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  • CLASSES

    All Other Respiratory Agents for Reactive and Obstructive Airway Diseases
    Cardiac Stimulants Excluding Dopaminergic Agents
    Mydriatics and Cycloplegics
    Respiratory Short-Acting Beta-2 Agonists (SABA)
    Topical Nasal Decongestants
    Vasopressors

    DEA CLASS

    Rx, OTC

    DESCRIPTION

    Nonselective adrenergic agonist
    Used for hemodynamic/inotropic support and bronchodilation
    Drug of choice for anaphylaxis; not routinely recommended for asthma

    COMMON BRAND NAMES

    Adrenaclick, Adrenalin, Auvi-Q, EpiPen, Primatene Mist, SYMJEPI, Twinject

    HOW SUPPLIED

    Adrenaclick/Adrenalin/Auvi-Q/Epinephrine/Epinephrine Hydrochloride/EpiPen/SYMJEPI/Twinject Intramuscular Inj Sol: 0.1mg, 0.15mg, 0.3mg, 0.3mL, 1dose, 1mg, 1mL
    Adrenaclick/Adrenalin/Auvi-Q/Epinephrine/Epinephrine Hydrochloride/EpiPen/SYMJEPI/Twinject Subcutaneous Inj Sol: 0.1mg, 0.15mg, 0.3mg, 0.3mL, 1dose, 1mg, 1mL
    Adrenalin Nasal Sol: 1mg, 1mL
    Adrenalin/Epinephrine/Epinephrine Hydrochloride Intracardiac Inj Sol: 0.1mg, 1mL, 1mg
    Adrenalin/Epinephrine/Epinephrine Hydrochloride Intraocular Inj Sol: 1mg, 1mL
    Adrenalin/Epinephrine/Epinephrine Hydrochloride Intravenous Inj Sol: 0.1mg, 1mL, 1mg
    Primatene Mist Respiratory (Inhalation) Inhalant: 0.125mg

    DOSAGE & INDICATIONS

    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.
    Intramuscular or Subcutaneous dosage
    Adults

    0.3 to 0.5 mg subcutaneously or IM; may be repeated if necessary every 5 to 10 minutes.

    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.

    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.

    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.

    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. 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.

    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.

    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.

    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. 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.

    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. 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.

    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.

    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).

    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.

    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. Guidelines for asthma treatment do not recommend use; prescribe a selective short-acting beta-agonist (SABA).

    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. Guidelines for asthma treatment do not recommend use; prescribe a selective short-acting beta-agonist (SABA).

    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.

    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.

    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.

    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. 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.

    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. 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.

    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. 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.

    For the treatment of laryngotracheobronchitis (croup).
    Nebulized dosage

    NOTE: Also see Racepinephrine monograph

    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.
    For the treatment of low blood pressure or persistent bradycardia with a pulse in a patient with an at-risk myocardium to prevent cardiac arrest and allow time to treat an acute reversible problem†.
    Intravenous or Intraosseous dosage
    Infants, Children, and Adolescents

    0.001 mg/kg/dose IV or IO (one-tenth the standard resuscitation dose); titrate to desired hemodynamic effect. A continuous infusion of 0.01 to 0.2 mcg/kg/minute IV or IO has also been recommended.[63412]

    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).

    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).

    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.

    Endotracheal dosage

    NOTE: Vascular access (IV or IO) is the preferred route of epinephrine administration during CPR; endotracheal (ET) administration should only be used if vascular access is delayed or cannot be obtained. Effectiveness of endotracheal epinephrine is controversial; drug absorption is unpredictable, and optimal doses are unknown. Animal studies suggest that the lower epinephrine blood concentrations attained after ET drug administration may result in transient beta-2 vasodilation, resulting in decreased blood pressure, lower coronary artery perfusion pressure and flow, and a reduced potential for return of spontaneous circulation.[32367] [32368] [43713] [60636]

    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.

