1 INDICATIONS AND USAGE 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.
3 DOSAGE FORMS AND STRENGTHS MIRVASO (brimonidine) topical gel, 0.33% is a white to light yellow opaque aqueous gel. Each gram of gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base. Gel, 0.33%; Each gram of gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base.
4 CONTRAINDICATIONS None None.
5 WARNINGS AND PRECAUTIONS Potentiation of Vascular Insufficiency (5.1) Severe Cardiovascular Disease (5.2) Serious Adverse Reactions Following Ingestion of MIRVASO topical gel (5.3) Erythema and Flushing (5.4) 5.1 Potentiation of Vascular Insufficiency MIRVASO 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. MIRVASO 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 MIRVASO topical gel Two young children of a subject in a clinical trial experienced serious adverse reactions following accidental ingestion of MIRVASO 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 MIRVASO topical gel out of reach of children. 5.4 Erythema and Flushing Some subjects in the clinical trials discontinued use of MIRVASO topical gel because of erythema or flushing. The effect of MIRVASO topical gel may begin to diminish hours after application. For some subjects in the clinical trials, erythema was reported to return worse compared to the severity at baseline [ see Adverse Reactions (6) ]. Intermittent flushing occurred in some subjects treated with MIRVASO topical gel. The onset of flushing relative to application of MIRVASO topical gel varied, ranging from approximately 30 minutes to several hours [ see Adverse Reactions (6) ]. Erythema and flushing appeared to resolve after discontinuation of MIRVASO topical gel.
6 ADVERSE REACTIONS 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 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). 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) table-1-adverse
7 DRUG INTERACTIONS 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.
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category B. There are no adequate and well-controlled studies of MIRVASO topical gel in pregnant women. In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. MIRVASO topical gel should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Brimonidine tartrate was not teratogenic when given at oral doses up to 2.5 mg/kg/day in pregnant rats during gestation days 6 through 15 and 5 mg/kg/day in pregnant rabbits during gestation days 6 through 18. 8.3 Nursing Mothers It is not known whether brimonidine tartrate is excreted in human milk, although in animal studies, brimonidine tartrate has been shown to be excreted in breast milk. Because of the potential for serious adverse reactions from MIRVASO topical gel in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use Keep MIRVASO topical gel out of reach of children. Serious adverse reactions were experienced by two children of a subject in a clinical trial who accidentally ingested MIRVASO topical gel [ See Warnings and Precautions (5.3) ]. Safety and effectiveness in pediatric patients have not been established. 8.5 Geriatric Use One hundred and five subjects aged 65 and older were included in clinical trials with MIRVASO topical gel. No overall differences in safety or effectiveness were observed between subjects > 65 years of age and younger adult subjects. Clinical studies of MIRVASO topical gel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects.