Brimonidineside effects

The following adverse drug reactions are discussed in greater detail in other sections of the label: Systemic Adverse Reactions of Alpha-2 Adrenergic Agonists Local Vasomotor Adverse Reactions Hypersensitivity In controlled clinical trials with MIRVASO topical gel the most common adverse reactions (incidence > 1%) included erythema, flushing, skin burning sensation, and contact dermatitis. To report SUSPECTED ADVERSE REACTIONS, contact Galderma Laboratories, L.P. at 1-866-735-4137 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical

Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. During clinical trials, 1210 subjects were exposed to MIRVASO topical gel. A total of 833 subjects were treated for persistent (nontransient) erythema associated with rosacea, and 330 of those were treated once daily for 29 days in vehicle-controlled trials. Adverse reactions that occurred in at least 1% of subjects treated with MIRVASO topical gel once daily for 29 days and for which the rate for MIRVASO topical gel exceeded the rate for vehicle are presented in Table 1. Table 1 - Adverse Reactions Reported in Clinical Trials by at Least 1% of Subjects Treated for 29 Days Preferred Term MIRVASO Topical Gel (N=330) n (%) Vehicle Gel (N=331) n (%) Subjects with at least one adverse reaction, Number (%) of Subjects 109 91 Erythema 12 (4%) 3 (1%) Flushing 9 (3%) 0 Skin burning sensation 5 (2%) 2 (1%) Dermatitis contact 3 (1%) 1 (<1%) Dermatitis 3 (1%) 1 (<1%) Skin warm 3 (1%) 0 Paraesthesia 2 (1%) 1 (<1%) Acne 2 (1%) 1 (<1%) Pain of skin 2 (1%) 0 Vision blurred 2 (1%) 0 Nasal congestion 2 (1%) 0 Open-label, Long-term Study An open-label study of MIRVASO topical gel when applied once daily for up to one year was conducted in subjects with persistent (nontransient) facial erythema of rosacea. Subjects were allowed to use other rosacea therapies. A total of 276 subjects applied MIRVASO topical gel for at least one year. The most common adverse events ( > 4% of subjects) for the entire study were flushing (10%), erythema (8%), rosacea (5%), nasopharyngitis (5%), skin burning sensation (4%), increased intraocular pressure (4%), and headache (4%). Allergic contact dermatitis Allergic contact dermatitis to MIRVASO topical gel was reported in approximately 1% of subjects across the clinical development program. Two subjects underwent patch testing with individual product ingredients. One subject was found to be sensitive to brimonidine tartrate, and one subject was sensitive to phenoxyethanol (a preservative).

6.2 Postmarketing

Experience The following adverse reactions have been identified during post-approval use of MIRVASO topical gel. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

Cardiovascular disorders: bradycardia, hypotension (including orthostatic hypotension) Immune system disorders: angioedema, hypersensitivity, lip swelling, swollen tongue, throat tightness, urticaria Nervous systemic disorders: dizziness Skin and subcutaneous disorders: pallor