Included as part of the "PRECAUTIONS" Section
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.
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.
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 the reach of children.
Systemic Adverse Reactions Of Alpha 2-Adrenergic Agonists
Postmarketing cases of bradycardia, hypotension (including orthostatic hypotension) and dizzieness have been reported. Some cases required hospitalization. Some cases involved application of MIRVASO topical gel in unapproved dosing regimens and for unapproved indications, including the application of MIRVASO topical gel following laser procedures.
Avoid applying MIRVASO topical gel to irritated skin or open wounds.
Local Vasomotor Adverse Reactions
Some subjects in the clinical trials discontinued use of MIRVASO 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 MIRVASO topical gel [see ADVERSE REACTIONS].
The treatment effect of MIRVASO 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.
Some subjects in the clinical trials discontinued use of MIRVASO topical gel because of flushing.
Intermittent flushing occurred in some subjects treated with MIRVASO topical gel in the clinical trials. The onset of flushing relative to application of MIRVASO topical gel varied, ranging from approximately 30 minutes to several hours [see ADVERSE REACTIONS]. Flushing appeared to resolve after discontinuation of MIRVASO 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 MIRVASO topical gel.
Allergic contact dermatitis was reported in the clinical trials for MIRVASO topical gel [see ADVERSE REACTIONS].
Events reported post marketing with the use of MIRVASO topical gel include angioedema, throat tightening, tongue swelling, and urticarial [see ADVERSE REACTIONS]. Institute appropriate therapy and discontinue MIRVASO topical gel, if clinically significant hypersensitivity reaction occurs.
Patient Counseling Information
See FDA-approved patient labeling (PATIENT INFORMATION and Instructions for Use) Patients using MIRVASO topical gel should receive the following information and instructions:
- This medication is to be used as directed by the physician.
- It is for external use only.
- MIRVASO topical gel should not be applied to irritated skin or open wounds.
- Avoid contact with the eyes and lips.
- Patients should wash their hands immediately after applying the medication.
- Some patients using MIRVASO topical gel may experience erythema, flushing or excessive whitening.
- Patients should report any adverse reactions to their physician.
- Keep out of reach of children.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
In a 21-month oral (diet) mouse carcinogenicity study and a 24-month oral (diet) rat carcinogenicity study, no drug-related neoplasms were observed in mice at oral doses of brimonidine tartrate up to 2.5 mg/kg/day or in rats at oral doses of brimonidine tartrate up to 1 mg/kg/day.
In a dermal rat carcinogenicity study with MIRVASO topical gel, brimonidine tartrate was administered to Wistar rats at topical doses of 0.9 (0.03% gel), 1.8 (0.06% gel), and 5.4 mg/kg/day (0.18% gel) in males and 5.4 (0.18% gel), 30 (1% gel) during Days 1-343/10.8 (0.36% gel) thereafter, and 60 (2% gel) during Days 1-343/21.6 mg/kg/day (0.72% gel) thereafter in females once daily for 24 months. No drug-related neoplasms were observed in this study.
In a 12-month dermal photo-carcinogenicity study, topical doses of 0% (MIRVASO topical gel vehicle), 0.18%, 1% and 2% brimonidine tartrate gel were administered to hairless albino mice once daily, five days per week, with concurrent exposure to simulated sunlight. No drug-related adverse effects were observed in this study. The results of this study suggest that topical treatment with MIRVASO topical gel would not enhance photo-carcinogenesis.
Brimonidine tartrate was not mutagenic or clastogenic in a series of in vitro and in vivo studies, including the Ames test, a chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, and three studies in CD1 mice (a host-mediated assay, a cytogenetic study, and a dominant lethal assay).
Impairment Of Fertility
Reproduction and fertility studies in rats with brimonidine tartrate demonstrated no adverse effects on male or female fertility at oral doses up to 1 mg/kg/day.
Use In Specific Populations
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.
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.
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].
Safety and effectiveness in pediatric patients have not been established.
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.