brimonidine 0.0033 MG/MG Topical Gel [Mirvaso]

INDICATIONS & USAGE Brimonidine tartrate ophthalmic solution, 0.2% is indicated for lowering intraocular pressure in patients with open-angle glaucoma or ocular hypertension. The IOP lowering efficacy of Brimonidine tartrate ophthalmic solution, 0.2% diminishes over time in some patients. This loss of effect appears with a variable time of onset in each patient and should be closely monitored. Brimonidine Tartrate Ophthalmic Solution, 0.2% is an alpha adrenergic agonist indicated for lowering intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. ( 1 )

DOSAGE AND ADMINISTRATION Apply a pea-sized amount once daily to each of the five areas of the face: central forehead, chin, nose, each cheek. Brimonidine 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 brimonidine topical gel. Brimonidine 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 brimonidine topical gel. ( 2 ) • For topical use only ( 2 ) • Not for oral, ophthalmic, or intravaginal use. ( 2 )

WARNINGS AND PRECAUTIONS • Potentiation of Vascular Insufficiency ( 5.1 ) • Severe Cardiovascular Disease ( 5.2 ) • Serious Adverse Reactions Following Ingestion of brimonidine topical gel ( 5.3 ) • Systemic Adverse Reactions of Alpha-2 Adrenergic Agonists ( 5.4 ) • Local Vasomotor Adverse Reactions ( 5.5 ) • Hypersensitivity ( 5.6 ) 5.1 Potentiation of Vascular Insufficiency Brimonidine topical gel should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, thrombangiitis obliterans, scleroderma, or Sjögren’s syndrome. 5.2 Severe Cardiovascular Disease Alpha-2 adrenergic agonists can lower blood pressure. Brimonidine topical gel should be used with caution in patients with severe or unstable or uncontrolled cardiovascular disease. 5.3 Serious Adverse Reactions Following Ingestion of Brimonidine Topical Gel Two young children of a subject in a clinical trial experienced serious adverse reactions following accidental ingestion of brimonidine topical gel. Adverse reactions experienced by one or both children included lethargy, respiratory distress with apneic episodes (requiring intubation), sinus bradycardia, confusion, psychomotor hyperactivity, and diaphoresis. Both children were hospitalized overnight and discharged the following day without sequelae. Keep brimonidine topical gel out of the reach of children. 5.4 Systemic Adverse Reactions of Alpha 2-adrenergic agonists Postmarketing cases of bradycardia, hypotension (including orthostatic hypotension) and dizziness have been reported. Some cases required hospitalization. Some cases involved application of brimonidine topical gel in unapproved dosing regimens and for unapproved indications, including the application of brimonidine topical gel following laser procedures. Avoid applying brimonidine topical gel to irritated skin or open wounds. 5.5 Local Vasomotor Adverse Reactions Erythema Some subjects in the clinical trials discontinued use of brimonidine topical gel because of erythema. Some subjects in the clinical trials reported a rebound phenomenon, where erythema was reported to return worse compared to the severity at baseline. Erythema appeared to resolve after discontinuation of brimonidine topical gel [ see Adverse Reactions ( 6.1 ) ]. The treatment effect of brimonidine topical gel may begin to diminish hours after application. From postmarketing reports, some patients have experienced erythema involving areas of the face that were previously not affected by erythema and in areas (e.g., neck and chest) outside of the treatment sites. Flushing Some subjects in the clinical trials discontinued use of brimonidine topical gel because of flushing. Intermittent flushing occurred in some subjects treated with brimonidine topical gel in the clinical trials. The onset of flushing relative to application of brimonidine topical gel varied, ranging from approximately 30 minutes to several hours [ see Adverse Reactions ( 6.1 ) ]. Flushing appeared to resolve after discontinuation of brimonidine topical gel. From postmarketing reports, some patients have experienced increased frequency of flushing and/or increased depth of erythema with the flushing. Additionally, some patients reported new onset of flushing. Pallor and Excessive Whitening From postmarketing reports, some patients have experienced pallor or excessive whitening at or outside the application site following treatment with brimonidine topical gel. 5.6 Hypersensitivity Allergic contact dermatitis was reported in the clinical trials for brimonidine topical gel [ see Adverse Reactions ( 6.1 ) ]. Events reported post marketing with the use of brimonidine topical gel include angioedema, throat tightening, tongue swelling, and urticarial [ see Adverse Reactions ( 6.2 ) ]. Institute appropriate therapy and discontinue brimonidine topical gel, if clinically significant hypersensitivity reaction occurs.

CONTRAINDICATIONS Brimonidine Tartrate Ophthalmic Solution, 0.2% is contraindicated in patients with hypersensitivity to brimonidine tartrate or any component of this medication. It is also contraindicated in patients receiving monoamine oxidase (MAO) inhibitor therapy. Neonates and infants (under the age of 2 years). ( 4.1 ) 4.1 Neonates and Infants (under the age of 2 years) Brimonidine tartrate ophthalmic solution, 0.2% is contraindicated in neonates and infants (under the age of 2 years) [ see Use in Specific Populations ( 8.4)] . 4.2 Hypersensitivity Reactions Brimonidine tartrate ophthalmic solution, 0.2% is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this medication in the past [ see Adverse Reactions ( 6.1 ) and ( 6.2 )].

Mechanism of Action Brimonidine tartrate ophthalmic solution 0.1% and 0.15% is a relatively selective alpha-2 adrenergic receptor agonist with a peak ocular hypotensive effect occurring at two hours post-dosing. Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow.