epinephrine (Rx)

Frequency Not Defined

Angina

Anxiety

Apprehensiveness

Cardiac arrhythmias

Dizziness

Dyspnea

Flushing

Headache

Hypertension

Nausea

Nervousness

Pallor

Palpitations

Respiratory difficulties

Restlessness

Stress cardiomyopathy

Sweating

Tachycardia

Tremor

Vasoconstriction

Vomiting

Weakness

Postmarketing Reports

Necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene)

Contraindications

There are no contraindications for life-threatening situations

Nonanaphylactic shock

Narrow-angle glaucoma

Coadministration during genral anesthesia with halogenated hydrocarbons or cyclopropane

Labor

Situations where vasopressors may be contraindicated, including thyrotoxicosis, diabetes

Maternal blood pressure in excess of 130/80 mm Hg in hypertension and other cardiovascular disorders

Cautions

Use caution in patients with cardiac disease, angina (especially with history of CAD) or that are receiving drugs that sensitize the myocardium; treatment may induce cardiac arrhythmias

Pulmonary edema may occur as the result of cardiac stimulation and peripheral constriction

Decreased urine output may occur as the result of renal blood vessel constriction

Use caution in cerebrovascular insufficiency

Use with caution in patients with hypertension, diabetes mellitus, thyroid disease, prostatic hypertrophy, geriatric patients, pregnancy, and previous hospitalization for asthma

Rapid IV administration, although necessary in pulesless arrest, may cause death from cerebrovascular hemorrhage or cardiac arrhythmias

Patients that are sulfite-sensitive, should still be treated during a serious allergic reaction or other emergency even if products available contain sulfites

May cause worsening of symptoms in patients with Parkinson disease

Avoid extravasation; ensure proper needle or catheter placement prior to and during infusion

Correct blood volume depletion before administering any vasopressor

Rare cases of serious skin and soft tissue infections, including necrotizing fasciitis and myonecrosis caused by Clostridia (gas gangrene), reported at injection site following injection for anaphylaxis; to decrease risk, do not inject into buttock; advise patients to seek medical care if they develop signs or symptoms of infection, such as persistent redness, warmth, swelling, or tenderness, at epinephrine injection site; cleansing with alcohol does not kill bacterial spores, and therefore, does not lower risk of infection

Multiple-dose vial not for ophthalmic use; contains chlorobutanol which may be harmful to corneal endothelium

Solutions must be diluted prior to intraocular use; other epinephrine products containing sodium bisulfite have been associated with corneal endothelial damage when used in the eye at undiluted concentrations (1 mg/mL)

Autoinjector is to be used in conjunction with immediate medical or hospital care; more than two sequential doses of epinephrine should only be administered under direct medical supervision

Extravasation

• Avoid extravasation; ensure proper needle or catheter placement prior to and during infusion
• To prevent sloughing and necrosis in areas has extravasation, infiltrate the area with 10-15 mL of 0.9% NaCl solution containing phentolamine 5-10 mg
• Use a syringe with a fine hypodermic needle, with solution being infiltrated liberally throughout the area, which has a cold, hard, and pallid appearance
• Phentolamine may cause immediate and conspicuous local hyperemic changes if area is infiltrated within 12 hr

Injection related complications

• Injection into buttock may not provide effective treatment of anaphylaxis
• Accidental injection into hands, digits, or feet may result in local reactions including injection site coldness, pallor, and hypoesthesia or injury resulting in bruising, discoloration, erythema, bleeding, or skeletal injury
• To minimize the risk of injection-related injury when administering autoinjector to children or infants, instruct caregivers to firmly hold child’s leg in place and limit movement prior to and during injection

Drug interactions overview

• Coadministration with cardiac glycosides, diuretics, or anti-arrhythmics should be observed carefully for the development of cardiac arrhythmias
• Effects of epinephrine may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine, tripelennamine, and diphenhydramine
• Cardiostimulating and bronchodilating effects of epinephrine are antagonized by beta-adrenergic blocking drugs, such as propranolol
• Vasoconstricting and hypertensive effects of epinephrine are antagonized by alpha-adrenergic blocking drugs, such as phentolamine
• Ergot alkaloids may reverse the pressor effects of epinephrine

Pregnancy

Epinephrine crosses the placenta

During pregnancy, anaphylaxis can be catastrophic and can lead to hypoxic-ischemic encephalopathy and permanent central nervous system damage or death in the mother and, more commonly, in the fetus or neonate; the prevalence of anaphylaxis occurring during pregnancy is reported to be approximately 3 cases per 100,000 deliveries; epinephrine is first-line medication of choice for treatment of anaphylaxis during pregnancy in humans; epinephrine should be used for treatment of anaphylaxis during pregnancy in same manner as it is used in non-pregnant patients

Administration of epinephrine used during pregnancy only if the potential benefit justifies the potential risk to the fetus (fetal anoxia, spontaneous abortion, or both) Epinephrine is teratogenic in rabbits, mice, and hamsters dosed during organogenesis

Use with caution during labor and delivery; although epinephrine improves maternal hypotension associated with anaphylaxis, it may result in uterine vasoconstriction, decreased uterine blood flow, and fetal anoxia

