Epinephrine is a nonselective adrenergic agonist with a high affinity for beta1-, beta2-, and alpha1-receptors. Exogenous epinephrine is a sympathomimetic catecholamine with dose-dependent effects; beta-adrenergic effects (e.g., inotropy, vasodilation) are more pronounced at low doses and alpha-adrenergic effects (e.g., vasoconstriction) at high doses. Epinephrine has many therapeutic applications. Intramuscular epinephrine is the drug of choice for anaphylaxis. Intravenous epinephrine is recommended during cardiopulmonary resuscitation, specifically for the treatment of symptomatic bradycardia, cardiac arrest, and as an adjunct to electrical defibrillation in ventricular fibrillation/pulseless ventricular tachycardia. Additionally, epinephrine is used for hypotension, fluid-resistant shock, and inotropic support in a variety of settings (e.g., postresuscitation and postoperative). Intravenous epinephrine is the vasopressor of choice in anaphylactic shock, as it provides beta2 stimulation. In patients with sinus node dysfunction or second- or third-degree atrioventricular block associated with symptoms of hemodynamic compromise who are at a low likelihood of coronary ischemia, epinephrine may be considered to increase heart rate, improve atrioventricular conduction, increase ventricular rate, and improve symptoms. Inhaled epinephrine is used as a bronchodilator for the treatment of severe croup symptoms in young children. However, clinical guidelines do not recommend inhaled epinephrine in asthma or bronchiolitis. Additionally, injectable epinephrine is only recommended as an adjunct to standard asthma therapy for an acute exacerbation associated with anaphylaxis and angioedema or for an exacerbation unresponsive to standard therapy.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use solutions that are pinkish to brownish in color, cloudy, or contain a precipitate or particulate matter.
-Avoid extravasation and inadvertent digital or intraarterial injection.
-Never inject epinephrine or epinephrine-containing products into extremities such as fingers, toes, hands, or feet.
-Do not administer repeated injections at the same site.
-If extravasation or accidental injection occurs, infiltrate the ischemic area as soon as possible with phentolamine.
-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.
Intravenous Administration
-Use a central vein whenever possible. If peripheral administration is necessary, use a 20-gauge or larger catheter. Administration via a low-lying umbilical venous catheter provides the most rapid and reliable medication delivery in neonates. Avoid administration in an ankle vein.
-Check the infusion site 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.
-Epinephrine is inactivated in alkaline solutions; it is incompatible with sodium bicarbonate.
IV Push
-May administer at a concentration of 0.1 mg/mL directly into the vein.
-Do not interrupt CPR to administer epinephrine. Administer epinephrine during chest compressions; the timing of drug administration is less important than the need to minimize chest compression interruption.
-Follow administration with a saline flush to promote entry into central circulation.
Continuous IV infusion
Dilution
-Dilute with a compatible IV solution prior to administration. 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.
-ASHP Recommended Standard Concentrations for Adult Continuous Infusions: 20 mcg/mL or 40 mcg/mL.
-ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 20 mcg/mL or 40 mcg/mL.
-Infants, children, and adolescents: Concentrations of 16 mcg/mL, 32 mcg/mL, and 64 mcg/mL have been commonly used; maximum concentration should not exceed 64 mcg/mL.
-Neonates: Maximum concentration should not exceed 60 mcg/mL.
Administration
-Administer via a large vein, whenever possible. Avoid using a catheter tie-in technique.
-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.
Extravasation Management
-Stop the infusion or injection immediately.
-Before removing the catheter or needle, attempt to aspirate fluid from the extravasated area.
-Elevate the affected limb to minimize swelling and encourage lymphatic resorption of the drug.
-Apply warm compresses to modify viscosity, increase local blood flow, and enhance drug removal.
-Adults: Infiltrate the area with 10 to 15 mL of a saline solution containing 5 to 10 mg of phentolamine.
-Infants, children, and adolescents: Infiltrate the area with 1 to 5 mL (in 5 divided doses) of a solution containing preservative free saline and phentolamine at a concentration of 0.5 to 1 mg/mL. FDA-approved labeling recommends infiltrating the area with 10 to 15 mL of a saline solution containing 5 to 10 mg of phentolamine.
-Neonates: Infiltrate the area with 1 mL (in 5 divided doses of 0.2 mL) of a solution containing preservative free saline 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. The solution can also be administered through the infiltrated cannula, if still in place.
