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Nov.20.2020

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

  • anaphylactic shock
  • bradycardia
  • cardiogenic shock
  • chloroquine overdose
  • epistaxis
† Off-label indication

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

Intermittent Intravenous or Intraosseus† dosage

Adults

1 mg (10 mL of a 0.1 mg/mL solution) IV or IO; may repeat every 3 to 5 minutes. 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).[45649] [60266]

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/dose 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 or IO; 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

Adults

2 to 2.5 mg (i.e., 2 to 2.5 times the IV dose) ET; may repeat every 3 to 5 minutes until vascular access obtained. Dilute dose in 5 to 10 mL of Sterile Water for Injection or 0.9% Sodium Chloride Injection. Do not interrupt CPR to administer drug therapy.[45649] [60266]

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]

Intracardiac dosage†

Adults

0.3 to 0.5 mg intracardially.[32537]

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]

Infants†, Children†, and Adolescents†

0.1 to 1 mcg/kg/minute continuous IV or IO infusion may be used to maintain cardiac output and/or stabilize the patient after resuscitation. Titrate to desired effect. There is great interpatient variability in response. In general, low-dose infusions (less than 0.3 mcg/kg/minute) generally produce beta-adrenergic effects (tachycardia, inotropy, decreased systemic vascular resistance), while higher-dose infusions (more than 0.3 mcg/kg/minute) cause alpha-adrenergic vasoconstriction.[43713] [60636]

Neonates†

0.1 to 1 mcg/kg/minute continuous IV or IO infusion may be used to maintain cardiac output and/or stabilize the patient after resuscitation. Titrate to desired effect. There is great interpatient variability in response. In general, low-dose infusions (less than 0.3 mcg/kg/minute) generally produce beta-adrenergic effects (tachycardia, inotropy, decreased systemic vascular resistance), while higher-dose infusions (more than 0.3 mcg/kg/minute) cause alpha-adrenergic vasoconstriction.[43713] [60636]

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, anaphylactic shock†, cardiogenic shock†)

Intravenous dosage

Adults

0.05 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. After hemodynamic stabilization, wean incrementally by decreasing the infusion rate every 10 to 30 minutes.[56575] [60589] Septic shock guidelines recommend adding epinephrine to norepinephrine and potentially substituting for norepinephrine to raise the mean arterial pressure (MAP). Target a MAP of 65 mmHg initially. Titrate to an endpoint reflecting perfusion; reduce rate or discontinue the vasopressor if worsening hypotension or arrhythmias occur.[61770]

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] [60636] [64934]

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] [60636] [64934]

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 topical dosage

Adults

Apply 1% solution topically to nasal area as drops, spray, or with a sterile swab. See manufacturer's product literature for specifics of dilution and use.[46634]

Children and Adolescents 6 to 17 years

Apply 1% solution topically to nasal area as drops, spray, or with a sterile swab. See manufacturer's product literature for specifics of dilution and use.[46634]

Infants and Children younger than 6 years

Apply 1% solution topically to nasal area as drops, spray, or with a sterile swab. See manufacturer's product literature for specifics of dilution and use. Use with caution and only under prescriber supervision due to greater sensitivity to sympathomimetic effects in this population.[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 indication
Revision Date: 11/20/2020, 04:40:37 PM

References

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Circulation 2010;122 (suppl 3):S909-19.45649 - Neumar RW, Otto CW, Link MS, et al. Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S729-S767.46634 - Adrenalin (epinephrine) nasal solution package insert. Chestnut Ridge, NY; Par Pharmaceutical: 2018 Mar.52326 - Kattwinkel J, ed. Textbook of neonatal resuscitation. 6th ed. American Academy of Pediatrics and American Heart Association; 2010.54140 - EpiPen (epinephrine injection) package insert. Morgantown, WV: Mylan Specialty L.P..; 2020 Dec.54245 - Rosekrans JA. Viral croup: current diagnosis and treatment. Mayo Clin Proc 1998;73:1102-1107.54247 - Rotta AT, Wiryawan B. Respiratory emergencies in children. Respir Care 2003;48:248-258.54249 - Wright RB, Pomerantz WJ, Luria JW. New approaches to respiratory infections in children: bronchiolitis and croup. Emerg Med Clin North Am 2002;20:93-114.54250 - Waisman Y, Klein BL, Boenning DA. Prospective randomized double-blind study comparing l-epinephrine and racemic epinephrine aerosols in the treatment of laryngotracheitis (croup). Pediatrics 1992;89:302-306.54254 - Lieberman P, Nicklas RA, Oppenheimer J. The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010;126:477-480.54255 - Kemp SF, Lockey RF, Simons FE. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy 2008;63:1061-1070.54257 - Auvi-Q (epinephrine injection) auto-injector. Richmond, VA: Kaleo, Inc.;2019 Sept.54288 - Pharmacology. In: Pediatric Advanced Life Support Provider Manual. Chameides L, Samson RA, Schexnayder SM, (eds.) United States of America: American Heart Association; 2011:199-232.54293 - Sicherer SH, Simons ER. Self-injectable epinephrine for first-aid management of anaphylaxis. Pediatrics 2007;119:638-646.56575 - Adrenalin (epinephrine) 1 mg/mL injection package insert. Chestnut Ridge, NJ: Par Pharmaceutical Companies, Inc.; 2019 Jan.57081 - Adrenaclick (epinephrine injection) package insert. Bridgewater, NJ: Amneal Pharmaceuticals LLC. 2021 Feb.59632 - Toward Optimized Practice (TOP) Working Group for Croup. Guideline for the diagnosis and management of croup. Edmonton (AB): Toward Optimized Practice;2003 (revised 2014). Accessed on the World Wide Web: www.topalbertadoctors.org/download/252/croup_guideline.pdf May 15, 2015.60266 - Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S444-64.60589 - Epinephrine 1 mg/mL injection package insert. Largo, FL: Belcher Pharmaceuticals, LLC; 2017 Feb.60636 - de Caen AR, Berg MD, Chameides L. Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S526-S542.61541 - Wyckoff MH, Aziz K, Escobedo MB, et al. Part 13: Neonatal resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132 (suppl 2):S543-S560.61770 - Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med 2017;45:486-552.62025 - Symjepi (epinephrine injection) package insert. San Diego, CA: Adamis Pharmaceuticals; 2019 Ma.63412 - Marino BS, Tabutt S, MacLaren G, et al. Cardiopulmonary resuscitation in infants and children with cardiac disease: a scientific statement from the American Heart Association. Circulation 2018;137:e691-e782.63740 - Primatene Mist (epinephrine aerosol spray) package insert. Canton, MA: Armstrong Pharmaceuticals Inc. 2018 Nov.63867 - Kusumoto FM, Schoenfeld MH, Barret C, et al. 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay. Circulation 2019;140:e382-e482.64807 - Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org. Accessed May 20th, 2020.64934 - Shenoi RP, Timm N, AAP Committee on Drugs, AAP Committee on Emergency Medicine. Drugs used to treat pediatric emergencies. Pediatrics 2020;145:e20193450.65040 - Tunkel DE, Anne S, Payne SC, et al. Clinical practice guideline: nosebleed (epistaxis). Otolaryngol Head Neck Surg 2020;162:S1-S38.65041 - Smith J, Hanson J, Chowdhury R, et al. Community-based management of epistaxis: Who bloody knows? Can Pharm J (Ott) 2019;152:164-176.65042 - Womack JP, Kropa J, Jimenez Stabile M. Epistaxis: outpatient management. Am Fam Physician 2018;98:240-245.

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)Adrenalin 1mg/mL Nasal Solution package photo

Epinephrine Hydrochloride Nasal spray, solution

Adrenalin 1mg/mL Nasal Solution (42023-0103) (Par Pharmaceuticals, an Endo Company) null

Epinephrine Hydrochloride Nasal spray, solution

Adrenalin 1mg/mL Nasal Solution (61570-0300) (Par Pharmaceuticals, an Endo Company) (off market)

Epinephrine 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)Epifrin 1% Ophthalmic Solution package photo

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 Solution for Injection (00074-4901) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:10,000 Solution for Injection (00409-4901) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:10,000 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 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 Solution for Injection (00548-3316) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)Epinephrine Hydrochloride 1:10,000 Solution for Injection package photo

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:10,000 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 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 Solution for Injection (63739-0456) (McKesson Packaging Inc) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:10,000 Solution for Injection (LifeShield) (00074-4921) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:10,000 Solution for Injection (LifeShield) (00409-4921) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 Solution for Injection (00517-1071) (American Regent Inc, a division of Luitpold Pharmaceuticals) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 Solution for Injection (00517-1130) (American Regent Inc, a division of Luitpold Pharmaceuticals) (off market)Epinephrine Hydrochloride 1:1000 Solution for Injection package photo

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 Solution for Injection (00517-1061) (American Regent Inc, a division of Luitpold Pharmaceuticals) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 Solution for Injection (00143-9984) (Hikma Pharmaceuticals USA Inc.) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 Solution for Injection (00409-7241) (Hospira Worldwide, Inc., a Pfizer Company) (off market)Epinephrine Hydrochloride 1:1000 Solution for Injection package photo

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 Solution for Injection (00074-7241) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 Solution for Injection (76329-9061) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) (off market)Epinephrine Hydrochloride 1:1000 Solution for Injection package photo

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 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 Solution for Injection (63739-0467) (McKesson Packaging Inc) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine Hydrochloride 1:1000 Solution for Injection (NOVAPLUS) (00409-7241) (Hospira Worldwide, Inc., a Pfizer Company) (off market)

Epinephrine Hydrochloride Solution for injection

Epinephrine 1mg/10mL (0.1mg/1mL) Solution for Injection (76329-3316) (International Medication Systems, Ltd a Division Amphastar Pharmaceuticals Inc) null

Epinephrine Hydrochloride Solution for injection

Epinephrine 1mg/10mL (0.1mg/mL) Solution for Injection (LifeShield) (00409-4921) (Hospira Worldwide, Inc., a Pfizer Company) null

Epinephrine Hydrochloride Solution for injection

Epinephrine 1mg/10mL (0.1mg/mL) Solution for Injection (LifeShield) (00409-4933) (Hospira Worldwide, Inc., a Pfizer Company) null

Epinephrine 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 (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) null

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 (42023-0159) (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) (off market)

Epinephrine Hydrochloride Solution for injection

Adrenalin 30mg/30mL Solution for Injection (42023-0168) (Par Pharmaceuticals, an Endo Company) null

Epinephrine Hydrochloride Solution for injection

Adrenalin 30mg/30mL Solution for Injection (NOVAPLUS) (42023-0168) (Par Pharmaceuticals, an Endo Company) null

Epinephrine Hydrochloride Solution for injection

Adrenalin 30mg/30mL Solution for Injection (PREMIER ProRx) (42023-0168) (Par Pharmaceuticals, an Endo Company) null

Epinephrine Hydrochloride Solution for injection

Epinephrine 1mg/mL Solution for Injection (54288-0103) (BPI Labs) null

Epinephrine Hydrochloride Solution for injection

Epinephrine 1mg/mL Solution for Injection (71266-8110) (Fagron Compounding Services dba Fagron Sterile Services LLC dba JCB Laboratories) null

Epinephrine 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) null

Epinephrine 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) null

Epinephrine 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.) null

Epinephrine 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) nullWalgreens Bronchial Mist 0.22mg/actuation Inhalation Aerosol package photo

