EPINEPHrine (EENT) (Monograph)

Brand names: Adrenalin Chloride, Epifrin
Drug class: Mydriatics
ATC class: S01EA01
VA class: OP105
CAS number: 51-42-3

Introduction

An endogenous catecholamine that is a mydriatic and vasoconstrictor.

Uses for EPINEPHrine (EENT)

Open-Angle Glaucoma

Reduction of elevated IOP in patients with open-angle glaucoma. Generally used adjunctively with topical miotics, topical β-adrenergic blocking agents, osmotic agents, and/or systemically administered carbonic anhydrase inhibitors; may have an additive effect on IOP lowering. Epinephrine in conjunction with miotics may reduce miosis and ciliary spasm that often occur when miotics are used alone.

Patient response to epinephrine is highly variable; some patients are unresponsive. Repeated tonometric readings are advisable during the course of treatment, especially in geriatric patients.

Diagnosis of open-angle glaucoma by careful gonioscopic and slit lamp studies; use in patients with angle-closure glaucoma or those who may be predisposed to angle closure is contraindicated.

Mydriasis for Surgery

Although less effective than other mydriatics in normal eyes, epinephrine produces effective mydriasis when the permeability of the eye is increased by trauma (e.g., during surgery).

Induction of rapid mydriasis during surgery (e.g., cataract extraction) via topical application to the conjunctiva or injection into the anterior chamber of the eye.

Mydriasis for Synechiae

Prolonged topical contact (e.g., via a saturated cotton wick) with the eye to induce sufficient mydriasis to break posterior synechiae^{† [off-label]}.

Administered subconjunctivally concomitantly with atropine and cocaine to produce mydriasis and thereby break posterior synechiae^{† [off-label]} unresponsive to topical therapy.

Mydriasis for Ophthalmoscopy

Although generally contraindicated in patients with angle-closure glaucoma, epinephrine may be used to produce mydriasis for ophthalmoscopy^{† [off-label]} in patients predisposed to angle closure. Give a carbonic anhydrase inhibitor and an osmotic agent (e.g., glycerin) orally prior to the examination. However, even these measures may not prevent attacks of acute angle-closure glaucoma unresponsive to treatment; surgery may be required.

Superficial Bleeding

Used locally as a hemostatic agent to control superficial bleeding from arterioles and capillaries in the skin and mucous membranes of the eye, nose, mouth, throat or larynx, mainly during surgery. Ineffective for bleeding from larger vessels.

Especially useful to prevent oozing from small vessels that obscures surgical details during ophthalmic surgery.

Especially useful as a hemostatic agent in dental surgery.

Adjunct to Local Anesthesia

Added to solutions of some local anesthetics to decrease the rate of their vascular absorption (to localize and prolong the duration of anesthesia). Risk of systemic toxicity caused by the local anesthetic also is decreased, and bleeding in the operative field may be reduced.

Adjunct to Other Local Drugs

Enhancement of intraocular penetration of subconjunctivally injected drugs^{† [off-label]}. Local vasoconstriction enhances local effect secondary to decreased drug loss from the subconjunctival depot into systemic circulation, with resultant increased intraocular penetration.

Vasoconstriction to decrease conjunctival hyperemia and thus enhance location of extraocular muscles prior to botulinum toxin injection into these muscles^{† [off-label]}. Also reduces the risk of subconjunctival hemorrhage secondary to conjunctival vessel damage.

Conjunctivitis

Decongestion when applied topically to the conjunctiva for conjunctivitis secondary to nonspecific chronic irritation or allergy. Decongestion usually persists less than 1 hour and may be followed by reactive hyperemia. Longer-acting decongestants are preferred.

Nasal Congestion

Decongestion for allergic or nonallergic rhinitis or acute sinusitis when applied topically to the nasal mucosa. Duration of action is short and rebound congestion frequently occurs. Longer-acting decongestants are preferred.

EPINEPHrine (EENT) Dosage and Administration

Administration

Apply topically to the skin and mucous membranes of the eye, nose, mouth, throat, or larynx.

For ophthalmic use, parenteral preparations may be injected intracamerally or subconjunctivally.

For local oral use, parenteral preparations may be infiltrated into buccal and mucosal vestibules.

Ophthalmic Administration

Ophthalmic solutions are intended for topical use only and must not be injected. For injection, only parenteral preparations should be used.