-Sympathetic blockade with phentolamine causes immediate and noticeable local hyperemic changes if the area is infiltrated within 12 hours of extravasation.
-May redose phentolamine if the patient remains symptomatic.
-Alternatives to phentolamine include topical nitroglycerin 2% (apply 1-inch strip to area, may redose every 8 hours) and terbutaline (1 mg in 10 mL saline, injected locally).
-Digital ischemia may require smaller administration volumes.
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 injection into or near smaller muscles, such as the deltoid, due to possible differences in absorption.
-Instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during the injection.
-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.
-Consult product-specific labeling for device use instructions. Recommended "hold times" may vary among devices.
-Most auto-injectors and prefilled syringes are for single-use only. Instruct patients to carry 2 auto-injectors in case 2 doses are needed or if the first auto-injector is activated before the dose can be given.
-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 into the anterolateral aspect of the thigh, through clothing if necessary. Do NOT inject into the buttock, digits, hands, or feet. Avoid injection into or near smaller muscles, such as the deltoid, due to possible differences in absorption.
-Instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during the injection.
-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.
-Consult product-specific labeling for device use instructions. Recommended "hold times" may vary among devices.
-Most auto-injectors and prefilled syringes are for single-use only. Instruct patients to carry 2 auto-injectors in case 2 doses are needed or if the first auto-injector is activated before the dose can be given.
-Instruct patients to seek medical attention immediately after administration of the first injection.
Other Injectable Administration
Intraosseous Administration
NOTE: Epinephrine is not FDA-approved for intraosseous administration.
-During cardiopulmonary resuscitation, the same dosage may be given via the intraosseous route if IV access is unsuccessful or not feasible.
-Follow administration with a saline flush to promote entry into central circulation.
Intracardiac Administration
-Reserve for extreme emergencies. Use only if physical or electromechanical methods are unsuccessful and there is not sufficient time to establish an intravenous route.
-Only medical personnel well-trained in technique should administer intracardiac medications.
-Follow administration with external cardiac massage to permit the drug to enter the coronary circulation.
Topical Administration
Other Topical Formulations
Topical Nasal Administration
-Do not use solutions that are pinkish to brownish in color.
-Dilute the 1 mg/mL epinephrine solution with isotonic salt solution to a final concentration of 0.1, 0.2, or 0.5 mg/mL prior to administration.
-Apply locally as drops, spray, or with a sterile swab.
Inhalation Administration
Oral Inhalation Administration
Inhalation Solution (Primatene Mist Aerosol Spray, nonprescription product)
-Before first use, activate the inhaler by shaking well and then prime into the air with 4 pumps.
-Shake well and then prime into the air with 1 pump before each subsequent use.
-Exhale completely and place mouthpiece into mouth. Inhale deeply while pressing down on the top of inhaler, then continue the deep breath.
-Hold breath as long as possible before exhaling.
-Wait at least 1 minute. If symptoms are not relieved, take a second inhalation.
-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.
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 the product 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.
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 a final concentration of 1 to 10 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 a final concentration of 2.5 to 10 mcg/mL.
-Inject a bolus dose of 0.1 mL of diluted solution intracamerally.
Other Administration Route(s)
Endotracheal Administration
NOTE: Epinephrine is not FDA-approved for endotracheal (ET) administration.
-Consider ET administration only when other access is not available. ET administration is the least-preferred route of administration due to its association with unpredictable (but generally low) drug concentrations and lower rates of ROSC and survival.
-If CPR is in progress, stop chest compressions briefly and administer the medication.
-Adults: Dilute the dose in 5 to 10 mL of saline or sterile water. Studies suggest dilution with sterile water may achieve better drug absorption compared to saline.
-Infants, children, and adolescents: Use the 1 mg/mL parenteral solution. Dilute the dose in 1 to 5 mL of saline or follow drug administration with a saline flush (5 mL or more) and 5 consecutive positive-pressure ventilations.
-Neonates: Use the 0.1 mg/mL parenteral solution. Dilute the dose in 1 to 5 mL of saline or follow drug administration with a saline flush and 5 consecutive positive-pressure ventilations. If response is inadequate, it may be reasonable to administer an epinephrine dose as soon as IV or IO access is obtained, regardless of the interval.