    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.

    Intracardiac dosage†

    NOTE: Intracardiac administration should be reserved for use only during open cardiac massage or in extreme emergencies when other routes of administration are unavailable. The risks of intracardiac injection include myocardial puncture and cardiac tamponade, coronary artery rupture, pneumothorax, and the need to cease chest compression and ventilation.

    Adults

    0.3 to 0.5 mg intracardially.

    Continuous Intravenous or Intraosseus† Infusion dosage for postresuscitation stabilization
    Adults

    2 to 10 mcg/minute continuous IV or IO infusion; titrate to desired effect.

    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.

    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.

    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 nasal congestion.
    Nasal dosage (0.1 to 0.5 mg/mL solution)
    Adults

    Apply topically to nose as drops, spray, or with a sterile swab as needed.

    Children and Adolescents 6 to 17 years

    Apply topically to nose as drops, spray, or with a sterile swab as needed.

    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. 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. Check product specific labels; only use 1 mg/mL single-use products intended for ophthalmic administration.

    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).

    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.

    Endotracheal dosage

    NOTE: Vascular access (IV or IO) is the preferred route of epinephrine administration during CPR; endotracheal (ET) administration should only be used if vascular access is delayed or cannot be obtained. Effectiveness of endotracheal epinephrine is controversial; drug absorption is unpredictable and optimal doses are unknown. Animal studies suggest that the lower epinephrine blood concentrations attained after ET drug administration may result in transient beta-2 vasodilation, resulting in decreased blood pressure, lower coronary artery perfusion pressure and flow, and a reduced potential for return of spontaneous circulation.

    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.

    For the treatment of hypotension, including during shock (e.g., septic shock, cardiogenic shock†).
    Continuous Intravenous Infusion dosage
    Adults

    0.01 to 2 mcg/kg/minute continuous IV infusion. Titrate by 0.05 to 0.2 mcg/kg/minute every 10 to 15 minutes to clinical response.[56575] [60589] After hemodynamic stabilization, wean incrementally every 10 to 30 minutes over a 12- to 24-hour period.[56575] [60589] Guidelines consider epinephrine as an alternative to norepinephrine in settings where norepinephrine is not available and suggest adding epinephrine to norepinephrine and vasopressin if inadequate mean arterial pressure (MAP) for patients with septic shock. Epinephrine may be useful in refractory septic shock patients with myocardial dysfunction.

    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]  [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]  [64934]

    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.

    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]

    †Indicates off-label use

    MAXIMUM DOSAGE

    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

    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. [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.
    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.
    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.

    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.
    After injection, flush with saline to promote medication entry into the central circulation.
     
    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.

    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.

    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.
     
    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.
     
    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.

    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]

    STORAGE

    Generic:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not refrigerate
    - Protect from freezing
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in the original carton to protect from light
    Adrenaclick:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Adrenalin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Auvi-Q:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    EpiPen:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Primatene Mist:
    - Store between 59 to 77 degrees F
    SYMJEPI:
    - Avoid extreme temperatures
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not refrigerate
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in original container
    Twinject:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not refrigerate
    - Protect from freezing
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    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.

    Cardiac disease, cardiomyopathy, coronary artery disease, hypovolemia, shock

    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]

    Sulfite hypersensitivity

    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.

    Closed-angle glaucoma

    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.

    Extravasation, infection, intraarterial administration

    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).

    Cerebrovascular disease, organic brain syndrome

    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.

    Hypertension

    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.

    Hyperthyroidism, pheochromocytoma, thyroid disease, thyrotoxicosis

    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.

    Diabetes mellitus

    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.

    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]

    Ophthalmic administration

    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).

    Parkinson's disease

    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.

    Renal disease

    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.

    Children, infants

    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. 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.

