [54323] [60589]
Affected cytochrome P450 isoenzymes: none
Following intravenous injection, epinephrine produces an immediate response and is rapidly cleared from the plasma with an effective half-life of less than 5 minutes. Steady state is achieved within 10 to 15 minutes after initiating a continuous infusion. In patients with septic shock, epinephrine displays dose-proportional pharmacokinetics in the infusion range of 0.03 to 1.7 mcg/kg/minute.[60589]
Absorption is complete and rapid after intramuscular (IM) administration of epinephrine into the anterolateral thigh (vastus lateralis muscle).[54255] In an adult study of epinephrine absorption, peak plasma concentrations were significantly higher in those who received epinephrine 0.3 mg administered as an IM injection into the thigh (EpiPen Cmax = 12,222 pg/mL; epinephrine 1 mg/mL Cmax = 9,722 pg/mL), compared to those who received either IM or subcutaneous administration into the deltoid (IM Cmax = 1,821 pg/mL; subcutaneous Cmax = 2,877 pg/mL), most likely due to greater blood flow in the thigh.[54322] Absorption of an IM dose may be increased by massaging the area of injection, which increases local blood flow. In a study comparing IM and subcutaneous absorption in children (4 to 12 years of age weighing 15 to 40 kg), those receiving epinephrine 0.3 mg IM (in the vastus lateralis) as a single dose reached a mean Cmax of 2,136 +/- 351 pg/mL within 8 +/- 2 minutes; 75% of children achieved Tmax within 5 minutes. AUC was 108 +/- 18 ng/mL/minute, clearance was 147 +/- 38 mL/kg/minute, and elimination half-life was 4 +/- 15 minutes.[54323]
When compared to intramuscular (IM) administration, the absorption of subcutaneously administered epinephrine is variable and delayed with lower peak plasma concentrations. In an adult study of epinephrine absorption, Cmax was 2,877 pg/mL after subcutaneous administration of epinephrine 0.3 mg into the deltoid. While IM administration of the same dose into the deltoid produced a Cmax of 1,821 pg/mL, IM administration into the thigh produced significantly higher concentrations (EpiPen Cmax = 12,222 pg/mL; epinephrine 1 mg/mL Cmax = 9,722 pg/mL), most likely due to greater blood flow in the thigh.[54322] In a study comparing subcutaneous and IM absorption in children (4 to 12 years of age weighing 15 to 40 kg), those receiving epinephrine 0.3 mg subcutaneously as a single dose reached a mean Cmax of 1,802 +/- 214 pg/mL within 34 +/- 14 minutes (range: 5 to 120 minutes); only 22% of children achieved Tmax within 5 minutes. This was significantly slower compared to the IM group (Tmax: 8 +/- 2 minutes). AUC was 67 +/- 13 ng/mL/minute; absorption was too variable to calculate other pharmacokinetic parameters.[54323]
Bronchodilation occurs within 1 minute after administration of orally inhaled epinephrine.[54288][54328]
Endotracheal Route
Epinephrine administered via the endotrachael (ET) tube is absorbed by the lungs and enters the blood that drains directly into the heart. Medication absorption from the lungs is slower and more unpredictable than if administered directly into the bloodstream.[52326]
Intraocular Route
The extent of epinephrine systemic exposure at the FDA-approved intraocular dose in humans has not been evaluated; however, significant systemic concentrations or plasma exposure are not expected with intraocular use.[60589]
Neonates
Endotracheal (ET) administration of epinephrine is slower and more unpredictable than if given directly into the bloodstream in patients of all ages. In neonates, multiple factors make it particularly difficult for a patient to achieve adequate absorption of ET epinephrine during cardiopulmonary resuscitation, including fluid-filled alveoli that may dilute ET epinephrine. In addition, shunting of blood through fetal pathways, particularly during acidemia and hypoxia, may cause circulation to bypass the lung and prevent absorption and distribution of ET epinephrine.[52326]
In a pharmacokinetic study of 45-minute epinephrine infusions administered to healthy men aged 20 to 25 years and healthy men aged 60 to 65 years, the mean plasma metabolic clearance rate of epinephrine at steady state was greater among older men (144.8 vs. 78 mL/kg/minute for a 14.3 ng/kg/minute infusion).[60589]
Body weight influences epinephrine pharmacokinetics; higher body weight is associated with a lower concentration plateau and higher plasma clearance.[60589]
Do not withhold or delay life-sustaining therapy during pregnancy due to potential concerns regarding the effects of epinephrine on the fetus. Limited published data on epinephrine use in human pregnancy are not sufficient to determine a drug-associated risk of major birth defects or miscarriage. In animal reproduction studies, epinephrine demonstrated adverse developmental effects (e.g., gastroschisis, embryonic lethality, delayed skeletal ossification) when administered during organogenesis at doses approximately 2 to 15 times the maximum recommended daily dose. Avoid epinephrine during the second stage of labor or during obstetric delivery when the maternal blood pressure exceeds 130/80 mmHg. Epinephrine usually inhibits spontaneous or oxytocin-induced uterine contractions and may delay the second stage of labor, potentially resulting in a prolonged period of uterine atony with hemorrhage. Although epinephrine may improve maternal hypotension associated with septic shock and anaphylaxis, it can cause uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia.[56575] Although there are no absolute contraindications to the use of parenteral epinephrine when used in acute, life-threatening situations, some product labeling describe epinephrine as contraindicated during labor or in obstetrics when the maternal blood pressure exceeds 130/80 mmHg.[45416] [49567]
Parenteral epinephrine is the first-line medication for acute, life-threatening situations; it should be used in the same manner for breast-feeding and non-breast-feeding persons. There is no information regarding the presence of epinephrine in human milk or its effects on the breast-fed infant or milk production. Epinephrine exposure is expected to be very low in the breast-fed infant due to poor bioavailability and short half-life. The lack of clinical data during lactation precludes a clear determination of the risk of epinephrine to a breast-fed infant.[56575] [60589]
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