Drug class: Mydriatics

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Introduction

Phenylephrine hydrochloride, a synthetic sympathomimetic amine, is a mydriatic.

Uses for Phenylephrine Hydrochloride (EENT) (Mydriatic)

Ophthalmologic Examinations

Phenylephrine is used to produce mydriasis without cycloplegia as an aid in ophthalmoscopy, retinal photography, and other diagnostic procedures. To achieve maximal mydriasis, phenylephrine is frequently administered with atropine sulfate or other cycloplegic drugs which have a mechanism of action different from that of phenylephrine. Mydriatic drugs are less effective in dark than in light colored eyes; repeated instillations of phenylephrine or concomitant administration of an antimuscarinic drug may be necessary to produce effective mydriasis in patients with black, brown, or hazel eyes. Examination of the peripheral retina requires more complete mydriasis than is achieved with phenylephrine alone; cyclopentolate or tropicamide hydrochloride are frequently used instead of phenylephrine but may be supplemented with phenylephrine if necessary. In addition, concomitant administration of a cycloplegic drug will prevent constriction of the pupil caused by intense light stimulation during indirect ophthalmoscopy or retinal photography.

Phenylephrine may be used to produce mydriasis for ophthalmoscopy in patients with open-angle glaucoma and is effective even if the patient is being treated with a miotic. If necessary, tropicamide may be used concomitantly; phenylephrine reduces or abolishes the tendency of tropicamide to increase IOP. Although generally contraindicated in patients with angle-closure glaucoma, phenylephrine may be used if necessary to produce mydriasis for ophthalmoscopy in patients predisposed to angle closure. (See Cautions: Ocular Effects.) Sympathomimetic agents appear to be safer than parasympathomimetic cycloplegic drugs for use in these patients; however, extreme caution must be exercised. Patients with angle-closure glaucoma should receive a carbonic anhydrase inhibitor such as acetazolamide and an osmotic agent such as glycerin orally or mannitol or urea IV prior to the examination. However, even these measures may not prevent attacks of acute angle-closure glaucoma unresponsive to medical treatment; surgery may be required. After the examination is completed, miosis should be achieved with a topical miotic and the patient carefully observed for signs of increased intraocular pressure.

Phenylephrine may be used in the diagnosis of Horner’s or Raeder’s syndrome or to reverse the miosis and ptosis occurring in this condition. The drug has also been used as a provocative test for angle block in patients with glaucoma. One manufacturer states that phenylephrine may be used as an aid in determination of errors of refraction, usually as an adjunct to atropine sulfate or other cycloplegic drugs. However, these drugs are rarely used for this purpose.

Ocular Surgery and Posterior Synechiae

Phenylephrine is used in conjunction with atropine to produce maximal dilation of the pupil prior to intraocular surgery, especially in patients undergoing round pupil cataract extraction or surgery to correct retinal detachment. The drug also produces vasoconstriction and aids in controlling superficial bleeding during surgery.

Phenylephrine also is used postoperatively or as an adjunct in the treatment of anterior uveitis to prevent the formation of posterior synechiae. If inflammation is mild, phenylephrine may be used alone; however, atropine or scopolamine may be required instead of phenylephrine for more severe cases. After surgery for congenital cataracts, it is necessary to administer phenylephrine concomitantly with atropine or scopolamine until the cortex is completely absorbed. Phenylephrine may also be used alone or in conjunction with atropine sulfate to break posterior synechiae after they have formed.

Glaucoma

Since mydriatics, including phenylephrine, may occasionally increase IOP, the drugs generally are not used in patients with glaucoma; however, the benefits of temporary phenylephrine-induced mydriasis occasionally may outweigh the risks when pupillary dilation may free adhesions or when vasoconstriction of intrinsic blood vessels may decrease IOP. Phenylephrine may be used to lower IOP temporarily in patients with open-angle glaucoma. If administered with a miotic, phenylephrine may reduce the ciliary and conjunctival congestion and accommodative myopia often occurring when miotics are used alone without compromising the effectiveness of glaucoma therapy. Phenylephrine may also be used with topical atropine and a systemic osmotic drug such as glycerin to treat glaucoma caused by aphakic pupillary block or posterior synechiae. If malignant glaucoma results from pupillary block following surgery for angle-closure glaucoma, a carbonic anhydrase inhibitor should also be administered; therapy should be continued for at least 4 days before surgery is considered.