Avoid epinephrine during second stage of labor; in dosage sufficient to reduce uterine contractions, the drug may cause a prolonged period of uterine atony with hemorrhage; avoid epinephrine in obstetrics when maternal blood pressure exceeds 130/80 mmHg

Lactation

There is no information on presence of epinephrine in human milk, effects on breastfed infants, or on milk production; epinephrine is first line-medication of choice for treatment of anaphylaxis; it should be used in same manner in breastfeeding and non- breastfeeding patients

Because many drugs are excreted in human milk, caution should be exercised when epinephrine is administered to a nursing woman

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Strong alpha-adrenergic effects, which cause an increase in cardio output and HR, a decrease in renal perfusion and PVR, and a variable effect on BP, resulting in systemic vasoconstriction and increased vascular permeability

Strong beta1- and moderate beta2-adrenergic effects, resulting in bronchial smooth muscle relaxation

Secondary relaxation effect on smooth muscle of stomach, intestine, uterus, and urinary bladder

Absorption

Onset: 5-10 min (SC); 1 min (inhalation)

Duration: 4 hr

Metabolism

Metabolized by MAO and COMT in adrenergic neuron

Metabolites: Metadrenaline, sulfate conjugates, and hydroxy derivatives of mandelic acid (inactive)

Elimination

Excretion: Urine

IV Incompatibilities

Solution: Na-bicarbonate 5%, Ionosol PSL, Ionosol T/D5

Additive: Aminophylline, hyaluronidase, mephentermine, Na-bicarbonate

Syringe: Na-bicarbonate(?)

Y-site: Ampicillin, thiopental

Not specified: Atropine, carbenicillin, diazepam, erythromycin, lidocaine

IV Compatibilities

Solution: D5W, D10W, dextrose-Ringer's, dextrose-saline, NS, LR, Ringer's

Additive: Amikacin, cimetidine, dobutamine, floxacillin, furosemide, metaraminol, ranitidine, verapamil

Syringe: Caffeine, doxapram, heparin, milrinone

Y-site: Amiodarone, atracurium, bivalirudin, CaCl2, Ca gluconate, cefpirome, cisatracurium, dexmedetomidine, diltiazem, dobutamine, dopamine, famotidine, fenoldopam, fentanyl, furosemide, heparin, Hextend, hydrocortisone Na succinate, hydromorphone, inamrinone, labetalol, levofloxacin, lorazepam, midazolam, milrinone, morphine SO4, nicardipine, nitroglycerin, norepinephrine, pancuronium, phytonadione, KCl, propofol, ranitidine, remifentanil, nitroprusside, tirofiban, vasopressin, vecuronium, vitamin B/C, warfarin

Not specified: Meperidine

IV Preparation

Dilute epinephrine in D5W or D5W 0.9% NaCl

Administration in saline solution alone is not recommended

Add 1 mL (1 mg) of epinephrine from its ampule to 1000 mL of a D5W containing solution

Each mL of this dilution contains 1 mcg of epinephrine

Solution: 1 mg in 250 mL D5W or NS (4 mcg/mL) to make up concentration of 15-60 mL/hr (1-4 mcg/min)

IV Administration

Correct blood volume depletion as fully as possible prior to administering any vasopressor

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

Whenever possible, administer epinephrine infusions into a large vein

Avoid using a catheter tie-in technique, because the obstruction to blood flow around the tubing may cause stasis and increased local concentration of the drug

Central line; infusion pump required

Do not mix with alkaline solutions

Discard after 24 hours or if solution is discolored or contains precipitate

Store in light-resistant container

Intraocular Preparation

Epinephrine must be diluted prior to intraocular use

Dilute 1 mL of epinephrine 1 mg/mL (1:1000) in 100 to 1000 mL of an ophthalmic irrigation fluid to create an epinephrine concentration of 1:100,000 to 1:1,000,000 (10-1 mcg/mL)

Use the irrigating solution as needed for the surgical procedure

Intraocular Administration

After dilution in an ophthalmic irrigating fluid, inject intracamerally

SC/IM Administration

SC or IM administration only

Inject IM or SC into the anterolateral aspect of the thigh, through clothing if necessary

Do not administer autoinjector IV; administer only in outer thigh to ensure SC or IM administration

Do not inject into buttock, or into digits, hands, or feet

To minimize the risk of injection-related injury, instruct caregivers to hold the child's leg firmly in place and limit movement prior to and during injection when administering to young children

Discard remaining volume after dose has been administered

In conjunction with use, seek immediate medical or hospital care

Storage

Injection

• Unused vials

  • Store at room temperature, 20-25°C (68-77°F)
  • Protect from light until ready to use; do not refrigerate; protect from freezing
  • Protect from alkalis and oxidizing agents

• Diluted solutions

  • Store at room temperature (25°C) or refrigeration (4°C) is 24 hr

Autoinjector

• Store at room temperature 20-25°C (68-77°F); excursions permitted to 15-30°C (59-86°F; do not refrigerator
• The trainer for AUVI-Q should not be used at temperatures <50ºF (10ºC) or >104ºF (40ºC)
• Store the trainer for AUVI-Q in its outer case; keep away from dirt, chemicals, and water