    ADVERSE REACTIONS

    Severe

    stroke / Early / Incidence not known
    apnea / Delayed / Incidence not known
    myocardial infarction / Delayed / Incidence not known
    pulmonary edema / Early / Incidence not known
    ventricular tachycardia / Early / Incidence not known
    ventricular fibrillation / Early / Incidence not known
    cardiomyopathy / Delayed / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known
    necrotizing fasciitis / Delayed / Incidence not known
    tissue necrosis / Early / Incidence not known
    lactic acidosis / Delayed / Incidence not known
    oliguria / Early / Incidence not known

    Moderate

    excitability / Early / Incidence not known
    memory impairment / Delayed / Incidence not known
    dyspnea / Early / Incidence not known
    angina / Early / Incidence not known
    hypertension / Early / Incidence not known
    chest pain (unspecified) / Early / Incidence not known
    palpitations / Early / Incidence not known
    sinus tachycardia / Rapid / Incidence not known
    premature ventricular contractions (PVCs) / Early / Incidence not known
    supraventricular tachycardia (SVT) / Early / Incidence not known
    erythema / Early / Incidence not known
    skin laceration / Delayed / Incidence not known
    peripheral vasoconstriction / Rapid / Incidence not known
    metabolic acidosis / Delayed / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known
    hypokalemia / Delayed / Incidence not known
    corneal edema / Early / Incidence not known

    Mild

    infection / Delayed / 0-1.0
    paresthesias / Delayed / Incidence not known
    drowsiness / Early / Incidence not known
    headache / Early / Incidence not known
    agitation / Early / Incidence not known
    hyperactivity / Early / Incidence not known
    dizziness / Early / Incidence not known
    restlessness / Early / Incidence not known
    weakness / Early / Incidence not known
    anxiety / Delayed / Incidence not known
    tremor / Early / Incidence not known
    diaphoresis / Early / Incidence not known
    pallor / Early / Incidence not known
    vomiting / Early / Incidence not known
    nausea / Early / Incidence not known
    hypoesthesia / Delayed / Incidence not known
    ecchymosis / Delayed / Incidence not known
    injection site reaction / Rapid / Incidence not known
    skin discoloration / Delayed / Incidence not known
    insulin resistance / Delayed / Incidence not known