Transient and moderate anxiety, disorientation, hyperactivity, restlessness, apprehension, excitability, memory impairment, nervousness, panic, psychomotor agitation, weakness, dizziness, drowsiness, lightheadedness, headache, tingling, and tremor may occur with therapeutic doses of systemic epinephrine and are more likely in patients with hypertension or hyperthyroidism. Paresthesias, stroke, and central nervous system bleeding have been reported with intravenous epinephrine infusion.
Adrenergically modulated vasoactive and smooth muscle responses to epinephrine can result in nausea, vomiting, diaphoresis, pallor, respiratory distress, respiratory weakness, dyspnea, or apnea. These reactions can occur with therapeutic doses of epinephrine and are more likely to occur in patients with heart disease, hypertension, or hyperthyroidism.
Cardiac arrhythmias (or arrhythmia exacerbation), including palpitations, premature ventricular contractions (PVCs), sinus tachycardia, supraventricular tachycardia (SVT), and severe ventricular arrhythmias (ventricular fibrillation, ventricular tachycardia), are well described potential adverse effects of epinephrine due to beta-stimulation of the myocardium and conduction system. Myocardial ischemia and myocardial infarction have also been associated with epinephrine infusion. Chest pain (unspecified) and angina may occur, the latter occurring more frequently in adult patients with coronary artery disease. Stress cardiomyopathy has been reported rarely in patients treated with systemic epinephrine. Patients at risk for epinephrine-induced arrhythmias and ischemia include those with organic heart disease, coronary artery disease, cerebrovascular disease, high blood pressure, and those receiving drugs that sensitize the myocardium. Severe hypertension may occur in patients receiving intravenous epinephrine. Hypertension occurring quickly has resulted in cerebral hemorrhage, especially in patients with cardiovascular disease. When epinephrine is administered as a continuous intravenous infusion, vital signs should be monitored during titration; invasive arterial blood pressure monitoring and central venous pressure monitoring are recommended. Peripheral constriction and cardiac stimulation produced by intravenous administration of epinephrine may result in pulmonary edema. If pulmonary edema occurs, administer a rapid acting alpha-adrenergic blocking drug (e.g., phentolamine) and provide respiratory support. Rales have also been reported. The potential for these serious cardiovascular risks should not outweigh the beneficial effects of the use of epinephrine for acute, life-threatening conditions.
Epinephrine administration may lead to local and/or peripheral vasoconstriction depending on the route of administration. Accidental injection into the fingers, hands, or feet may result in loss of blood flow to those areas which may present as site pallor, coldness, or hypoesthesia. Extravasation of epinephrine, especially with repeated injections or high infusion rates, can result in an injection site reaction leading to severe tissue damage and tissue necrosis. When epinephrine is administered intravenously, the infusion site should be checked frequently for free flow. If skin blanching along the course of the infused vein occurs, consider changing the infusion site at intervals to allow the effects of local vasoconstriction to subside. If extravasation of intravenous drug or accidental digital injection occurs, infiltrate a diluted phentolamine solution into the area as soon as possible to antagonize vasoconstriction and reduce and/or prevent devastating sloughing and tissue necrosis. Phentolamine causes sympathetic blockage resulting in immediate and conspicuous local hyperemic changes if the area is infiltrated within 12 hours. Skin laceration and bent or embedded needles have been reported when epinephrine has been injected into the thigh of young children who are uncooperative; caregivers should be instructed to hold the child's leg firmly to limit movement prior to and during injection. Rare cases of serious skin and soft tissue infection, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene) have been reported at the epinephrine injection site when used for anaphylaxis. Cleansing with alcohol does not kill bacterial spores and does not lower the risk; intramuscular and subcutaneous epinephrine for anaphylaxis should only be administered into the anterolateral aspect of the thigh (not the buttock). Patients should seek medical care if they develop signs and symptoms of infection at the injection site (e.g., persistent redness, warmth, swelling, tenderness). Injection site ecchymosis, bleeding, skin discoloration, erythema, and skeletal injury have also been associated with intramuscular and subcutaneous use. Piloerection, a common sympathetic reflex, has been associated with intravenous administration.
Transient increases in blood sugar or hyperglycemia may occur in diabetic patients administered inhaled or systemic epinephrine. Hypoglycemia and insulin resistance also has been reported with the intravenous use of epinephrine. Hypokalemia has been reported. Metabolic acidosis secondary to lactic acidosis has been associated with long-term administration or overdose of epinephrine.
