Drug class: Vasoconstrictors

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

Introduction

Phenylephrine hydrochloride, synthetic sympathomimetic amine, is a vasoconstrictor.

Uses for Phenylephrine Hydrochloride (EENT) (Vasoconstrictor)

Ophthalmic Disorders

Phenylephrine is applied topically to the conjunctiva to temporarily relieve congestion, itching, and minor irritation caused by mechanical or chemical irritants and to whiten the eye. The drug may be useful in relieving symptoms resulting from allergic reactions such as acute atopic conjunctivitis but is ineffective in delayed hypersensitivity reactions such as contact dermatoconjunctivitis. In patients with episcleritis, phenylephrine provides symptomatic relief but does not substantially suppress the generalized inflammation. Use of phenylephrine as an ocular decongestant may be followed by reactive hyperemia. Phenylephrine may be administered in combination with zinc sulfate which provides a mild astringent effect. The drug sometimes is administered in combination products containing antihistamines, corticosteroids, and/or anti-infective drugs. Topically applied antihistamines, however, are relatively ineffective histamine antagonists.

The vasoconstricting effects of phenylephrine are used during some ocular diagnostic procedures. The drug may be used to improve visualization (via slit-lamp examination) of the typical vascular appearance observed in patients with sickle-cell disease. The “blanching test” has been used to differentiate vasodilation produced by conjunctivitis from that caused by iridocyclitis; however, slit-lamp examinations are generally used for this purpose.

Topical application of phenylephrine to the conjunctiva prior to or during ocular surgery aids in controlling superficial bleeding. Topical epinephrine generally is preferable to phenylephrine except in patients receiving halogenated hydrocarbon general anesthetics.

Nasal Disorders

Phenylephrine may be applied topically to the nasal mucosa for self-medication to relieve nasal and/or sinus congestion associated with the common cold, hay fever, or upper respiratory allergies. However, the drug has a short duration of action and rebound congestion frequently occurs. Phenylephrine may be used as an adjunct to analgesics, systemic antihistamines, antitussives, expectorants, or antibiotics when indicated. Topical application of phenylephrine should be limited to acute conditions. Prolonged use should be avoided because chronic swelling of the nasal mucosa may result (see Cautions: Nasal Effects), and orally administered nasal decongestants are preferred for chronic conditions. In patients with otic inflammation or infection, application of the drug to the nasal mucosa may be useful in opening obstructed eustachian ostia. Phenylephrine also may be used to reduce swelling and facilitate visualization of nasal and pharyngeal membranes prior to surgery or diagnostic procedures. Some commercially available nasal solutions contain phenylephrine in combination with antihistamines and/or other decongestants, but the value of these combination preparations as compared with single-entity preparations in producing nasal decongestion has not been proven.

Nasal decongestants, including phenylephrine, are labeled and have been used for self-medication for the temporary relief of nasal congestion associated with sinusitis. However, because efficacy data are lacking and/or controversial, and because there are potential harmful effects in delaying medical evaluation and definitive treatment by a clinician, the US Food and Drug Administration (FDA) no longer considers oral or topical nasal decongestants appropriate for self-medication of sinusitis. In October 2005, the agency issued a final rule amending the final monograph for nonprescription (over-the-counter; OTC) nasal decongestant preparations to remove the indication for relief of nasal congestion associated with sinusitis from labeling and prohibiting use of the term “sinusitis” elsewhere in labeling. For a more complete discussion of FDA’s final rule, see Uses: Nasal Congestion in Phenylephrine 12:12.

Other Uses

Phenylephrine may be added to solutions of some local anesthetics to decrease the rate of vascular absorption of the anesthetic, thereby localizing anesthesia and prolonging the duration of anesthesia. The risk of systemic toxicity caused by the local anesthetic also is decreased. (See Local Anesthetics, Parenteral, General Statement 72:00.) Phenylephrine is less effective than epinephrine in prolonging local anesthesia but may be preferable when cardiostimulation is undesirable.