Usually apply topically to the conjunctiva of the affected eye(s).

To avoid visual disturbances resulting from mydriasis, administer at bedtime whenever possible.

Ophthalmic preparations generally should not be used in conjunction with the wearing of soft contact lenses, since epinephrine may cause adrenochrome staining (black discoloration) of the lenses.

When separate solutions of epinephrine and a topical miotic are used, the miotic should be instilled 2–10 minutes prior to epinephrine because of the limited capacity of the conjunctival sac.

May be injected intracamerally (into the anterior chamber of the eye) or subconjunctivally (beneath Tenon’s capsule) (e.g., to control hemorrhage or produce mydriasis).

To provide rapid mydriasis during surgery (e.g., cataract extraction), apply topically to the conjunctiva or inject into the anterior chamber of the eye.

To break posterior synechiae^†, apply topically via a saturated cotton wick placed in the lower conjunctival cul-de-sac or inject subconjunctivally for synechiae unresponsive to topical therapy.

Nasal Administration

Nasal solutions are intended for topical use only and must not be injected.

Apply topically to nasal mucosa as drops or spray or with a sterile swab.

Dosage

Available as epinephrine hydrochloride; dosage expressed in terms of epinephrine.

When epinephrine is used as a mydriatic, it is less effective in dark than in light colored eyes; higher concentrations and/or dosages may be needed in patients with brown or hazel eyes.

Ocular discomfort and conjunctival irritation associated with topical instillation in the eye may be decreased by switching to a lower concentration.

Pediatric Patients

Nasal Congestion

Intranasal Local

Children ≥6 years of age: To produce nasal decongestion, apply a 0.1% (1:1000) solution topically as drops or spray to mucosa as required. Solution concentrations of 1:10,000 to 1:2000 also have been used.

Adults

Open-Angle Glaucoma

Ophthalmic Topical

Usual dosage is 1 or 2 drops of a 1 or 2% ophthalmic solution once or twice daily instilled in the affected eye(s); however, dosing frequency may vary from once every 2–4 days to 4 times daily.

Adjust concentration and dosage to individual requirements and responses as determined by tonometric readings before and during therapy.

Mydriasis for Surgery

Ophthalmic Topical

Apply 1 or more drops of a 0.1% (1:1000) solution topically to the conjunctiva 1–3 times or as necessary to control bleeding or to provide a mydriatic effect during surgery^†.

Ophthalmic Local Injection

Intraocular injections of 1:10,000 (0.01%) to 1:1000 (0.1%) concentrations can be used to provide mydriasis during surgery; this also can control bleeding.

In round-pupil cataract extraction, 0.2 mL (0.2 mg) of a 1:1000 injection may be injected intracamerally; in other cases of cataract extraction, 0.1 mL (0.1 mg) of a 1:1000 injection may be injected subconjunctivally.

Mydriasis for Synechiae

Ophthalmic Topical

To break posterior synechiae^†, a cotton wick saturated with epinephrine is placed in the lower conjunctival cul-de-sac.

Ophthalmic Local Injection

To break posterior synechiae^† unresponsive to topical therapy, 0.1 mL of a solution containing equal parts of 0.1% (1:1000) epinephrine, 4% cocaine, and 1% atropine may be injected at the limbus.

Mydriasis for Ophthalmoscopy

Ophthalmic Topical

To provide mydriasis for ophthalmoscopy^† in patients predisposed to angle closure, a carbonic anhydrase inhibitor (e.g., 250 mg of acetazolamide) and glycerin 1–1.5 g/kg are given orally 2 hours and 1 hour, respectively, prior to epinephrine. After the eye is anesthetized topically with a drug other than cocaine, the tip of a 1 × 5 mm strip of filter paper moistened with 1 or 2% epinephrine ophthalmic solution is inserted in the inferior cul-de-sac for 1–3 minutes.

Superficial Bleeding

EENT Topical

As a topical hemostatic agent, solution concentrations of 1:50,000 (0.002%) to 1:1000 (0.1%) may be sprayed or applied with cotton or gauze to the skin or mucous membranes of the eye, nose, mouth, throat, or larynx.

To control mucosal bleeding, a 0.1% (1:1000) solution can be applied topically as drops or spray to mucosa as required.

