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Epinephrine
Indications/Dosage
Labeled
- anaphylaxis
- angioedema
- asthma exacerbation
- bronchospasm
- cardiac arrest
- cardiopulmonary resuscitation
- glaucoma
- hypotension
- laryngotracheobronchitis (croup)
- mydriasis induction
- nasal congestion
- pulseless electrical activity
- septic shock
- surgical bleeding
- urticaria
- ventricular asystole
- ventricular fibrillation
Off-Label
- bradycardia
- cardiogenic shock
- chloroquine overdose
- epistaxis
For the treatment of anaphylaxis
NOTE: Epinephrine absorption is rapid and complete if administered IM in the anterolateral aspect of the thigh. Subcutaneous epinephrine is not routinely recommended due to delayed absorption.[54255] [54288]
Intramuscular or Subcutaneous dosage
Adults
0.3 to 0.5 mg subcutaneously or IM; may be repeated if necessary every 5 to 10 minutes.[56575] [60589]
Children and Adolescents weighing more than 30 kg
0.01 mg/kg/dose (0.01 mL/kg/dose of a 1 mg/mL solution) IM (preferred) or subcutaneous. Max: 0.5 mg/dose. May repeat every 5 to 15 minutes as needed for up to 3 injections; more frequent administration may be appropriate in certain circumstances, as judged by the clinician. If there is no response after 3 to 4 injections, consider an intravenous infusion. Monitor for reaction severity and cardiac effects.[54254] [54255] [56575] [60589] [64934]
Infants and Children weighing 30 kg or less
0.01 mg/kg/dose (0.01 mL/kg/dose of a 1 mg/mL solution) IM (preferred) or subcutaneous. Max: 0.3 mg/dose. May repeat every 5 to 15 minutes as needed for up to 3 injections; more frequent administration may be appropriate in certain circumstances, as judged by the clinician. If there is no response after 3 to 4 injections, consider an intravenous infusion. Monitor for reaction severity and cardiac effects.[54254] [54255] [56575] [60589] [64934]
Intramuscular or Subcutaneous dosage (e.g., Auvi-Q auto-injector)
Adults
0.3 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat for severe persistent anaphylaxis; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257]
Children and Adolescents weighing 30 kg or more
0.3 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat for severe persistent anaphylaxis; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257]
Children weighing 25 to 29 kg
0.3 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh has been recommended by some experts; however, the FDA-approved dosage is 0.15 mg/dose IM or subcutaneously via auto-injector.[54255] [54257] [54293] Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat for severe persistent anaphylaxis; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257]
Infants and Children weighing 15 to 24 kg
0.15 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat for severe persistent anaphylaxis; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257]
Infants and Children weighing 7.5 to 14 kg
0.1 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat for severe persistent anaphylaxis; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54257]
Intramuscular or Subcutaneous dosage (e.g., EpiPen, EpiPen Jr, Adrenaclick auto-injectors)
Adults
0.3 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat every 5 to 20 minutes as needed; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54255] [54293] [57081]
Children and Adolescents weighing 30 kg or more
0.3 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat every 5 to 20 minutes as needed; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54255] [54293] [57081]
Children weighing 25 to 29 kg
0.3 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh has been recommended by some experts; however, the FDA-approved dosage is 0.15 mg/dose IM or subcutaneously via auto-injector.[54140] [54255] [54293] [57081] Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat every 5 to 20 minutes as needed; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [57081]
Infants and Children weighing 15 to 24 kg
0.15 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat every 5 to 20 minutes as needed; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[54140] [54255] [54293] [57081]
Infants and Children weighing 10 to 14 kg†
0.15 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh has been recommended by some experts; however, FDA-approved labeling does not recommend auto-injector use for patients weighing less than 15 kg.[54255] [54293] Patients should be instructed to seek medical attention immediately after administration of the first injection.
Intramuscular or Subcutaneous dosage (e.g., Symjepi prefilled syringe)
Adults
0.3 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat for severe persistent anaphylaxis; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[62025]
Children and Adolescents weighing 30 kg or more
0.3 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat for severe persistent anaphylaxis; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[62025]
Children weighing 15 to 29 kg
0.15 mg/dose IM or subcutaneously into the anterolateral aspect of the thigh. Patients should be instructed to seek medical attention immediately after administration of the first injection. May repeat for severe persistent anaphylaxis; the patient should not administer more than 2 sequential doses unless under direct medical supervision.[62025]
Intermittent Intravenous dosage
Adults
0.1 to 0.25 mg (of a 0.1 mg/mL solution) IV may be required for severe reactions; may repeat every 5 to 15 minutes.
Infants, Children, and Adolescents
0.01 mg/kg/dose (0.1 mL/kg/dose of a 0.1 mg/mL solution) IV may be required for severe reactions; may repeat every 3 to 5 minutes. Max: 1 mg/dose (10 mL/dose of a 0.1 mg/mL solution).[54254] [54255] [54288]
Continuous IV Infusion dosage
Adults
1 to 4 mcg/minute continuous IV infusion may be considered if low blood pressure persists despite fluid administration and intermittent IV epinephrine administration.
Infants, Children, and Adolescents
0.1 to 1 mcg/kg/minute continuous IV infusion may be considered if low blood pressure persists despite fluid administration and intermittent IM or IV epinephrine administration.[54288] [64934]
For the temporary relief of mild symptoms of intermittent asthma (i.e., transient mild bronchospasm or episodic wheezing)
Oral Inhalation dosage (non-prescription oral inhaler; e.g., Primatene Mist)
Adults
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]
Children and Adolescents 12 to 17 years
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]
For asthma exacerbation (e.g., acute care management)
Subcutaneous dosage
Adults
0.3 to 0.5 mg subcutaneously every 20 minutes for 3 doses. Guidelines state there is no proven advantage of systemic therapy over the use of inhaled short-acting beta-agonists.[33558] [64807]
Adolescents
0.3 to 0.5 mg subcutaneously every 20 minutes for 3 doses. Guidelines state there is no proven advantage of systemic therapy over the use of inhaled short-acting beta-agonists.[33558] [64807]
Children 1 to 12 years
0.01 mg/kg/dose (Max: 0.5 mg/dose) subcutaneously every 20 minutes for 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]
Intramuscular dosage
Adults
0.3 to 0.5 mg/dose IM every 5 to 15 minutes as needed for up to 3 injections. 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]
Children and Adolescents weighing 30 kg or more
0.01 mg/kg/dose (Max: 0.5 mg/dose) IM every 5 to 15 minutes as needed for up to 3 injections. 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]
Infants and Children weighing less than 30 kg
0.01 mg/kg/dose (Max: 0.3 mg/dose) IM every 5 to 15 minutes as needed for up to 3 injections. 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]
For the treatment of laryngotracheobronchitis (croup)
Nebulized dosage
Infants and Children 6 months to 12 years
0.05 to 0.1 mL/kg/dose of 2.25% racemic epinephrine solution (Max: 0.5 mL/dose) diluted in 2 to 2.5 mL of normal saline and given via nebulizer; may repeat every 20 minutes as needed. Some experts use 0.5 mL/dose for all patients, regardless of size. Alternatively, if racemic epinephrine is not available, L-epinephrine 1 mg/mL can be substituted in a dosage of 0.5 mL/kg/dose (Max: 5 mL/dose) and given via nebulizer; 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; closely observe patients for recurrence of symptoms for 2 to 3 hours after administration.[54245] [54247] [54249] [54250] [59632] [64934]
For the treatment of acute, severe urticaria or angioedema associated with systemic symptoms
Intramuscular or Subcutaneous dosage
Adults
0.3 to 0.5 mL of 1 mg/mL solution subcutaneously or IM every 1 to 2 hours.