In one study, a 1:20,000 (0.005%) phenylephrine injection was infiltrated into the buccal and labial vestibules of the maxilla and mandible of patients undergoing extensive oral surgery to minimize blood loss.

Phenylephrine Hydrochloride (EENT) (Vasoconstrictor) Dosage and Administration

Administration

Phenylephrine hydrochloride ophthalmic solutions are applied topically to the conjunctiva. Digital pressure should be applied on the lacrimal sac for 1–2 minutes following topical instillation of ophthalmic solutions to minimize drainage into the nose and throat and reduce the risk of absorption and systemic reactions. Excess solution around the eye should be removed with a tissue.

For intranasal applications, phenylephrine may be administered in solution as drops or spray. Vicks Sinex (with mist spray nozzle) nasal solution is administered by nasal inhalation using a special nasal inhaler that produces metered droplet sprays. Care must be taken to avoid contamination of the dropper, inhaler, or spray. Except in young children in whom sprays are difficult to use, nasal sprays may be preferable to drops because of the lesser risk of swallowing the drug and resultant systemic absorption. Drops should be applied to the dependent (lower) nostril, with the patient in a lateral head-low position. The patient should remain in the same position for 5 minutes, then the solution should be applied to the other nostril in a similar manner. Alternatively, drops may be instilled when the patient is reclining with the head tilted back as far as possible. Sprays should be delivered or pumped (Vicks Sinex metered spray) into each nostril with the patient’s head erect so that excess solution is not released. The nose should be blown thoroughly 3–5 minutes later. Prior to initial use of the metered sprays, the nasal inhaler must be primed by depressing the pump firmly several times. To minimize the risk of spreading infections, droppers, inhalers, and spray dispensers should not be used by more than one person, and tips of the dispensers, inhalers, or droppers should be rinsed with hot water following use.

Phenylephrine nasal solutions also may be applied to a tampon or nasal pack for insertion into nasal passages. However, this method of application should be restricted to use in diagnostic or surgical procedures performed under medical supervision because mechanical injury may occur.

Dosage

To produce decongestion of the conjunctiva, 1 or 2 drops of a 0.12–0.25% ophthalmic solution of phenylephrine hydrochloride may be applied topically to the conjunctiva every 3–4 hours (up to 4 times daily for self-medication) as needed. Vasoconstriction for diagnosis of ocular congestion or to improve visualization of ocular blood vessels in sickle-cell disease may be achieved by application of 1 or 2 drops of a 2.5% solution. In the “blanching test”, congestion probably is caused by conjunctivitis rather than iridocyclitis if the drug produces perilimbal blanching in the congested eye. A 2.5 or 10% solution of the drug may also be administered prior to surgery to produce mydriasis and aid in controlling hemorrhage.

To produce nasal decongestion in adults and children 12 years of age or older, the usual dosage is 2 or 3 drops, 1–3 sprays, or 1–3 metered sprays instilled in each nostril. In cases of extreme nasal congestion in adults, a 1% solution may be used initially. To produce nasal decongestion in children 6–12 years of age, 2 or 3 drops or 1 or 2 sprays of a 0.25% solution may be instilled in each nostril. Doses of the drug as drops or spray may be repeated in 4 hours if needed. Phenylephrine nasal solutions should not be used for self-medication for longer than 3 days; if symptoms persist, the drug should be discontinued and a physician consulted. Intranasal application of phenylephrine should generally be used for no longer than 3–5 days.

For use with local anesthetics, phenylephrine hydrochloride may be used in concentrations of 1:2500 to 1:20,000.

