epinephrine
Bronkaid Mist, Bronkaid Mistometer◆, EpiPen, EpiPen Jr., Primatene Mist, Sus-Phrine

epinephrine bitartrate
AsthmaHaler Mist

epinephrine hydrochloride
Adrenalin Chloride, AsthmaNefrin, Epifrin, Glaucon, microNefrin, Vaponefrin

epinephryl borate
Epinal

Available forms
Available by prescription only
Injection: 0.01 mg/ml (1:100,000), 0.1 mg/ml (1:10,000), 0.5 mg/ml (1:2,000), 1 mg/ml (1:1,000) parenteral; 5 mg/ml (1:200) parenteral suspension
Ophthalmic: 0.1%, 0.5%, 1%, 2% solution

Aerosol inhaler: 160 mcg, 200 mcg, 250 mcg/metered spray
Nasal solution: 0.1%
Nebulizer inhaler: 1% (1:100), 1.25%, 2.25%

Indications and dosages
 Bronchospasm, hypersensitivity reactions, anaphylaxis. Adults: Initially, 0.1 to 0.5 mg (0.1 to 0.5 ml of a 1:1,000 solution) S.C. or I.M.; may be repeated at 10- to 15-minute intervals, p.r.n. Or, 0.1 to 0.25 mg (1 to 2.5 ml of a 1:10,000 solution) I.V. slowly over 5 to 10 minutes. May be repeated q 5 to 15 minutes if needed or followed by a 1 to 4 mcg/minute I.V. infusion.
Children: 0.01 mg/kg (0.01 ml/kg of a 1:1,000 solution) or 0.3 mg/m² (0.3 ml/ m² of a 1:1,000 solution) S.C. Dose not to exceed 0.5 mg. May be repeated at 20-minute to 4-hour intervals, p.r.n. Or, 0.02 to 0.025 mg/kg (0.004 to 0.005 ml/kg) or 0.625 mg/m² (0.125 ml/m²) of a 1:200 solution. May be repeated but not more often than q 6 hours. Or, 0.1 mg (10 ml of a 1:100,000 dilution) I.V. slowly over 5 to 10 minutes followed by a 0.1 to 1.5 mcg/ kg/minute I.V. infusion.
 Bronchodilator. Adults and children: 1 inhalation via metered aerosol, repeated once if needed after 1 minute; subsequent doses shouldn’t be repeated for at least 3 hours. Or, 1 or 2 deep inhalations via hand-bulb nebulizer of a 1% (1:100) solution; may be repeated at 1- to 2-minute intervals. Or, 0.03 ml (0.3 mg) of a 1% solution via intermittent positive pressure breathing.
 To restore cardiac rhythm in cardiac arrest. Adults: Initially, 0.5 to 1 mg (range, 0.1 to 1 mg to 10 ml of a 1:10,000 solution) I.V. bolus; may be repeated q 3 to 5 minutes, p.r.n. Or, initial dose followed by 0.3 mg S.C. or 1 to 4 mcg/minute I.V. infusion. Or, 1 mg (10 ml of a 1:10,000 solution) intratracheally, or 0.1 to 1 mg (1 to 10 ml of a 1:10,000 solution) by intracardiac injection.
Children: Initially, 0.01 mg/kg (0.1 ml/kg of a 1:10,000 solution) I.V. bolus or intratracheally; may be repeated q 5 minutes, p.r.n. Or, initially, 0.1 mcg/kg/ minute; may increase in increments of 0.1 mcg/kg/ minute to a maximum of 1 mcg/kg/minute. Or, 0.005 to 0.01 mg/kg (0.05 to 0.1 ml/kg of a 1:10,000 solution) by intracardiac injection.
Infants: Initially, 0.01 to 0.03 mg/kg (0.1 to 0.3 ml/kg of a 1:10,000 solution) I.V. bolus or by intratracheal injection. May be repeated q 5 minutes, p.r.n.
 Hemostatic use. Adults: 1:50,000 to 1:1,000, applied topically.
 To prolong local anesthetic effect. Adults and children: 1:500,000 to 1:50,000 mixed with local anesthetic.
 Open-angle glaucoma. Adults: 1 or 2 drops of 1% to 2% solution daily or b.i.d.
 Nasal congestion, local superficial bleeding. Adults and children: Instill 1 or 2 drops of solution.