For use in cardiopulmonary resuscitation (CPR), specifically, for the treatment of cardiac arrest (pulseless electrical activity or ventricular asystole), or as an adjunct to electrical defibrillation in the treatment of ventricular fibrillation/pulseless ventricular tachycardia
Intravenous or Intraosseus† dosage
Adults
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]
Infants†, Children†, and Adolescents†
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]
Neonates†
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]
Endotracheal dosage
Adults
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]
Infants†, Children†, and Adolescents†
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]
Neonates†
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]
Intracardiac dosage†
Adults
0.3 to 0.5 mg intracardially. Follow administration with external cardiac massage to permit the drug to enter the coronary circulation.[45416] [49567]
Continuous Intravenous or Intraosseus† Infusion dosage for postresuscitation stabilization
Adults
2 to 10 mcg/minute continuous IV or IO infusion; titrate to desired effect.[45649] [66054]
Infants†, Children†, and Adolescents†
0.1 to 1 mcg/kg/minute continuous IV or IO infusion; titrate to desired effect.[43713] [66053]
Neonates†
0.1 to 1 mcg/kg/minute continuous IV or IO infusion; titrate to desired effect.[43713] [66053]
for the treatment of low blood pressure or persistent bradycardia with a pulse in a patient with an at-risk myocardium to prevent cardiac arrest and allow time to treat an acute reversible problem†
Intravenous or Intraosseous dosage
Infants, Children, and Adolescents
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]
For the treatment of symptomatic bradycardia† unresponsive to atropine or external pacing
Intravenous or Intraosseus† dosage
Adults
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]
Infants, Children, and Adolescents
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]
Neonates
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]
Endotracheal dosage
Infants, Children, and Adolescents
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]
Neonates
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]
For the treatment of hypotension, including during shock (e.g., septic shock, cardiogenic shock†)
Continuous Intravenous Infusion dosage
Adults
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]
Infants†, Children†, and Adolescents†
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]
Neonates†
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]
For the treatment or prevention of surgical bleeding along a surgical incision
Topical dosage
Adults
Apply 0.002% to 0.1% solutions topically.
For the treatment of open-angle glaucoma
Ophthalmic dosage (epinephrine ophthalmic solution 0.5%, 1% or 2%; e.g., Epifrin)
Adults
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.
For the treatment of acute chloroquine overdose† in combination with diazepam
Intravenous dosage
Adults
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]
For the treatment of nasal congestion
Nasal dosage (0.1 to 0.5 mg/mL solution)
Adults
Apply topically to nose as drops, spray, or with a sterile swab as needed.[46634]
Children and Adolescents 6 to 17 years
Apply topically to nose as drops, spray, or with a sterile swab as needed.[46634]
For mydriasis induction and maintenance during intraocular surgery
Ophthalmic dosage
Adults
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.
Infants, Children, and Adolescents
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.
For the treatment of epistaxis†
Nasal dosage
Adults
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]
Therapeutic Drug Monitoring
Maximum Dosage Limits
- Adults
Dependent on route of administration and indication for therapy.
- Geriatric
Dependent on route of administration and indication for therapy.
- Adolescents
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).
- Children
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).
- Infants
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).
- Neonates
Dependent on route of administration and indication for therapy. For CPR, 0.03 mg/kg/dose IV and 0.1 mg/kg/dose ET.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
† Off-label indicationReferences
How Supplied
Epinephrine Hydrochloride Inhalation vapour, solution
Adrenalin 10mg/mL Solution for Inhalation (61570-0301) (Monarch Pharmaceuticals Inc a Pfizer Company) (off market)Epinephrine Hydrochloride Nasal spray, solution
Adrenalin 1mg/mL Nasal Solution (61570-0300) (Monarch Pharmaceuticals Inc a Pfizer Company) (off market)
Epinephrine Hydrochloride Nasal spray, solution
Adrenalin 1mg/mL Nasal Solution (61570-0300) (Par Pharmaceuticals, an Endo Company) (off market)Epinephrine Hydrochloride Nasal spray, solution
Adrenalin 1mg/mL Nasal Solution (42023-0103) (Par Pharmaceuticals, an Endo Company) nullEpinephrine Hydrochloride Ophthalmic drops, solution
Epifrin 0.5% Ophthalmic Solution (11980-0119) (Allergan USA, Inc.) (off market)Epinephrine Hydrochloride Ophthalmic drops, solution
Epifrin 1% Ophthalmic Solution (11980-0122) (Allergan USA, Inc.) (off market)
Epinephrine Hydrochloride Ophthalmic drops, solution
Epifrin 2% Ophthalmic Solution (11980-0058) (Allergan USA, Inc.) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (00074-4901) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (00409-4901) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (00548-1014) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (00548-1016) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (00548-2016) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (00548-3316) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)
Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (76329-3316) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (63739-0456) (McKesson Packaging Inc) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (LifeShield) (00074-4921) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:10,000 0.1mg/mL Solution for Injection (LifeShield) (00409-4921) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (00517-1061) (American Regent Inc, a division of Luitpold Pharmaceuticals) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (00517-1071) (American Regent Inc, a division of Luitpold Pharmaceuticals) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (00517-1130) (American Regent Inc, a division of Luitpold Pharmaceuticals) (off market)
Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (00143-9984) (Hikma Pharmaceuticals USA Inc.) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (00074-7241) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (00409-7241) (Hospira Worldwide, Inc., a Pfizer Company) (off market)
Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (00548-9061) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (76329-9061) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)
Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (63739-0467) (McKesson Packaging Inc) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine Hydrochloride 1:1000 1mg/mL Solution for Injection (NOVAPLUS) (00409-7241) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine 1mg/10mL Solution for Injection (76329-3316) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) nullEpinephrine Hydrochloride Solution for injection
Epinephrine 1mg/10mL Solution for Injection (LifeShield) (00409-4921) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine 1mg/10mL Solution for Injection (LifeShield) (00409-4933) (Hospira Worldwide, Inc., a Pfizer Company) nullEpinephrine Hydrochloride Solution for injection
Adrenalin 1mg/mL Solution for Injection (61570-0401) (Monarch Pharmaceuticals Inc a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Adrenalin 1mg/mL Solution for Injection (61570-0418) (Monarch Pharmaceuticals Inc a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Adrenalin 1mg/mL Solution for Injection (61570-0401) (Par Pharmaceuticals, an Endo Company) (off market)Epinephrine Hydrochloride Solution for injection
Adrenalin 1mg/mL Solution for Injection (61570-0418) (Par Pharmaceuticals, an Endo Company) (off market)Epinephrine Hydrochloride Solution for injection
Adrenalin 1mg/mL Solution for Injection (42023-0101) (Par Pharmaceuticals, an Endo Company) (off market)Epinephrine Hydrochloride Solution for injection
Adrenalin 1mg/mL Solution for Injection (42023-0122) (Par Pharmaceuticals, an Endo Company) (off market)Epinephrine Hydrochloride Solution for injection
Adrenalin 1mg/mL Solution for Injection (42023-0159) (Par Pharmaceuticals, an Endo Company) (off market)Epinephrine Hydrochloride Solution for injection
Adrenalin 1mg/mL Solution for Injection (42023-0159) (Par Pharmaceuticals, an Endo Company) nullEpinephrine Hydrochloride Solution for injection
Adrenalin 30mg/30mL Solution for Injection (42023-0168) (Par Pharmaceuticals, an Endo Company) (off market)Epinephrine Hydrochloride Solution for injection
Adrenalin 30mg/30mL Solution for Injection (42023-0168) (Par Pharmaceuticals, an Endo Company) nullEpinephrine Hydrochloride Solution for injection
Adrenalin 30mg/30mL Solution for Injection (NOVAPLUS) (42023-0168) (Par Pharmaceuticals, an Endo Company) nullEpinephrine Hydrochloride Solution for injection
Adrenalin 30mg/30mL Solution for Injection (PREMIER ProRx) (42023-0168) (Par Pharmaceuticals, an Endo Company) nullEpinephrine Hydrochloride Solution for injection
Epinephrine 10mg/10mL Solution for Injection (54288-0120) (BPI Labs, LLC) null
Epinephrine Hydrochloride Solution for injection