To control bleeding during ocular surgery, apply 1 or more drops of a 0.1% (1:1000) solution topically to the conjunctiva 1–3 times or as necessary.

EENT Local Injection

Injections of 1:10,000 (0.01%) to 1:1000 (0.1%) concentrations can be used to control bleeding (e.g., during surgery). To control ocular bleeding, inject these concentrations into the anterior chamber of the eye or subconjunctivally.

For use as a local hemostatic agent in combination with local anesthetics (e.g., during ocular surgery), epinephrine may be used in concentrations of 1:200,000 to 1:50,000; 1:200.000 is used most commonly.

To control bleeding during oral surgery^†, infiltrate the buccal and labial vestibules of the maxilla and mandible in each quadrant with 4 mL of a 0.0005% (1:200,000) solution.

Adjunct to Local Anesthesia

EENT Local Injection

To localize and prolong the duration of local anesthesia, epinephrine may be used in concentrations of 1:500,000 to 1:50,000; 1:200.000 is used most commonly.

Adjunct to Other Local Drugs

Ophthalmic Local Injection

To enhance intraocular penetration and prolong the duration of subconjuntivally injected drugs^†, epinephrine may be used in concentrations of 1:200,000 to 1:50,000; 1:200.000 is used most commonly.

Ophthalmic Topical

To aid in botulinum toxin therapy for strabismus^†, instill 1 drop of an epinephrine ophthalmic solution in the affected eye as a local vasoconstrictor.

Conjunctivitis

Ophthalmic Local

For conjunctrival decongestion, apply 1 or more drops of a 0.1% (1:1000) solution topically to the conjunctiva 1–3 times or as necessary.

Nasal Congestion

Intranasal Local

To produce nasal decongestion, apply a 0.1% (1:1000) solution topically as drops or spray to mucosa as required. Solution concentrations of 1:10,000 to 1:2000 also have been used.

Special Populations

Geriatric Patients

No specific dosage recommendations, but repeated tonometric readings during glaucoma therapy are especially advisable in this age group.

Cautions for EPINEPHrine (EENT)

Contraindications

• Angle-closure glaucoma. Dilation of the pupil may trigger an acute attack.

• Use cautiously, if at all, if the nature of the glaucoma has not been established.

• Known hypersensitivity to epinephrine or any ingredient in the formulation.

• Organic brain syndrome.

• Cardiac dilatation and coronary insufficiency.

• Contraindicated in conjunction with local anesthetics for use in the ears, nose, fingers, toes, or genitalia.

Warnings/Precautions

Warnings

Narrow Angle

Caution in patients with a narrow angle since pupil dilation may precipitate an acute attack of angle-closure glaucoma.

Aphakia

Chronic therapy may produce reversible macular edema in aphakic patients; caution is advised.

Changes in central vision in aphakic patients should prompt evaluation for maculopathy; epinephrine discontinuance usually is followed by improvement in visual acuity and ophthalmoscopic findings within 1 month but may not be maximal for 6 months or longer.

Cardiovascular Effects

Consider cardiovascular status before initiating therapy.

Use with caution in patients with vascular hypertension or cardiac disorders, including arrhythmias and cardiovascular disease (e.g., coronary artery disease).

Use with extreme caution in patients with degenerative heart disease. (See Asthma and Emphysema under Cautions.)

Use with caution, if at all, prior to or during surgery with cyclopropane or halogenated hydrocarbon anesthetics such as halothane. The danger of ventricular arrhythmias such as VPCs, tachycardia, or fibrillation may be increased.

If epinephrine is used prior to ocular surgery, especially for injection with a local anesthetic, systemic sympathomimetic effects may occur; surgery should not be started until restlessness has subsided.

Overdosage or inadvertent IV administration may cause cerebrovascular hemorrhage secondary to a marked increase in blood pressure.

Asthma and Emphysema

Use with extreme caution in patients with long-standing bronchial asthma or emphysema who have developed degenerative heart disease.

Diabetes, Hyperthyridism, and Cerebral Arteriosclerosis

Use with caution in diabetic and hyperthyroid patients and those with cerebral arteriosclerosis.

Sensitivity Reactions

Allergic Reactions

Ophthalmic use may cause allergic reactions (sensitization reaction to chronic therapy) characterized by diffuse vascular engorgement, follicular hypertrophy, chemosis, conjunctivitis, and/or iritis. Allergic contact dermatitis of the eyelids, producing such symptoms as edema of the lower lids, thick yellow discharge, and crusting and fissuring of the skin of the eyelids, also may occur.

