Oxymetazoline hydrochloride, an imidazoline-derivative sympathomimetic amine, is a vasoconstrictor.
Oxymetazoline hydrochloride is applied topically to relieve nasal congestion associated with acute or chronic rhinitis, the common cold, and hay fever or other upper respiratory allergies;111 its effectiveness appears to be similar to that of other topical vasoconstrictors.
Nasal decongestants, including oxymetazoline, are labeled and have been used for self-medication for the temporary relief of nasal congestion associated with sinusitis.107, 111 However, prospective studies of nasal decongestants for this use are lacking,108 and data on their use as adjunctive therapy in the management of sinusitis are limited and controversial.107, 109 Furthermore, evidence from an ex vivo study using animal tissues indicates that topical nasal decongestants may increase the degree of sinus inflammation,110 potentially delaying the resolution of sinusitis.107 Because current labeling for nonprescription (over-the-counter; OTC) nasal decongestant preparations includes use for sinusitis, there are concerns that consumers will assume that nasal decongestants are effective in the treatment of sinusitis, thereby choosing self-medication over medical evaluation and definitive treatment by a clinician; such delay in medical evaluation could result in a lost opportunity for early diagnosis of another serious medical condition (e.g., bacterial sinusitis).107 As a result, the US Food and Drug Administration (FDA) no longer considers oral or topical nasal decongestants appropriate for self-medication of sinusitis.107 In October 2005, the agency issued a final rule amending the final monograph for 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.107 The compliance date for preparations with annual sales less than $25,000 is October 11, 2007; the compliance date for all other preparations is April 11, 2007.107
Topical nasal decongestants provide only temporary relief of congestion, and some degree of rebound congestion usually results. Some clinicians prefer topical nasal decongestants to oral preparations for short-term treatment of nasal congestion. When nasal decongestants are required for prolonged periods, however, oral preparations may be preferable because of the propensity of topical preparations to cause mucosal irritation and more pronounced rebound congestion. Intranasal oxymetazoline also may be used to reduce swelling and facilitate visualization of nasal and pharyngeal membranes prior to surgery or diagnostic procedures and to open obstructed eustachian ostia in patients with ear inflammation.
Oxymetazoline hydrochloride ophthalmic solution is applied topically to the conjunctiva to temporarily relieve congestion and redness due to minor irritation.112
Oxymetazoline hydrochloride nasal solution has been used topically for self-medication in the symptomatic prevention of otitic barotrauma† (aerotitis [barotitis] media).101, 103, 105 Otitic barotrauma, commonly known as middle ear squeeze, refers to tissue damage caused by failure of the middle ear to equilibrate its internal pressure to accommodate changes in atmospheric pressure (e.g., during descent of an aircraft, underwater diving, hyperbaric oxygenation).100, 101, 102, 103, 104, 106 Clinical manifestations include a sensation of otic blockage or discomfort, otalgia, tinnitus, vertigo, and transient conductive hearing loss; these manifestations may be accompanied by tympanic membrane congestion or hemorrhage, hemotympanum, or membrane perforation or rupture. 100, 101, 102
Although topical (e.g., oxymetazoline) or oral (e.g., pseudoephedrine) decongestants generally have been recommended for prevention or treatment of otitic barotrauma, few clinical studies have been conducted to evaluate such use,100, 101, 102, 104, 106 and limited data indicate that oxymetazoline is no more effective than placebo in reducing the incidence of otitic barotrauma.101 In a randomized, double-blind, comparative study in healthy adult air travelers, manifestations of otitic barotrauma (e.g., otalgia, blockage) reportedly occurred in 64, 34, or 71% of individuals receiving oxymetazoline hydrochloride (0.05%) nasal spray, extended-release pseudoephedrine hydrochloride (120 mg) tablets, or placebo, respectively, at least 30 minutes before flight departure.101 Oxymetazoline also does not appear to be effective in reducing the incidence of otitic barotrauma associated with hyperbaric oxygen therapy.101, 105 In a randomized, double-blind, placebo-controlled study in which oxymetazoline hydrochloride nasal spray or placebo was administered 15 minutes before hyperbaric oxygen therapy, otic discomfort during hyperbaric oxygen therapy was reported in 63% of patients who received oxymetazoline and in 67% of those who received placebo.105
Oxymetazoline hydrochloride nasal solutions are applied topically to the nasal mucosa as sprays. Oxymetazoline hydrochloride nasal solutions also are administered by a nasal pump that produces metered sprays. Ophthalmic solutions of the drug are applied topically to the conjunctiva.112 Care must be taken to avoid contamination of the dropper, inhaler, or spray dispenser.112 It is recommended that contact lenses be removed before topical administration of the ophthalmic solution.112
Sprays (including metered sprays) should be delivered or pumped into each nostril with the patient's head erect so that excess solution is not released. Prior to initial use of metered sprays, the nasal inhalers should 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 or wiped clean following use.
