Epinephrine eent

Open-Angle Glaucoma

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

Dipivefrin, a prodrug of epinephrine, may be preferred in certain patients because of increased intraocular penetration (lower doses are needed) and resultant decreased adverse extraocular effects.c f

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

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.a b c

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).a c

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.a c

Mydriasis for Synechiae

Prolonged topical contact (e.g., via a saturated cotton wick) with the eye to induce sufficient mydriasis to break posterior synechiae†.a c

Administered subconjunctivally concomitantly with atropine and cocaine to produce mydriasis and thereby break posterior synechiae† unresponsive to topical therapy.a

Mydriasis for Ophthalmoscopy

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

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.a b c Ineffective for bleeding from larger vessels.a c

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

Especially useful as a hemostatic agent in dental surgery.a

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).a c d Risk of systemic toxicity caused by the local anesthetic also is decreased, and bleeding in the operative field may be reduced.a c

Adjunct to Other Local Drugs

Enhancement of intraocular penetration of subconjunctivally injected drugs†.c Local vasoconstriction enhances local effect secondary to decreased drug loss from the subconjunctival depot into systemic circulation, with resultant increased intraocular penetration.c

Vasoconstriction to decrease conjunctival hyperemia and thus enhance location of extraocular muscles prior to botulinum toxin injection into these muscles†.c Also reduces the risk of subconjunctival hemorrhage secondary to conjunctival vessel damage.c

Conjunctivitis

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

Nasal Congestion

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

Administration

Apply topically to the skin and mucous membranes of the eye, nose, mouth, throat, or larynx.a b c d h

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

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

Ophthalmic Administration

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

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

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

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.a b c

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.a

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).a c

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

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.a c

Nasal Administration

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

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

Dosage

Available as epinephrine hydrochloride; dosage expressed in terms of epinephrine.a b d

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.a c

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

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.a Solution concentrations of 1:10,000 to 1:2000 also have been used.h

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.a b

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

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†.a c d

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.a d

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.a

Mydriasis for Synechiae Ophthalmic Topical

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

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.a

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.a 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.a

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.a d e

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

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.a

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).a d To control ocular bleeding, inject these concentrations into the anterior chamber of the eye or subconjunctivally.a

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;a c 1:200.000 is used most commonly.c e

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.a

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;a c e 1:200.000 is used most commonly.c e

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;a c 1:200.000 is used most commonly.c e

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.c

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.a c

Nasal Congestion Intranasal Local

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

Special Populations

Geriatric Patients

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

Absorption

Bioavailability

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

Onset

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

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

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

Duration

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

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

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

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.a

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

Systemically absorbed epinephrine distributes into milk.a

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.b

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.a

Epinephrine and its metabolites are excreted by the kidneys.

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.a b d

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

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

Injection

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

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

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

Nasal Solution

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

Ophthalmic Solution

Protect from light and excessive heat.b

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

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

• 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.a b c

• 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.a

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

• 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.a b c

• 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.a

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

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

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

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

• Importance of informing patients of other important precautionary information.a b d h (See Cautions.)