Epinephrine Pressurized inhalation, solution

Walgreens Bronchial Mist 0.22mg/actuation Inhalation Aerosol (Refill) (00363-5046) (Walgreens Co) nullWalgreens Bronchial Mist 0.22mg/actuation Inhalation Aerosol (Refill) package photo

Epinephrine Solution for injection

Auvi-Q 2-Pack Auto-Injector 0.1mg/0.1mL Solution for Injection (60842-0021) (Kaleo, Inc.) 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) null

Epinephrine Solution for injection

Auvi-Q 2-Pack Auto-Injector 0.15mg/0.15mL Solution for Injection (60842-0022) (Kaleo, Inc.) null

Epinephrine Solution for injection

Auvi-Q 2-Pack Auto-Injector 0.15mg/0.15mL Solution for Injection (00024-5831) (Sanofi U.S. LLC) (off market)Auvi-Q 2-Pack Auto-Injector 0.15mg/0.15mL Solution for Injection package photo

Epinephrine Solution for injection

Epinephrine 0.15mg/0.15ml Auto-Injector Solution for Injection (59762-0172) (Greenstone Ltd) null

Epinephrine Solution for injection

Epinephrine 0.15mg/0.15ml Auto-Injector Solution for Injection (54505-0101) (Lineage Therapeutics) nullEpinephrine 0.15mg/0.15ml Auto-Injector Solution for Injection package photo

Epinephrine Solution for injection

Epinephrine 0.15mg/0.15mL Auto-Injector Solution for Injection (00115-1695) (Impax Generics, a division of Impax Laboratories, Inc.) nullEpinephrine 0.15mg/0.15mL Auto-Injector Solution for Injection package photo

Epinephrine Solution for injection

Epinephrine 2-Pack Auto-Injector 0.15mg/0.3mL Solution for Injection (49502-0101) (Mylan Specialty L.P.) nullEpinephrine 2-Pack Auto-Injector 0.15mg/0.3mL Solution for Injection package photo

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

Epipen Jr 2-Pack Auto-Injector 0.15mg/0.3mL Solution for Injection (49502-0501) (Mylan Specialty L.P.) nullEpipen Jr 2-Pack Auto-Injector 0.15mg/0.3mL Solution for Injection package photo

Epinephrine Solution for injection

Epipen Jr Auto-Injector 0.15mg/0.3ml Solution for Injection (49502-0501) (Mylan Specialty L.P.) (off market)Epipen Jr Auto-Injector 0.15mg/0.3ml Solution for Injection package photo

Epinephrine Solution for injection

SYMJEPI 0.15mg/0.3mL Solution for Injection (00781-3448) (Sandoz Inc. a Novartis Company) null

Epinephrine Solution for injection

SYMJEPI 0.15mg/0.3mL Solution for Injection (78670-0131) (USWM, LLC) null

Epinephrine Solution for injection

Twinject 0.15mg/0.15ml Auto Injector Solution For Injection (13436-0701) (Shionogi USA, Inc.) (off market)Twinject 0.15mg/0.15ml Auto Injector Solution For Injection package photo

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)Twinject 0.15mg/0.15ml Auto Injector Solution For Injection package photo

Epinephrine 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) null

Epinephrine Solution for injection

Auvi-Q 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (60842-0023) (Kaleo, Inc.) null

Epinephrine Solution for injection

Auvi-Q 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (00024-5833) (Sanofi U.S. LLC) (off market)Auvi-Q 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection package photo

Epinephrine Solution for injection

Epinephrine 0.3mg/0.3ml Auto-Injector Solution For Injection (42291-0425) (AvKARE, Inc.) null

Epinephrine Solution for injection

Epinephrine 0.3mg/0.3ml Auto-Injector Solution For Injection (59762-0171) (Greenstone Ltd) nullEpinephrine 0.3mg/0.3ml Auto-Injector Solution For Injection package photo

Epinephrine Solution for injection

Epinephrine 0.3mg/0.3ml Auto-Injector Solution For Injection (54505-0102) (Lineage Therapeutics) nullEpinephrine 0.3mg/0.3ml Auto-Injector Solution For Injection package photo

Epinephrine Solution for injection

Epinephrine 0.3mg/0.3mL Auto-Injector Solution For Injection (00115-1694) (Impax Generics, a division of Impax Laboratories, Inc.) nullEpinephrine 0.3mg/0.3mL Auto-Injector Solution For Injection package photo

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 0.3mg/0.3mL Solution for Injection (49502-0102) (Mylan Specialty L.P.) nullEpinephrine 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection package photo

Epinephrine Solution for injection

Epinephrine 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (00093-5986) (Teva Pharmaceuticals USA) nullEpinephrine 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection package photo

Epinephrine Solution for injection

Epipen 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection (49502-0500) (Mylan Specialty L.P.) nullEpipen 2-Pack Auto-Injector 0.3mg/0.3mL Solution for Injection package photo

Epinephrine Solution for injection

Epipen Auto-Injector 0.3mg/0.3ml Solution for Injection (49502-0500) (Mylan Specialty L.P.) (off market)Epipen Auto-Injector 0.3mg/0.3ml Solution for Injection package photo

Epinephrine Solution for injection

SYMJEPI 0.3mg/0.3mL Solution for Injection (00781-3442) (Sandoz Inc. a Novartis Company) null

Epinephrine Solution for injection

SYMJEPI 0.3mg/0.3mL Solution for Injection (78670-0130) (USWM, LLC) null

Epinephrine Solution for injection

Twinject 0.3mg/0.3ml Auto Injector Solution For Injection (13436-0700) (Shionogi USA, Inc.) (off market)Twinject 0.3mg/0.3ml Auto Injector Solution For Injection package photo

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)Twinject 0.3mg/0.3ml Auto Injector Solution For Injection package photo

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][61770][66053][66054] 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
    • Vasopressors
  • 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
    • Nasal Agents
      • Topical Nasal Decongestants
  • Sensory Organs
    • Ophthalmologicals
      • Mydriatics and Cycloplegics
Revision Date: 01/27/2021, 04:24:44 PM

References

43713 - Kleinman ME, Chameides L, Schexnayder SM, et al. Part 14: pediatric advanced life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122:S876-90845649 - Neumar RW, Otto CW, Link MS, et al. Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S729-S767.54334 - Lymperopoulos A, Koch WJ. Autonomic Pharmacology. In: Waldman SA, Hamilton SM, eds. Pharmacology and therapeutics: principles to practice. 1st ed. Philadelphia, PA;2009:115-139.54335 - Overgaard CB, Dzavik V. Inotropes and vasopressors: review of physiology and clinical use in cardiovascular disease. Circulation 2008;118:1047-1056.58442 - Ralson SL, Lieberthal AS, Meissner HC. Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics 2014;134:e1474-1502.59632 - Toward Optimized Practice (TOP) Working Group for Croup. Guideline for the diagnosis and management of croup. Edmonton (AB): Toward Optimized Practice;2003 (revised 2014). Accessed on the World Wide Web: www.topalbertadoctors.org/download/252/croup_guideline.pdf May 15, 2015.61770 - Rhodes A, Evans LE, Alhazzani W, et al. Surviving Sepsis Campaign: International Guidelines for Management of Sepsis and Septic Shock: 2016. Crit Care Med 2017;45:486-552.63867 - Kusumoto FM, Schoenfeld MH, Barret C, et al. 2018 ACC/AHA/HRS guideline on the evaluation and management of patients with bradycardia and cardiac conduction delay. Circulation 2019;140:e382-e482.64807 - Global Strategy for Asthma Management and Prevention. Global Initiative for Asthma (GINA) 2020. Available from: http://www.ginasthma.org. Accessed May 20th, 2020.64934 - Shenoi RP, Timm N, AAP Committee on Drugs, AAP Committee on Emergency Medicine. Drugs used to treat pediatric emergencies. Pediatrics 2020;145:e20193450.65559 - Smith N, Lopez RA, Silberman M. Distributive shock. [Updated 2020 Apr 24]. In: StatPearls [Internet]. Treasure Island, FL: StatPearls Publishing; 2020 Jan.66053 - Topjian AA, Raymond TT, Atkins D, et al. Part 4: Pediatric Basic and Advanced Life Support: 2020 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2020;142:S469-S523.66054 - Panchal AR, Bartos JA, Cabanas JG, et al. Part 3: Adult Basic and Advanced Cardiovascular Life Support: 2020 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2020;142:S366-S468.66106 - Shaker MS, Wallace DV, Golden DB, et al. Anaphylaxis - a 2020 practice parameter update, systematic review, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) analysis. J Allergy Clin Immunol 2020;145:1082-1123.66299 - Expert Panel Working Group of the National Heart, Lung, and Blood Institute (NHLBI) administered and coordinated National Asthma Education and Prevention Program Coordinating Committee (NAEPPCC), et al. 2020 Focused Updates to the Asthma Management Guidelines: A Report from the National Asthma Education and Prevention Program Coordinating Committee Expert Panel Working Group. J Allergy Clin Immunol. 2020;146:1217-1270.

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 Database

Epinephrine hydrochloride

pH Range
pH 2.2 to 5
ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
ReferencesEpiPen (Epinephrine) injection package insert. Morgantown, WV. Mylan Specialty L.P.. 2020; Dec
Osmolality/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.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
ReferencesBretschneider H. Osmolalities of commercially supplied drugs often used in anesthesia. Anesth Analg. 1987; 66
ReferencesErnst JA, Williams JM, Glick MR, et al. Osmolality of substances used in the intensive care nursery. Pediatrics. 1983; 72
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.
ReferencesAllegra JR, Brennan J, Lanier V, et al. Storage temperatures of out-of-hospital medications. Acad Emerg Med. 1999; 6
ReferencesBarab H, Schwedt G. Identifizerung von epinephrin (adrenalin) zersetzungprodukten in infusionlosungen mittels HPLC und multidetektion. Pharmazie. 1993; 48
ReferencesBrown LH, Bailey LC, Medwick T, et al. Medication storage on US ambulances: a prospective multi-center observational study. Pharm Forum. 2003; 29
ReferencesChurch WH, Hu SS, Henry AJ. Thermal degradation of injectable epinephrine. Am J Emerg Med. 1994; 12
ReferencesConnors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals, A handbook for pharmacists. New York: John Wiley & Sons, 1986. 1986;
ReferencesDe Winter S, Vanbrabant P, Tuong VI NT, et al. Impact of temperature exposure on stability of drugs in a real-world out-of-hospital setting. Ann Emerg Med. 2013; 62
ReferencesDolder R. Redox systems in pharmacy. Pharm Acta Helv. 1952; 27
ReferencesDonnelly RF, Yen M. Epinephrine stability in plastic syringes and glass vials. Can J Hosp Pharm. 1996; 49
ReferencesGammon DL, Su S, Huckfeldt R, et al. Alteration in prehospital drug concentration after thermal exposure. Am J Emerg Med. 2008; 26
ReferencesGill MA, Kislik AZ, Goree L, et al. Stability of advanced life support drugs in the field. Am J Health-Syst Pharm. 2004; 61
ReferencesGrant TA, Carroll RG, Church WH, et al. Environmental temperature variations cause degradations in epinephrine concentration and biological activity. Am J Emerg Med. 1994; 12
ReferencesGrunert R, Wollman H. Effect of ultraviolet, visible light on drugs of the phenylalkylamine series with a view toward their stability in plastic containers. Pharmazie. 1982; 37
ReferencesHoellein L, Holzgrabe U. Ficts and facts of epinephrine and norepinephrine stability in injectable solutions. Int J Pharm. 2012; 434
ReferencesKerddonfak S, Manuyakorn W, Kamchaisatian W, et al. The stability and sterility of epinephrine prefilled syringe. Asian Pac J Allergy Immunol. 2010; 28
ReferencesKuselman I, Schumacher I, Pennecchi F, et al. Long-term stability study of drug products and out-of-specificatio test results. Accred Qual Assur. 2011; 16
ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
ReferencesNewton DW, Fung EYY, Williams DA. Stability of five catecholamines and terbutaline sulfate in 5% dextrose injection in the absence and presence of aminophylline. Am J Hosp Pharm. 1981; 38
ReferencesPalmer RG, Zimmerman J, Brown PC. Altered states. The influence of temperature on prehospital drugs. JEMS: J Emerg Med Serv. 1985; 10
ReferencesPatterson MJ, Tjokrosetio R, Hett KF. Stability of adrenaline injection BP following sterilization. Austral J Hosp Pharm. 1981; 11
ReferencesRawas-Qalaji M, Simons FER, Collins D, et al. Long-term stability of epinephrine dispensed in unsealed syringes for the first-aid treatment of anaphylaxis. Ann Allergy Asthma Immunol. 2009; 102
ReferencesRudland SV, Annus T, Dickinson J, et al. Adrenaline degradation in general practice. Br J Gen Pract. 1997; 47
ReferencesThoma K, Struve M. Untersuchungen zur photo- und thermostatbilitat von adrenalin-losungen. Pharm Acta Helv. 1986; 61
ReferencesWolf L, Scherbel C. Adrenalin- und Noradrenalin- Verdunnungen. Krankenhauspharmazie. 2011; 32
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.
ReferencesConnors KA, Amidon GL, Stella VJ. Chemical stability of pharmaceuticals, A handbook for pharmacists. New York: John Wiley & Sons, 1986. 1986;
ReferencesHoellein L, Holzgrabe U. Ficts and facts of epinephrine and norepinephrine stability in injectable solutions. Int J Pharm. 2012; 434
ReferencesLarson PO, Ragi G, Swandby M, et al. Stability of buffered lidocaine and epinephrine used for local anesthesia. J Dermatol Surg Oncol. 1991; 17
ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
ReferencesMurakami CS, Odland PB, Ross BK. Buffered local anesthetics and epinephrine degradation. J Dermatol Surg Oncol. 1994; 20
ReferencesNewton DW, Fung EYY, Williams DA. Stability of five catecholamines and terbutaline sulfate in 5% dextrose injection in the absence and presence of aminophylline. Am J Hosp Pharm. 1981; 38
ReferencesParker EA. Compatibility Digest: Xylocaine hydrochloride 2% injection. Am J Hosp Pharm. 1971; 28
ReferencesParker EA. Parenteral incompatibilities. Hosp Pharm. 1969; 4
ReferencesRobinson J, Fernando R, Sun Wai WYS, et al. Chemical stability of bupivacaine, lidocaine and epinephrine in pH-adjusted solutions. Anaesthesia. 2000; 55
ReferencesStewart JH, Cole GW, Klein JA. Neutralized lidocaine with epinephrine for local anesthesia. J Dermatol Surg Oncol. 1989; 15
ReferencesThoma K, Struve M. Untersuchungen zur photo- und thermostatbilitat von adrenalin-losungen. Pharm Acta Helv. 1986; 61
ReferencesTuleu C, Allam J, Gill H, et al. Short term stability of pH-adjusted lidocaine-adrenaline epidural solution used for emergency caesarean section. Int J Obstet Anesth. 2008; 17
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.
ReferencesAnon. Manufacturer's information and labeling. (Package insert).
ReferencesBrustugun J, Kristensen S, Hjorth Tonnesen H. Photostability of epinephrine - the influence of bisulfite and degradation products. Pharmazie. 2004; 59
ReferencesBrustugun J, Kristensen S, Hjorth Tonnesen H. Photostability of sympathomimetic agents in commonly used infusion media in the absence and presence of bisulfite. PDA J Pharm Sci Tech. 2004;
ReferencesBrustugun J, Tonnesen HH, Klem W, et al. Photodestabilization of epinephrine by sodium bisulfite. PDA J Pharm Sci Tech. 2000; 54
ReferencesGrunert R, Wollman H. Effect of ultraviolet, visible light on drugs of the phenylalkylamine series with a view toward their stability in plastic containers. Pharmazie. 1982; 37
ReferencesHoellein L, Holzgrabe U. Ficts and facts of epinephrine and norepinephrine stability in injectable solutions. Int J Pharm. 2012; 434
ReferencesNewton DW, Fung EYY, Williams DA. Stability of five catecholamines and terbutaline sulfate in 5% dextrose injection in the absence and presence of aminophylline. Am J Hosp Pharm. 1981; 38
ReferencesSanchez-Quiles I, Najera-Perez MD, Espuny-Miro A, et al. Revision de la estabilidad de los medicamentos fotosensibles [Review of the stability of photosensitive medications]. Farm Hosp. 2010;
ReferencesWollman H, Grunert R. The effect of visible light on the stability of isoprenaline, epinephrine, and levarenol solutions in various containers. Pharmazie. 1984; 39
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.
ReferencesWolf L, Scherbel C. Adrenalin- und Noradrenalin- Verdunnungen. Krankenhauspharmazie. 2011; 32
Filtration
Pall reports that epinephrine hydrochloride 0.1 mg/mL underwent no loss due to filtration through a Supor membrane filter.
ReferencesAnon. Pall Medical Supor-membrane IV filter device drug-adsorption data. Data on file. 2004; 8
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.
ReferencesAllwood MC. The stability of four catecholamines in 5% glucose infusions. J Clin Pharm Ther. 1991; 16
ReferencesCarr RR, Decarie D, Ensom MHH. Stability of epinephrine at standard concentrations. Can J Hosp Pharm. 2014; 67
ReferencesDonnelly RF, Yen M. Epinephrine stability in plastic syringes and glass vials. Can J Hosp Pharm. 1996; 49
ReferencesKerddonfak S, Manuyakorn W, Kamchaisatian W, et al. The stability and sterility of epinephrine prefilled syringe. Asian Pac J Allergy Immunol. 2010; 28
ReferencesPeddicord TE, Olsen KM, Zumbrunnen TL, et al. Stability of high-concentration dopamine hydrochloride, norepinephrine bitartrate, epinephrine hydrochloride, and nitroglycerin in 5% dextrose injection. Am J Health-Syst Pharm. 1997; 54
ReferencesSilvers KM, Darlow BA, Winterbourn CC. Pharmacologic levels of heparin do not destabilize neonatal parenteral nutrition. J Parenter Enter Nutr. 1998; 22
ReferencesXu QA, Zhang Y, Trissel LA, et al. Adequacy of a new chlorhexidine-bearing polyurethane central catheter for administration of 82 selected parenteral drugs. Ann Pharmacother. 2000; 34
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.
ReferencesAllen LV Jr, Stiles ML, Wang DP, et al. Stability of bupivacaine hydrochloride, epinephrine hydrochloride, and fentanyl citrate in portable infusion-pump reservoirs. Am J Hosp Pharm. 1993; 50
ReferencesKjonniksen I, Brustugun J, Niemi G, et al. Stability of an epidural analgesic solution containing adrenaline, bupivacaine and fentanyl. Acta Anaesth Scand. 2000; 44
ReferencesMcEvoy GK (ed). AHFS Drug Information (current edition). Bethesda, MD: American Society of Health-System Pharmacists.
ReferencesParker EA. Compatibility Digest: Xylocaine hydrochloride 2% injection. Am J Hosp Pharm. 1971; 28
Stability Max
Maximum reported stability period: In D5W- 30 days under refrigeration and at room temperature protected from light.
ReferencesCarr RR, Decarie D, Ensom MHH. Stability of epinephrine at standard concentrations. Can J Hosp Pharm. 2014; 67
Revision Date: 07/02/2020, 12:23:11 PMCopyright 2004-2021 by Lawrence A. Trissel. All Rights Reserved.

References

29493 - Epinephrine injection 1:1000 package insert. Shirley, NY: American Regent, Inc.; 2005 Nov.32366 - ECC Committee, Subcommittees and Task Forces of the American Heart Association. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Advanced Cardiac Life Support Part 7.2: management of cardiac arrest. Circulation 2005;112:58-66.32367 - Niemann JT, Stratton SJ, Cruz B, et al. Endotracheal drug administration during out-of-hospital resuscitation: where are the survivors? Resuscitation 2002;53:153-7.32368 - Niemann JT, Stratton SJ. Endotracheal versus intravenous epinephrine and atropine in out-of-hospital 'primary' and postcountershock asystole. Crit Care Med 2000;28:1815-9.32537 - Epinephrine injection 1:10,000 Abboject syringe package insert. Lake Forest, IL: Hospira; 2004 Oct.32868 - International Guidelines for Neonatal Resuscitation. An Excerpt From the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science Contributors and Reviewers for the Neonatal Resuscitation Guidelines. Pediatrics 2000;106:e29.43713 - Kleinman ME, Chameides L, Schexnayder SM, et al. Part 14: pediatric advanced life support: 2010 American Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2010;122:S876-90844520 - Kattwinkel J, Perlman JM, Aziz K, et al. Part 15: Neonatal resuscitation: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122 (suppl 3):S909-19.45416 - Epinephrine injection 0.1 mg/mL package insert. Lake Forest, IL: Hospira Inc.; 2018 Nov.45649 - Neumar RW, Otto CW, Link MS, et al. Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2010;122:S729-S767.51889 - Institute for Safe Medication Practices (ISMP) and Vermont Oxford Network (VON). Standard concentrations of neonatal drug infusions. Retrieved September 28, 2012. Available on the World Wide Web at: http://www.ismp.org/tools/PediatricConcentrations.pdf.52326 - Kattwinkel J, ed. Textbook of neonatal resuscitation. 6th ed. American Academy of Pediatrics and American Heart Association; 2010.52507 - Phillips MS. Standardizing i.v. infusion concentrations: national survey results. Am J Health Syst Pharm 2011;68:2176-2182.52618 - Tschudy MM, Arcara KM. The Harriet Lane handbook: a manual for pediatric house officers 19th ed. Philadelphia, PA: Mosby;2012.54140 - EpiPen (epinephrine injection) package insert. Morgantown, WV: Mylan Specialty L.P..; 2020 Dec.54255 - Kemp SF, Lockey RF, Simons FE. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy 2008;63:1061-1070.54257 - Auvi-Q (epinephrine injection) auto-injector. Richmond, VA: Kaleo, Inc.;2019 Sept.54288 - Pharmacology. In: Pediatric Advanced Life Support Provider Manual. Chameides L, Samson RA, Schexnayder SM, (eds.) United States of America: American Heart Association; 2011:199-232.54309 - Velissariou I, Cottrell S, Berry K. Management of adrenaline (epinephrine) induced digital ischaemia in children after accidental injection from an EpiPen. Emerg Med J 2004;21:387-388.54685 - Patel R, Kumar R. Epinephrine induced digital ischemia after accidental injection from an auto-injector device. Indian Pediatrics 2013;50:247.56575 - Adrenalin (epinephrine) 1 mg/mL injection package insert. Chestnut Ridge, NJ: Par Pharmaceutical Companies, Inc.; 2019 Jan.57081 - Adrenaclick (epinephrine injection) package insert. Bridgewater, NJ: Amneal Pharmaceuticals LLC. 2021 Feb.60266 - Link MS, Berkow LC, Kudenchuk PJ, et al. Part 7: Adult Advanced Cardiovascular Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2015;132:S444-64.60589 - Epinephrine 1 mg/mL injection package insert. Largo, FL: Belcher Pharmaceuticals, LLC; 2017 Feb.60636 - de Caen AR, Berg MD, Chameides L. Part 12: Pediatric Advanced Life Support: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132:S526-S542.61541 - Wyckoff MH, Aziz K, Escobedo MB, et al. Part 13: Neonatal resuscitation: 2015 American Heart Association Guidelines Update for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation 2015;132 (suppl 2):S543-S560.62025 - Symjepi (epinephrine injection) package insert. San Diego, CA: Adamis Pharmaceuticals; 2019 Ma.63740 - Primatene Mist (epinephrine aerosol spray) package insert. Canton, MA: Armstrong Pharmaceuticals Inc. 2018 Nov.64020 - American Society of Health-System Pharmacists. Standardize 4 Safety Initiative, IV adult continuous infusion guidelines. Retrieved March 19th, 2019. Available at: https://www.ashp.org/-/media/assets/pharmacy-practice/s4s/docs/s4s-proposed-standard-concentrations-adult-continuous-infusions.ashx64923 - Lidocaine HCl and epinephrine injection package insert. Lake Forest, IL: Hospira, Inc.; 2019 Nov.64934 - Shenoi RP, Timm N, AAP Committee on Drugs, AAP Committee on Emergency Medicine. Drugs used to treat pediatric emergencies. Pediatrics 2020;145:e20193450.65168 - Dear Health Care Provider letter: Important safety information on the EpiPen and Epi Pen Jr Auto-injections and their authorized generic versions. Available on the World Wide Web at https://www.fda.gov/media/136389/download?utm_campaign=FDA%20alerts%20patients%20and%20health%20care%20professionals%20of%20EpiPen%20auto-injector%20errors&utm_medium=email&utm_source=Eloqua65833 - US Food and Drug Administration (FDA). Information for health care facilities and providers on "in-use time". Available on the World Wide Web at https://www.fda.gov/drugs/coronavirus-covid-19-drugs/information-health-care-facilities-and-providers-use-time-covid-19. Accessed August 13, 2020.