Cautions for Phenylephrine Hydrochloride (EENT) (Vasoconstrictor)

Ocular Effects

In concentrations usually used as an ocular decongestant, phenylephrine rarely causes serious adverse effects. However, prolonged or indiscriminate use of the drug should be avoided because symptoms of serious eye disease may be neglected. The 2.5% solution of the drug used in diagnostic tests may produce burning or stinging and/or dilution of the drug secondary to lacrimation. These reactions may be prevented by topical application of a local anesthetic a few minutes prior to the phenylephrine; however, butacaine sulfate should not be used because it is incompatible with phenylephrine. Ophthalmic use of phenylephrine may cause headache or browache, blurred vision, irritation, and transient epithelial keratitis. Like other ophthalmic vasoconstrictors, rebound hyperemia can occur with prolonged use of phenylephrine and may result in overuse of the drug. Hypersensitivity reactions such as allergic conjunctivitis or dermatitis may also occur. In some instances, allergic reactions may be caused by preservatives in the preparations. The drug should be discontinued if sensitivity develops or if the original irritation persists or increases.

Mydriasis, which may result from ophthalmic use of phenylephrine, 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.

Ophthalmic application of solutions containing 2.5% or more phenylephrine hydrochloride may lower intraocular pressure in normal eyes or in patients with open-angle glaucoma, and false-normal tonometry readings may result. The drug only infrequently causes an increase in intraocular pressure 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.

Phenylephrine, especially in high concentrations, 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.

Nasal Effects

After intranasal application, phenylephrine may cause transient burning, stinging, sneezing, increased nasal discharge, and/or dryness of the mucosa. Rebound nasal congestion frequently occurs and may result in overuse of the drug. Prolonged use of phenylephrine should be avoided because chronic swelling of the nasal mucosa and rhinitis may occur. The mucosa may become edematous and turn red or pale gray in color, resembling nonseasonal allergic rhinitis. These signs usually abate after the drug is discontinued for 1 week or longer.

Systemic Effects

Ophthalmic or intranasal use of phenylephrine occasionally causes systemic sympathomimetic effects such as palpitation, tachycardia, ventricular premature 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). Nausea, dizziness, CNS stimulation, and nervousness may also follow intranasal use of the drug. 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., trauma, 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. After intranasal use of phenylephrine, the possibility of substantial absorption and systemic effects is increased after overdosage or swallowing excess solution. Use of phenylephrine nasal spray rather than drops so that the head may be kept erect during administration may minimize the amount of solution swallowed.

Precautions and Contraindications

The cardiovascular status of the patient should be considered before phenylephrine is administered. Phenylephrine ophthalmic solution should be used with caution in patients with marked hypertension, cardiac disorders, advanced arteriosclerotic changes, insulin-dependent (type I) 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. (See Cautions: Systemic Effects.) Some 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 ophthalmic solution may cause false-normal tonometry readings (see Cautions: Ocular Effects), tonometry should be performed before phenylephrine is administered.

Patients using phenylephrine hydrochloride ophthalmic solutions should be advised to discontinue the drug and consult a physician if ocular pain or visual changes occur, they experience continued ocular redness or irritation, or the condition worsens or persists for more than 72 hours. Patients also should be informed that overuse of ophthalmic vasoconstrictors may produce increased redness of the eye (rebound hyperemia). Patients using phenylephrine hydrochloride nasal solutions should be advised to discontinue the drug and consult a physician if symptoms (e.g., nasal stuffiness) persist after 3 days of therapy.

Phenylephrine ophthalmic solutions generally are not used in patients with glaucoma, since drugs with mydriatic effects may occasionally increase intraocular pressure. In addition, patients with glaucoma should be advised not to use ophthalmic solutions of the drug for self medication except under the advice and supervision of a physician. Phenylephrine generally is contraindicated for ophthalmic use in patients with angle-closure glaucoma and in those with known hypersensitivity to phenylephrine or other components of the commercially available solutions or in those with aneurysm. Some manufacturers state that the ophthalmic solutions should not be used in patients with soft contact lenses. Nasal solutions containing phenylephrine should not be administered further to patients who have developed insomnia, tremor, asthenia, dizziness, or arrhythmias from previous doses of the drug. In conjunction with local anesthetics, phenylephrine is contraindicated for use in ears, nose, fingers, toes, or genitalia.

Some commercially available formulations of phenylephrine hydrochloride contain sulfites, which 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.