Intravenously administered epinephrine may initially produce constriction of renal blood vessels, resulting in oliguria. Renal insufficiency has been associated with intravenous infusion.
Appropriate product selection and proper dilution with the intraocular use of epinephrine are imperative. Certain excipients may be harmful to the eye when used ophthalmically. For example, epinephrine products containing sodium bisulfite have been associated with corneal endothelial damage and corneal edema when used in the eye at undiluted concentrations (1 mg/mL).
Although there are no absolute contraindications to the use of parenteral epinephrine when used in acute, life-threatening situations, some product labeling describe epinephrine as contraindicated in persons with known hypersensitivity to sympathomimetic amines, such as epinephrine.
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. Certain epinephrine formulations that are intended only for hypersensitivity reactions, cardiac resuscitation, ophthalmological use, or regional anesthesia are contraindicated in nonanaphylactic shock. 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.
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.
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.
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).
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.
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.
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.
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.
Use systemic epinephrine cautiously in persons with renal impairment. When administered intravenously, epinephrine may produce constriction of renal blood vessels and a decrease in urine formation.
Dilute epinephrine injection prior to intraocular use. Use only the 1 mg/mL single use vial or ampule specifically intended for ophthalmic administration; concentration and formulation affect the safety of ophthalmic administration. Epinephrine products containing sodium bisulfite have been associated with corneal endothelial damage when used in the eye at undiluted concentrations (1 mg/mL).
Use epinephrine with caution in persons with Parkinson's disease. Persons with Parkinson's disease may experience psychomotor agitation or a temporary worsening of symptoms.
Geriatric persons may be particularly sensitive to the effects of epinephrine at greater risk of developing adverse reactions when epinephrine is administered parenterally. In general, use caution in selecting the epinephrine dose for older adults, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Avoid administration in the veins of the leg in older adults.
Lacerations, bent needles, and embedded needles have been reported when epinephrine has been injected into the thigh of infants and young children who are uncooperative and kick or move during an injection. To minimize the risk of injury, instruct caregivers to hold the leg of young children firmly in place and limit movement prior to and during injection.
Do not withhold or delay life-sustaining therapy during pregnancy due to potential concerns regarding the effects of epinephrine on the fetus. Limited published data on epinephrine use in human pregnancy are not sufficient to determine a drug-associated risk of major birth defects or miscarriage. In animal reproduction studies, epinephrine demonstrated adverse developmental effects (e.g., gastroschisis, embryonic lethality, delayed skeletal ossification) when administered during organogenesis at doses approximately 2 to 15 times the maximum recommended daily dose. Avoid epinephrine during the second stage of labor or during obstetric delivery when the maternal blood pressure exceeds 130/80 mmHg. Epinephrine usually inhibits spontaneous or oxytocin-induced uterine contractions and may delay the second stage of labor, potentially resulting in a prolonged period of uterine atony with hemorrhage. Although epinephrine may improve maternal hypotension associated with septic shock and anaphylaxis, it can cause uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia. Although there are no absolute contraindications to the use of parenteral epinephrine when used in acute, life-threatening situations, some product labeling describe epinephrine as contraindicated during labor or in obstetrics when the maternal blood pressure exceeds 130/80 mmHg.
Parenteral epinephrine is the first-line medication for acute, life-threatening situations; it should be used in the same manner for breast-feeding and non-breast-feeding persons. There is no information regarding the presence of epinephrine in human milk or its effects on the breast-fed infant or milk production. Epinephrine exposure is expected to be very low in the breast-fed infant due to poor bioavailability and short half-life. The lack of clinical data during lactation precludes a clear determination of the risk of epinephrine to a breast-fed infant.
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 in the treatment of anaphylaxis due to delayed absorption.
Intramuscular or Subcutaneous dosage (general dosing):
Adults: 0.2 to 0.5 mg IM or subcutaneously; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.
Children and Adolescents weighing more than 30 kg: 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM or subcutaneously; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.
Infants and Children weighing 30 kg or less: 0.01 mg/kg/dose (Max: 0.3 mg/dose) IM or subcutaneously; may repeat the dose every 5 to 15 minutes as needed for up to 3 injections. If there is no response after 3 to 4 injections, consider an intravenous infusion.
Intramuscular or Subcutaneous dosage (Adrenaclick, Auvi-Q, EpiPen, Symjepi auto-injector/prefilled syringe):
Adults: 0.3 mg/dose IM or subcutaneously; may repeat the dose 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; may repeat the dose 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: 0.15 mg/dose IM or subcutaneously; may repeat the dose for severe persistent anaphylaxis. Some experts recommend 0.3 mg/dose. 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; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.
Infants and Children weighing 10 to 14 kg: 0.1 mg/dose IM or subcutaneously; may repeat the dose for severe persistent anaphylaxis. Some experts recommend 0.15 mg/dose. The patient should not administer more than 2 sequential doses unless under direct medical supervision.
Infants and Children weighing 7.5 to 9 kg: 0.1 mg/dose IM or subcutaneously; may repeat the dose for severe persistent anaphylaxis. The patient should not administer more than 2 sequential doses unless under direct medical supervision.
Intravenous dosage:
Adults: 0.05 to 0.1 mg (of a 0.1 mg/mL solution) IV every 5 to 15 minutes as needed. Intravenous epinephrine given by boluses may be considered for anaphylactic shock when an IV line is in place.
Infants, Children, and Adolescents: 0.01 mg/kg/dose (0.1 mL/kg/dose of a 0.1 mg/mL solution) IV every 3 to 5 minutes as needed. Max: 1 mg/dose (10 mL/dose of a 0.1 mg/mL solution).
Continuous Intravenous Infusion dosage:
Adults: 2 mcg/minute continuous IV infusion, initially. Titrate dose according to blood pressure, cardiac rate, and oxygenation. Max: 15 mcg/minute. Intravenous epinephrine given by continuous infusion may be considered if inadequate response to IM epinephrine and intravenous saline or as an alternative to IV boluses for anaphylactic shock in persons not in cardiac arrest.
Infants, Children, and Adolescents: 0.1 to 1 mcg/kg/minute continuous IV infusion. Titrate dose according to blood pressure, cardiac rate, and oxygenation. Intravenous epinephrine given by continuous infusion may be considered if inadequate response to IM epinephrine and intravenous saline.
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 as needed for up to 3 doses. Guidelines state there is no proven advantage of systemic therapy over the use of inhaled short-acting beta-agonists.
Adolescents: 0.3 to 0.5 mg subcutaneously every 20 minutes as needed for up to 3 doses. Guidelines state there is no proven advantage of systemic therapy over the use of inhaled short-acting beta-agonists.
Children 1 to 12 years: 0.01 mg/kg/dose (Max: 0.5 mg/dose) subcutaneously every 20 minutes as needed for up to 3 doses may be given if an inhaled short-acting beta-agonist (e.g., albuterol) is not available. Guidelines state there is no proven advantage of systemic therapy over the use of inhaled short-acting beta-agonists.
Intramuscular dosage:
Adults: 0.3 to 0.5 mg/dose IM every 5 to 15 minutes as needed for up to 3 doses. Reserved for patients with poor inspiratory flow, those who cannot cooperate with inhaled therapy, or those with severe asthma with suboptimal response to initial aerosolized therapy. 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 doses. Reserved for patients with poor inspiratory flow, those who cannot cooperate with inhaled therapy, or those with severe asthma with suboptimal response to initial aerosolized therapy. 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 doses. Reserved for patients with poor inspiratory flow, those who cannot cooperate with inhaled therapy, or those with severe asthma with suboptimal response to initial aerosolized therapy. 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)*:
Respiratory (Inhalation) dosage (solution for injection):
Infants and Children 6 months to 12 years: 0.5 mL/kg/dose (Max: 5 mL/dose) of 1 mg/mL solution diluted in 2 to 2.5 mL of saline inhaled by nebulizer every 20 minutes as needed as an alternative if racemic epinephrine is not available; 5 mL of L-epinephrine 1 mg/mL is equivalent to 0.5 mL of racemic epinephrine 2.25%. In general, improvement is seen within 10 to 30 minutes and lasts 2 hours after administration.
For the treatment of acute, severe urticaria or angioedema associated with systemic symptoms:
Intramuscular or Subcutaneous dosage:
Adults: 0.3 to 0.5 mL of 1 mg/mL solution subcutaneously or IM every 1 to 2 hours.