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]

Revision Date: 09/01/2018, 06:47:53 PM

References

45416 - Epinephrine injection 0.1 mg/mL package insert. Lake Forest, IL: Hospira Inc.; 2018 Nov.49567 - Epinephrine 1 mg/mL injection package insert. Shirley, NY: American Regent, Inc.; 2009 Jan.52618 - Tschudy MM, Arcara KM. The Harriet Lane handbook: a manual for pediatric house officers 19th ed. Philadelphia, PA: Mosby;2012.54140 - EpiPen (epinephrine injection) package insert. Morgantown, WV: Mylan Specialty L.P..; 2020 Dec.54685 - Patel R, Kumar R. Epinephrine induced digital ischemia after accidental injection from an auto-injector device. Indian Pediatrics 2013;50:247.56575 - Adrenalin (epinephrine) 1 mg/mL injection package insert. Chestnut Ridge, NJ: Par Pharmaceutical Companies, Inc.; 2019 Jan.57081 - Adrenaclick (epinephrine injection) package insert. Bridgewater, NJ: Amneal Pharmaceuticals LLC. 2021 Feb.60589 - Epinephrine 1 mg/mL injection package insert. Largo, FL: Belcher Pharmaceuticals, LLC; 2017 Feb.

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]

Revision Date: 06/17/2020, 02:02:29 PM

References

31822 - NAEPP Working Group Report on Managing Asthma During Pregnancy. Recommendations for Pharmacologic Treatment-Update 2004. NIH Publication No. 05-3279. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute, 200445416 - Epinephrine injection 0.1 mg/mL package insert. Lake Forest, IL: Hospira Inc.; 2018 Nov.49567 - Epinephrine 1 mg/mL injection package insert. Shirley, NY: American Regent, Inc.; 2009 Jan.53965 - Siwy BK, Sadove AM. Acute management of dopamine infiltration injury with Regitine. Plast Reconstr Surg 1987;80(4):610-612.54140 - EpiPen (epinephrine injection) package insert. Morgantown, WV: Mylan Specialty L.P..; 2020 Dec.54685 - Patel R, Kumar R. Epinephrine induced digital ischemia after accidental injection from an auto-injector device. Indian Pediatrics 2013;50:247.54686 - Roberts JR, Krisanda TJ. Accidental intra-arterial injection of epinephrine treated with phentolamine. Ann Emerg Med 1989;18:424-425.54687 - Kim SY, Han SH, Kim KH. Gastric ischemia after epinephrine injection in a patient with liver cirrhosis. World J Gastroenterol 2013;19:411-414.56575 - Adrenalin (epinephrine) 1 mg/mL injection package insert. Chestnut Ridge, NJ: Par Pharmaceutical Companies, Inc.; 2019 Jan.57081 - Adrenaclick (epinephrine injection) package insert. Bridgewater, NJ: Amneal Pharmaceuticals LLC. 2021 Feb.60589 - Epinephrine 1 mg/mL injection package insert. Largo, FL: Belcher Pharmaceuticals, LLC; 2017 Feb.63740 - Primatene Mist (epinephrine aerosol spray) package insert. Canton, MA: Armstrong Pharmaceuticals Inc. 2018 Nov.

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 PM

References

24251 - Menon K, et al. A randomized trial comparing the efficacy of epinephrine with salbutamol in the treatment of acute bronchiolitis. J Pediatr 1995;126:1004-7.

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]

Revision Date: 02/07/2019, 01:04:13 PM

References

45416 - Epinephrine injection 0.1 mg/mL package insert. Lake Forest, IL: Hospira Inc.; 2018 Nov.52326 - Kattwinkel J, ed. Textbook of neonatal resuscitation. 6th ed. American Academy of Pediatrics and American Heart Association; 2010.54255 - Kemp SF, Lockey RF, Simons FE. Epinephrine: the drug of choice for anaphylaxis. A statement of the World Allergy Organization. Allergy 2008;63:1061-1070.54288 - Pharmacology. In: Pediatric Advanced Life Support Provider Manual. Chameides L, Samson RA, Schexnayder SM, (eds.) United States of America: American Heart Association; 2011:199-232.54322 - Simons FE, Gu X, Simons KJ. Epinephrine absorption in adults: intramuscular versus subcutaneous injection. J Allergy Clin Immunol 2001;108:871-873.54323 - Simons FE, Roberts JR, Gu X. Epinephrine absorption in children with a history of anaphylaxis. J Allergy Clin Immunol 1998;101:33-37.54328 - Mellem H, Lande K, Kjeldsen SE. Faster and more reliable absorption of adrenaline by aerosol inhalation than by subcutaneous injection. Br J Clin Pharmacol 1991;31:677-681.60589 - Epinephrine 1 mg/mL injection package insert. Largo, FL: Belcher Pharmaceuticals, LLC; 2017 Feb.

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]

Revision Date: 02/01/2019, 12:32:47 PM

References

31822 - NAEPP Working Group Report on Managing Asthma During Pregnancy. Recommendations for Pharmacologic Treatment-Update 2004. NIH Publication No. 05-3279. Bethesda, MD: U.S. Department of Health and Human Services; National Institutes of Health; National Heart, Lung, and Blood Institute, 200445416 - Epinephrine injection 0.1 mg/mL package insert. Lake Forest, IL: Hospira Inc.; 2018 Nov.54140 - EpiPen (epinephrine injection) package insert. Morgantown, WV: Mylan Specialty L.P..; 2020 Dec.56575 - Adrenalin (epinephrine) 1 mg/mL injection package insert. Chestnut Ridge, NJ: Par Pharmaceutical Companies, Inc.; 2019 Jan.60589 - Epinephrine 1 mg/mL injection package insert. Largo, FL: Belcher Pharmaceuticals, LLC; 2017 Feb.

Interactions

Level 1 (Severe)

  • Halothane
  • Isocarboxazid
  • Monoamine oxidase inhibitors
  • Phenelzine
  • Tranylcypromine

Level 2 (Major)

  • Ambrisentan
  • Amobarbital
  • Amoxapine
  • Atomoxetine
  • Belladonna Alkaloids; Ergotamine; Phenobarbital
  • Bosentan
  • Butyrophenone
  • Caffeine; Ergotamine
  • Cardiac glycosides
  • Cocaine
  • Digitoxin
  • Digoxin
  • Dihydroergotamine
  • Dinoprostone, Prostaglandin E2
  • Epoprostenol
  • Ergoloid Mesylates
  • Ergonovine
  • Ergot alkaloids
  • Ergotamine
  • Etomidate
  • food
  • Iloprost
  • Iobenguane I 131
  • Isoproterenol
  • Levomilnacipran
  • Linezolid
  • Loxapine
  • Macitentan
  • Mecamylamine
  • Metaproterenol
  • Methohexital
  • Methylergonovine
  • Methysergide
  • Milnacipran
  • Non-Ionic Contrast Media
  • Ozanimod
  • Paliperidone
  • Pergolide
  • Procarbazine
  • Propofol
  • Reserpine
  • Riociguat
  • Risperidone
  • Selexipag
  • Sibutramine
  • St. John's Wort, Hypericum perforatum
  • Terbutaline
  • Thiopental
  • Treprostinil
  • Tricyclic antidepressants
  • Yohimbine
  • Ziprasidone

Level 3 (Moderate)