Other Uses

In some patients with poor vision because of cataracts and who are unwilling or unable to undergo surgery, phenylephrine-induced mydriasis may improve vision.

A 2.5% solution of phenylephrine hydrochloride prevents formation of iris cysts during topical therapy with some drugs including echothiophate (no longer commercially available in the US) if administered simultaneously with the echothiophate. The reason for the cyst formation and the mechanism by which phenylephrine prevents it are unknown.

Phenylephrine Hydrochloride (EENT) (Mydriatic) Dosage and Administration

Administration

Phenylephrine hydrochloride ophthalmic solutions are applied topically to the conjunctiva or cornea. A local anesthetic other than butacaine (See Chemistry and Stability: Stability) may be instilled prior to phenylephrine to prevent stinging and lacrimation.

Dosage

Ophthalmoscopy and Retinal Photography

To produce mydriasis for ophthalmoscopy or retinal photography, 1 or 2 drops of a 2.5% or 10% solution of phenylephrine hydrochloride may be applied on the upper limbus. Instillation may be repeated in 10–60 minutes if necessary. 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 phenylephrine.

The mydriatic effects of phenylephrine may be enhanced if 3 drops of a 10% solution are applied to a cotton pad placed in the lower cul-de-sac, following administration of a local anesthetic. The patient then closes his eyes for 30 minutes. This method of administration has been suggested for producing mydriasis in eyes with flat or shallow chambers or after cataract extraction.

Refraction

For determination of refraction errors in adults, a cycloplegic drug has been administered 5–15 minutes prior to and 5–10 minutes after 1 drop of 2.5% phenylephrine hydrochloride. If desired, the phenylephrine solution may be mixed with the cycloplegic drug for simultaneous application. For simultaneous use, it may be necessary to increase the concentration of the cycloplegic drug in order to achieve the desired effect because of variability in patient response to the additive effect.

Diagnosis of Horner’s and Raeder’s Syndromes

For the diagnosis of Horner’s or Raeder’s syndrome, a 10% solution of phenylephrine hydrochloride is instilled in both eyes. This causes pupillary dilation in both denervated and normal eyes. Although the pupil of the denervated eye will dilate more rapidly and more widely than that of the normal eye, these differences may be difficult to assess clinically. If a 1% solution of phenylephrine hydrochloride is used, only the pupil of the denervated eye will be substantially affected. In ptosis caused by Horner’s syndrome, elevation of the eyelid to a cosmetically acceptable level within 15 minutes after administration of phenylephrine indicates that surgical resection and advancement of Müller’s muscle is likely to be effective in correcting the ptosis.

Ocular Surgery and Posterior Synechiae

To dilate the pupil prior to intraocular surgery, 1 or 2 drops of a 2.5% or 10% solution of phenylephrine hydrochloride may be administered 30–60 minutes prior to surgery. The drug usually is given with other mydriatics such as atropine sulfate.

To prevent or break posterior synechiae in patients with anterior uveitis, 1 drop of 10% phenylephrine hydrochloride is instilled 3 or more times daily in conjunction with 1 or 2 drops of 1% or 2% atropine sulfate solution or 1% atropine sulfate ophthalmic ointment. To prevent formation of posterior synechiae following iridectomy, 1 drop of 10% phenylephrine hydrochloride may be administered once or twice daily. If inflammation is severe, atropine sulfate should be used instead of phenylephrine. After cyclodialysis, 1 drop of 10% phenylephrine hydrochloride may be administered daily for 3 days; 1 drop of 1% atropine sulfate solution should be administered instead of phenylephrine beginning on the fourth day. After congenital cataract surgery, 1 drop of 10% phenylephrine hydrochloride and 1 drop of 1% atropine sulfate are administered until all cortex is absorbed. The frequency of instillation is determined by the pupillary response.