    DRUG INTERACTIONS

    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.
    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.
    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.
    Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
    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.
    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.
    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.
    Acetaminophen; Chlorpheniramine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Acetaminophen; Diphenhydramine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
    Acetaminophen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    Acrivastine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    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.
    Aliskiren: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine.
    Aliskiren; Amlodipine: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine.
    Aliskiren; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Aliskiren; Valsartan: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    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.
    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.
    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.
    Amiloride: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    Amlodipine; Benazepril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Amlodipine; Olmesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Amlodipine; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Amobarbital: (Major) Amobarbital increases cardiac irritability via myocardial sensitization to catecholamines and can produce ventricular arrhythmias and/or hypertension when used concomitantly with epinephrine.
    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.
    Amphetamines: (Moderate) Amphetamines may potentiate the pressor effects of epinephrine.
    Angiotensin II receptor antagonists: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Angiotensin-converting enzyme inhibitors: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Atenolol; Chlorthalidone: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (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.
    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.
    Azelastine; Fluticasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Azilsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Azilsartan; Chlorthalidone: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Beclomethasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Benazepril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Bendroflumethiazide; Nadolol: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (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.
    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.
    Betamethasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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.
    Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
    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.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (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.
    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.
    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.
    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.
    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.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Brompheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Budesonide: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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. (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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. (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Bumetanide: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
    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.
    Caffeine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
    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.
    Calcium-channel blockers: (Moderate) Antihypertensives, including calcium-channel blockers, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    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.
    Candesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Captopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Carbetapentane; Chlorpheniramine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
    Carbetapentane; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Carbinoxamine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    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.
    Cetirizine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Chlorothiazide: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Codeine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Dextromethorphan: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Hydrocodone: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Phenylephrine: (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    Chlorpheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics. (Moderate) Chlorpheniramine may potentiate the arrhythmogenic effects of epinephrine.
    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.
    Chlorthalidone: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Chlorthalidone; Clonidine: (Moderate) Clonidine may potentiate the pressor effects of epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Ciclesonide: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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.
    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.
    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.
    Clonidine: (Moderate) Clonidine may potentiate the pressor effects of epinephrine.
    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.
    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.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    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.
    Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    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.
    Corticosteroids: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Cortisone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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.
    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.
    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.
    Deflazacort: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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.
    Desloratadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    Dexamethasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Dexbrompheniramine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    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.
    Diethylpropion: (Major) Diethylpropion has vasopressor effects. Coadministration with other vasopressors may have the potential for serious cardiac adverse effects such as hypertensive crisis and cardiac arrhythmias.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Dihydroergotamine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    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.
    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.
    Diphenhydramine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
    Diphenhydramine; Ibuprofen: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
    Diphenhydramine; Naproxen: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
    Diphenhydramine; Phenylephrine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
    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.
    Dobutamine: (Moderate) Dobutamine may potentiate the pressor effects of epinephrine.
    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.
    Dopamine: (Moderate) Monitor blood pressure during concomitant use of dopamine and other vasopressors, such as epinephrine, due to the risk for severe hypertension.
    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.
    Doxapram: (Moderate) Doxapram may potentiate the pressor effects of epinephrine.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Enalapril, Enalaprilat: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Enalapril; Felodipine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    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.
    Eplerenone: (Moderate) Antihypertensives, including eplerenone, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    Eprosartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Ergoloid Mesylates: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Ergonovine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Ergot alkaloids: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Ergotamine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Ergotamine; Caffeine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension. (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
    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.
    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.
    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.
    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.
    Ethacrynic Acid: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    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.
    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.
    Fexofenadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    Fludrocortisone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Flunisolide: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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.
    Fluticasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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. (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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. (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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. (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Food: (Major) Avoid concurrent use of marijuana and epinephrine as 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.
    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.
    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. (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Fosinopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Furosemide: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    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.
    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.
    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.
    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.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Guaifenesin; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Guanabenz: (Moderate) Sympathomimetics can antagonize the antihypertensive effects of guanabenz when administered concomitantly. Patients should be monitored for loss of blood pressure control.