  • Acarbose
  • Acetaminophen; Aspirin, ASA; Caffeine
  • Acetaminophen; Butalbital; Caffeine
  • Acetaminophen; Butalbital; Caffeine; Codeine
  • Acetaminophen; Caffeine
  • Acetaminophen; Caffeine; Dihydrocodeine
  • Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine
  • Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine
  • Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine
  • Acetaminophen; Dextromethorphan; Phenylephrine
  • Acetaminophen; Dextromethorphan; Pseudoephedrine
  • Acetaminophen; Diphenhydramine
  • Acetaminophen; Guaifenesin; Phenylephrine
  • Acetaminophen; Pseudoephedrine
  • Aclidinium; Formoterol
  • Acrivastine; Pseudoephedrine
  • Albiglutide
  • Albuterol
  • Albuterol; Ipratropium
  • 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; Hydrochlorothiazide, HCTZ; Olmesartan
  • Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan
  • Amlodipine; Olmesartan
  • Amlodipine; Telmisartan
  • Amlodipine; Valsartan
  • 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; Dihydrocodeine
  • Aspirin, ASA; Caffeine; Orphenadrine
  • Atenolol; Chlorthalidone
  • Azelastine; Fluticasone
  • Azilsartan
  • Azilsartan; Chlorthalidone
  • Beclomethasone
  • Benazepril
  • Benazepril; Hydrochlorothiazide, HCTZ
  • Bendroflumethiazide; Nadolol
  • Betamethasone
  • Bethanechol
  • Bisoprolol; Hydrochlorothiazide, HCTZ
  • Bretylium
  • Bromocriptine
  • Brompheniramine; Carbetapentane; Phenylephrine
  • Brompheniramine; Dextromethorphan; Phenylephrine
  • Brompheniramine; Hydrocodone; Pseudoephedrine
  • Brompheniramine; Pseudoephedrine
  • Budesonide
  • Budesonide; Formoterol
  • Budesonide; Glycopyrrolate; Formoterol
  • Bumetanide
  • Caffeine
  • Caffeine; Sodium Benzoate
  • Calcium-channel blockers
  • Canagliflozin
  • Canagliflozin; Metformin
  • Candesartan
  • Candesartan; Hydrochlorothiazide, HCTZ
  • Captopril
  • Captopril; Hydrochlorothiazide, HCTZ
  • Carbetapentane; Chlorpheniramine
  • Carbetapentane; Chlorpheniramine; Phenylephrine
  • Carbetapentane; Diphenhydramine; Phenylephrine
  • Carbetapentane; Guaifenesin; Phenylephrine
  • Carbetapentane; Phenylephrine
  • Carbetapentane; Phenylephrine; Pyrilamine
  • Carbetapentane; Pseudoephedrine
  • Carbidopa; Levodopa; Entacapone
  • Carbinoxamine; Dextromethorphan; Pseudoephedrine
  • Carbinoxamine; Hydrocodone; Phenylephrine
  • Carbinoxamine; Hydrocodone; Pseudoephedrine
  • Carbinoxamine; Phenylephrine
  • Carbinoxamine; Pseudoephedrine
  • Cetirizine; Pseudoephedrine
  • Chlophedianol; Dexchlorpheniramine; Pseudoephedrine
  • Chlophedianol; Guaifenesin; Phenylephrine
  • Chlorothiazide
  • Chlorpheniramine
  • Chlorpheniramine; Codeine
  • Chlorpheniramine; Dextromethorphan
  • Chlorpheniramine; Dextromethorphan; Phenylephrine
  • Chlorpheniramine; Dihydrocodeine; Phenylephrine
  • Chlorpheniramine; Dihydrocodeine; Pseudoephedrine
  • Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine
  • Chlorpheniramine; Hydrocodone
  • Chlorpheniramine; Hydrocodone; Phenylephrine
  • Chlorpheniramine; Hydrocodone; Pseudoephedrine
  • Chlorpheniramine; Phenylephrine
  • Chlorpheniramine; Pseudoephedrine
  • Chlorpromazine
  • Chlorthalidone
  • Chlorthalidone; Clonidine
  • Ciclesonide
  • Class IA Antiarrhythmics
  • Class IB Antiarrhythmics
  • Class IC Antiarrhythmics
  • Clonidine
  • Clozapine
  • Codeine; Phenylephrine; Promethazine
  • Codeine; Promethazine
  • COMT inhibitors
  • Corticosteroids
  • Cortisone
  • Dapagliflozin
  • Dapagliflozin; Metformin
  • Dapagliflozin; Saxagliptin
  • Deflazacort
  • Desflurane
  • Desloratadine; Pseudoephedrine
  • Dexamethasone
  • Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine
  • Dexmethylphenidate
  • Dextromethorphan; Diphenhydramine; Phenylephrine
  • Dextromethorphan; Guaifenesin; Phenylephrine
  • Dextromethorphan; Guaifenesin; Pseudoephedrine
  • Dextromethorphan; Promethazine
  • Dextromethorphan; Quinidine
  • Dichlorphenamide
  • Diethylpropion
  • Dihydrocodeine; Guaifenesin; Pseudoephedrine
  • Dipeptidyl Peptidase-4 Inhibitors
  • Diphenhydramine
  • Diphenhydramine; Hydrocodone; Phenylephrine
  • Diphenhydramine; Ibuprofen
  • Diphenhydramine; Naproxen
  • Diphenhydramine; Phenylephrine
  • Disopyramide
  • Dobutamine
  • Dofetilide
  • Dopamine
  • Doxapram
  • Doxazosin
  • Dronabinol
  • Dronedarone
  • Droxidopa
  • Dulaglutide
  • Dyphylline
  • Dyphylline; Guaifenesin
  • Empagliflozin
  • Empagliflozin; Linagliptin
  • Empagliflozin; Linagliptin; Metformin
  • Empagliflozin; Metformin
  • Enalapril, Enalaprilat
  • Enalapril; Felodipine
  • Enalapril; Hydrochlorothiazide, HCTZ
  • Encainide
  • Enflurane
  • Entacapone
  • Ephedrine
  • Ephedrine; Guaifenesin
  • Eplerenone
  • Eprosartan
  • Eprosartan; Hydrochlorothiazide, HCTZ
  • Ertugliflozin
  • Ertugliflozin; Metformin
  • Ertugliflozin; Sitagliptin
  • Ethacrynic Acid
  • Exenatide
  • Fexofenadine; Pseudoephedrine
  • Flecainide
  • Fludrocortisone
  • Flunisolide
  • Fluoxetine; Olanzapine
  • Fluphenazine
  • Fluticasone
  • Fluticasone; Salmeterol
  • Fluticasone; Umeclidinium; Vilanterol
  • Fluticasone; Vilanterol
  • Formoterol
  • Formoterol; Mometasone
  • Fosinopril
  • Fosinopril; Hydrochlorothiazide, HCTZ
  • Furosemide
  • Glimepiride; Pioglitazone
  • Glimepiride; Rosiglitazone
  • Glycopyrrolate; Formoterol
  • Green Tea
  • Guaifenesin; Hydrocodone; Pseudoephedrine
  • Guaifenesin; Phenylephrine
  • Guaifenesin; Pseudoephedrine
  • Guanabenz
  • Guanfacine
  • Hydralazine; Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ
  • Hydrochlorothiazide, HCTZ; Irbesartan
  • Hydrochlorothiazide, HCTZ; Lisinopril
  • Hydrochlorothiazide, HCTZ; Losartan
  • Hydrochlorothiazide, HCTZ; Methyldopa
  • Hydrochlorothiazide, HCTZ; Metoprolol
  • Hydrochlorothiazide, HCTZ; Moexipril
  • Hydrochlorothiazide, HCTZ; Olmesartan
  • Hydrochlorothiazide, HCTZ; Propranolol
  • Hydrochlorothiazide, HCTZ; Quinapril
  • Hydrochlorothiazide, HCTZ; Spironolactone
  • Hydrochlorothiazide, HCTZ; Telmisartan
  • Hydrochlorothiazide, HCTZ; Triamterene
  • Hydrochlorothiazide, HCTZ; Valsartan
  • Hydrocodone; Phenylephrine
  • Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine
  • Hydrocodone; Pseudoephedrine
  • Hydrocortisone
  • Ibuprofen; Pseudoephedrine
  • Ibutilide
  • Incretin Mimetics
  • Indacaterol
  • Indacaterol; Glycopyrrolate
  • Indapamide
  • Insulin Degludec; Liraglutide
  • Insulin Glargine; Lixisenatide
  • Insulins
  • Irbesartan
  • Isoflurane
  • Ketamine
  • Levalbuterol
  • Levothyroxine
  • Levothyroxine; Liothyronine (Porcine)
  • Levothyroxine; Liothyronine (Synthetic)
  • Liothyronine
  • Liraglutide
  • Lisinopril
  • Lixisenatide
  • Loop diuretics
  • Loratadine; Pseudoephedrine
  • Losartan
  • Maprotiline
  • Meglitinides
  • Mepenzolate
  • Meperidine; Promethazine
  • Mesoridazine
  • Metformin; Pioglitazone
  • Metformin; Rosiglitazone
  • Methyclothiazide
  • Methyldopa
  • Methylphenidate
  • Methylprednisolone
  • Metolazone
  • Midodrine
  • Miglitol
  • Moexipril
  • Mometasone
  • Moricizine
  • Nabilone
  • Naproxen; Pseudoephedrine
  • Nebivolol; Valsartan
  • Nicotine
  • Nitrates
  • Norepinephrine
  • Olanzapine
  • Olmesartan
  • Opicapone
  • Oxytocin
  • Perindopril
  • Perindopril; Amlodipine
  • Perphenazine
  • Perphenazine; Amitriptyline
  • Phendimetrazine
  • Phenothiazines
  • Phenoxybenzamine
  • Phentermine
  • Phentermine; Topiramate
  • Phentolamine
  • Phenylephrine
  • Phenylephrine; Promethazine
  • Pioglitazone
  • Pirbuterol
  • Potassium-sparing diuretics
  • Pramlintide
  • Prazosin
  • Prednisolone
  • Prednisone
  • Procainamide
  • Prochlorperazine
  • Promethazine
  • Propafenone
  • Pseudoephedrine
  • Quinapril
  • Quinidine
  • Racepinephrine
  • Ramipril
  • Rasagiline
  • Rosiglitazone
  • Sacubitril; Valsartan
  • Safinamide
  • Salmeterol
  • Selegiline
  • Semaglutide
  • Sevoflurane
  • SGLT2 Inhibitors
  • Spironolactone
  • Sulfonylureas
  • Telmisartan
  • Terazosin
  • Theophylline, Aminophylline
  • Thiazide diuretics
  • Thiazolidinediones
  • Thiethylperazine
  • Thioridazine
  • Thiothixene
  • Thyroid hormones
  • Tolcapone
  • Torsemide
  • Trandolapril
  • Trandolapril; Verapamil
  • Triamcinolone
  • Triamterene
  • Trifluoperazine
  • Umeclidinium; Vilanterol
  • Valsartan
  • Vasodilators
  • Vasopressin, ADH
  • Vasopressors

Level 4 (Minor)