Glaucoma

In patients with glaucoma, the presence of angle block may be demonstrated by an increase in IOP of 3–5 mm Hg after production of mydriasis by a 2.5% solution of phenylephrine hydrochloride if goniscopy shows the angle to be closed.

In treating glaucoma secondary to pupillary block caused by aphakia or posterior synechiae, 1 or 2 drops of 2–4% atropine sulfate is instilled several times. For enhanced effects, 1 drop of 10% phenylephrine hydrochloride may be instilled in addition. For maintenance, 2% atropine sulfate and 10% phenylephrine hydrochloride may be administered 4 times daily.

Initial treatment of postoperative malignant glaucoma consists of 1 drop of 1% to 4% atropine sulfate and 1 drop of 10% phenylephrine hydrochloride 3 or more times daily as necessary. A carbonic anhydrase inhibitor and an osmotic agent usually are also given. Therapy should be continued for at least 4 days before surgery is considered. If the IOP remains low, the osmotic drug may be discontinued and the dosage of the carbonic anhydrase inhibitor may be reduced or the drug discontinued. Phenylephrine may later be withdrawn also but atropine must be continued in reduced dosage indefinitely.

Cautions for Phenylephrine Hydrochloride (EENT) (Mydriatic)

Ocular Effects

Topical application of phenylephrine to the conjunctiva frequently causes transient burning or stinging and dilution of the drug because of lacrimation. These reactions may be prevented by topical application of a local anesthetic a few minutes prior to phenylephrine; however, butacaine sulfate should not be used because it is incompatible with phenylephrine. Use of phenylephrine in the eye also may cause headache or browache, blurred vision, reactive hyperemia, and transient keratitis. Hypersensitivity reactions such as allergic conjunctivitis or dermatitis also may occur. In some instances, allergic reactions may be caused by the preservatives in the preparations. Phenylephrine therapy should be discontinued if sensitivity develops.

Phenylephrine, like other mydriatics, may cause sensitivity to light which may persist for several hours. In patients with angle-closure glaucoma, dilation of the pupil may precipitate an acute attack. It has been suggested that dilation of the pupil for ophthalmologic examination in patients predisposed to angle closure (those with structurally narrow angles and shallow anterior chambers) be undertaken only if a major ocular problem such as retinal detachment or melanoma is suspected.

Phenylephrine may lower IOP in normal eyes or in patients with open-angle glaucoma, and false-normal tonometry readings may result. However, the drug infrequently causes an increase in IOP in patients with open-angle glaucoma. This is less likely to occur if the patient is being treated with a miotic and may respond to therapy with a miotic and/or a carbonic anhydrase inhibitor such as acetazolamide. Rarely, phenylephrine has precipitated angle-closure glaucoma when administered following peripheral iridectomy.

Phenylephrine may liberate pigment granules presumably from the iris, especially in geriatric patients with dark irides. These granules may appear in the aqueous humor within 30–45 minutes after the drug is administered and may give the appearance of iritis, anterior uveitis, or microscopic hyphema. Pigment floaters may be differentiated from iritis by the absence of other signs of inflammation, and they generally disappear within 12–24 hours.

In patients older than 50 years of age, phenylephrine appears to alter the response of the dilator muscle of the pupil so that rebound miosis may occur the day after the drug is administered. In addition, the pupillary response to further administration of phenylephrine is reduced. This effect may be of special clinical importance when the drug is used prior to retinal detachment or cataract surgery.