For use in cardiopulmonary resuscitation (CPR), specifically, for the treatment of cardiac arrest (pulseless electrical activity or ventricular asystole), or as an adjunct to electrical defibrillation in the treatment of ventricular fibrillation/pulseless ventricular tachycardia:
Intravenous or Intraosseus* dosage:
Adults: 1 mg IV or IO every 3 to 5 minutes as needed. For a nonshockable rhythm, administer epinephrine as soon as possible. For a shockable rhythm, administer epinephrine after initial defibrillation attempts have failed. High-dose epinephrine is not recommended for routine use. Do not interrupt CPR to administer drug therapy.
Infants*, Children*, and Adolescents*: 0.01 mg/kg/dose (Max: 1 mg/dose) IV or IO every 3 to 5 minutes as needed. High-dose epinephrine is not recommended for routine use. Do not interrupt CPR to administer drug therapy.
Neonates*: 0.01 to 0.03 mg/kg/dose IV or IO every 3 to 5 minutes as needed. High-dose epinephrine is not recommended for routine use. Do not interrupt CPR to administer drug therapy.
Endotracheal dosage:
NOTE: Endotracheal drug administration is the least preferred route of administration because of its association with unpredictable (but generally low) drug concentrations and lower rates of survival.
Adults: 2 to 2.5 mg ET every 3 to 5 minutes as needed until vascular access is obtained. For a nonshockable rhythm, administer epinephrine as soon as possible. For a shockable rhythm, administer epinephrine after initial defibrillation attempts have failed.
Infants*, Children*, and Adolescents*: 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET every 3 to 5 minutes as needed until vascular access obtained.
Neonates*: 0.05 to 0.1 mg/kg/dose ET every 3 to 5 minutes as needed until vascular access is obtained.
Intracardiac dosage*:
NOTE: Reserve for extreme emergencies. Use only if physical or electromechanical methods are unsuccessful and there is not sufficient time to establish an intravenous route. Only medical personnel well-trained in technique should administer intracardiac medications.
Adults: 0.3 to 0.5 mg intracardially. Follow administration with external cardiac massage to permit the drug to enter the coronary circulation.
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; titrate to desired effect.
Neonates*: 0.1 to 1 mcg/kg/minute continuous IV or IO infusion; titrate to desired effect.
-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.
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.
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.
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. After hemodynamic stabilization, wean incrementally every 10 to 30 minutes over a 12- to 24-hour period. 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.
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.
For the treatment or prevention of surgical bleeding along a surgical incision:
Topical dosage:
Adults: Apply 0.002% to 0.1% solutions topically.
For the treatment of open-angle glaucoma:
Ophthalmic dosage (epinephrine ophthalmic solution 0.5%, 1% or 2%; e.g., Epifrin):
Adults: NOTE: These products are discontinued in the U.S. Instill 1 to 2 drops of 0.5%, 1% or 2% ophthalmic solution into affected eye(s) once or twice daily.
For the treatment of acute chloroquine overdose* in combination with diazepam:
Intravenous dosage:
Adults: Initially, 0.25 mcg/kg/minute and increase by 0.25 mcg/kg/minute to maintain a systolic blood pressure of 100 mmHg or more in combination with IV diazepam, general anesthesia with thiopental, and FiO2 40%. Diazepam was continued for 2 to 4 additional days. Other vasopressors and/or inotropic agents were used as necessary. Eleven cases of acute chloroquine overdose (total ingested dose ranged from 5 to 12 g) were treated with epinephrine; 10 patients were discharged alive from the hospital. The 1 patient who died ingested the largest total dose (15 g) of chloroquine.
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 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.
Maximum Dosage Limits:
-Adults
Dependent on route of administration and indication for therapy.
-Geriatric
Dependent on route of administration and indication for therapy.
-Adolescents
Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.5 mg/dose IM/subcutaneously and 1 mg/dose IV). For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM/subcutaneously or 8 oral inhalations/24 hours of epinephrine 0.125 mg oral inhalation (e.g., Primatene Mist inhaler, non-prescription).
-Children
12 years: Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.5 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM/subcutaneously or 8 oral inhalations/24 hours of epinephrine 0.125 mg oral inhalation (e.g., Primatene Mist inhaler, non-prescription).
4 to 11 years weighing more than 30 kg: Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.5 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose) IM/subcutaneously.