The 0.05% oxymetazoline hydrochloride nasal solution should be used only in adults and children 6 years of age and older. Oxymetazoline nasal solutions should not be used for self-medication for longer than 3 days; if symptoms persist, the drug should be discontinued and a clinician consulted.
The usual dosage of 0.05% oxymetazoline hydrochloride nasal solution for adults and children 6 years of age and older is 2 or 3 sprays in each nostril every 10-12 hours (usually in the morning and evening), not to exceed twice in 24 hours.111
To produce decongestion of the conjunctiva in adults and children 6 years of age and older, 1 or 2 drops of the 0.025% oxymetazoline hydrochloride ophthalmic solution may be instilled in the affected eye(s); doses of the drug may be repeated every 6 hours as needed or as directed by a clinician.112
The incidence of serious adverse effects is low in patients receiving therapeutic dosages of topical oxymetazoline hydrochloride.
Intranasal administration of oxymetazoline may cause transient burning, stinging, increased nasal discharge or dryness of the nasal mucosa, and sneezing.111 Rebound congestion, characterized by chronic redness, swelling, and rhinitis, frequently occurs with prolonged use and may result in overuse of the drug.111 Prolonged use of nasal decongestant solutions should be avoided for these reasons.
Intranasal use of oxymetazoline may occasionally cause systemic sympathomimetic effects such as hypertension, nervousness, nausea, dizziness, headache, insomnia, palpitation, or reflex bradycardia.
Accidental ingestion of imidazoline derivatives (i.e., oxymetazoline, naphazoline, tetrahydrozoline) in children has resulted in serious adverse events requiring hospitalization (e.g., coma, bradycardia, decreased respiration, sedation, somnolence).1001, 1002, 1003, 1004, 1005, 1006, 1007
Precautions and Contraindications
Excessive dosage and/or prolonged or too frequent intranasal use of oxymetazoline may irritate nasal mucosa and, especially in children, cause adverse systemic effects. Excessive dosage or inadvertent ingestion in children may cause profound CNS depression, possibly necessitating intensive supportive care. CNS depression, shock-like hypotension, and coma have occurred following overdosage of naphazoline and tetrahydrozoline; the possibility that this may occur with oxymetazoline should be considered.
When nasal decongestants are applied topically in recommended dosages, the usual restrictions to the use of sympathomimetics in patients with hyperthyroidism, heart disease (including angina), hypertension, advanced arteriosclerotic conditions, or diabetes mellitus, or in those receiving monoamine oxidase inhibitors usually do not apply; however, some caution and observation of these patients may be warranted.111 In addition, some manufacturers of oxymetazoline hydrochloride 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 oxymetazoline hydrochloride nasal solutions unless directed by a clinician. Patients using oxymetazoline hydrochloride nasal solutions should be advised to discontinue the drug and consult a clinician if symptoms (e.g., nasal stuffiness) persist after 3 days of therapy.111
Patients using oxymetazoline hydrochloride ophthalmic solution should be advised to discontinue the drug and consult a clinician if ocular pain or visual changes occur, they continue to experience ocular redness or irritation, or the condition worsens or persists for more than 72 hours.112 Patients also should be informed that overuse of oxymetazoline hydrochloride ophthalmic solution may produce increased redness of the eye (rebound hyperemia).