Epinephrine 1mg/mL Solution for Injection (00517-1171) (American Regent Inc, a division of Luitpold Pharmaceuticals) nullEpinephrine Hydrochloride Solution for injection
Epinephrine 1mg/mL Solution for Injection (54288-0103) (BPI Labs, LLC) nullEpinephrine Hydrochloride Solution for injection
Epinephrine 1mg/mL Solution for Injection (00409-7241) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine 1mg/mL Solution for Injection (76329-9061) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) nullEpinephrine Hydrochloride Solution for injection
Epinephrine 1mg/mL Solution for Injection (NOVAPLUS) (00409-7241) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride Solution for injection
Epinephrine 30mg/30mL Solution for Injection (76329-9060) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) nullEpinephrine Inhalation vapour, solution
Epinephrine 5.5mg/actuation Inhalation Aerosol (17270-0970) (Armstrong Pharmaceuticals Inc., a subsidiary of Amphastar Pharmaceuticals, Inc.) (off market)Epinephrine Inhalation vapour, solution
Primatene Mist 0.22mg/actuation Inhalation Aerosol (00573-2910) (GlaxoSmithKline Consumer Healthcare) (off market)Epinephrine Pressurized inhalation, solution
Primatene Mist 0.125mg/actuation Inhalation Aerosol (17270-0553) (Armstrong Pharmaceuticals Inc., a subsidiary of Amphastar Pharmaceuticals, Inc.) nullEpinephrine Pressurized inhalation, solution
Primatene Mist 0.22mg/actuation Inhalation Aerosol Refill (00573-2910) (GlaxoSmithKline Consumer Healthcare) (off market)Epinephrine Pressurized inhalation, solution
Walgreens Bronchial Mist 0.22mg/actuation Inhalation Aerosol (00363-5036) (Walgreens Co) null
Epinephrine Pressurized inhalation, solution
Walgreens Bronchial Mist 0.22mg/actuation Inhalation Aerosol (Refill) (00363-5046) (Walgreens Co) null
Epinephrine Solution for injection
Adrenaclick 0.15mg/0.15ml Auto Injector Solution For Injection (59630-0803) (Shionogi USA, Inc.) (off market)Epinephrine Solution for injection
Adrenaclick 0.15mg/0.15ml Auto-Injector Solution for Injection (52054-0803) (Amneal Specialty, a division of Amneal Pharmaceutical, LLC) nullEpinephrine Solution for injection
Adrenaclick 0.3mg/0.3ml Auto Injector Solution For Injection (59630-0804) (Shionogi USA, Inc.) (off market)Epinephrine Solution for injection
Adrenaclick 0.3mg/0.3ml Auto-Injector Solution For Injection (52054-0804) (Amneal Specialty, a division of Amneal Pharmaceutical, LLC) nullEpinephrine Solution for injection
Auvi-Q 2-Pack Auto-Injector 0.15mg/0.15mL Solution for Injection (60842-0022) (Kaleo, Inc.) nullEpinephrine Solution for injection
Auvi-Q 2-Pack Auto-Injector 0.15mg/0.15mL Solution for Injection (00024-5831) (Sanofi U.S. LLC) (off market)
Epinephrine Solution for injection
Auvi-Q 2-Pack Auto-Injector 0.1mg/0.1mL Solution for Injection (60842-0021) (Kaleo, Inc.) nullEpinephrine Solution for injection
Auvi-Q 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (60842-0023) (Kaleo, Inc.) nullEpinephrine Solution for injection
Auvi-Q 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (00024-5833) (Sanofi U.S. LLC) (off market)
Epinephrine Solution for injection
Epinephrine 0.15mg/0.15mL Auto-Injector Solution for Injection (59762-0172) (Greenstone Ltd) nullEpinephrine Solution for injection
Epinephrine 0.15mg/0.15mL Auto-Injector Solution for Injection (00115-1695) (Impax Generics, a division of Impax Laboratories, Inc.) null
Epinephrine Solution for injection
Epinephrine 0.15mg/0.15mL Auto-Injector Solution for Injection (54505-0101) (Lineage Therapeutics) (off market)
Epinephrine Solution for injection
Epinephrine 0.3mg/0.3mL Auto-Injector Solution For Injection (42291-0425) (AvKARE, Inc.) nullEpinephrine Solution for injection
Epinephrine 0.3mg/0.3mL Auto-Injector Solution For Injection (59762-0171) (Greenstone Ltd) null
Epinephrine Solution for injection
Epinephrine 0.3mg/0.3mL Auto-Injector Solution For Injection (00115-1694) (Impax Generics, a division of Impax Laboratories, Inc.) null
Epinephrine Solution for injection
Epinephrine 0.3mg/0.3mL Auto-Injector Solution For Injection (54505-0102) (Lineage Therapeutics) (off market)
Epinephrine Solution for injection
Epinephrine 0.3mg/0.3mL Solution for Injection (38739-0030) (Adamis Laboratories, Inc.) (off market)Epinephrine Solution for injection
Epinephrine 2-Pack Auto-Injector 0.15mg/0.3mL Solution for Injection (49502-0101) (Mylan Specialty L.P.) null
Epinephrine Solution for injection
Epinephrine 2-Pack Auto-Injector 0.15mg/0.3mL Solution for Injection (00093-5985) (Teva Pharmaceuticals USA) null
Epinephrine Solution for injection
Epinephrine 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (49502-0102) (Mylan Specialty L.P.) null
Epinephrine Solution for injection
Epinephrine 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (00093-5986) (Teva Pharmaceuticals USA) null
Epinephrine Solution for injection
Epipen 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (49502-0500) (Mylan Specialty L.P.) null
Epinephrine Solution for injection
Epipen 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (49502-0500) (Mylan Specialty L.P.) nullEpinephrine Solution for injection
Epipen Auto-Injector 0.3mg/0.3ml Solution for Injection (49502-0500) (Mylan Specialty L.P.) (off market)
Epinephrine Solution for injection
Epipen Jr 2-Pack Auto-Injector 0.15mg/0.3mL Solution for Injection (49502-0501) (Mylan Specialty L.P.) null
Epinephrine Solution for injection
Epipen Jr Auto-Injector 0.15mg/0.3ml Solution for Injection (49502-0501) (Mylan Specialty L.P.) (off market)
Epinephrine Solution for injection
SYMJEPI 0.15mg/0.3mL Solution for Injection (00781-3448) (Sandoz Inc. a Novartis Company) nullEpinephrine Solution for injection
SYMJEPI 0.15mg/0.3mL Solution for Injection (78670-0131) (USWM, LLC) nullEpinephrine Solution for injection
SYMJEPI 0.3mg/0.3mL Solution for Injection (00781-3442) (Sandoz Inc. a Novartis Company) nullEpinephrine Solution for injection
SYMJEPI 0.3mg/0.3mL Solution for Injection (78670-0130) (USWM, LLC) nullEpinephrine Solution for injection
Twinject 0.15mg/0.15ml Auto Injector Solution For Injection (13436-0701) (Shionogi USA, Inc.) (off market)
Epinephrine Solution for injection
Twinject 0.15mg/0.15ml Auto Injector Solution For Injection (59630-0801) (Shionogi USA, Inc.) (off market)Epinephrine Solution for injection
Twinject 0.15mg/0.15ml Auto Injector Solution For Injection (13436-0701) (Verus Pharmaceuticals, Inc) (off market)Epinephrine Solution for injection
Twinject 0.3mg/0.3ml Auto Injector Solution For Injection (13436-0700) (Shionogi USA, Inc.) (off market)
Epinephrine Solution for injection
Twinject 0.3mg/0.3ml Auto Injector Solution For Injection (59630-0802) (Shionogi USA, Inc.) (off market)Epinephrine Solution for injection
Twinject 0.3mg/0.3ml Auto Injector Solution For Injection (13436-0700) (Verus Pharmaceuticals, Inc) (off market)Description/Classification
Description
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]
Classifications
- Cardiovascular System
- Cardiac Therapy
- Cardiac Stimulants Excluding Cardiac Glycosides
- Cardiac Stimulants Excluding Dopaminergic Agents
- Cardiac Stimulants Excluding Cardiac Glycosides
- Vasopressors
- Cardiac Therapy
- Respiratory System
- Agents for Reactive and Obstructive Airway Diseases
- Beta-2 Agonists
- Respiratory Short-Acting Beta-2 Agonists (SABA)
- Other Agents for Reactive and Obstructive Airway Diseases
- All Other Respiratory Agents for Reactive and Obstructive Airway Diseases
- Beta-2 Agonists
- Nasal Agents
- Topical Nasal Decongestants
- Agents for Reactive and Obstructive Airway Diseases
- Sensory Organs
- Ophthalmologicals
- Mydriatics and Cycloplegics
- Ophthalmologicals
References
Administration Information
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
- Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use solutions that are pinkish to brownish in color, cloudy, or contain a precipitate or particulate matter.[45416] [54140] [60589]
- Avoid IV extravasation and accidental injection (e.g., from an auto-injector device). Do not inject epinephrine in fingers, toes, nose, and genitalia because it can cause severe tissue necrosis due to vasoconstriction of small blood vessels. Also, avoid injection of epinephrine-containing local anesthetics into these areas. If extravasation or accidental injection occurs, infiltrate the affected ischemic area as soon as possible with phentolamine to counteract dermal vasoconstriction.[54140] [54309] [56575] [64923]
- Updates for coronavirus disease 2019 (COVID-19): The FDA is allowing epinephrine 1 mg/mL and 30 mg/30 mL to be used beyond the labeled in-use time to help ensure access during COVID-related drug shortages. This period should be as short as possible, and for a maximum of 2 hours at room temperature or 4 hours when refrigerated. In-use time is defined as the maximum amount of time allowed to elapse between penetration of a closed-container system or after reconstitution of a lyophilized drug before patient administration.[65833]
Intravenous Administration
- Though central IV access is preferred, epinephrine may be administered peripherally. In neonates, epinephrine may be administered via the umbilical vein.[32868]
- Check the infusion site frequently for free flow. Avoid extravasation into the tissues to prevent local necrosis. 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.[60589]
- Epinephrine is inactivated in alkaline solutions; it is incompatible with sodium bicarbonate.[29493] [54288]
IV Push
- May administer at a concentration of 0.1 mg/mL directly into the vein.