  • Acebutolol
  • Atenolol
  • Beta-blockers
  • Betaxolol
  • Bisoprolol
  • Brimonidine; Timolol
  • Carteolol
  • Carvedilol
  • Colchicine
  • Colchicine; Probenecid
  • Desmopressin
  • Dorzolamide; Timolol
  • Esmolol
  • Ginger, Zingiber officinale
  • Labetalol
  • Levobetaxolol
  • Levobunolol
  • Metoprolol
  • Nadolol
  • Nebivolol
  • Penbutolol
  • Pindolol
  • Propranolol
  • Sotalol
  • Timolol
Acarbose: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Acebutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Acetaminophen; Butalbital; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Acetaminophen; Diphenhydramine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Acetaminophen; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Aclidinium; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Acrivastine; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Albiglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Albuterol: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28532] Albuterol; Ipratropium: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28532] Aliskiren: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. [56575] Aliskiren; Amlodipine: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. [56575] Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Aliskiren; Valsartan: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Alogliptin; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Alpha-blockers: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [49263] [56575] Alpha-glucosidase Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ambrisentan: (Major) Sympathomimetics can antagonize the effects of vasodilators when administered concomitantly. Patients should be monitored for reduced efficacy if taking ambrisentan with a sympathomimetic. [2843] [6275] [6289] Amiloride: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [56575] Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Amiodarone: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Amlodipine; Benazepril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Amlodipine; Olmesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Amlodipine; Telmisartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Amlodipine; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Amobarbital: (Major) Amobarbital increases cardiac irritability via myocardial sensitization to catecholamines and can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. [6234] Amoxapine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, such as epinephrine, however, the data are not consistent. [5288] Amphetamines: (Moderate) Amphetamines may potentiate the pressor effects of epinephrine. [56575] Angiotensin II receptor antagonists: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Angiotensin-converting enzyme inhibitors: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Arformoterol: (Moderate) Caution and close observation should be used when arformoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [9749] Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Aspirin, ASA; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Atenolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Atenolol; Chlorthalidone: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Atomoxetine: (Major) Due to the potential for additive increases in blood pressure and heart rate, atomoxetine should be used cautiously with vasopressors such as epinephrine. Consider monitoring the patient's blood pressure and heart rate at baseline and regularly if vasopressors are coadministered with atomoxetine. [28405] Azelastine; Fluticasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Azilsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Azilsartan; Chlorthalidone: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Beclomethasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Benazepril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Bendroflumethiazide; Nadolol: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Beta-blockers: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Betamethasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Betaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects. [29416] [29831] Bisoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Bosentan: (Major) Avoid use of sympathomimetic agents with bosentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including bosentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [28496] [29534] [30000] [53320] [58486] [60482] [63622] Bretylium: (Moderate) Monitor blood pressure and heart rate closely when sympathomimetics are administered with bretylium. The pressor and arrhythmogenic effects of catecholamines are enhanced by bretylium. [56575] [64910] Brimonidine; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Bromocriptine: (Moderate) One case report documented worsening headache, hypertension, premature ventricular complexes, and ventricular tachycardia in a post-partum patient receiving bromocriptine for lactation suppression who was subsequently prescribed acetaminophen; dichloralphenazone; isometheptene for a headache. A second case involved a post-partum patient receiving bromocriptine who was later prescribed phenylpropanolamine; guaifenesin and subsequently developed hypertension, tachycardia, seizures, and cerebral vasospasm. Also, ergot alkaloids, which are chemically related to bromocriptine, should not be administered with other vasoconstrictors. Therefore, until more data become available, concurrent use of bromocriptine and some sympathomimetics such as vasopressors (e.g., norepinephrine, dopamine, phenylephrine), cocaine, epinephrine, phenylpropanolamine, ephedra, ma huang, ephedrine, pseudoephedrine, amphetamines, and phentermine should be approached with caution. [5585] [7139] Brompheniramine; Carbetapentane; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Brompheniramine; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Budesonide: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Budesonide; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Budesonide; Glycopyrrolate; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Bumetanide: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine. [28429] [56575] Butyrophenone: (Major) Use of epinephrine to treat droperidol or haloperidol -induced hypotension can result in a paradoxical lowering of blood pressure due to droperidol's alpha-blocking effects. Avoid using epinephrine concurrently with droperidol and haloperidol. [5468] Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Caffeine; Ergotamine: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Caffeine; Sodium Benzoate: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants. [4666] Calcium-channel blockers: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine. [56575] Canagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Canagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Candesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Captopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Carbetapentane; Chlorpheniramine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Carbetapentane; Guaifenesin; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Carbetapentane; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Carbetapentane; Phenylephrine; Pyrilamine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Carbetapentane; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Carbidopa; Levodopa; Entacapone: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine. [42112] [56575] Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Carbinoxamine; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Carbinoxamine; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Cardiac glycosides: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics. [28272] [33363] Carteolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Carvedilol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Cetirizine; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Chlophedianol; Guaifenesin; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Chlorothiazide: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Chlorpheniramine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Chlorpheniramine; Codeine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Chlorpheniramine; Dextromethorphan: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Chlorpheniramine; Hydrocodone: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Chlorpheniramine; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Chlorpheniramine; Pseudoephedrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Chlorpromazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Chlorthalidone: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Chlorthalidone; Clonidine: (Moderate) Clonidine may potentiate the pressor effects of epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Ciclesonide: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Class IA Antiarrhythmics: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Class IB Antiarrhythmics: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Class IC Antiarrhythmics: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Clonidine: (Moderate) Clonidine may potentiate the pressor effects of epinephrine. [56575] Clozapine: (Moderate) Clozapine may induce significant alpha-adrenergic blockade during clozapine overdose, leading to profound hypotension. Epinephrine should generally not be used to treat clozapine-induced hypotension due to the unopposed beta-activity, which potentially could worsen the hypotension. [28262] Cocaine: (Major) Avoid concomitant use of additional vasoconstrictor agents with cocaine. If unavoidable, prolonged vital sign and ECG monitoring may be required. Myocardial ischemia, myocardial infarction, and ventricular arrhythmias have been reported after concomitant administration of topical intranasal cocaine and vasoconstrictor agents during nasal and sinus surgery. The risk for nervousness, irritability, convulsions, and other cardiac arrhythmias may increase during coadministration. [63591] [64935] Codeine; Phenylephrine; Promethazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Codeine; Promethazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine. [8783] Colchicine; Probenecid: (Minor) The response to sympathomimetics may be enhanced by colchicine. [8783] COMT inhibitors: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine. [42112] [56575] Corticosteroids: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Cortisone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Dapagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dapagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dapagliflozin; Saxagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Deflazacort: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Desflurane: (Moderate) Monitor patients who are concomitantly receiving epinephrine and desflurane for the development of arrhythmias. Halogenated anesthetics, such as desflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. [45416] [56575] [60589] Desloratadine; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Desmopressin: (Minor) The antidiuretic response to desmopressin may be reduced in patients receiving high doses of epinephrine concomitantly. Caution should be used when coadministering these agents. [6234] Dexamethasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Dexmethylphenidate: (Moderate) Dexmethylphenidate may potentiate the pressor effects of epinephrine. [56575] Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Dextromethorphan; Promethazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Dextromethorphan; Quinidine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Dichlorphenamide: (Moderate) Use dichlorphenamide and epinephrine together with caution. Metabolic acidosis is associated with the use of dichlorphenamide and has been reported with the long-term use epinephrine. Concurrent use may increase the severity of metabolic acidosis. Measure sodium bicarbonate concentrations at baseline and periodically during dichlorphenamide treatment. If metabolic acidosis occurs or persists, consider reducing the dose or discontinuing dichlorphenamide therapy. [56575] [60122] Diethylpropion: (Moderate) Diethylpropion may potentiate the pressor effects of epinephrine. [56575] Digitoxin: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics. [28272] [33363] Digoxin: (Major) Concomitant use of cardiac glycosides with sympathomimetics can cause arrhythmias because sympathomimetics enhance ectopic pacemaker activity. Caution is warranted during co-administration of digoxin and sympathomimetics. [28272] [33363] Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Dihydroergotamine: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Dinoprostone, Prostaglandin E2: (Major) Oxytocics have inherent vasopressor properties; hypertensive episodes have been reported in laboring women during induction with oxytoxin. Because epinephrine is a vasopressor, concomitant use may result in severe, prolonged hypertension. In addition, epinephrine, secondary to beta2-receptor agonism, can interfere with the oxytocic action of drugs such as dinoprostone or oxytocin. [5861] Dipeptidyl Peptidase-4 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Diphenhydramine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Diphenhydramine; Ibuprofen: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Diphenhydramine; Naproxen: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] Diphenhydramine; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine. [54140] [56575] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Disopyramide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Dobutamine: (Moderate) Dobutamine may potentiate the pressor effects of epinephrine. [56575] Dofetilide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Dopamine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Dorzolamide; Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Doxapram: (Moderate) Doxapram may potentiate the pressor effects of epinephrine. [56575] Doxazosin: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [49263] [56575] Dronabinol: (Moderate) Concurrent use of dronabinol, THC with sympathomimetics may result in additive hypertension, tachycardia, and possibly cardiotoxicity. Dronabinol, THC has been associated with occasional hypotension, hypertension, syncope, and tachycardia. In a study of 7 adult males, combinations of IV cocaine and smoked marijuana, 1 g marijuana cigarette, 0 to 2.7% delta-9-THC, increased the heart rate above levels seen with either agent alone, with increases plateauing at 50 bpm. [28488] [30431] [33363] Dronedarone: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Droxidopa: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Dulaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Dyphylline: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias. [30227] Dyphylline; Guaifenesin: (Moderate) Use of sympathomimetics with dyphylline should be approached with caution. Coadministration may lead to adverse effects, such as tremors, insomnia, seizures, or cardiac arrhythmias. [30227] Empagliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Empagliflozin; Linagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Empagliflozin; Linagliptin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Empagliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Enalapril, Enalaprilat: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Enalapril; Felodipine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Encainide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Enflurane: (Moderate) Monitor patients who are concomitantly receiving epinephrine and enflurane for the development of arrhythmias. Halogenated anesthetics, such as enflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. [45416] [56575] [60589] Entacapone: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine. [42112] [56575] Ephedrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Ephedrine; Guaifenesin: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Eplerenone: (Moderate) Antihypertensives, including eplerenone, antagonize the vasopressor effects of parenteral epinephrine. [56575] Epoprostenol: (Major) Avoid use of sympathomimetic agents with epoprostenol. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including epoprostenol. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [28168] [29534] [30000] [53320] [58486] [60482] [63622] Eprosartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Ergoloid Mesylates: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Ergonovine: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Ergot alkaloids: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Ergotamine: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Ertugliflozin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ertugliflozin; Metformin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Ertugliflozin; Sitagliptin: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Esmolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Ethacrynic Acid: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine. [28429] [56575] Etomidate: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. [6234] Exenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Fexofenadine; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Flecainide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Fludrocortisone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Flunisolide: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Fluoxetine; Olanzapine: (Moderate) Olanzapine may induce significant alpha-adrenergic blockade in overdose, leading to profound hypotension. Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity since the beta-stimulation may worsen hypotension in the setting of olanzapine overdose. [28785] Fluphenazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Fluticasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Fluticasone; Salmeterol: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [30000] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Fluticasone; Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [54633] [56564] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Fluticasone; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [54633] [56564] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Food: (Major) Avoid administering marijuana and epinephrine together as concurrent use may result in adverse cardiovascular effects, such as tachycardia and cardiac arrhythmias. Marijuana is known to produce significant increases in heart rate and cardiac output lasting for 2 to 3 hours. Further, rare case reports of myocardial infarction and cardiac arrhythmias have been associated with marijuana use. Epinephrine has also been reported to produce a wide range of cardiovascular effects including cardiac arrhythmias, palpitations, hypertension, premature ventricular contractions (PVCs), and sinus tachycardia. [42294] [43081] [6234] Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Formoterol; Mometasone: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Fosinopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Furosemide: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine. [28429] [56575] Ginger, Zingiber officinale: (Minor) In vitro studies have demonstrated the positive inotropic effects of ginger, Zingiber officinale. It is theoretically possible that ginger could affect the action of inotropic agents, however, no clinical data are available. [2217] Glimepiride; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Glimepiride; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Glycopyrrolate; Formoterol: (Moderate) Caution and close observation should be used when formoterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5038] Green Tea: (Moderate) Some, but not all, green tea products contain caffeine. Caffeine should be avoided or used cautiously with epinephrine. CNS stimulants and sympathomimetics are associated with adverse effects such as nervousness, irritability, insomnia, and cardiac arrhythmias. [4666] Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Guaifenesin; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Guaifenesin; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Guanabenz: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of guanabenz when administered concomitantly. Patients should be monitored for loss of blood pressure control. [26181] [26815] [26816] [29332] [29548] [33263] [33363] [49571] [53320] [60070] [61368] Guanfacine: (Moderate) Antihypertensives, including guanfacine, antagonize the vasopressor effects of parenteral epinephrine. [56575] Halothane: (Contraindicated) The manufacturer for epinephrine contraindicates the use of epinephrine with halogenated anesthetics. Halothane is known to increase cardiac irritability via myocardial sensitization to catecholamines. General anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. [6234] Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Irbesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Lisinopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Losartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Metoprolol: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Olmesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Propranolol: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Hydrochlorothiazide, HCTZ; Quinapril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Spironolactone: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Telmisartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Triamterene: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrochlorothiazide, HCTZ; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Hydrocodone; Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Hydrocodone; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Hydrocortisone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Ibuprofen; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Ibutilide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Iloprost: (Major) Avoid use of sympathomimetic agents with iloprost. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including iloprost. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [30774] [53320] [58486] [60482] [63622] Incretin Mimetics: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Indacaterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [44979] Indacaterol; Glycopyrrolate: (Moderate) Administer sympathomimetics with caution with beta-agonists such as indacaterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [44979] Indapamide: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of vasodilators when administered concomitantly. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. [2843] [5917] [6234] [6275] Insulin Degludec; Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Insulin Glargine; Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Insulins: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Iobenguane I 131: (Major) Discontinue sympathomimetics for at least 5 half-lives before the administration of the dosimetry dose or a therapeutic dose of iobenguane I-131. Do not restart sympathomimetics until at least 7 days after each iobenguane I-131 dose. Drugs that reduce catecholamine uptake or deplete catecholamine stores, such as sympathomimetics, may interfere with iobenguane I-131 uptake into cells and interfere with dosimetry calculations resulting in altered iobenguane I-131 efficacy. [63402] Irbesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Isocarboxazid: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. [27957] [28862] [29656] [30438] [61173] [61932] Isoflurane: (Moderate) Monitor patients who are concomitantly receiving epinephrine and isoflurane for the development of arrhythmias. Halogenated anesthetics, such as isoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of isoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg. [28970] [45416] [56575] [60589] Isoproterenol: (Major) Do not administer isoproterenol and epinephrine simultaneously due to additive cardiac stimulation, which may induce serious arrhythmias. These drugs may be administered alternately provided a proper interval has elapsed between doses. [28004] [56575] Ketamine: (Moderate) Closely monitor vital signs when ketamine and epinephrine are coadministered; consider dose adjustment individualized to the patient's clinical situation. Epinephrine may enhance the sympathomimetic effects of ketamine. [43431] Labetalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Levalbuterol: (Moderate) Caution and close observation should be used when albuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [28532] Levobetaxolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Levobunolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Levomilnacipran: (Major) Due to the effects of levomilnacipran on noradrenergic pathways, paroxysmal hypertension and arrhythmias may occur during concurrent use of epinephrine. [55469] Levothyroxine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Levothyroxine; Liothyronine (Porcine): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Levothyroxine; Liothyronine (Synthetic): (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Linezolid: (Major) Linezolid may enhance the hypertensive effect of epinephrine. Initial doses of epinephrine, if given by intravenous infusion, should be reduced and subsequent dosing titrated to desired response. Closely monitor blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as epinephrine. [28599] [29493] [32308] Liothyronine: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Liraglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Lisinopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Lixisenatide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Loop diuretics: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine. [28429] [56575] Loratadine; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Losartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Loxapine: (Major) Patients taking loxapine can have reduced pressor response to ephedrine, phenylephrine, metaraminol, or norepinephrine, but these drugs are preferred over epinephrine if a vasopressor agent is required. The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of loxapine. This reaction can result in an apparently paradoxical condition called 'epinephrine reversal.' Epinephrine reversal can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. [5355] Macitentan: (Major) Avoid use of sympathomimetic agents with macitentan. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including macitentan. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [53320] [56260] [58486] [60482] [63622] Maprotiline: (Moderate) Use maprotiline and sympathomimetics together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Maprotiline has pharmacologic activity similar to tricyclic antidepressant agents and may cause additive sympathomimetic effects when combined with agents with adrenergic/sympathomimetic activity. [28759] Mecamylamine: (Major) The cardiovascular effects of sympathomimetics may reduce the antihypertensive effects produced by mecamylamine. Close monitoring of blood pressure or the selection of alternative therapeutic agents may be needed. [29332] [53320] [60070] Meglitinides: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Mepenzolate: (Moderate) Anticholinergics, such as mepenzolate, antagonize the effects of antiglaucoma agents. Mepenzolate is contraindicated in patients with glaucoma and therefore should not be coadministered with medications being prescribed for the treatment of glaucoma. In addition, anticholinergic drugs taken concurrently with corticosteroids in the presence of increased intraocular pressure may be hazardous. [42281] Meperidine; Promethazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Mesoridazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Metaproterenol: (Major) Caution and close observation should also be used when metaproterenol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5272] Metformin; Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Metformin; Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Methohexital: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. [6234] Methyclothiazide: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Methyldopa: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine. [56575] Methylergonovine: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Methylphenidate: (Moderate) Methylphenidate may potentiate the pressor effects of epinephrine. [56575] Methylprednisolone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Methysergide: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Metolazone: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Metoprolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Midodrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Miglitol: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Milnacipran: (Major) Concomitant use of milnacipran with drugs that increase blood pressure and heart rate has not been systematically evaluated and such combinations should be used with caution. Due to the effects of milnacipran on noradrenergic pathways, paroxysmal hypertension and arrhythmias may occur during concurrent use of epinephrine. Monitor heart rate and blood pressure, and the patients clinical response to therapy if co-use is necessary. Milnacipran is associated with a mean increase in heart rate of 7 to 8 beats per minute, and higher increases in heart rate (13 beats per minute or more) occur more commonly in patients treated with milnacipran than in those receiving placebo. The mean increase from baseline was 5 to 6 mmHg in systolic blood pressure (SBP) and diastolic blood pressure (DBP), and cases of hypertension with milnacipran have been reported, some requiring immediate treatment. [23431] Moexipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Mometasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Monoamine oxidase inhibitors: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. [27957] [28862] [29656] [30438] [61173] [61932] Moricizine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Nabilone: (Moderate) Concurrent use of nabilone with sympathomimetics (e.g., amphetamine or cocaine) may result in additive hypertension, tachycardia, and possibly cardiotoxicity. In a study of 7 adult males, combinations of cocaine (IV) and smoked marijuana (1 g marijuana cigarette, 0 to 2.7% delta-9-THC) increased the heart rate above levels seen with either agent alone, with increases reaching a plateau at 50 bpm. [32226] Nadolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Naproxen; Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Nebivolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Nebivolol; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Nicotine: (Moderate) Nicotine use may potentiate the effects of the adrenergic agonists and the ergot alkaloids. If significant changes in nicotine intake occur, the dosages of these drugs may need adjustment. [5585] Nitrates: (Moderate) Sympathomimetics can antagonize the antianginal effects of nitrates, and can increase blood pressure and/or heart rate. Anginal pain may be induced when coronary insufficiency is present. [26181] [26815] [29493] [29548] [53320] Non-Ionic Contrast Media: (Major) Do not administer non-ionic contrast media intra-arterially after the administration of vasopressors since they strongly potentiate neurologic effects. [28958] Norepinephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Olanzapine: (Moderate) Olanzapine may induce significant alpha-adrenergic blockade in overdose, leading to profound hypotension. Do not use epinephrine, dopamine, or other sympathomimetics with beta-agonist activity since the beta-stimulation may worsen hypotension in the setting of olanzapine overdose. [28785] Olmesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Opicapone: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine. [42112] [56575] Oxytocin: (Moderate) Oxytocin may potentiate the pressor effects of epinephrine. Severe hypertension has been reported when oxytocin was given 3 to 4 hours after prophylactic administration of a vasoconstrictor in conjunction with caudal block anesthesia. [47239] [56575] Ozanimod: (Major) Coadministration of ozanimod with sympathomimetics such as epinephrine is not routinely recommended due to the potential for hypertensive crisis. If coadministration is medically necessary, closely monitor the patient for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Sympathomimetics may increase blood pressure by increasing norepinephrine concentrations and monoamine oxidase inhibitors (MAOIs) are known to potentiate these effects. Concomitant use of ozanimod with pseudoephedrine did not potentiate the effects on blood pressure. However, hypertensive crisis has occurred with administration of ozanimod alone and also during coadministration of sympathomimetic medications and other selective or nonselective MAO inhibitors. [56575] [65169] Paliperidone: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of paliperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The use of other agents for vascular support is recommended when needed. [5732] Penbutolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Pergolide: (Major) Avoid concomitant use of ergot alkaloids and epinephrine due to synergistic vasoconstriction and severe hypertension. Ergot alkaloids may also antagonize the pressor effects of epinephrine via alpha-blockade. [48628] [52447] [52524] [54140] [56575] Perindopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Perindopril; Amlodipine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Perphenazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Perphenazine; Amitriptyline: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Phendimetrazine: (Moderate) Phendimetrazine may potentiate the pressor effects of