4 to 11 years weighing 30 kg or less: Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.3 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose subcutaneously and 0.3 mg/dose IM).
1 to 3 years: Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.3 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose subcutaneously and 0.3 mg/dose IM).
-Infants
Dependent on route of administration and indication for therapy. For CPR, 0.01 mg/kg/dose (Max: 1 mg/dose) IV/IO and 0.1 mg/kg/dose (Max: 2.5 mg/dose) ET. For anaphylaxis, 0.01 mg/kg/dose (Max: 0.3 mg/dose IM/subcutaneously and 1 mg/dose IV). For croup, 0.5 mL/dose of a 2.25% racemic epinephrine solution. For bronchospasm, 0.01 mg/kg/dose (Max: 0.5 mg/dose subcutaneously and 0.3 mg/dose IM).
-Neonates
Dependent on route of administration and indication for therapy. For CPR, 0.03 mg/kg/dose IV and 0.1 mg/kg/dose ET.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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; Aspirin; Diphenhydramine: (Moderate) Diphenhydramine may potentiate the arrhythmogenic effects of epinephrine.
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; Pyrilamine: (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; 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) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic 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.
Albuterol: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
Albuterol; Budesonide: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Aliskiren: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including aliskiren, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Alogliptin; Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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) Monitor blood pressure and heart rate during concomitant amphetamine and epinephrine use. 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; 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; Orphenadrine: (Moderate) Caffeine is a CNS-stimulant and such actions are expected to be additive when coadministered with other CNS stimulants or psychostimulants.
Atenolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Atenolol; Chlorthalidone: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Atomoxetine: (Moderate) Use atomoxetine with caution and monitor blood pressure in patients receiving concomitant epinephrine due to potential effects on blood pressure.
Azelastine; Fluticasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Beclomethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Beta-blockers: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Betamethasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Betaxolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bethanechol: (Moderate) Bethanechol offsets the effects of sympathomimetics at sites where sympathomimetic and cholinergic receptors have opposite effects.
Bexagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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.
Bisoprolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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; 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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Budesonide; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Bumetanide: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. 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.
Butalbital; Aspirin; 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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.
Cardiac glycosides: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
Carteolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Carvedilol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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; Hydrocodone: (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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Chlorthalidone; Clonidine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. Clonidine may potentiate the pressor effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Ciclesonide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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.
Clonidine: (Moderate) Monitor blood pressure and heart rate during concomitant clonidine and epinephrine use. 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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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.
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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Cortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Dapagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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.
Digoxin: (Moderate) Carefully monitor patients receiving cardiac glycosides and vasopressors concurrently due to the increased risk of arrhythmia.
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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking dipeptidyl peptidase-4 (DPP-4) inhibitors. 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; 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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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; Hydrochlorothiazide, HCTZ: (Moderate) Antihypertensives, including angiotensin-converting enzyme inhibitors, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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.
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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Ethacrynic Acid: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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.
Fludrocortisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Flunisolide: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Fluphenazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Fluticasone; Salmeterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects.
Formoterol; Mometasone: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic effects. (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Furosemide: (Moderate) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. 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.
Glycopyrrolate; Formoterol: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and formoterol use. Concomitant use may potentiate sympathetic 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; 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.
Guanfacine: (Moderate) Antihypertensives, including guanfacine, antagonize the vasopressor effects of parenteral epinephrine.
Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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; 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking insulin. 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) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Levalbuterol: (Moderate) Monitor blood pressure and heart rate during concomitant albuterol and epinephrine use. Concomitant use may potentiate sympathetic effects.
Levobunolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Levomilnacipran: (Major) Due to the effects of levomilnacipran on noradrenergic pathways, paroxysmal hypertension and arrhythmias may occur during concurrent use of epinephrine.
Levothyroxine: (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Levothyroxine; Liothyronine (Porcine): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Levothyroxine; Liothyronine (Synthetic): (Moderate) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
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) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Liraglutide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Lixisenatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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.
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.
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.
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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Metolazone: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Metoprolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. 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.
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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nebivolol; Valsartan: (Moderate) Antihypertensives, including angiotensin II receptor antagonists, antagonize the vasopressor effects of parenteral epinephrine. (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Nicotine: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and nicotine use. Concomitant use may potentiate sympathetic effects.
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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Olopatadine; Mometasone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic 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.