- Do not interrupt CPR to administer epinephrine. Epinephrine should be administered during chest compressions; however, the timing of drug administration is less important than the need to minimize chest compression interruption. After medication administration, flush with 0.9% Sodium Chloride Injection to promote medication entry into the central circulation.[43713] [44520] [60636] [61541]
Continuous IV infusion
Dilution
- Dilute with a compatible IV solution (e.g., 5% Dextrose Injection, 10% Dextrose Injection, 0.9% Sodium Chloride Injection) prior to administration of IV infusion. Although FDA-approved labeling recommends dilution in dextrose-containing solutions to protect against significant loss of potency by oxidation, dilution in 0.9% Sodium Chloride Injection is physically compatible.[60589]
- ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 20 mcg/mL and 40 mcg/mL.[64020]
- Institute for Safe Medication Practices (ISMP)/Vermont Oxford Network (VON) Recommended Standard Concentration for Neonatal Infusions: 10 mcg/mL.[51889]
- Neonates: Maximum concentration should not exceed 60 mcg/mL.
- Infants, children, and adolescents: Concentrations of 16 mcg/mL, 32 mcg/mL, and 64 mcg/mL are commonly used; maximum concentration should not exceed 64 mcg/mL.[52507]
- Storage: Epinephrine diluted in 5% Dextrose Injection or 5% Dextrose and 0.9% Sodium Chloride Injection is stable for 4 hours at room temperature or 24 hours refrigerated.[56575] Protect from light.[45416]
Administration
- Administer via a large vein, whenever possible. Avoid veins of the leg in elderly patients or those with occlusive vascular disease.[56575]
- Adjust the rate of infusion as needed to maintain desired response. In general, low-dose infusions (less than 0.3 mcg/kg/minute) produce beta-adrenergic effects (e.g., tachycardia, inotropy, decreased systemic vascular resistance), while higher dose infusions (more than 0.3 mcg/kg/minute) cause alpha-adrenergic vasoconstriction.[43713] [60636]
Extravasation Management
- For adults: If extravasation or inadvertent digital injection occurs, infiltrate the site with 10 to 15 mL of a saline solution containing 5 to 10 mg phentolamine.[60589]
- For infants, children, and adolescents: If extravasation or inadvertent digital injection occurs, infiltrate the site with 1 to 5 mL (as 5 divided doses) of a solution containing 0.9% Sodium Chloride Injection and phentolamine at a concentration of 0.5 to 1 mg/mL.[52618] [54685] FDA-approved labeling recommends infiltrating the area with 10 to 15 mL of a saline solution containing 5 to 10 mg of phentolamine.[60589]
- For neonates: If extravasation occurs, infiltrate the site with 1 mL (as 5 divided doses of 0.2 mL) of a solution containing preservative-free 0.9% Sodium Chloride Injection and phentolamine at a concentration of 0.25 to 0.5 mg/mL.
- Use a syringe with a fine hypodermic needle and liberally infiltrate throughout the ischemic area which is easily identified by its cold, hard, and pallid appearance.[60589]
- Administer phentolamine solution as quickly as possible after extravasation to minimize tissue damage; sympathetic blockade with phentolamine causes immediate and noticeable local hyperemic changes if the area is infiltrated within 12 hours of extravasation.[52618] [54685]
Intramuscular Administration
- Inject epinephrine into the anterolateral aspect of the thigh, through clothing if necessary. Do NOT inject into the buttock, digits, hands, or feet. Avoid administration into or near smaller muscles, such as the deltoid muscle, due to differences in absorption observed with this use.[56575][60589]
- If administering to a young child who may be uncooperative, hold the leg firmly in place, and limit movement prior to and during the injection.
- Avoid repeated injections at the same site because resulting vasoconstriction can lead to tissue necrosis.[56575]
- Most auto-injectors and prefilled syringes are for single-use only.
- Device failure has been reported with epinephrine auto-injectors. Device failure may result from spontaneous activation caused by using a sideways force to remove the blue safety release, inadvertent or spontaneous activation due to a raised blue safety release, or difficulty removing the device from the carrier tube. Review appropriate use instructions with patients and their caregivers. Prior to dispensing or using, ensure that the auto-injector slides out of the carrier tube and that the blue safety release is not raised. If the blue safety release is raised, the auto-injector should not be used because the device could activate by accident. Do not try to push the blue safety release back down. A device that has been activated by accident cannot be used for a patient in an emergency.[54140][65168]
- Consult product-specific labeling for device use instructions. Recommended "hold times" may vary among devices.[54140][54257][56575][57081][62025]
- Instruct patients to seek medical attention immediately after administration of the first injection.
Subcutaneous Administration
- Subcutaneous epinephrine is not routinely recommended in the treatment of anaphylaxis due to delayed absorption.[54255]
- Inject epinephrine subcutaneously taking care not to inject intradermally. Massage injection site well after administration to enhance absorption and to decrease local vasoconstriction. Injection can cause tissue irritation.[45416]
- If administering to a young child who may be uncooperative, hold the leg firmly in place and limit movement prior to and during the injection.
- Avoid repeated injections at the same site, as resulting vasoconstriction may lead to tissue necrosis.[56575]
Other Injectable Administration
Intraosseous Administration
NOTE: Epinephrine is not FDA-approved for intraosseous administration.
- During cardiopulmonary resuscitation, the same epinephrine dosage may be given via the intraosseous route when IV access is not available. Of note, intraosseous lines are not commonly used in neonates because of the availability of the umbilical vein, the fragility of small bones, and the small intraosseous space available.[32868][60266]
- After injection, flush with saline to promote medication entry into the central circulation.[43713]
Intracardiac Administration
NOTE: Epinephrine is not FDA-approved for intracardiac administration.
- Intracardiac epinephrine administration should be reserved for extreme emergencies. Intracardiac injection should only be performed by properly trained medical personnel. The risks of intracardiac injection include myocardial puncture and cardiac tamponade, coronary artery rupture, pneumothorax, and the need to cease chest compression and ventilation.[32537]
Inhalation Administration
Oral Inhalation Administration
Inhalation Solution (Primatene Mist Aerosol Spray, non-prescription product)
- For oral inhalation use only.
- Before using the inhaler for the first time, activate the new inhaler by removing the red cap, shaking well, and then spraying into the air 4 separate times.
- Shake well before each use. Remove the red cap.
- Have the patient exhale completely. Place mouthpiece in patient's mouth with their lips closed around the opening. The patient should inhale deeply while pressing down on the top of inhaler, then continue the deep breath.
- Hold breath as long as possible. Release finger and remove inhaler from mouth then exhale slowly.