epinephrine. [56575] Phenelzine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. [27957] [28862] [29656] [30438] [61173] [61932] Phenothiazines: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Phenoxybenzamine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [49263] [56575] Phentermine: (Moderate) Phentermine may potentiate the pressor effects of epinephrine. [56575] Phentermine; Topiramate: (Moderate) Phentermine may potentiate the pressor effects of epinephrine. [56575] Phentolamine: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [49263] [56575] Phenylephrine: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Phenylephrine; Promethazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Pindolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Pioglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Pirbuterol: (Moderate) Caution and close observation should also be used when pirbuterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [5263] Potassium-sparing diuretics: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [56575] Pramlintide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Prazosin: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [49263] [56575] Prednisolone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Prednisone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Procainamide: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Procarbazine: (Major) Because procarbazine exhibits some monoamine oxidase inhibitory (MAOI) activity, sympathomimetic drugs should be avoided. As with MAOIs, the use of a sympathomimetic drug with procarbazine may precipitate hypertensive crisis or other serious side effects. In the presence of MAOIs, drugs that cause release of norepinephrine induce severe cardiovascular and cerebrovascular responses. In general, do not use a sympathomimetic drug unless clinically necessary (e.g., medical emergencies, agents like dopamine) within the 14 days prior, during or 14 days after procarbazine therapy. If use is necessary within 2 weeks of the MAOI drug, in general the initial dose of the sympathomimetic agent must be greatly reduced. Patients should be counseled to avoid non-prescription (OTC) decongestants and other drug products, weight loss products, and energy supplements that contain sympathomimetic agents. [28518] [32121] [32223] [45905] [46595] [60070] Prochlorperazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Promethazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Propafenone: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Propofol: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. [6234] Propranolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Pseudoephedrine: (Moderate) Pseudoephedrine may potentiate the pressor effects of epinephrine. [56575] Quinapril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Quinidine: (Moderate) Monitor patients who receive epinephrine while concomitantly taking antiarrhythmics for the development of arrhythmias. Epinephrine may produce ventricular arrhythmias in patients who are on drugs that may sensitize the heart to arrhythmias. [54140] Racepinephrine: (Moderate) Racepinephrine may potentiate the pressor effects of epinephrine. [56575] Ramipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetics was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and sympathomimetics including stimulants for ADHD and weight loss, non-prescription nasal, oral, and ophthalmic decongestants, and weight loss dietary supplements containing Ephedra. Although sympathomimetics are contraindicated for use with other non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. One case of elevated blood pressure has been reported in a patient during concurrent use of the recommended dose of rasagiline and ophthalmic tetrahydrozoline. One case of hypertensive crisis has been reported in a patient taking the recommended dose of another MAO-B inhibitor, selegiline, in combination with ephedrine. It should be noted that the MAO-B selectivity of rasagiline decreases in a dose-related manner as increases are made above the recommended daily dose and interactions with sympathomimetics may be more likely to occur at these higher doses. [32223] [60070] Reserpine: (Major) Reserpine can increase the tissue sensitivity to epinephrine leading to severe hypertension and arrhythmias. Reserpine causes increased receptor sensitivity secondary to depletion of either norepinephrine or epinephrine from adrenergic nerve endings. Epinephrine should be used cautiously in patients receiving reserpine. [6237] Riociguat: (Major) Avoid use of sympathomimetic agents with riociguat. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including riociguat. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [53320] [56096] [58486] [60482] [63622] Risperidone: (Major) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of risperidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of risperidone. The use of other agents for vascular support is recommended when needed. [28997] Rosiglitazone: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Sacubitril; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Safinamide: (Moderate) Severe hypertensive reactions, including hypertensive crisis, have been reported in patients taking monoamine oxidase inhibitors (MAOIs), such as safinamide, and sympathomimetic medications, such as epinephrine. If concomitant use of safinamide and epinephrine is necessary, monitor for hypertension and hypertensive crisis. [61825] Salmeterol: (Moderate) Caution and close observation should also be used when salmeterol is used concurrently with other adrenergic sympathomimetics, administered by any route, to avoid potential for increased cardiovascular effects. [30000] Selegiline: (Moderate) Monitor blood pressure for hypertension during concomitant use of selegiline and sympathomimetics such as epinephrine. The use of these drugs together may produce substantial elevations in blood pressure. If a hypertensive crisis occurs, selegiline should be discontinued and therapy to lower blood pressure should be instituted immediately. [32026] [32436] [56575] Selexipag: (Major) Avoid use of sympathomimetic agents with selexipag. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including selexipag. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [53320] [56096] [58486] [60482] [63622] Semaglutide: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Sevoflurane: (Moderate) Monitor patients who are concomitantly receiving epinephrine and sevoflurane for the development of arrhythmias. Halogenated anesthetics, such as sevoflurane, sensitize the myocardium and may potentiate the arrhythmogenic effects of epinephrine. If occur, such arrhythmias may respond to beta-blocker administration. A study investigating the epinephrine induced arrhythmogenic effect of sevoflurane in adult patients undergoing transsphenoidal hypophysectomy demonstrated that the threshold dose of epinephrine (i.e., the dose at which the first sign of arrhythmia was observed) producing multiple ventricular arrhythmias was 5 mcg/kg. [28970] [45416] [56575] [60589] SGLT2 Inhibitors: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Sibutramine: (Major) Concurrent use of sibutramine with other serotonergic agents may increase the potential for serotonin syndrome or neuroleptic malignant syndrome-like reactions. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome. [5340] Sotalol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Spironolactone: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [56575] St. John's Wort, Hypericum perforatum: (Major) St. John's wort, Hypericum Perforatum may reduce the neuronal uptake of monoamines and should be used cautiously with sympathomimetics or drugs with sympathomimetic-like actions. [4935] Sulfonylureas: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [29413] [29418] [35040] [43364] [44662] [51002] Telmisartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Terazosin: (Moderate) Alpha-blockers antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by an alpha-blocker, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [49263] [56575] Terbutaline: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate. [5197] Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with sympathomimetics can produce excessive stimulation manifested by skeletal muscle activity, agitation, and hyperactivity. [41358] (Moderate) Theophylline may potentiate the hypokalemic effects of epinephrine. [56575] Thiazide diuretics: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [41355] [56575] Thiazolidinediones: (Moderate) Sympathomimetic agents and adrenergic agonists tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when pseudoephedrine, phenylephrine, and other sympathomimetics are administered to patients taking antidiabetic agents. Epinephrine and other sympathomimetics, through stimulation of alpha- and beta- receptors, increase hepatic glucose production and glycogenolysis and inhibit insulin secretion. Also, adrenergic medications may decrease glucose uptake by muscle cells. For treatment of cold symptoms, nasal decongestants may be preferable for short term, limited use (1 to 3 days) as an alternative to systemic decongestants in patients taking medications for diabetes. [44662] [51002] Thiethylperazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Thiopental: (Major) General anesthetics are known to increase cardiac irritability via myocardial sensitization to catecholamines. These anesthetics can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine. [6234] Thioridazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Thiothixene: (Moderate) The alpha-adrenergic effects of epinephrine can be blocked during concurrent administration of thiothixene. This blockade can cause an apparently paradoxical condition called epinephrine reversal, which can lead to severe hypotension, tachycardia, and, potentially, myocardial infarction. [5838] [5864] Thyroid hormones: (Moderate) Sympathomimetic amines should be used with caution in patients with thyrotoxicosis since these patients are unusually responsive to sympathomimetic amines. Based on the cardiovascular stimulatory effects of sympathomimetic drugs, the concomitant use of sympathomimetics and thyroid hormones can enhance the effects on the cardiovascular system. Patients with coronary artery disease have an increased risk of coronary insufficiency from either agent. Concomitant use of these agents may increase this risk further. In addition, dopamine at a dose of >= 1 mcg/kg/min and dopamine agonists (e.g., apomorphine, bromocriptine, levodopa, pergolide, pramipexole, ropinirole, rotigotine) may result in a transient reduction in TSH secretion. The reduction in TSH secretion is not sustained; hypothyroidism does not occur. [29548] [43942] Timolol: (Minor) Close monitoring of blood pressure or the selection of alternative therapeutic agents to the sympathomimetic agent may be needed in patients receiving a beta-blocker. Sympathomimetics, such as amphetamines, phentermine, and decongestants (e.g., pseudoephedrine, phenylephrine), and many other drugs, may increase both systolic and diastolic blood pressure and may counteract the activity of the beta-blockers. Concurrent use increases the risk of unopposed alpha-adrenergic activity. Increased blood pressure, bradycardia, or heart block may occur due to excessive alpha-adrenergic receptor stimulation. [24172] [26181] [27369] [29332] [46537] [46594] [53320] [60070] Tolcapone: (Moderate) Use COMT inhibitors and epinephrine, regardless of route, together with caution due to potential for increased heart rate, arrhythmias, and excessive changes in blood pressure. Epinephrine is metabolized by catechol-O-methyltransferase (COMT), therefore COMT inhibitors potentiate the pressor effects of epinephrine. [42112] [56575] Torsemide: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine. [28429] [56575] Trandolapril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Trandolapril; Verapamil: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. [56575] Tranylcypromine: (Contraindicated) In general, sympathomimetics should be avoided in patients receiving MAOIs due to an increased risk of hypertensive crisis. This applies to sympathomimetics including stimulants for ADHD, narcolepsy or weight loss, nasal, oral, and ophthalmic decongestants and cold products, and respiratory sympathomimetics (e.g., beta agonist drugs). Some local anesthetics also contain a sympathomimetic (e.g., epinephrine). In general, medicines containing sympathomimetic agents should not be used concurrently with MAOIs or within 14 days before or after their use. [27957] [28862] [29656] [30438] [61173] [61932] Treprostinil: (Major) Avoid use of sympathomimetic agents with treprostinil. Sympathomimetics counteract the medications used to stabilize pulmonary hypertension, including treprostinil. Sympathomimetics can increase blood pressure, increase heart rate, and may cause vasoconstriction resulting in chest pain and shortness of breath in these patients. Patients should be advised to avoid amphetamine drugs, decongestants (including nasal decongestants) and sympathomimetic anorexiants for weight loss, including dietary supplements. Intravenous vasopressors may be used in the emergency management of pulmonary hypertension patients when needed, but hemodynamic monitoring and careful monitoring of cardiac status are needed to avoid ischemia and other complications. [24656] [26181] [29534] [30000] [30210] [53320] [58486] [60482] [63622] Triamcinolone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine. [56575] Triamterene: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. [56575] Tricyclic antidepressants: (Major) Tricyclic antidepressants may potentiate the pressor effects of epinephrine. Monitor blood pressure and heart rate closely and carefully adjust dosages as required. Avoid decongestants and local anesthetics that contain epinephrine. [28557] [41163] [56575] Trifluoperazine: (Moderate) Phenothiazines antagonize the pressor effects of epinephrine. Do not use epinephrine to counteract hypotension caused by a phenothiazine, as a reversal of the pressor effect of epinephrine may result in paradoxical further lowering of blood pressure. [28997] [56575] [60589] Umeclidinium; Vilanterol: (Moderate) Administer sympathomimetics with caution with beta-agonists such as vilanterol. The cardiovascular effects of beta-2 agonists may be potentiated by concomitant use. Monitor the patient for tremors, nervousness, increased heart rate, or other additive side effects. [54633] [56564] Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. [56575] Vasodilators: (Moderate) Use sympathomimetic agents with caution in patients receiving therapy for hypertension. Patients should be monitored to confirm that the desired antihypertensive effect is achieved. Sympathomimetics can increase blood pressure and heart rate, and antagonize the antihypertensive effects of vasodilators when administered concomitantly. Anginal pain may be induced when coronary insufficiency is present. [26181] [26815] [26816] [29332] [29548] [33263] [33363] [53320] [60070] Vasopressin, ADH: (Moderate) Monitor hemodynamics and adjust drug doses as needed when vasopressin and epinephrine are used concomitantly. Use together is expected to result in an additive effect on mean arterial blood pressure and other hemodynamic parameters. [58023] Vasopressors: (Moderate) Vasopressors may potentiate the pressor effects of epinephrine. [56575] Yohimbine: (Major) At high doses, yohimbine may nonselectively inhibit monoamine oxidase and also, at normal doses, activates the sympathetic nervous system via selective central alpha 2-adrenoceptor antagonism. Traditional MAOIs can cause serious adverse effects when taken concomitantly with sympathomimetics. [6282] [6283] Ziprasidone: (Major) The alpha-adrenergic effects of epinephrine, and possibly of other adrenergic agonists, can be blocked during concurrent administration of ziprasidone. This blockade can cause an apparently paradoxical condition called 'epinephrine reversal'. The vasoconstrictive properties of dopamine infusion can be decreased due to the alpha-adrenergic blocking capability of ziprasidone. Hypotension and circulatory collapse should be treated with appropriate measures such as intravenous fluids. If sympathomimetic agents are used for vascular support, epinephrine and dopamine should not be used, since beta stimulation combined with alpha-1 antagonism associated with ziprasidone may worsen hypotension. Similarly, it is reasonable to expect that the alpha-adrenergic-blocking properties of bretylium might be additive to those of ziprasidone, resulting in problematic hypotension. [4959]
Revision Date: 04/02/2021, 02:36:00 AM

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Monitoring Parameters

  • blood pressure
  • heart rate
  • pulmonary function tests (PFTs)

US Drug Names

  • Adrenaclick
  • Adrenalin
  • Auvi-Q
  • Epifrin
  • EpiPen
  • Primatene Mist
  • SYMJEPI
  • Twinject