Systemic Effects

Ophthalmic use of phenylephrine occasionally causes systemic sympathomimetic effects such as palpitation, tachycardia, premature ventricular contractions, occipital headache, pallor or blanching, trembling or tremors, increased perspiration, and hypertension. In one patient, hypertension severe enough to cause subarachnoid hemorrhage followed insertion of a cotton wick saturated with 10% phenylephrine hydrochloride in the lower conjunctival cul-de-sac. Phenylephrine-induced hypertension may be relieved by administration of an α-adrenergic blocking agent (e.g., phentolamine). Systemic effects occur only rarely after topical application of solutions containing 2.5% or less of phenylephrine hydrochloride to the conjunctiva but are more likely to occur if the drug is instilled after the corneal epithelium has been damaged (e.g., by trauma or instrumentation) or permeability is increased by tonometry, inflammation, surgery of the eye or adnexa, or topical application of a local anesthetic; when the eye or adnexa are diseased; or when lacrimation is suppressed such as during anesthesia. The risk of severe hypertension is greatest in infants receiving instillations of 10% phenylephrine hydrochloride solutions.

Precautions and Contraindications

The cardiovascular status of the patient should be considered before phenylephrine is administered. The drug should be used with caution in patients with marked hypertension, cardiac disorders, advanced arteriosclerotic changes, type 1 (insulin-dependent, IDDM) diabetes mellitus, or hyperthyroidism; in children of low body weight; and in geriatric patients. Blood pressure should be carefully monitored if the 10% solution is used in these patients or in other patients who develop symptoms. Phenylephrine should be administered with caution to patients at increased risk of adverse systemic effects of the drug. (See Cautions: Systemic Effects.) The manufacturers warn that severe and sometimes fatal cardiovascular reactions, including ventricular arrhythmias and myocardial infarction, have occurred rarely following topical application of 10% phenylephrine hydrochloride ophthalmic solutions; these reactions have occurred most frequently in geriatric patients with preexisting cardiovascular disease.

Because phenylephrine may cause false-normal tonometry readings (see Cautions: Ocular Effects), tonometry should be performed before phenylephrine is administered.

Some commercially available formulations of phenylephrine hydrochloride contain sodium bisulfite, a sulfite that may cause allergic-type reactions, including anaphylaxis and life-threatening or less severe asthmatic episodes, in certain susceptible individuals. The overall prevalence of sulfite sensitivity in the general population is unknown but probably low; such sensitivity appears to occur more frequently in asthmatic than in nonasthmatic individuals.

Mydriatics, including phenylephrine, generally are not used in patients with glaucoma, since these drugs may occasionally increase IOP. (See Uses: Glaucoma.) Phenylephrine generally is contraindicated for ophthalmic use in patients with angle-closure glaucoma and is contraindicated in those with known hypersensitivity to phenylephrine or other components of the commercially available solutions or in those with aneurysm. Some manufacturers state that phenylephrine ophthalmic solutions should not be used in patients with soft contact lenses.

Pediatric Precautions

Because of the risk of precipitating severe hypertension, it has been recommended that only the 2.5% solution should be used in infants younger than 1 year of age, and the manufacturers state that the 10% solution is contraindicated in infants.

Mutagenicity and Carcinogenicity

Long-term animal or other studies to determine the carcinogenic and/or mutagenic potential of phenylephrine have not been performed to date.

Pregnancy and Lactation

Pregnancy

Animal reproduction studies have not been performed with phenylephrine. It is not known whether topically applied phenylephrine can cause fetal harm when administered to pregnant women. Parenterally administered phenylephrine in late pregnancy or labor may cause fetal anoxia. Topically applied phenylephrine should be used during pregnancy only when clearly needed.

Lactation

Since it is not known whether phenylephrine is distributed into milk, the drug should be used with caution in nursing women.

Drug Interactions

Concomitant administration of phenylephrine with cycloplegic antimuscarinic drugs such as atropine sulfate, cyclopentolate hydrochloride, homatropine hydrobromide, or scopolamine hydrobromide produces increased dilation of the pupil which is of clinical value.

Administration of a 10% solution of phenylephrine hydrochloride to patients pretreated with 2% pilocarpine hydrochloride produces mydriasis but to a lesser degree than occurs in patients who are not receiving the miotic. Pilocarpine may prevent or reduce visual disturbances and the risk of increased intraocular pressure associated with mydriasis in some patients and may be used to hasten recovery from mydriasis after ophthalmologic examination. Phenylephrine may reduce ciliary and conjunctival congestion and accommodative myopia often encountered when miotics are used alone in the treatment of glaucoma, without compromising the effectiveness of glaucoma therapy.

