Clinical Pharmacokinetics of Oxymetazoline Cream Following Topical Facial Administration for the Treatment of Erythema Associated With Rosacea

February 2018 | Volume 17 | Issue 2 | Original Article | 213 | Copyright © February 2018

Amy W. Kuang PhD,a Janet DuBois MD,b Mayssa Attar PhD,a Gurpreet Ahluwalia PhDa

aAllergan plc, Irvine, CA bDermResearch, Inc., Austin, TX

BACKGROUND: Oxymetazoline cream 1.0% is FDA-approved for the topical treatment of persistent facial erythema associated with rosacea in adults. This phase 2, multicenter, randomized, double-blind, parallel-group study assessed the pharmacokinetics, safety, and tolerability of oxymetazoline in patients with moderate to severe erythema associated with rosacea. METHODS: Eligible patients were randomized to 1 of 8 treatment groups (oxymetazoline cream 0.5%, 1.0%, or 1.5% or vehicle applied topically either once or twice daily for 28 days). Pharmacokinetic analyses were conducted in patients receiving oxymetazoline. Plasma samples for pharmacokinetic assessments were collected prior to dosing and 6 times postdose on days 1 and 28. RESULTS: A total of 356 patients were included in the safety population (oxymetazoline, n=268; vehicle, n=88). Thirty patients (11.2%) in the oxymetazoline group reported treatment-related treatment-emergent adverse events, most of which were mild to moderate application-site reactions. Oxymetazoline, at all concentrations, was generally safe and well tolerated. Mean maximum observed plasma concentrations were ≤115 pg/mL across all groups; the highest mean values for area under the plasma concentration-time curve from time 0 to 24 hours following once- and twice-daily administration of oxymetazoline 1.5% were 1680 pg•h/mL and 2660 pg•h/mL, respectively. Systemic exposure to oxymetazoline increased dose proportionally with once- and twice-daily administration. Conclusion: These findings support the use of oxymetazoline for the treatment of persistent facial erythema associated with rosacea.J Drugs Dermatol. 2018;17(2):213-220.


Rosacea is a common, chronic skin disorder affecting more than 16 million people in the United States.1,2 Typically affecting the central facial area including cheeks, chin, nose, and forehead, rosacea is characterized by flushing (or transient facial erythema), persistent facial erythema, papules and pustules, and/or telangiectasias.3-5 Various combinations of clinical features define 4 major subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular rosacea. Although understanding of the pathophysiology is limited, data suggest 2 primary mechanisms: abnormal innate immune detection and neurovascular dysregulation. Activation of these pathways leads to specific clinical manifestations of rosacea.5,6 Acute and chronic facial vasodilation and an impaired stratum corneum permeability barrier have been documented in rosacea.6Although currently available treatments target some rosacea manifestations, none offers a cure.7-10 Goals are to alleviate signs and symptoms, improve the skin’s appearance, and delay or prevent disease progression. Treatment is selected based on the individual’s predominant signs and symptoms, and may comprise multiple modalities, including topical pharmacologic agents and nonpharmacologic options. Pharmacologic treatments for inflammatory lesions of rosacea include topical clindamycin, metronidazole, sulfacetamide, azelaic acid, or combination products,7,11-13 and oral antimicrobial agents.7,13Treatments for the persistent, diffuse erythema associated with rosacea are limited, but FDA-approved options include oxymetazoline and brimonidine.7,14-16 Because the cutaneous circulation is partially regulated by the sympathetic nervous system, it may be targeted by α-adrenoceptor agonists such as these to reduce erythema.14-16 Oxymetazoline binds selectively to α1A receptors, causing vasoconstriction and reduction of erythema following topical application.14 The Phase 3 REVEAL clinical trials demonstrated the efficacy, safety, and tolerability of oxymetazoline cream 1.0% applied topically once daily for 29 days in adults with moderate to severe persistent facial erythema associated with rosacea.17,18Oxymetazoline pharmacokinetics data are limited, but ocular absorption studies in rabbits have demonstrated that oxymetazoline is poorly absorbed,19 indicating low systemic exposure. Although intranasal oxymetazoline is believed to be an effective decongestant for up to 12 hours,20 intraocular administration of oxymetazoline to healthy adults lost its