Serious adverse events requiring hospitalization have been reported in children following accidental ingestion of nonprescription (over-the-counter, OTC) ophthalmic solutions or nasal sprays containing imidazoline derivatives (i.e., oxymetazoline, naphazoline, tetrahydrozoline).1001 If accidental ingestion of oxymetazoline hydrochloride ophthalmic or nasal solution occurs, a poison control center should be contacted, and patients should be advised to seek emergency help immediately.1001
Oxymetazoline is contraindicated in patients with known sensitivity to the drug or any component in the formulation and in patients with known sensitivity to the pharmacologic effects of adrenergic drugs. Patients with angle-closure glaucoma should be advised not to use oxymetazoline hydrochloride ophthalmic solutions except under the advice and supervision of a clinician.112
Oxymetazoline 0.05% nasal solution or 0.025% ophthalmic solution is not recommended for self-medication in children younger than 6 years of age.111, 112 Irritation of nasal mucosa and adverse systemic effects (including profound CNS depression) may occur with excessive dosage, prolonged or too frequent use, or inadvertent ingestion of oxymetazoline nasal solution.
Serious adverse events requiring hospitalization have been reported in children following accidental ingestion of small amounts (1-2 mL) of nonprescription ophthalmic solutions or nasal sprays containing imidazoline derivatives (i.e., oxymetazoline, naphazoline, tetrahydrozoline).1001 Patients should be advised to keep oxymetazoline hydrochloride ophthalmic and nasal solutions out of the reach of children.1001
Safe use of oxymetazoline during pregnancy has not been established. Oxymetazoline hydrochloride ophthalmic or nasal solutions should be used during pregnancy only when instructed by a clinician.
It is not known whether oxymetazoline is distributed into milk.114 Topical oxymetazoline preparations should be used with caution in nursing women.113
The minimum toxic dose of imidazoline derivatives (e.g., oxymetazoline, naphazoline, tetrahydrozoline) has not been established in pediatric patients;1003 however, ingestion of 2-5 mL of a 0.05% tetrahydrozoline solution is capable of producing coma.1001
Serious adverse events requiring hospitalization have been reported in pediatric patients following accidental ingestion of nonprescription (over-the-counter, OTC) ophthalmic solutions or nasal sprays containing imidazoline derivatives (i.e., oxymetazoline, naphazoline, tetrahydrozoline).1001 Between 1985 and October 2012, 96 cases of accidental ingestion were reported in children 1 month to 5 years of a the amount of drug ingested ranged from 0.6-45 mL.1001 While no deaths were reported, more than half of these cases reported serious adverse events requiring hospitalization, including nausea, vomiting, lethargy, tachycardia, decreased respiration, bradycardia, hypotension, hypertension, sedation, somnolence, mydriasis, stupor, hypothermia, drooling, and coma.1001 Respiratory depression, CNS depression, and/or lethargy were reported in a 23-month-old and a 2-year-old infant following accidental ingestion of 6 or 2-3 mL, respectively, of 0.05% tetrahydrozoline ophthalmic solution;1002, 1007 in addition, urinary incontinence was reported in a 36-month-old child following accidental ingestion of 30 mL of 0.05% tetrahydrozoline ophthalmic solution.1004
Symptoms develop rapidly in children (i.e., within 15 minutes to 4 hours following ingestion) and generally resolve within 24 hours.1002, 1003, 1004 Imidazoline derivatives stimulate central and peripheral α-adrenergic receptors; therefore, symptoms of acute intoxication in children may alternate between CNS depression and agitation or hyperactivity.1006