    Guanfacine: (Moderate) Antihypertensives, including guanfacine, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    Hydralazine; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Hydrocodone; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Hydrocortisone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Ibuprofen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Ionic Contrast Media: (Major) The intravascular injection of a contrast medium should never be made after the administration of vasopressors since they strongly potentiate neurologic effects. Serious neurologic sequelae, including permanent paralysis, have been reported after cerebral arteriography, selective spinal arteriography, and arteriography of vessels supplying the spinal cord.
    Ipratropium; 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.
    Irbesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Levomilnacipran: (Major) Due to the effects of levomilnacipran on noradrenergic pathways, paroxysmal hypertension and arrhythmias may occur during concurrent use of epinephrine.
    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.
    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.
    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.
    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.
    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.
    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.
    Lisinopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    Loop diuretics: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    Loratadine; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Losartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Methyclothiazide: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Methyldopa: (Moderate) Antihypertensives, including methyldopa, antagonize the vasopressor effects of parenteral epinephrine.
    Methylergonovine: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Methylphenidate Derivatives: (Moderate) Methylphenidate derivatives can potentiate the actions of both exogenous (such as dopamine and epinephrine) and endogenous (such as norepinephrine) vasopressors. It is advisable to monitor cardiac function if these medications are coadministered. Vasopressors include medications such as epinephrine, dopamine, midodrine, and non-prescription medications such as pseudoephedrine and phenylephrine.
    Methylprednisolone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Methysergide: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Metolazone: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (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.
    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.
    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.
    Moexipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Mometasone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    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.
    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.
    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.
    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.
    Naproxen; Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    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.
    Nebivolol; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (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.
    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.
    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.
    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.
    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.
    Olanzapine; Fluoxetine: (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.
    Olanzapine; Samidorphan: (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.
    Olmesartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    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.
    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.
    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.
    Pergolide: (Major) Avoid concomitant use of ergot alkaloids and vasopressors due to synergistic vasoconstriction and severe hypertension.
    Perindopril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Perindopril; Amlodipine: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    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.
    Phendimetrazine: (Major) Phendimetrazine is a phenylalkaline sympathomimetic agent. All sympathomimetics and psychostimulants, including other anorexiants, should be used cautiously or avoided in patients receiving phendimetrazine. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmia.
    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.
    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.
    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.
    Phentermine: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias.
    Phentermine; Topiramate: (Major) Because phentermine is a sympathomimetic and anorexic agent (i.e., psychostimulant) it should not be used in combination with other sympathomimetics. The combined use of these agents may have the potential for additive side effects, such as hypertensive crisis or cardiac arrhythmias.
    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.
    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.
    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.
    Pioglitazone; Glimepiride: (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.
    Pioglitazone; 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.
    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.
    Potassium-sparing diuretics: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    Prednisolone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Prednisone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Probenecid; Colchicine: (Minor) The response to sympathomimetics may be enhanced by colchicine.
    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.
    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.
    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.
    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.
    Promethazine; Dextromethorphan: (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.
    Promethazine; Phenylephrine: (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.
    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.
    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.
    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.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (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.
    Pseudoephedrine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Pseudoephedrine; Triprolidine: (Major) Pseudoephedrine can potentiate the effects and increase the toxicity of other sympathomimetics by adding to their sympathomimetic activity. Although no data are available, pseudoephedrine should be used cautiously in patients using significant quantities of other sympathomimetics.
    Quinapril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using racepinephrine inhalation are advised to avoid other non-prescription products containing sympathomimetics since additive adverse effects on the cardiovascular and nervous system are possible, some which may be undesirable. Side effects such as nausea, tremor, nervousness, difficulty with sleep, and increased heart rate or blood pressure may be additive. Patients should avoid use of non-prescription decongestants, such as phenylephrine and pseudoephedrine, while using racepinephrine inhalations. Patients should avoid dietary supplements containing ingredients that are reported or claimed to have a stimulant or weight-loss effect, such as ephedrine and ephedra, Ma huang, and phenylpropanolamine.
    Ramipril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    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.
    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.
    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.
    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.
    Sacubitril; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Solriamfetol: (Moderate) Monitor blood pressure and heart rate during coadministration of solriamfetol, a norepinephrine and dopamine reuptake inhibitor, and vasopressors. Concurrent use of solriamfetol and other medications that increase blood pressure and/or heart rate may increase the risk of such effects. Coadministration of solriamfetol with other drugs that increase blood pressure or heart rate has not been evaluated.
    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.
    Spironolactone: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    Telmisartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Telmisartan; Amlodipine: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    Terbutaline: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Theophylline, Aminophylline: (Moderate) Concurrent administration of theophylline or aminophylline with sympathomimetics can produce excessive stimulation manifested by skeletal muscle activity, agitation, and hyperactivity. (Moderate) Theophylline may potentiate the hypokalemic effects of epinephrine.
    Thiazide diuretics: (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    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.
    Torsemide: (Moderate) Loop diuretics may antagonize the pressor effects and potentiate the arrhythmogenic and hypokalemic effects of epinephrine.
    Trandolapril: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    Trandolapril; Verapamil: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine.
    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.
    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.
    Triamcinolone: (Moderate) Corticosteroids may potentiate the hypokalemic effects of epinephrine.
    Triamterene: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    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.
    Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine.
    Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
    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.
    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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    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]

    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.
     
    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.

    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

    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.

    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.

    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.
     
    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.