Pharmacodynamics
Epinephrine acts directly by stimulating alpha- and beta-adrenergic receptors in the sympathetic nervous system. Its main therapeutic effects include relaxation of bronchial smooth muscle, cardiac stimulation, and dilation of skeletal muscle vasculature.
Bronchodilator action: Epinephrine relaxes bronchial smooth muscle by stimulating beta₂-adrenergic receptors. Epinephrine constricts bronchial arterioles by stimulating alpha-adrenergic receptors, resulting in relief of bronchospasm, reduced congestion and edema, and increased tidal volume and vital capacity. By inhibiting histamine release, it may reverse bronchiolar constriction, vasodilation, and edema.
CV and vasopressor actions: As a cardiac stimulant, epinephrine produces positive chronotropic and inotropic effects by action on beta₁-receptors in the heart, increasing cardiac output, myocardial oxygen consumption, and force of contraction and decreasing cardiac efficiency. Vasodilation results from its effect on beta₂-receptors; vasoconstriction results from alpha-adrenergic effects.
Local anesthetic (adjunct) action: Epinephrine acts on alpha receptors in skin, mucous membranes, and viscera; it produces vasoconstriction, which reduces absorption of local anesthetic, thus prolonging its duration of action, localizing anesthesia, and decreasing risk of anesthetic’s toxicity.
Local vasoconstriction action: Epinephrine’s effect results from action on alpha receptors in skin, mucous membranes, and viscera, which produces vasoconstriction and hemostasis in small vessels.
Antiglaucoma action: Epinephrine’s exact mechanism of lowering intraocular pressure is unknown. When applied topically to the conjunctiva or injected into the interior chamber of the eye, epinephrine constricts conjunctival blood vessels, contracts the dilator muscle of the pupil, and may dilate the pupil.

Pharmacokinetics
Absorption: Well absorbed after S.C. or I.M. injection; epinephrine has a rapid onset of action and short duration of action.
Distribution: Distributed widely throughout the body.
Metabolism: Metabolized at sympathetic nerve endings, liver, and other tissues to inactive metabolites.
Excretion: Excreted in urine, mainly as its metabolites and conjugates.

Contraindications and precautions
Contraindicated in patients with angle-closure glaucoma, shock (other than anaphylaxis), organic brain damage, cardiac dilation, arrhythmias, coronary insufficiency, or cerebral arteriosclerosis. Also contraindicated in patients during general anesthesia with halogenated hydrocarbons or cyclopropane and in patients in labor (may delay second stage).
 Some commercial products contain sulfites; contraindicated in patients with sulfite allergies except when epinephrine is being used for treatment of serious allergic reactions or other emergencies.
 In conjunction with local anesthetics, epinephrine is contraindicated for use on fingers, toes, ears, nose, and genitalia.
 Ophthalmic preparation is contraindicated in patients with angle-closure glaucoma or when nature of the glaucoma hasn’t been established, in patients hypersensitive to the drug, and in those with organic mental syndrome or cardiac dilation and coronary insufficiency. Nasal solution is contraindicated in patients hypersensitive to drug.
 Use extremely cautiously in patients with longstanding bronchial asthma and emphysema in whom degenerative heart disease has developed. Also use cautiously in elderly patients and in those with hyperthyroidism, CV disease, hypertension, psychoneurosis, and diabetes.
 Use ophthalmic preparation cautiously in elderly patients and in patients with diabetes, hypertension, Parkinson’s disease, hyperthyroidism, aphakia (eye without lens), cardiac disease, cerebral arteriosclerosis, or bronchial asthma.

Interactions
Drug-drug. Alpha blockers: Antagonizes vasoconstriction and hypertension. Avoid use together.
Antidiabetics: Decreases blood glucose effects. Dosage adjustments may be needed.
Antihistamines, thyroid hormones, tricyclic antidepressants: May potentiate adverse cardiac effects of epinephrine. Avoid use together.
Beta blockers, such as propranolol: Antagonize cardiac and bronchodilating effects of epinephrine. Monitor patient carefully.
Carbonic anhydrase inhibitors, osmotic agents, topical beta blockers, topical miotics: May cause additive lowering of intraocular pressure. Avoid use together.
Cardiac glycosides, general anesthetics (especially cyclopropane, halothane): May sensitize the myocardium to effects of epinephrine, causing arrhythmias. Provide ECG monitoring.
Doxapram, mazindol, methylphenidate: May enhance CNS stimulation or pressor effects. Monitor patient closely.
Ergot alkaloids, oxytocics: May cause severe hypertension. Avoid use together.
Guanadrel, guanethidine: Decreases hypotensive effects and potentiated effects of epinephrine, resulting in hypertension and arrhythmias. Monitor patient and blood pressure closely.
Levodopa: Increases risk of cardiac arrhythmias. Monitor patient carefully.
MAO inhibitors: Increases risk of hypertensive crisis. Monitor blood pressure closely.
Miotics: Decreases ciliary spasm, mydriasis, blurred vision and increased intraocular pressure. May be used for this reason.
Phenothiazines: Reverses pressor effects. Avoid use together.
Sympathomimetics: Causes additive effects and toxicity. Avoid use together.

Adverse reactions
CNS: nervousness, tremor, vertigo, headache, disorientation, agitation, drowsiness, fear, pallor, dizziness, weakness, cerebral hemorrhage, CVA, pain. In patients with Parkinson’s disease, drug may increase rigidity, tremor, brow ache, headache, and light-headedness with ophthalmic form; nervousness and excitation with nasal form.
CV: palpitations; widened pulse pressure; hypertension; ventricular fibrillation; shock; angina; ECG changes, including a decreased T-wave amplitude; palpitations; tachycardia; arrhythmias; hypertension with ophthalmic preparation; tachycardia with nasal solution.
EENT: corneal or conjunctival pigmentation or corneal edema in long-term use; follicular hypertrophy; chemosis; conjunctivitis; iritis; hyperemic conjunctiva; maculopapular rash; eye pain; allergic lid reaction; ocular irritation; eye stinging, burning, and tearing on instillation of ophthalmic form; rebound nasal congestion; slight sting upon application of nasal solution.
GI: nausea, vomiting .
Metabolic: hyperglycemia.
Respiratory: dyspnea.
Skin: urticaria, hemorrhage (at injection site).