Treatment of acute toxicity associated with imidazoline derivatives (e.g., oxymetazoline) is primarily symptomatic and supportive and is aimed at reversing the toxic cardiovascular and CNS effects of the drugs.1002 Cardiorespiratory resuscitation, including tracheal intubation and mechanical ventilation, is considered a mainstay of care for imidazoline-derivative intoxication.1002 Neurologic and hemodynamic status of the patient should be closely observed for at least 24 hours.1006
Because imidazoline derivatives are rapidly absorbed following ingestion, GI decontamination (e.g., activated charcoal, ipecac-induced emesis, gastric lavage) appears to have limited value.1002, 1006, 1007 However, if GI decontamination is used, some clinicians state that gastric lavage is preferred over induction of emesis.1002, 1007 Administration of activated charcoal and a cathartic is recommended by some clinicians; however, safety and efficacy of repeated administration of activated charcoal have not been established.1007
There is no known specific antidote for imidazoline-derivative intoxication.1006, 1007 Because symptoms of imidazoline-derivative and clonidine intoxication are similar and are mediated via the same central α2-adrenergic receptors, and because naloxone has been effective in reversing CNS depression in some instances of clonidine overdose, some clinicians have hypothesized that naloxone may be useful for the management of imidazoline-derivative intoxication.1003, 1004, 1006, 1007 However, data are limited and conflicting, and the role of naloxone in the management of imidazoline-derivative intoxication remains to be established.1002, 1004, 1006, 1007
The mechanism of action of oxymetazoline has not been conclusively determined. Most pharmacologists believe that the drug directly stimulates α-adrenergic receptors of the sympathetic nervous system and exerts little or no effect on β-adrenergic receptors. Intranasal application of oxymetazoline results in constriction of dilated arterioles and reduction in nasal blood flow and congestion. In addition, obstructed eustachian ostia may be opened. Nasal ventilation and aeration are improved temporarily; however, rebound vasodilation and congestion usually occur to some degree. Following topical application of oxymetazoline hydrochloride ophthalmic solution, conjunctival congestion is temporarily relieved, but overuse of the drug may produce rebound hyperemia.
Following intranasal application of oxymetazoline hydrochloride solutions, local vasoconstriction usually occurs within 5-10 minutes and persists for 5-6 hours with a gradual decline over the next 6 hours. Following topical application of oxymetazoline hydrochloride ophthalmic solution, local vasoconstriction usually occurs within minutes and may persist for up to 6 hours. Occasionally, enough oxymetazoline may be absorbed to produce systemic effects. Information on the distribution and elimination of the drug in humans is not available.
Oxymetazoline hydrochloride is an imidazoline derivative sympathomimetic amine. The drug is structurally and pharmacologically related to naphazoline, tetrahydrozoline, and xylometazoline. Oxymetazoline hydrochloride occurs as a hygroscopic, white to practically white, fine crystalline powder and has solubilities of approximately 149 mg/mL in water and 278 mg/mL in alcohol at 25°C. Oxymetazoline hydrochloride nasal solutions are solutions of the drug in water adjusted to a suitable tonicity; the commercially available nasal solutions also may contain a suitable preservative (e.g., benzalkonium chloride, phenylmercuric acetate, thimerosal). Nasal solutions of the drug have a pH of 4-6.5. Some nasal solutions are administered by special nasal inhalers that produce metered droplet sprays; these commercially available preparations of oxymetazoline hydrochloride nasal solution do not contain a propellant (e.g., fluorocarbons).
Oxymetazoline hydrochloride ophthalmic solutions are sterile, isotonic solutions of the drug in water. The ophthalmic solution contains a suitable preservative (e.g., benzalkonium chloride, edetate disodium) and also may contain boric acid, sodium borate, and sodium chloride.