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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Pioglitazone: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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.
Potassium-sparing diuretics: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. 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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Prednisone: (Moderate) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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.
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: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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.
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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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) Monitor blood pressure and heart rate during concomitant epinephrine and salmeterol use. Concomitant use may potentiate sympathetic 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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 tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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.
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.
Sotagliflozin: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking SGLT2 inhibitors. 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.
Sotalol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Spironolactone: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
St. John's Wort, Hypericum perforatum: (Moderate) Monitor blood pressure during concomitant use of epinephrine and St. John's Wort. Patients receiving St. John's Wort may experience severe, prolonged hypertension when given epinephrine. St. John's Wort has been shown to weakly inhibit monoamine oxidase and may potentiate the pressor effects of epinephrine.
Sulfonylureas: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking sulfonylureas. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Thiazolidinediones: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking thiazolidinediones. 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.
Thioridazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor hemodynamic parameters during concomitant sympathomimetic agent and thyroid hormone use; dosage adjustments may be necessary. Concomitant use may increase the effects of sympathomimetics or thyroid hormone.
Timolol: (Moderate) Monitor hemodynamic parameters and for loss of efficacy during concomitant sympathomimetic agent and beta-blocker use; dosage adjustments may be necessary. Concomitant use may antagonize the cardiovascular effects of either drug.
Tirzepatide: (Moderate) Sympathomimetic agents tend to increase blood glucose concentrations when administered systemically. Monitor for loss of glycemic control when sympathomimetics are administered to patients taking incretin mimetics. 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.
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) Monitor blood pressure, heart rate, and serum potassium during concomitant epinephrine and loop diuretic use. 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) Monitor potassium concentrations during concomitant corticosteroid and epinephrine use due to risk for additive hypokalemia; potassium supplementation may be necessary. Corticosteroids may potentiate the hypokalemic effects of epinephrine.
Triamterene: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and potassium-sparing diuretic use. Potassium-sparing diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine. (Moderate) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. Thiazide diuretics may antagonize the pressor effects and potentiate the arrhythmogenic effects of epinephrine.
Tricyclic antidepressants: (Major) Avoid use of epinephrine and tricyclic antidepressants as tricyclic antidepressants may potentiate the vasopressor effects of epinephrine.
Trifluoperazine: (Moderate) Monitor blood pressure during concomitant epinephrine and phenothiazine use. 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) Monitor blood pressure and heart rate during concomitant epinephrine and thiazide diuretic use. 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.
Zavegepant: (Moderate) Administer intranasal decongestants at least 1 hour after zavegepant administration. Simultaneous coadministration may decrease zavegepant absorption which may reduce its efficacy.
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.
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.
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.
Affected cytochrome P450 isoenzymes: none
-Route-Specific Pharmacokinetics
Intravenous Route
Following intravenous injection, epinephrine produces an immediate response and is rapidly cleared from the plasma with an effective half-life of less than 5 minutes. Steady state is achieved within 10 to 15 minutes after initiating a continuous infusion. In patients with septic shock, epinephrine displays dose-proportional pharmacokinetics in the infusion range of 0.03 to 1.7 mcg/kg/minute.
Intramuscular Route
Absorption is complete and rapid after intramuscular (IM) administration of epinephrine into the anterolateral thigh (vastus lateralis muscle). 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. 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.
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. 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.
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.
-Special Populations
Pediatrics
Neonates
Endotracheal (ET) administration of epinephrine is slower and more unpredictable than if given directly into the bloodstream in patients of all ages. In neonates, multiple factors make it particularly difficult for a patient to achieve adequate absorption of ET epinephrine during cardiopulmonary resuscitation, including fluid-filled alveoli that may dilute ET epinephrine. In addition, shunting of blood through fetal pathways, particularly during acidemia and hypoxia, may cause circulation to bypass the lung and prevent absorption and distribution of ET epinephrine.
Geriatric
In a pharmacokinetic study of 45-minute epinephrine infusions administered to healthy men aged 20 to 25 years and healthy men aged 60 to 65 years, the mean plasma metabolic clearance rate of epinephrine at steady state was greater among older men (144.8 vs. 78 mL/kg/minute for a 14.3 ng/kg/minute infusion).
Obesity
Body weight influences epinephrine pharmacokinetics; higher body weight is associated with a lower concentration plateau and higher plasma clearance.
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