Rebound erythema and burning sensation from a new topical brimonidine tartrate gel 0.33%
Authors: Ethan T. Routt, Jacob O. Levitt
Journal: Journal of the American Academy of Dermatology (2014)

To the Editor: Brimonidine tartrate (BT) gel 0.33% (Mirvaso, Galderma Laboratories LP), an alpha-2 selective adrenergic receptor agonist and vasoconstrictor, reduces erythema of rosacea.1Fowler Jr., J. Jackson M. Moore A. Jarratt M. Jones T. Meadows K. et al.Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema a of rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies.J Drugs Dermatol. 2013; 12: 650-656PubMed Google Scholar, 2Rhaman M.Q. Ramaesh K. Montgomery D.M. Brimonidine for glaucoma.Expert Opin Drug Saf. 2010; 9: 483-491Crossref PubMed Scopus (52) Google Scholar, 3Galderma Laboratories LP. Mirvaso (brimondine) 0.33% topical gel package insert. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204708lbl.pdf.Google Scholar The top 3 reported adverse events related to BT are erythema worse than baseline (4%), flushing (3%), and burning (2%). At least 1% of patients had an adverse reaction to the medication.1Fowler Jr., J. Jackson M. Moore A. Jarratt M. Jones T. Meadows K. et al.Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema a of rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies.J Drugs Dermatol. 2013; 12: 650-656PubMed Google Scholar, 3Galderma Laboratories LP. Mirvaso (brimondine) 0.33% topical gel package insert. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204708lbl.pdf.Google Scholar We report severe erythema in conjunction with burning sensation in 3 patients using BT. All reported reduced erythema 1 to 6 hours after application, followed by self-limited erythema, more severe than baseline, accompanied by burning over the next 12 hours and lasting roughly 12 hours. This phenomenon worsens with continued use. Urticaria and facial edema were absent. Even though the Mirvaso package insert reports infrequent erythema worse than baseline, this number may be higher in practice.1Fowler Jr., J. Jackson M. Moore A. Jarratt M. Jones T. Meadows K. et al.Efficacy and safety of once-daily topical brimonidine tartrate gel 0.5% for the treatment of moderate to severe facial erythema a of rosacea: results of two randomized, double-blind, vehicle-controlled pivotal studies.J Drugs Dermatol. 2013; 12: 650-656PubMed Google Scholar, 2Rhaman M.Q. Ramaesh K. Montgomery D.M. Brimonidine for glaucoma.Expert Opin Drug Saf. 2010; 9: 483-491Crossref PubMed Scopus (52) Google Scholar Patient 1. A 36-year-old Latina woman with long-standing rosacea and Hashimoto thyroiditis applied BT to cheeks and nose as directed. Erythema reduction lasting 4 hours was followed by erythema, notably elevated over baseline, and burning in the areas where the BT was applied (Fig 1). This reaction resolved after 5 hours. The patient continued to use the BT over the course of 5 days, applying in 5 areas, as directed, to her forehead, each cheek, nose, and chin. She felt the reduction in erythema was satisfactory but noted that patchy erythema and burning developed 5 to 10 hours after application. On the 5th day of use, 12 hours after application, she experienced erythema, much worse than at baseline, in all areas where the medication had been applied and she had a severe skin burning sensation (Fig 2). The erythema and burning resolved 12 hours later and she discontinued use of BT.Fig 2Rosacea, patient 1. Twelve hours after application of brimonidine tartrate to forehead, cheeks, nose, and chin. Erythema is present in all of the areas where the medication was applied.View Large Image Figure ViewerDownload Hi-res image Download (PPT) Patient 2. A 41-year-old Caucasian woman with long-standing rosacea, psoriasis, and anxiety reported reduced erythema following one application of BT, followed 3 hours later by significant erythema, skin burning, and pruritus where BT was applied. These resolved slowly over the next 12 hours. Concurrent medications included infliximab, methotrexate, folic acid, venlafaxine, zolpidem, clonazepam, and trazodone. Patient 3. A 28-year-old Caucasian woman with long-standing rosacea and Hashimoto thyroiditis, taking levothyroxine, tramadol, and norethindrone/ethinyl estradiol, applied BT to cheeks and chin once daily for 2 weeks. She noted significant reduction in erythema followed 6 to 8 hours later by erythema and burning in the areas of application. She continued therapy for 2 weeks with progressively worsening rebound erythema and burning. These symptoms resolved temporarily with reapplication of BT. There is no current photo documentation of this side effect at www.mirvaso.com or in the literature.3Galderma Laboratories LP. Mirvaso (brimondine) 0.33% topical gel package insert. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2013/204708lbl.pdf.Google Scholar We propose that this reaction constitutes rebound dilation of the capillaries caused by down-regulation of alpha-2 adrenergic receptors following use of BT. This may be similar to rhinitis medicamentosa, observed with overuse of alpha-adrenergic agonist nasal sprays (eg, oxymetazoline and xylometazoline).4Mortuaire G. de Gabory L. Francois M. Masse G. Bloch F. Brion N. et al.Rebound congestion and rhinitis medicamentosa: nasal decongestants in clinical practice. Critical review of the literature by a medical panel.Eur Ann Otorhinolaryngol Head Neck Dis. 2013; 130: 137-144Crossref PubMed Scopus (63) Google Scholar This reaction directly opposes the goal of therapy. Counseling about the potential for worsening erythema, use of a test area, and limiting use to special occasions may be warranted. Viewing images of this adverse reaction prior to use may alleviate patient distress.