- Wait at least 1 minute. If symptoms are not relieved, take a second inhalation by repeating the steps above.
- Do not exceed recommended daily dosage. Wait at least 4 hours between doses.
- Wash inhaler after each day of use by running water through the mouthpiece for 30 seconds.
- Contents are under pressure; do not expose to heat, flame, or puncture as this may cause injury.[63740]
Intranasal Inhalation Administration
- Instruct patient on the proper technique for administering epinephrine nasal solution.
- To avoid the spread of infection, do not use the container for more than one person.
Ophthalmic Administration
- Epinephrine injection MUST be diluted prior to intraocular use.
- Only use the 1 mg/mL single-use vial or ampule intended for ophthalmic administration.
- Visually inspect for particulate matter and discoloration prior to administration. Do not use solutions that are pinkish to brownish in color, cloudy, or contain a precipitate or particulate matter.[60589]
Irrigation for intraocular use
- Dilute 1 mL of epinephrine 1 mg/mL solution 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 as an irrigating solution as needed for surgical procedure.[60589]
Intracameral injection for intraocular use
- Dilute 1 mL of epinephrine 1 mg/mL solution in an ophthalmic irrigation fluid to create an epinephrine concentration of 10 mcg/mL to 2.5 mcg/mL.
- Inject a bolus dose of 0.1 mL of diluted solution intracamerally.[60589]
Other Administration Route(s)
Endotracheal (ET) Administration
- ET administration should only be used if access to intravenous (IV) or intraosseous (IO) routes can not be achieved or access is delayed. ET administration is associated with lower drug concentrations compared to IV administration and may be less effective. Animal studies suggest that the lower epinephrine blood concentrations attained after ET drug administration may result in transient beta2-adrenergic effects with potential for hypotension.[32366] [32367] [32368] [45649]
- Adults: Dilute dose in 5 to 10 mL of 0.9% Sodium Chloride Injection or sterile distilled water. Administer via ET tube. Endotracheal absorption of epinephrine may be improved by diluting with water instead of 0.9% Sodium Chloride Injection.[45649]
- Infants, Children, and Adolescents: Use the 1 mg/mL parenteral solution. 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]
- Neonates: Use the 0.1 mg/mL solution. 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]
Clinical Pharmaceutics Information
From Trissel's 2‚Ñ¢ Clinical Pharmaceutics DatabaseEpinephrine hydrochloride
pH Range
pH 2.2 to 5Osmolality/Osmolarity
The manufacturer indicates that epinephrine hydrochloride 1 mg/mL is isotonic. The osmolality was determined to be 348 mOsm/kg. Abbott epinephrine hydrochloride 0.1 mg/mL was also isotonic having an osmolality of 273 mOsm/kg.Stability
Epinephrine hydrochloride injection in intact containers is stable until the labeled expiration date. A labeled expiration date of 18 months from date of manufacture has been reported. Epinephrine hydrochloride decomposes upon exposure to light, heat, and air. Entering the multiple-dose vials introduces air and increases the rate of oxidation. Oxidation results in progressive color changes from the normal colorless to pink from adrenochrome formation to brown or black from melanin formation. However, substantial drug loss may occur without a color change being evident. Discolored solutions or a solution having a precipitate should not be used and should be discarded. Sodium bisulfite antioxidant in the formulation serves to slow the rate of oxidation. Also see pH Effects. Grant et al. reported 64% loss of epinephrine in 1:1000 solutions when heated to 70 degree C for up to 12 weeks. Church et al. reported the total loss of epinephrine in commercial epinephrine cartridges subjected to 65 degree C for 7 days; losses of about 31% occurred when the temperature was cycled being 65 degree C for 8 hours in 24 hours instead of being held constant. Rudland et al. reported some losses up to about 40% from physician-returned epinephrine vials from doctor's bags subjected to summer temperatures of 40 to 65 degree C in vehicles. However, Patterson et al. reported that epinephrine hydrochloride vials could be autoclaved one time to sterilize the exterior of the containers with no detectable difference in drug concentration by HPLC analysis. A second autoclaving resulted in 8% loss of drug. Packaged in Syringes: Donnelly and Yen reported the stability of epinephrine hydrochloride 0.1 and 0.7 mg/mL in sterile water for injection packaged in Becton Dickinson plastic syringes and stored at room temperature protected from exposure to light. The 0.1-mg/mL concentration exhibited about 4% loss in 7 days and 13% loss in 14 days. The 0.7 mg/mL concentration exhibited about 5% loss in 56 days. The stability of both concentrations was very similar to the same solutions packaged in glass vials. Rawas-Qalaji et al. evaluated the stability of epinephrine hydrochloride 1 mg/mL drawn into unsealed 1-mL Becton Dickinson polypropylene syringes for use in first aid treatment of anaphylaxis when stored at 38 degree C at high and low humidity and exposed to or protected from exposure to light. The intent was to simulate conditions that might occur in areas of the world that are hot and where conditions are suboptimal and epinephrine autoinjectors are unavailable. HPLC analysis of drug content found substantial loss of epinephrine occurred within two to three months under all storage conditions evaluated. The authors stated that such syringes should be replaced ''every few months'' because of this drug loss. However, the maintenance of sterility in these unsealed syringes was not evaluated, which is a critical issue. Kerddonfak et al. evaluated the stability of epinephrine hydrochloride 1 mg/mL drawn into unsealed 1-mL plastic syringes (Nipro) with 23-gauge needles for use in first aid treatment. Samples were stored for three months at 23 to 29 degree C protected from exposure to light. HPLC analysis found little or no loss of epinephrine hydrochloride occurred over three months of storage. Visual examination found that the solutions remained clear and colorless. However, brown particles were found at the needle. The particles were negative for bacteria or fungus. The authors speculated that the brown particles were formed by the epinephrine reacting with the atmosphere resulting in oxidation of the epinephrine to adrenochrome, which is a pink-brown in color. It is also possible that melanin had also formed with its characteristic brown color. After four months of storage the epinephrine hydrochloride solutions had turned pinkish-brown and were deemed unacceptable. Although the authors stated that the prefilled epinephrine syringes were stable for three months at room temperature protected from exposure to light, caution would indicate a shorter utility period may be warranted because of the oxidation that leads to the brown particulates. Wolf and Scherbel evaluated the stability of epinephrine hydrochloride (Suprarenin, Sanofi-Aventis) 0.1 mg/mL (1:10,000) and 0.01 mg/mL (10 mcg/mL, 1:100,000) in sodium chloride 0.9% packaged as prefilled syringes and stored frozen at -31 degree C for 7 weeks followed by 7 days at room temperature. HPLC analysis found no drug loss occurred in the 0.1 mg/mL concentration and less than 6% loss occurred in the 0.01 mg/mL concentration under the study conditions. Paramedic Vehicles: Gill et al. reported that Abbott epinephrine 1:10,000 in autoinjector syringes was stable for 45 days under use conditions in advanced life support paramedic vehicles. Temperatures ranged from 6 degree C (43.7 degree F) to 52 degree C (125.6 degree F) in high desert conditions varying with conditions and locations. No changes in color or clarity were found upon visual inspection. HPLC analysis found most samples exhibited no loss of epinephrine. The largest loss of 6% in 45 days occurred in a sample exposed to the highest temperature. Valenzuela et al. reported the stability of epinephrine hydrochloride injection exposed to temperatures ranging from 26 to 38 degree C under simulated summer conditions in paramedic vehicles over 4 weeks. Gas chromatography coupled with mass