Effects on lab test results
• May increase BUN, glucose, and lactic acid levels.

Overdose and treatment
Signs and symptoms of overdose may include a sharp increase in systolic and diastolic blood pressure, increase in venous pressure, severe anxiety, irregular heartbeat, severe nausea or vomiting, severe respiratory distress, unusually large pupils, unusual paleness and coldness of skin, pulmonary edema, renal failure, and metabolic acidosis.
 Treatment includes symptomatic and supportive measures because epinephrine is rapidly inactivated in the body. Monitor vital signs closely. Phentolamine may be needed for hypotension; beta blockers (such as propranolol) may be needed for arrhythmias.

Special considerations
• After S.C. or I.M. injection, massaging the site may hasten absorption.
• Epinephrine is destroyed by oxidizing agents, alkalis (including sodium bicarbonate), halogens, permanganates, chromates, nitrates, and salts of easily reducible metals such as iron, copper, and zinc.
• Avoid I.M. injection into buttocks. Epinephrine-induced vasoconstriction favors growth of the anaerobe Clostridium perfringens.
• Intracardiac administration requires external cardiac massage to move drug into coronary circulation.
• Breathing treatment should start with first symptoms of bronchospasm. Patient should use the fewest number of inhalations that provide relief. To prevent excessive dosage, at least 1 or 2 minutes should elapse before taking additional inhalations of epinephrine. Dosage requirements vary.
• Ophthalmic preparation may cause mydriasis with blurred vision and sensitivity to light in some patients being treated for glaucoma. Drug is usually administered at bedtime or after prescribed miotic to minimize these symptoms.
• When using separate solutions of epinephrine and a topical miotic, instill the miotic 2 to 10 minutes before epinephrine.
• Monitor blood pressure, pulse, respirations, and urine output; observe patient closely. Epinephrine may widen pulse pressure. If arrhythmias occur, discontinue epinephrine immediately. Watch for changes in intake and output ratio.
• Make sure patients, especially elderly ones, receive regular tonometry readings during continuous therapy.
Pregnant patients
• Drug inhibits spontaneous or oxytocin-induced labor. With dose sufficient to reduce uterine contractions, drug may cause prolonged uterine atony with hemorrhage. Use drug during pregnancy only if potential benefits to mother outweigh possible risks to fetus.
Breast-feeding patients
• Drug appears in breast milk. Patient should avoid breast-feeding during therapy.
Pediatric patients
• Safety and efficacy of ophthalmic epinephrine in children haven’t been established. Use cautiously.
Geriatric patients
• These patients may be more sensitive to effects of epinephrine; lower doses are indicated.

Patient education
• Urge patient to report diminishing effect. Repeated or prolonged use of epinephrine can cause tolerance to effects of drug. Continuing to take epinephrine despite tolerance can be hazardous. Interrupting drug therapy for 12 hours to several days may restore responsiveness to drug.
Inhalation therapy
• Instruct patient in correct use of inhaler.
• Warn patient that overuse or too-frequent use can cause severe adverse reactions.
• Tell patient to save applicator; refills may be available.
• Advise patient to call immediately if he has no relief within 20 minutes or if condition worsens.
Nasal therapy
• Tell patient to call if symptoms aren’t relieved in 20 minutes or if they become worse, and to report bronchial irritation, nervousness, or sleeplessness, which may require dosage reduction.
• Warn patient that intranasal applications may sting slightly and cause rebound congestion or drug-induced rhinitis after prolonged use. Nose drops should be used for 3 or 4 days only. Encourage patient to use drug exactly as prescribed.
• Tell patient to rinse nose dropper or spray tip with hot water after each use to avoid contaminating the solution.
• Instruct patient to gently press finger against nasolacrimal duct for at least 1 or 2 minutes immediately after drug instillation to avoid excessive systemic absorption.
Ophthalmic therapy
• To minimize systemic absorption, tell patient to press finger to lacrimal sac during and for 1 to 2 minutes after instillation of eye drops.
• To prevent contamination, tell patient not to touch applicator tip to any surface and to keep container tightly closed.
• Tell patient not to use epinephrine solution if it’s discolored or contains a precipitate.
• Advise patient to remove soft contact lenses before instilling eye drops to avoid staining or damaging them.
• Tell patient to apply a missed dose as soon as possible. If it’s close to time for next dose, the patient should wait and apply at regularly scheduled time.
• Tell patient to store drug away from heat and light (not in bathroom medicine cabinet where heat and moisture can cause drug to deteriorate) and out of reach of children.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use