Oxymetazoline hydrochloride nasal solutions should be stored in tight containers at a temperature less than 40°C, preferably at 2-30°C; freezing should be avoided.111 Oxymetazoline hydrochloride ophthalmic solutions should be stored at 15-30°C.112 Oxymetazoline is probably degraded in the presence of aluminum and, therefore, should not be stored in aluminum containers. Oxymetazoline hydrochloride ophthalmic solutions should not be used if they become discolored or cloudy.112
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.
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.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Nasal | Solution | 0.05%* | Afrin® No Drip Extra Moisturizing 12 Hour Pump Mist | |
Afrin® No Drip Original 12 Hour Pump Mist | Schering-Plough | |||
Afrin® No Drip Severe Congestion 12 Hour Pump Mist | Schering-Plough | |||
Afrin® No Drip Sinus 12 Hour Pump Mist | Schering-Plough | |||
Afrin® Original 12 Hour Spray | Schering-Plough | |||
Afrin® Severe Congestion 12 Hour Spray | Schering-Plough | |||
Afrin® Sinus 12 Hour Spray | Schering-Plough | |||
Dristan® 12 Hour Nasal Spray | ||||
Neo-Synephrine® 12 Hour Severe Sinus Congestion Spray | ||||
Nostrilla® 12 Hour Nasal Decongestant Metered Pump Spray | ||||
Oxymetazoline Hydrochloride Nasal Solution | ||||
Vicks Sinex® 12 Hour Nasal Decongestant Spray (with regular or metered pump mist spray) | Procter & Gamble | |||
Zicam® Extreme Congestion Relief Nasal Gel | ||||
Zicam® Intense Sinus Relief Nasal Gel | Matrixx | |||
Ophthalmic | Solution | 0.025% | Visine L.R.® Eye Drops | Pfizer |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Only references cited for selected revisions after 1984 are available electronically.
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107. Food and Drug Administration. Cold, cough, allergy, bronchodilator, and antiasthmatic drug products for over-the-counter human use; amendment of final monograph for over-the-counter nasal decongestant drug products. 21 CFR Parts 310 and 341. Final rule. [Docket No. 2004N- 0289] Fed Regist . 2005; 70:58974-7.
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111. Neo-Synephrine 12 Hour® (oxymetazoline hydrochloride) 0.05% nasal solution prescribing information. In PDR.net [database online]. Montvale, NJ: Thomson Healthcare; 2003. Updated 2003 Oct.
112. Visine L.R. Long Lasting® (oxymetazoline hydrochloride) 0.025% ophthalmic solution prescribing information. In PDR.net [database online]. Montvale, NJ: Thomson Healthcare; 2003. Updated 2003 Oct.
113. Wickersham, RM. Drug Facts and Comparisons. 2003. St Louis, MO: Facts and Comparisons; 2003: page 685.
114. Briggs GG, Freeman RK, Yaffe SJ. Drugs in pregnancy and lactation. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005:1227-8.
1001. US Food and Drug Administration. FDA drug safety communication: Serious adverse events from accidental ingestion by children of over-the-counter eye drops and nasal sprays. Rockville, MD; 2012 Oct 25. From FDA website. [Web]
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1003. Katar S, Taskesen M, Okur N. Naloxone use in a newborn with apnea due to tetrahydrozoline intoxication. Pediatr Int . 2010; 52:488-9. [PubMed 20723124]
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1005. Vitezic D, RozmanicV, Franulovic J et al. Naphazoline nasal drops intoxication in children. Arh Hig Rada Toksikol . 1994; 45:25-9. [PubMed 8067910]
1006. Mahieu LM, Rooman RP, Goossens E. Imidazoline intoxication in children. Eur J Pediatr . 1993; 152:944-6. [PubMed 8276031]
1007. Higgins GL, Campbell B, Wallace K et al. Pediatric poisoning from over-the-counter imidazoline-containing products. Ann Emerg Med . 1991; 20:655-8. [PubMed 2039105]