spectrometry found no change in the drug over 4 weeks under these simulated use conditions. However, the buffer in the injection was altered resulting in an increase in pH. Gammon et al. reported on the stability of a number of drugs used by paramedics when exposed to the temperature range that is found in ambulances as documented by Brown et al., Allegra et al., and Palmer et al. Epinephrine hydrochloride 0.1 mg/mL injection was stored at temperatures that cycled every 24 hours from -6 to 54 degree C (2.12 to 129.2 degree F) for 28 days. The drug was exposed to a total of 336 hours at each of the temperature extremes. The mean kinetic temperature was 33 degree C. HPLC and ultraviolet spectrophotometry found drugs losses of about 20% occurred over the 28-day test period. De Winter et al. evaluated the stability of epinephrine hydrochloride 0.8 mg/mL (Sterop) in intact containers under conditions they called "real-world out-of-hospital settings." Samples were stored under refrigeration at 2 to 8 degree C as the drug is labeled, at room temperature of 20 to 25 degree C, and at uncontrolled temperatures in emergency transport vehicles protected from exposure to light over a period of 12 months. According to the weather service, outdoor temperatures locally during the year-long study period ranged from -8 degree C to 35.8 degree C with a mean of 10.3 degree C. Temperatures inside the emergency transport vehicles were not reported. Stability-indicating HPLC analysis found less than 10% loss in 12 months for all three storage conditions. The time to 10% loss (t90) was calculated to be 22 months at room temperature and 38 months in the emergency transport vehicles.pH Effects
The principal determinant of epinephrine hydrochloride stability in solution is pH. Stable formulations should have a pH high enough so that racemization is not significant but low enough to slow oxidation. Maximum stability occurs in the pH range of 3 to 4. The drug is unstable in dextrose 5% solutions above pH 5.5. Thoma and Struve reported a doubling of the decomposition rate (5% up to 10% in 200 days at room temperature) when the pH was increased from 2.5 to 4.5. Epinephrine hydrochloride is known to be alkali-labile and should not be mixed with alkaline drugs such as sodium bicarbonate and aminophylline. Mixing lidocaine hydrochloride with epinephrine hydrochloride may raise the solution pH to about 6, which will result in epinephrine decomposition within a few hours. Such mixtures should be used promptly. Lidocaine hydrochloride with epinephrine hydrochloride injection is often buffered with sodium bicarbonate to reduce pain upon injection. However, alkalinization may result in decomposition of the epinephrine. Larson et al., Stewart et al., Murakami et al, Bonhomme et al., and Tuleu et al. reported relatively rapid losses of epinephrine after alkalinization of epinephrine-containing lidocaine hydrochloride formulations. Robinson J, et al. reported substantial losses of epinephrine hydrochloride occurred after neutralization with sodium bicarbonate and recommended against alkalization of such solutions. Tuleu et al. buffered lidocaine hydrochloride with epinephrine 5 mcg/mL to around pH 7.5 to 8 with sodium bicarbonate. Stability-indicating HPLC analysis found no loss of lidocaine hydrochloride but nearly 30% loss of epinephrine in 6 hours at 24 degree C exposed to light. If kept in the dark, epinephrine losses were about 9% in 20 hours at 24 degree C. The authors recommended not preparing the buffered injection well in advance of use.Light Exposure
Epinephrine hydrochloride should be protected from exposure to light during long-term storage. Grunert and Wollman demonstrated the degradation induced by exposure to ultraviolet light, sunlight, daylight, and artificial light. The bisulfite antioxidant present in many formulations can markedly decrease the photostability of epinephrine making protection from sunlight even more important for long-term storage. Exposure to light will cause gradual drug decomposition. In a study by Newton et al. of epinephrine hydrochloride 4 mcg/mL in dextrose 5%, 10% epinephrine loss was calculated to occur in 50 hours exposed to light and 1000 hours protected from light at room temperature.Freezing
Wolf and Scherbel evaluated the stability of epinephrine hydrochloride (Suprarenin, Sanofi-Aventis) 0.1 mg/mL (1:10,000) and 0.01 mg/mL (10 mcg/mL, 1:100,000) in sodium chloride 0.9% packaged as prefilled syringes and stored frozen at -31 degree C for 7 weeks followed by 7 days at room temperature. HPLC analysis found no drug loss occurred in the 0.1 mg/mL concentration and less than 6% loss occurred in the 0.01 mg/mL concentration under the study conditions.Filtration
Pall reports that epinephrine hydrochloride 0.1 mg/mL underwent no loss due to filtration through a Supor membrane filter.Sorption Leaching
Epinephrine hydrochloride has not been found to undergo substantial sorption to polyvinyl chloride (PVC), polyolefin bags, polypropylene (in syringes), or glass containers. In addition, Xu et al. reported no sorption occurred to a polyurethane central catheter from Arrow International as well as no leaching of the chlorhexidine antimicrobial in it.Other Information
Lidocaine: Mixing lidocaine hydrochloride with epinephrine hydrochloride may raise the solution pH to about 6, which will result in epinephrine decomposition within a few hours. Such mixtures should be used promptly. Trace elements: Epinephrine hydrochloride is easily oxidized and should not be mixed with easily reducible metal salts such as those of copper, zinc, or iron. Multiple Drug Mixtures: Fentanyl citrate 0.00125 mg/mL (1.25 mcg/mL) has been reported by Allen et al. to be stable and compatible in combination with epinephrine hydrochloride 0.069 mg/mL (69 mcg/mL) and bupivacaine hydrochloride 0.44 mg/mL for 30 days at room temperature and refrigerated. Epinephrine hydrochloride losses were about 9 to 10% in 30 days. Bupivacaine hydrochloride and fentanyl citrate exhibited no loss in 30 days. Kjonniksen et al. reported the long-term stability of a similar three-drug analgesic mixture for epidural administration. The preparation contained fentanyl citrate 1.93 mcg/mL, bupivacaine hydrochloride 0.935 mg/mL, and epinephrine bitartrate 2.07 mcg/mL with sodium metabisulfite approximately 2 mcg/mL and disodium acetate approximately 0.2 mcg/mL in sodium chloride 0.9%. The formulation was prepared by first compounding a concentrate that was packaged in vials and autoclaved. This concentrate was then diluted 1/11 in 500 mL of sodium chloride 0.9% in polyolefin-lined Excel multi-layer bags. The bags were stored refrigerated at 2 to 8 degree C for 180 days followed by 4 days at room temperature of 22 degree C exposed to ambient laboratory illumination. No visible changes were reported. Stability-indicating HPLC analysis found none of the drugs exhibited changes in concentration greater than 4%. The authors concluded that this drug combination was stable and could be given a shelf life of 6 months under refrigeration based on the chemical stability.Stability Max
Maximum reported stability period: In D5W- 30 days under refrigeration and at room temperature protected from light.References
Adverse Reactions
Mild
- agitation
- anxiety
- diaphoresis
- dizziness
- drowsiness
- ecchymosis
- headache
- hyperactivity
- hypoesthesia
- infection
- injection site reaction
- insulin resistance
- nausea
- pallor
- paresthesias
- restlessness
- skin discoloration
- tremor
- vomiting
- weakness
Moderate
- angina
- chest pain (unspecified)
- corneal edema
- dyspnea
- erythema
- excitability
- hyperglycemia
- hypertension
- hypoglycemia
- hypokalemia
- memory impairment
- metabolic acidosis
- palpitations
- peripheral vasoconstriction
- premature ventricular contractions (PVCs)
- sinus tachycardia
- skin laceration
- supraventricular tachycardia (SVT)
Severe
- apnea
- arrhythmia exacerbation
- cardiomyopathy
- lactic acidosis
- myocardial infarction
- necrotizing fasciitis
- oliguria
- pulmonary edema
- stroke
- tissue necrosis
- ventricular fibrillation
- ventricular tachycardia
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]
References
Contraindications/Precautions
Absolute contraindications are italicized.
