Pharmacology Update: Brimonidine Tartrate Topical Gel (Mirvaso®)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Chair, Formulary Committee, Northern
California Kaiser Permanente; and Assistant Professor
of Medicine, University of California, San Francisco.
Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA
Drs. Elliott and Chan report no financial relationships relevant to this field
A highly selective alpha-2 adrenergic receptor agonist has been approved by the FDA for the treatment of persistent facial erythema of rosacea in adults. Brimonidine has been used as an ophthalmic agent to treat glaucoma for years. It is marketed as a topical gel by Galderma Laboratories as Mirvaso.
Brimonidine gel is indicated for the topical treatment of persistent (nontransient) facial erythema of rosacea in adults.1
The recommended dose is to apply a small amount (pea size) once daily to five areas of the face (forehead, chin, nose, and each cheek).1 Brimonidine gel is available as a 0.33% gel in 30 g and 45 g tubes. Each gram contains 3.3 mg of brimonidine.
Brimonidine provides a topical agent with a different mechanism of action for the treatment of erythema of rosacea.
Brimonidine affects the symptom but not the basic pathophysiology of the condition (i.e., inflammation, altered innate immune response). Patients with depression, CAD, Raynaud’s, or other conditions that may be exacerbated by an alpha-2 adrenergic agonist should use the drug with caution. Some subjects in the clinical trial reported that when the drug wore off the return of erythema was worse than at baseline.1
Brimonidine is an alpha-2 adrenergic agonist that reduces erythema by direct vasoconstriction. This results in reduced erythema, a common symptom of rosacea. Efficacy in moderate-to-severe persistent rosacea was evaluated in two randomized, double-blind, vehicle-controlled trials.1 Subjects were randomized to brimonidine topical gel (0.33%) or vehicle, applied once daily for 4 weeks. Baseline disease severity was based on a 5-point Clinical Erythema Assessement (CEA) scale and a self-administered Patient Self Assessment (PSA) scale. The scale for CEA is as follows: 4 — severe erythema, fiery redness; 3 — moderate erythema, marked redness; 2 — mild erythema, definite redness; 1 — almost clear, slight redness; and 0 — clear skin with no sign of erythema.2 For PSA: 4 — completely unacceptable redness; 3 — more redness than I prefer; 2 — somewhat more redness than I prefer; 1 — nearly clear of unwanted redness; 0 — clear of unwanted redness.2 The primary efficacy endpoint was a 2-grade improvement in both CEA and PSA measured on hours 3, 6, 9, and at day 29. Response ranged from 23-31% in study 1 and 18-25% in study 2 for brimonidine compared to 9-11% for the vehicle. Topical brimonidine appears to be well tolerated. The most common adverse events were flushing and erythema that ranged from 3-4%.
Rosacea is a common inflammatory skin condition affecting more than 10 million Americans.3 Symptoms include erythema and flushing (dilated blood vessels) as well as papules and pustules. There is no cure for rosacea but treatment may control symptoms. Current topical medications include metronidazole, azelaic acid, and oral antibiotics (e.g., doxycycline).4 The primary objective of these treatments is to reduce the number of papules and/or pustules, although some reduction in erythema has been observed. Brimonidine on the other hand is used primarily to reduce erythema. This suggests combination therapy may be indicated in some patients. The wholesale cost for brimonidine gel is $247.20 for a 30 g tube. As a comparison, azelaic acid gel (15%) is $193.48 for 50 g and metronidazole cream (0.75%) is $448 for 45 g.
- Mirvaso Prescribing Information. Ft. Worth, TX: Galderma Laboratories; August 2013.
- Fowler J, et al. Once-daily topical brimonidine tartrate gel 0.5% is a novel treatment for moderate to severe facial erythema of rosacea: Results of two multicentre, randomized and vehicle-controlled studies. Br J Dermatol 2012;166:633-641.
- Yamasaki K, et al. The molecular pathology of rosacea. J Dermatol Sci 2009;55:77-81.
- van Zuuren EJ, et al. Interventions for rosacea.
Cochrane Database Syst Rev 2011;Mar 16:CD003262. doi:10.1002/14651858.CD003262.pub4.