Phenylephrine must be administered under careful supervision and in reduced dosage if used within 21 days after the patient has received a monoamine oxidase inhibitor because potentiation of the pressor effects of phenylephrine may result. The pressor response to phenylephrine may also be potentiated if a tricyclic antidepressant is administered concomitantly.

If phenylephrine is administered to a patient undergoing chronic oral therapy with guanethidine, the pupillary response to phenylephrine is greatly increased and the pressor response may also be potentiated. Phenylephrine should be administered cautiously to patients receiving guanethidine.

The mydriatic response to phenylephrine is decreased in patients receiving levodopa.

Pharmacology

After topical application to the conjunctiva, phenylephrine acts directly on α-adrenergic receptors in the eye producing contraction of the dilator muscle of the pupil and constriction of arterioles in the conjunctiva. In concentrations of 2.5–10%, phenylephrine hydrochloride is only slightly less effective in dilating the pupil than are cycloplegic drugs. In lower concentrations, phenylephrine may also produce mydriasis, especially when applied to a damaged corneal epithelium, after tonography, after postganglionic sympathetic denervation (as in Horner’s or Raeder’s syndrome), or when used with atropine sulfate or other antimuscarinic drugs which have a different mechanism of action. Phenylephrine may also relieve ptosis in patients with Horner’s or Raeder’s syndrome by a direct effect on the orbital muscle of the eye. The mydriatic effect of phenylephrine may prevent or break posterior synechiae. The drug produces only slight relaxation of the ciliary muscle so that substantial cycloplegia is not likely to occur.

Following topical application of 2.5–10% solutions of the drug to the conjunctiva, phenylephrine hydrochloride may decrease intraocular pressure (IOP) in normal eyes or in patients with open-angle (chronic simple) glaucoma by increasing aqueous outflow facility and/or by decreasing the production of aqueous humor. Rarely, a temporary but clinically important increase in IOP has occurred in patients with open-angle glaucoma. This may result from release of pigment particles, presumably from the iris, into the aqueous humor.

Phenylephrine Hydrochloride (EENT) (Mydriatic) Pharmacokinetics

Following topical application of a 2.5% solution of phenylephrine hydrochloride to the conjunctiva, maximal mydriasis occurs within 15–60 minutes and recovery occurs within 3 hours. Administration of a 10% solution of phenylephrine hydrochloride produces maximal mydriasis within 10–90 minutes; recovery occurs within 3–7 hours.

Occasionally, enough phenylephrine may be absorbed following topical application to the conjunctiva to cause systemic sympathomimetic effects. Circulating drug is metabolized in the liver by the enzyme monoamine oxidase (MAO). For information on the systemic pharmacokinetics of phenylephrine, see Pharmacokinetics in Phenylephrine Hydrochloride 12:12.04.

Chemistry and Stability

Chemistry

Phenylephrine hydrochloride is a synthetic sympathomimetic amine. The drug occurs as odorless, white or practically white crystals having a bitter taste and is freely soluble in water and in alcohol. Ophthalmic solutions containing phenylephrine hydrochloride are clear, colorless or slightly yellow, and have a pH of 4–7.5 if buffered and a pH of 3–4.5 if unbuffered.

Stability

Phenylephrine hydrochloride and solutions containing the drug are subject to oxidation and must be stored in tight, light-resistant containers. Phenylephrine ophthalmic solutions may darken on standing or exposure to air, light, and/or heat and must not be used if they are brown or contain a precipitate. However, oxidation of the drug resulting in loss of activity may occur without a color change being evident. Glass containers may be more effective than polyethylene in preventing oxidation of phenylephrine. Commercially available phenylephrine preparations contain a variety of preservatives. These preparations differ in stability, and the manufacturer’s recommendations should be followed with respect to storage requirements.

Phenylephrine hydrochloride is incompatible with butacaine sulfate, alkalies, ferric salts, oxidizing agents, and metals.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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