- closed-angle glaucoma
- breast-feeding
- cardiac disease
- cardiomyopathy
- cerebrovascular disease
- children
- coronary artery disease
- diabetes mellitus
- extravasation
- hypertension
- hyperthyroidism
- hypovolemia
- infants
- infection
- intraarterial administration
- labor
- obstetric delivery
- ophthalmic administration
- organic brain syndrome
- Parkinson's disease
- pheochromocytoma
- pregnancy
- renal disease
- shock
- sulfite hypersensitivity
- thyroid disease
- thyrotoxicosis
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 patients 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]
Prolonged experience with epinephrine use during human pregnancy does not identify a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, there are risks to the mother and fetus associated with epinephrine use during labor and obstetric delivery. In animal studies, subcutaneous epinephrine resulted in adverse developmental effects (e.g., gastroschisis, embryonic lethality, delayed skeletal ossification) when given during organogenesis at doses approximately 2 times the maximum recommended parenteral daily dose. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of epinephrine on the fetus. Delaying treatment in pregnant women with hypotension associated with septic shock may increase the risk of maternal and fetal morbidity and mortality.[56575] Epinephrine is the first-line medication of choice for the treatment of anaphylaxis and should be used during pregnancy in the same manner as it is used in non-pregnant patients.[54140] [56575] Although epinephrine can improve maternal hypotension associated with septic shock and anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia. Avoid use during the second stage of labor; epinephrine may cause a prolonged period of uterine atony with hemorrhage at dosages sufficient to reduce uterine contractions. Avoid use if the maternal blood pressure exceeds 130/80 mmHg.[56575] [60589]
There is no information regarding the presence of epinephrine in human milk or its effects on the breastfed infant or milk production. Epinephrine exposure is expected to be very low in the breastfed infant due to poor bioavailability and short half-life.[56575] Albuterol may be an alternative to inhaled epinephrine in a breast-feeding woman. According to the 2004 recommendations of the National Asthma Education and Prevention Program for managing asthma during pregnancy, there is no contraindication for the use of short-acting inhaled beta2-agonists, including albuterol, during lactation.[31822]
Epinephrine injection must be diluted 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 and corneal edema when used in the eye at undiluted concentrations (1 mg/mL).[60589]
Use epinephrine with caution in patients with Parkinson's disease. Patients with Parkinson's disease may experience psychomotor agitation or a temporary worsening of symptoms.[56575] [60589]
Use epinephrine cautiously in patients with renal disease. When administered intravenously, epinephrine may initially constrict the renal blood vessels resulting in a decrease in urine production. Renal insufficiency has been associated with intravenous infusion.[45416] [60589]
Lacerations, bent needles, and embedded needles have been reported when epinephrine has been injected into the thigh of infants or young children who are uncooperative and kick or move during an injection. To minimize the risk of injury, caregivers should be instructed to hold the leg of young children firmly in place and limit movement prior to and during injection.[57081] Safety and efficacy of non-prescription epinephrine for oral inhalation (e.g., Primatene Mist) has not been established in neonates, infants, or children less than 12 years of age.[63740]
References
Mechanism of Action
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: 07/22/2015, 09:57:20 PMReferences
Pharmacokinetics
Epinephrine 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
Route-Specific Pharmacokinetics
Intravenous Route
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]
Intramuscular Route
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]
Subcutaneous Route
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]
Inhalation Route
Bronchodilation occurs within 1 minute after administration of orally inhaled epinephrine.[54288][54328]
Other Route(s)
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]
Special Populations
Pediatrics
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]
Geriatric
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]
Obesity
Body weight influences epinephrine pharmacokinetics; higher body weight is associated with a lower concentration plateau and higher plasma clearance.[60589]
References
Pregnancy/Breast-feeding
labor, obstetric delivery, pregnancy
Prolonged experience with epinephrine use during human pregnancy does not identify a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. However, there are risks to the mother and fetus associated with epinephrine use during labor and obstetric delivery. In animal studies, subcutaneous epinephrine resulted in adverse developmental effects (e.g., gastroschisis, embryonic lethality, delayed skeletal ossification) when given during organogenesis at doses approximately 2 times the maximum recommended parenteral daily dose. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of epinephrine on the fetus. Delaying treatment in pregnant women with hypotension associated with septic shock may increase the risk of maternal and fetal morbidity and mortality.[56575] Epinephrine is the first-line medication of choice for the treatment of anaphylaxis and should be used during pregnancy in the same manner as it is used in non-pregnant patients.[54140] [56575] Although epinephrine can improve maternal hypotension associated with septic shock and anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia. Avoid use during the second stage of labor; epinephrine may cause a prolonged period of uterine atony with hemorrhage at dosages sufficient to reduce uterine contractions. Avoid use if the maternal blood pressure exceeds 130/80 mmHg.[56575] [60589]
breast-feeding
There is no information regarding the presence of epinephrine in human milk or its effects on the breastfed infant or milk production. Epinephrine exposure is expected to be very low in the breastfed infant due to poor bioavailability and short half-life.[56575] Albuterol may be an alternative to inhaled epinephrine in a breast-feeding woman. According to the 2004 recommendations of the National Asthma Education and Prevention Program for managing asthma during pregnancy, there is no contraindication for the use of short-acting inhaled beta2-agonists, including albuterol, during lactation.[31822]
References
Interactions
Level 1 (Severe)
- Isocarboxazid
- Monoamine oxidase inhibitors
- Phenelzine
- Tranylcypromine
Level 2 (Major)
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine
- Acetaminophen; Dextromethorphan; Pseudoephedrine
- Acetaminophen; Pseudoephedrine
- Acrivastine; Pseudoephedrine
- Ambrisentan
- Amobarbital
- Amoxapine
- Brompheniramine; Pseudoephedrine
- Brompheniramine; Pseudoephedrine; Dextromethorphan
- Butyrophenone
- Carbinoxamine; Dextromethorphan; Pseudoephedrine
- Carbinoxamine; Pseudoephedrine
- Cetirizine; Pseudoephedrine
- Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
- Chlorpheniramine; Dextromethorphan; Pseudoephedrine
- Chlorpheniramine; Ibuprofen; Pseudoephedrine
- Chlorpheniramine; Pseudoephedrine
- Cocaine
- Codeine; Guaifenesin; Pseudoephedrine
- Desloratadine; Pseudoephedrine
- Dexbrompheniramine; Pseudoephedrine
- Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
- Dextromethorphan; Guaifenesin; Pseudoephedrine
- Diethylpropion
