MIRVASO

MIRVASO (brimonidine) topical gel, 0.33% contains brimonidine tartrate, an alpha adrenergic agonist. The molecular formula of brimonidine tartrate is C 11 H 10 BrN 5 • C 4 H 6 O 6 . It has the following structural formula: Chemically, brimonidine tartrate is 5-Bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate. Brimonidine tartrate has a molecular weight of 442.24 and appears as white to slightly yellowish powder. Each gram of MIRVASO (brimonidine) topical gel, 0.33% contains 5 mg of the active ingredient brimonidine tartrate (equivalent to 3.3 mg of brimonidine free base), in a white to light yellow opaque gel composed of the inactive ingredients carbomer homopolymer type B, glycerin, methylparaben, phenoxyethanol, propylene glycol, purified water, sodium hydroxide, and titanium dioxide. chem-structure

MIRVASO (brimonidine) topical gel, 0.33% is an alpha adrenergic agonist indicated for the topical treatment of persistent (nontransient) erythema of rosacea in adults 18 years of age or older. MIRVASO (brimonidine) topical gel, 0.33% is an alpha adrenergic agonist indicated for the topical treatment of persistent (nontransient) facial erythema of rosacea in adults 18 years of age or older.( 1 )

Apply a pea-sized amount once daily to each of the five areas of the face: central forehead, chin, nose, each cheek. MIRVASO topical gel should be applied smoothly and evenly as a thin layer across the entire face avoiding the eyes and lips. Wash hands after applying MIRVASO topical gel. MIRVASO topical gel is for topical use only and not for oral, ophthalmic, or intravaginal use. Apply a pea-sized amount once daily to each of the five areas of the face (forehead, chin, nose, each cheek) avoiding the eyes and lips. ( 2 ) Hands should be washed immediately after applying MIRVASO topical gel. ( 2 ) For topical use only ( 2 ) Not for oral, ophthalmic, or intravaginal use. ( 2 )

MIRVASO topical gel is contratindicated in patients who have experienced a hypersensitivity reaction to any component. Reactions have included angioedema, urticaria, and contact dermatitis [ see Warnings and Precautions (5.6) and Adverse Reactions (6.1 , 6.2 ) ]. Known hypersensitivity to any component of MIRVASO topical gel ( 4 )

The following adverse drug reactions are discussed in greater detail in other sections of the label: Systemic Adverse Reactions of Alpha-2 Adrenergic Agonists [ see Warnings and Precautions ( 5.4 ) ] Local Vasomotor Adverse Reactions [ see Warnings and Precautions ( 5.5 ) ] Hypersensitivity [ see Warnings and Precautions ( 5.6 ) ] In controlled clinical trials with MIRVASO topical gel the most common adverse reactions (incidence > 1%) included erythema, flushing, skin burning sensation, and contact dermatitis. ( 6 ) 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 (33) 91 (28) 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

7.1 Anti-hypertensives/Cardiac Glycosides Alpha-2 agonists, as a class, may reduce blood pressure. Caution in using drugs such as beta-blockers, anti-hypertensives and/or cardiac glycosides is advised. 7.2 CNS Depressants Although specific drug-drug interactions studies have not been conducted with MIRVASO topical gel, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anaesthetics) should be considered. 7.3 Monoamine Oxidase Inhibitors Monoamine oxidase (MAO) inhibitors may theoretically interfere with the metabolism of brimonidine and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in patients taking MAO inhibitors which can affect the metabolism and uptake of circulating amines.