Oxymetazoline

Medical uses

Oxymetazoline is available over-the-counter as a topical decongestant in the form of oxymetazoline hydrochloride in nasal sprays.

Due to its vasoconstricting properties, oxymetazoline is also used to treat nosebleeds and eye redness due to minor irritation (marketed as Visine L.R. in the form of eye drops).

In the United States, oxymetazoline 1% cream was approved by the Food and Drug Administration (FDA) in January 2017 for topical treatment of persistent facial erythema (redness) associated with rosacea in adults.

In July 2020, oxymetazoline received approval by the FDA for the treatment of acquired blepharoptosis (drooping eyelid).

Side effects

Rebound congestion

Rebound congestion, or rhinitis medicamentosa, may occur. A 2006 review of the pathology of rhinitis medicamentosa concluded that use of oxymetazoline for more than three days may result in rhinitis medicamentosa and recommended limiting use to three days.

Nosebleeds

Although oxymetazoline can be used for treatment of nosebleeds, it can also cause them under certain conditions, especially when nasal passages are dry. Oxymetazoline is a nasal decongestant that constricts blood vessels in the nasal mucosa, thereby reducing swelling and improving airflow. However, its use can lead to dryness and irritation of the nasal lining, which can increase the likelihood of nosebleeds.

Australian regulatory submission

Novartis recommended a five day maximum usage period, rather than three days, in a submission to the Therapeutic Goods Administration. Novartis suggested that "the justification [for 3 days] was not based on evidence," cited an extensive body of evidence, and noted a range of recommended periods from five to ten days, which coincides with the typical duration of the common cold.

Pharmacology

Pharmacodynamics

Oxymetazoline is a sympathomimetic that selectively agonizes α1 and, partially, α2 adrenergic receptors. Since vascular beds widely express α1 receptors, the action of oxymetazoline results in vasoconstriction. In addition, the local application of the drug also results in vasoconstriction due to its action on endothelial postsynaptic α2 receptors; systemic application of α2 agonists, in contrast, causes vasodilation because of centrally-mediated inhibition of sympathetic tone via presynaptic α2 receptors. Vasoconstriction of vessels results in relief of nasal congestion in two ways: first, it increases the diameter of the airway lumen; second, it reduces fluid exudation from postcapillary venules. It can reduce nasal airway resistance (NAR) up to 35.7% and reduce nasal mucosal blood flow up to 50%.

When used for treating acquired blepharoptosis, oxymetazoline is believed to work by stimulating the α1 and α2 adrenergic receptors of Müller's muscle, which helps to lift the eyelid and improve vision.

Pharmacokinetics

Since imidazolines are sympathomimetic agents, their primary effects appear on α adrenergic receptors, with little if any effect on β adrenergic receptors. Like other imidazolines, Oxymetazoline is readily absorbed orally. Effects on α receptors from systemically absorbed oxymetazoline hydrochloride may persist for up to 7 hours after a single dose. The elimination half-life in humans is 5–8 hours. It is excreted unchanged both by the kidneys (30%) and in feces (10%).

History

The oxymetazoline brand Afrin was first sold as a prescription medication in 1966. After finding substantial early success as a prescription medication, it became available as an over-the-counter drug in 1975. Schering-Plough did not engage in heavy advertising until 1986.

Society and culture

Brand names

Brand names for Oxymetazoline include Afrin, ClariClear, Dristan, Drixine, Drixoral, Nasivin, Nasivion, Nezeril, Nostrilla, Logicin, Vicks Sinex, Visine L.R., Sudafed OM, Otrivin, Oxy, SinuFrin, Vicks Sinex Severe (Spray), and Mucinex Sinus-Max. A topical cream formulation is sold under the brand name Rhofade. Oxymetazoline ophthalmic solution for the treatment of acquired blepharoptosis is marketed as Upneeq.

References

References

1. https://pubmed.ncbi.nlm.nih.gov/20203244/
2. "Oxymetazoline". National Library of Medicine (US), National Center for Biotechnology Information.
3. "2-(2,6-dimethyl-3-hydroxy-4-tert-butyl-benzyl)-2-imidazoline, and acid addition salts thereof, and process for their manufacture".
4. "Oxymetazoline Drug Usage Statistics, United States, 2013 - 2022".
5. "Oxymetazoline". Merck.com.
6. (1990). "A comparison of cocaine, lidocaine with epinephrine, and oxymetazoline for prevention of epistaxis on nasotracheal intubation". Journal of Clinical Anesthesia.
7. (September 1995). "Use of oxymetazoline in the management of epistaxis". The Annals of Otology, Rhinology, and Laryngology.
8. Han, Da Hee. (19 January 2017). "New Topical Cream Approved for Persistent Redness with Rosacea".
9. (October 2017). "Oxymetazoline hydrochloride cream for facial erythema associated with rosacea". Expert Review of Clinical Pharmacology.
10. (8 July 2020). "UPNEEQ Label". accessdata.fda.gov.
11. (January 2025). "The Use of Oxymetazoline 0.1% Ophthalmic Solution for Acquired Blepharoptosis: A Systematic Review". The Laryngoscope.
12. (2006). "Rhinitis medicamentosa". Journal of Investigational Allergology & Clinical Immunology.
13. (2014). "Consultation submission: OTC nasal decongestant preparations for topical use: proposed advisory statements for medicines". Novartis Consumer Health Australasia.
14. "Goodman & Gilman's The Pharmacological Basis of Therapeutics".
15. "Basic & Clinical Pharmacology".
16. (1997). "Microvascular anatomy of the nose". Allergy.
17. (March 1986). "Vascular effects of topical oxymetazoline on human nasal mucosa". The Journal of Laryngology and Otology.
18. (2004). "Clinical veterinary toxicology". Mosby.
19. "Decongestants (Toxicity) - Toxicology".
20. (2017). "Veterinary toxicology for Australia and New Zealand". McGraw Hill LLC.
21. (20 October 1986). "Advertising; Afrin Goes After Users Of Nasal Decongestants". [[The New York Times]].
22. (May 2017). "Oxymetazoline cream (Rhofade) for rosacea". The Medical Letter on Drugs and Therapeutics.