- Dihydroergotamine
- Dinoprostone, Prostaglandin E2
- Epoprostenol
- Ergoloid Mesylates
- Ergonovine
- Ergot alkaloids
- Ergotamine
- Ergotamine; Caffeine
- Etomidate
- Fexofenadine; Pseudoephedrine
- Guaifenesin; Hydrocodone; Pseudoephedrine
- Guaifenesin; Pseudoephedrine
- Hydrocodone; Pseudoephedrine
- Ibuprofen; Pseudoephedrine
- Iloprost
- Iobenguane I 131
- Ionic Contrast Media
- Isoproterenol
- Levomilnacipran
- Linezolid
- Loratadine; Pseudoephedrine
- Loxapine
- Macitentan
- Mecamylamine
- Metaproterenol
- Methohexital
- Methylergonovine
- Milnacipran
- Naproxen; Pseudoephedrine
- Non-Ionic Contrast Media
- Ozanimod
- Paliperidone
- Phendimetrazine
- Phentermine
- Phentermine; Topiramate
- Procarbazine
- Propofol
- Pseudoephedrine
- Pseudoephedrine; Triprolidine
- Racepinephrine
- Reserpine
- Riociguat
- Risperidone
- Selexipag
- Sibutramine
- Terbutaline
- Treprostinil
- Tricyclic antidepressants
- Ziprasidone
Level 3 (Moderate)
- Acarbose
- Acebutolol
- Acetaminophen; Aspirin, ASA; Caffeine
- Acetaminophen; Aspirin; Diphenhydramine
- Acetaminophen; Caffeine
- Acetaminophen; Caffeine; Dihydrocodeine
- Acetaminophen; Caffeine; Pyrilamine
- Acetaminophen; Chlorpheniramine
- Acetaminophen; Chlorpheniramine; Dextromethorphan
- Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
- Acetaminophen; Chlorpheniramine; Phenylephrine
- Acetaminophen; Diphenhydramine
- Aclidinium; Formoterol
- Albiglutide
- Albuterol
- Aliskiren
- Aliskiren; Amlodipine
- Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ
- Aliskiren; Hydrochlorothiazide, HCTZ
- Aliskiren; Valsartan
- Alogliptin; Pioglitazone
- Alpha-blockers
- Alpha-glucosidase Inhibitors
- Amiloride
- Amiloride; Hydrochlorothiazide, HCTZ
- Amiodarone
- Amlodipine; Benazepril
- Amlodipine; Olmesartan
- Amlodipine; Valsartan
- Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ
- Amphetamines
- Angiotensin II receptor antagonists
- Angiotensin-converting enzyme inhibitors
- Arformoterol
- Aspirin, ASA; Butalbital; Caffeine
- Aspirin, ASA; Butalbital; Caffeine; Codeine
- Aspirin, ASA; Caffeine
- Aspirin, ASA; Caffeine; Orphenadrine
- Atenolol
- Atenolol; Chlorthalidone
- Atomoxetine
- Azelastine; Fluticasone
- Azilsartan
- Azilsartan; Chlorthalidone
- Beclomethasone
- Benazepril
- Benazepril; Hydrochlorothiazide, HCTZ
- Bendroflumethiazide; Nadolol
- Beta-blockers
- Betamethasone
- Betaxolol
- Bethanechol
- Bisoprolol
- Bisoprolol; Hydrochlorothiazide, HCTZ
- Bretylium
- Brimonidine; Timolol
- Bromocriptine
- Budesonide
- Budesonide; Formoterol
- Budesonide; Glycopyrrolate; Formoterol
- Bumetanide
- Butalbital; Acetaminophen; Caffeine
- Butalbital; Acetaminophen; Caffeine; Codeine
- Caffeine
- Caffeine; Sodium Benzoate
- Calcium-channel blockers
- Canagliflozin
- Canagliflozin; Metformin
- Candesartan
- Candesartan; Hydrochlorothiazide, HCTZ
- Captopril
- Captopril; Hydrochlorothiazide, HCTZ
- Carbidopa; Levodopa; Entacapone
- Cardiac glycosides
- Carteolol
- Carvedilol
- Chlorothiazide
- Chlorpheniramine
- Chlorpheniramine; Codeine
- Chlorpheniramine; Dextromethorphan
- Chlorpheniramine; Dextromethorphan; Phenylephrine
- Chlorpheniramine; Dihydrocodeine; Phenylephrine
- Chlorpheniramine; Hydrocodone
- Chlorpheniramine; Phenylephrine
- Chlorpromazine
- Chlorthalidone
- Chlorthalidone; Clonidine
- Ciclesonide
- Class IA Antiarrhythmics
- Class IB Antiarrhythmics
- Clonidine
- Clozapine
- Codeine; Phenylephrine; Promethazine
- Codeine; Promethazine
- COMT inhibitors
- Corticosteroids
- Cortisone
- Dapagliflozin
- Dapagliflozin; Metformin
- Dapagliflozin; Saxagliptin
- Deflazacort
- Desflurane
- Dexamethasone
- Dextromethorphan; Diphenhydramine; Phenylephrine
- Dextromethorphan; Quinidine
- Dichlorphenamide
- Digitoxin
- Digoxin
- Dipeptidyl Peptidase-4 Inhibitors
- Diphenhydramine
- Diphenhydramine; Ibuprofen
- Diphenhydramine; Naproxen
- Diphenhydramine; Phenylephrine
- Disopyramide
- Dobutamine
- Dofetilide
- Dopamine
- Dorzolamide; Timolol
- Doxapram
- Doxazosin
- Dronabinol
- Dronedarone
- Dulaglutide
- Dyphylline
- Dyphylline; Guaifenesin
- Empagliflozin
- Empagliflozin; Linagliptin
- Empagliflozin; Linagliptin; Metformin
- Empagliflozin; Metformin
- Enalapril, Enalaprilat
- Enalapril; Felodipine
- Enalapril; Hydrochlorothiazide, HCTZ
- Entacapone
- Eplerenone
- Eprosartan
- Eprosartan; Hydrochlorothiazide, HCTZ
- Ertugliflozin
- Ertugliflozin; Metformin
- Ertugliflozin; Sitagliptin
- Esmolol
- Ethacrynic Acid
- Exenatide
- Fludrocortisone
- Flunisolide
- Fluphenazine
- Fluticasone
- Fluticasone; Salmeterol
- Fluticasone; Umeclidinium; Vilanterol
- Fluticasone; Vilanterol
- Formoterol
- Formoterol; Mometasone
- Fosinopril
- Fosinopril; Hydrochlorothiazide, HCTZ
- Furosemide
- Glimepiride; Rosiglitazone
- Glycopyrrolate; Formoterol
- Green Tea
- Guanabenz
- Guanfacine
- Hydralazine; Hydrochlorothiazide, HCTZ
- Hydrochlorothiazide, HCTZ
- Hydrochlorothiazide, HCTZ; Methyldopa
- Hydrochlorothiazide, HCTZ; Moexipril
- Hydrocortisone
- Ibutilide
- Incretin Mimetics
- Indacaterol
- Indacaterol; Glycopyrrolate
- Indapamide
- Insulin Degludec; Liraglutide
- Insulin Glargine; Lixisenatide
- Insulins
- Ipratropium; Albuterol
- Irbesartan
- Irbesartan; Hydrochlorothiazide, HCTZ
- Isoflurane
- Ketamine
- Labetalol
- Levalbuterol
- Levobetaxolol
- Levobunolol
- Levothyroxine
- Levothyroxine; Liothyronine (Porcine)
- Levothyroxine; Liothyronine (Synthetic)
- Liothyronine
- Liraglutide
- Lisinopril
- Lisinopril; Hydrochlorothiazide, HCTZ
- Lixisenatide
- Loop diuretics
- Losartan
- Losartan; Hydrochlorothiazide, HCTZ
- Maprotiline
- Meglitinides
- Meperidine; Promethazine
- Metformin; Rosiglitazone
- Methyclothiazide
- Methyldopa
- Methylphenidate Derivatives
- Methylprednisolone
- Metolazone
- Metoprolol
- Metoprolol; Hydrochlorothiazide, HCTZ
- Miglitol
- Moexipril
- Mometasone
- Nabilone
- Nadolol
- Nebivolol
- Nebivolol; Valsartan
- Nicotine
- Nitrates
- Olanzapine
- Olanzapine; Fluoxetine
- Olanzapine; Samidorphan
- Olmesartan
- Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ
- Olmesartan; Hydrochlorothiazide, HCTZ
- Olopatadine; Mometasone
- Opicapone
- Oxytocin
- Penbutolol
- Perindopril
- Perindopril; Amlodipine
- Perphenazine
- Perphenazine; Amitriptyline
- Phenothiazines
- Phenoxybenzamine
- Phentolamine
- Pindolol
- Pioglitazone
- Pioglitazone; Glimepiride
- Pioglitazone; Metformin
- Potassium-sparing diuretics
- Pramlintide
- Prazosin
- Prednisolone
- Prednisone
- Procainamide
- Prochlorperazine
- Promethazine
- Promethazine; Dextromethorphan
- Promethazine; Phenylephrine
- Propranolol
- Propranolol; Hydrochlorothiazide, HCTZ
- Quinapril
- Quinapril; Hydrochlorothiazide, HCTZ
- Quinidine
- Ramipril
- Rasagiline
- Rosiglitazone
- Sacubitril; Valsartan
- Safinamide
- Salmeterol
- Selegiline
- Semaglutide
- Sevoflurane
- SGLT2 Inhibitors
- Solriamfetol
- Sotalol
- Spironolactone
- Spironolactone; Hydrochlorothiazide, HCTZ
- St. John's Wort, Hypericum perforatum
- Sulfonylureas
- Telmisartan
- Telmisartan; Amlodipine
- Telmisartan; Hydrochlorothiazide, HCTZ
- Terazosin
- Theophylline, Aminophylline
- Thiazide diuretics
- Thiazolidinediones
- Thiethylperazine
- Thioridazine
- Thiothixene
- Thyroid hormones
- Timolol
- Tirzepatide
- Tolcapone
- Torsemide
- Trandolapril
- Trandolapril; Verapamil
- Triamcinolone
- Triamterene
- Triamterene; Hydrochlorothiazide, HCTZ
- Trifluoperazine
- Umeclidinium; Vilanterol
- Valsartan
- Valsartan; Hydrochlorothiazide, HCTZ
- Vasodilators
Level 4 (Minor)
- Colchicine
- Desmopressin
- Ginger, Zingiber officinale
- Probenecid; Colchicine
References
Monitoring Parameters
- blood pressure
- heart rate
- pulmonary function tests (PFTs)
US Drug Names
- Adrenaclick
- Adrenalin
- Auvi-Q
- Epifrin
- EpiPen
- Epipen Jr
- Primatene Mist
- SYMJEPI
- Twinject