In case of accidental ingestion of phenylephrine hydrochloride nasal solutions, a clinician or a poison control center should be contacted immediately. Some manufacturers of the nasal solutions state that patients with heart disease, hypertension, thyroid disease, or diabetes mellitus and those who experience difficulty in urination secondary to enlargement of the prostate gland should not use phenylephrine hydrochloride nasal solutions unless directed by a clinician.

Pediatric Precautions

Infants and children may be more susceptible to systemic effects of the drug than are adults. Because of the risk of precipitating severe hypertension, it has been recommended that only ophthalmic solutions containing 0.5% or less should be used in infants younger than 1 year of age, and the manufacturers state that the 10% ophthalmic solution is contraindicated in infants. Although one manufacturer recommends that the 0.5% nasal solution not be used in children younger than 6 years of age, most manufacturers recommend that the 0.5% nasal solution not be used in children younger than 12 years of age unless under the direction and supervision of a physician. The 0.25% nasal solution should not be used in children younger than 6 years of age unless under the direction and supervision of a physician.

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

When applied topically to the conjunctiva (especially in concentrations of 2.5% or greater), phenylephrine hydrochloride must be administered under careful supervision and in reduced dosage if used within 21 days after the patient has received a monoamine oxidase (MAO) inhibitor because potentiation of the pressor effects of phenylephrine may result. Nasal solutions containing phenylephrine must not be given to a patient receiving an MAO inhibitor. The pressor response to phenylephrine may also be potentiated if a tricyclic antidepressant is administered concomitantly.

Concomitant administration of phenylephrine with cycloplegic antimuscarinic drugs such as atropine sulfate, cyclopentolate hydrochloride, homatropine hydrobromide, or scopolamine hydrobromide produces increased mydriatic effects.

Pharmacology

Following topical application to the conjunctiva or other mucosa, phenylephrine acts directly on α-adrenergic receptors producing constriction of arterioles. The drug produces local vasoconstriction and hemostasis in bleeding from small vessels but, like epinephrine, probably does not control bleeding from larger vessels. Topical application of phenylephrine to the nasal mucosa results in constriction of dilated arterioles and reduction in blood flow and nasal congestion. In addition, nasal secretions are reduced, drainage of sinus secretions is increased, and obstructed eustachian ostia may be opened. Nasal ventilation and aeration are improved temporarily; however, rebound vasodilation and congestion may occur. Conjunctival congestion is temporarily relieved following topical application of phenylephrine to the conjunctiva, but reactive hyperemia may occur.

Phenylephrine hydrochloride is an effective mydriatic in concentrations of 2.5–10%. In lower concentrations commonly used as ocular decongestants, the drug may also produce mydriasis, especially when applied to a damaged corneal epithelium, after tonography, or 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 Hydrochloride (EENT) (Vasoconstrictor) Pharmacokinetics

Following topical application of phenylephrine solutions to the conjunctiva, local vasoconstriction occurs almost immediately. The duration of decongestant effects following application to the conjunctiva or nasal mucosa is variable and may range from 30 minutes to 4 hours.

Occasionally, enough phenylephrine may be absorbed following topical application to the conjunctiva or mucosa 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 and nasal solutions containing the drug are clear and colorless or slightly yellow. Phenylephrine ophthalmic solutions have a pH of 4–7.5 if buffered and a pH of 3–4.5 if unbuffered; nasal solutions containing the drug are neutral or acidic. Vicks Sinex (ultra fine mist) nasal solution is administered by a special nasal inhaler that produces metered droplet sprays; these commercially available preparations of phenylephrine hydrochloride nasal solution do not contain a propellant (e.g., fluorocarbons). For information on phenylephrine hydrochloride injection, .

Stability

Phenylephrine hydrochloride and solutions containing the drug are subject to oxidation and must be stored in tight, light-resistant containers. Phenylephrine hydrochloride nasal and ophthalmic preparations should generally be stored at a temperature less than 40°C, preferably between 15–30°C; freezing should be avoided. 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 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.

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.

Preparations

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