Allergic reactions occasionally may be caused by the preservatives in the preparations.

Some ophthalmic formulations contain sulfites, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.

General Precautions

Ocular Irritation

Adverse local reactions occur frequently during topical ocular therapy and prolonged use may not be tolerated.

Topical application to the conjunctiva frequently causes ocular discomfort and conjunctival irritation including transient burning or stinging, lacrimation, pain or ache around or in the eye, and rebound conjunctival hyperemia.

Some of these local ocular effects may be reduced if a lower epinephrine concentration is used.

Ocular Pigmentary Changes

Prolonged use may result in localized melanin-like pigmentary (e.g., adrenochrome) deposits in the conjunctiva, eyelids, and/or roughened or edematous areas of the cornea. Such pigmenation may be increased by use of old or disclored solutions containing oxidixed epinephrine.

Large brownish-black casts occasionally may form in the lacrimal sac and nasolacrimal duct, resulting in obstruction and epiphora. These casts may be removed by irrigation.

Increased IOP

Rarely, a temporary but clinically important increase in IOP and impairment of outflow facility (even when the angle of the eye remained open) have occurred in glaucoma patients when epinephrine was used initially without a miotic.

Acute Angle Closure

In patients with angle-closure glaucoma, dilation of the pupil may precipitate an acute attack.

Mydriasis, Blurred Vision, and Light Sensitivity

Mydriasis, blurred vision, and sensitivity to light may occur in glaucoma patients; inconvenience may be minimized if epinephrine is administered at bedtime or following a miotic.

Corneal Effects

Prolonged ophthalmic use may cause corneal edema; after very prolonged use, superficial blood vessels in the eye may lose the ability to constrict.

Intracameral injection of epinephrine 1:1000 has been associated with endothelial damage, irreversible edema, and opacification of the cornea.

Other Local Effects

Headache or browache frequently occurs at the beginning of ocular therapy and may diminish with continued treatment.

Systemic Effects

Ophthalmic use occasionally causes systemic sympathomimetic effects such as palpitation, tachycardia, extrasystoles, ventricular premature complexes, hypertension, occipital headaches, pallor, trembling, faintness, and increased perspiration. Such effects are common with local ophthalmic injection.

Excessively large local dosages may cause cerebral hemorrhage and ventricular fibrillation. Patients with preexisting hypertension, hyperthyroidism, coronary artery disease, or advancedcerebral arteriosclerosis are particulaly susceptible.

Systemic sympathomimetic effects occur very rarely after application to the conjunctiva but are more likely to occur if the drug is instilled after the corneal epithelium has been damaged or permeability is increased by tonometry, surgery, inflammation, or topical application of a local anesthetic.

Systemic sympathomimetic effects also may occur with other mucosal (e.g., intranasal) use.

Use of Fixed Combination

When used in fixed combination with other agents, consider the cautions, precautions, and contraindications associated with the concomitant agents.

Specific Populations

Pregnancy

Category C.

Lactation

Risk unknown.

Pediatric Use

Safety and efficacy of ophthalmic solutions not established.

Nasal solutions should be used in children <6 years of age only under the advice af a clinician.

Geriatric Use

Use with caution. Melanin-like pigmentary deposits may occur within translucent conjunctival cysts.

Common Adverse Effects

Ocular use: irritation and discomfort, ocular pain or ache, browache, headache, conjunctival hyperemia, allergic lid reactions.

Intranasal use: CNS symptoms (e.g., nervousness, restlessness) rebound nasal congestion. Slight stinging after intranasal application (because of the presence of sodium bisulfite).

Interactions for EPINEPHrine (EENT)

Specific Drugs

EPINEPHrine (EENT) Pharmacokinetics

Absorption

Bioavailability

Occasionally, sufficient absorption following topical application to the conjunctiva or nasal mucosa or intraocular injection to cause systemic sympathomimetic effects may occur.

Onset

Following topical application to the conjunctiva, IOP reduction may occur within 1 hour and reach a maximum in 4–8 hours.

Following local ocular administration, mydriasis may occur within a few minutes.

Vasoconstriction usually occurs within 5 minutes after topical (e.g., ocular, intranasal) administration or intraocular injection.

Duration

Following topical application to the conjunctiva, IOP reduction may persist for 12–24 hours or longer.

Following local ocular administration, mydriasis may persist for several hours.

Vasoconstriction generally lasts less than 1 hour after topical (e.g., ocular, intranasal) administration or intraocular injection.

Distribution

Extent

Following topical application to the eye in rabbits, highest concentrations in tissues and fluids other than the eye occurred in the pituitary gland, with lower concentrations in the intestine, fat, adrenal gland, kidney, heart, lung, spleen, ovary, pancreas, liver, uterus, muscle, brain, and serum.

Systemically absorbed epinephrine crosses the placenta but not the blood-brain barrier.

Systemically absorbed epinephrine distributes into milk.

Elimination

Metabolism

Circulating epinephrine is metabolized in the liver and other tissues by a combination of reactions involving the enzymes catechol-O-methyltransferase (COMT) and MAO.

The major metabolites are metanephrine and 3-methoxy-4-hydroxymandelic acid (vanillylmandelic acid, VMA), both of which are inactive.

Elimination Route

Pharmacologic actions are terminated mainly by uptake and metabolism in sympathetic nerve endings.

Epinephrine and its metabolites are excreted by the kidneys.

Stability

Storage

Ophthalmic, Nasal, and Parenteral Solutions

Epinephrine, epinephrine salts, and solutions containing the drugs gradually darken on exposure to light and air and must be stored in tight, light-resistant containers.

Discard solutions with a color that is pinkish or darker than slightly yellow or that contain a precipitate.

Follow the manufacturer’s directions with respect to storage requirements for each product.

Injection

15–25°C; protect from light and freezing.

In some commercially available injections, air has been replaced with nitrogen to avoid oxidation.

Withdrawal of doses from multiple-dose vials introduces air into the vials, subjecting the remaining epinephrine to oxidation. Oxidation of epinephrine imparts first a pink, then a brown color.

Nasal Solution

15–25°C; protect from light and freezing.

Ophthalmic Solution

Protect from light and excessive heat.

Actions

• An endogenous catecholamine that is a mydriatic and vasoconstrictor.

• Lowers IOP and causes brief mydriasis and vasoconstriction in open-angle glaucoma; slight effect on IOP in the normal eye. Appears to lower IOP principally by stimulating α- and/or β₂-adrenergic receptors, resulting in an increase in both pressure-independent (uveoscleral) and, to a lesser extent, pressure-dependent (trabecular) aqueous humor outflow.

• Constricts arterioles in the skin and mucous membranes by its effect on α-adrenergic receptors.

• Constricts conjunctival blood vessels, contracts the dilator muscle of the pupil, and may dilate the pupil after topical application to the conjunctiva or injection into the anterior chamber of the eye.

• Induces mydriasis poorly in normal eyes; however, effective mydriasis occurs when the permeability of the eye is increased during surgery or trauma, after postganglionic sympathetic denervation (as in Horner’s syndrome or Raeder’s syndrome), and in patients with chronic renal hypertension, hyperthyroidism, or certain cases of glaucoma.

• Produces only slight relaxation of the ciliary muscle so that cycloplegia does not occur.

Advice to Patients

• Do not use solutions that are pinkish or darker than slightly yellow or if they contain a precipitate.

• Advise that ocular discomfort and conjunctival irritation (burning, stinging) are common with topical application to the conjunctiva.

• Advise that soft contact lenses generally should not be worn during ocular instillation because of risk of black discoloration, particularly during chronic use of epinephrine ophthalmic solutions.

• Advise glaucoma patients that mydriasis, blurred vision, and light sensitivity may occur and can be minimized by administering at bedtime or after a miotic, when possible.

• Advise glaucoma patients of the possibility of ocular pigmentary changes during prolonged therapy.

• Importance of aphakic patients reporting visual changes (e.g., loss of visual acuity, blurring and visual distortation) during chronic therapy since these may be signs of maculopathy.

• Importance of discontinuing use of epinephrine and consulting a clinician if signs of sensitivity develop or if irritation persists or increases during therapy with the drug.

• Importance of warning patients of possible systemic sympathomimetic effects if epinephrine is used prior to ocular surgery, especially for injection with a local anesthetic.

• Importance of contacting a clinician if prompt relief is not obtained with intranasal therapy.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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