1 INDICATIONS AND USAGE 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.

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.

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6 ADVERSE REACTIONS 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 brimonidine 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 Padagis ® at 1-866-634-9120 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 brimonidine 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 brimonidine topical gel once daily for 29 days and for which the rate for brimonidine 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 Brimonidine 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 brimonidine 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 brimonidine 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 brimonidine 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 brimonidine 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 system disorders: dizziness Skin and subcutaneous disorders: pallor