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.

{ "type": "p", "children": [], "text": "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." }

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.

{ "type": "p", "children": [], "text": "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.

{ "type": "p", "children": [], "text": "Wash hands after applying MIRVASO topical gel." }

MIRVASO topical gel is for topical use only and not for oral, ophthalmic, or intravaginal use.

{ "type": "p", "children": [], "text": "MIRVASO topical gel is for topical use only and not for oral, ophthalmic, or intravaginal use." }

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.

{ "type": "p", "children": [], "text": "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." }

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) ].

{ "type": "p", "children": [], "text": "MIRVASO topical gel is contratindicated in patients who have experienced a hypersensitivity reaction to any component. Reactions have included angioedema, urticaria, and contact dermatitis [\n \n see\n \n Warnings and Precautions (5.6)and\n \n Adverse Reactions (6.1,\n \n 6.2)\n \n ].\n\n " }

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.

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.

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.

Postmarketing cases of bradycardia, hypotension (including orthostatic hypotension) and dizziness 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.

Erythema

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 .[seeAdverse Reactions ( 6.1)].

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.

Flushing

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 ( 6.1) ]. 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 ( 6.1) ].

Events reported post marketing with the use of MIRVASO topical gel include angioedema, throat tightening, tongue swelling, and urticaria, [ see Adverse Reactions ( 6.2) ]. Institute appropriate therapy and discontinue MIRVASO topical gel, if clinically significant hypersensitivity reaction occurs.

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.

<div class="scrollingtable"><table border="1" cellpadding="4" cellspacing="0"> <caption> <span>Table 1 - Adverse Reactions Reported in Clinical Trials by at Least 1% of Subjects Treated for 29 Days</span> </caption> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Preferred Term</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">MIRVASO Topical Gel <br/> (N=330) <br/> n (%) </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Vehicle Gel <br/> (N=331) <br/> n (%) </span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule"><span class="Bold">Subjects with at least one adverse <br/> reaction, Number (%) of Subjects </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">109 (33)</span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">91 (28)</span></td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Erythema</td><td align="center" class="Botrule Lrule Rrule Toprule">12 (4%)</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Flushing</td><td align="center" class="Botrule Lrule Rrule Toprule">9 (3%)</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Skin burning sensation</td><td align="center" class="Botrule Lrule Rrule Toprule">5 (2%)</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Dermatitis contact</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (&lt;1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Dermatitis</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (&lt;1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Skin warm</td><td align="center" class="Botrule Lrule Rrule Toprule">3 (1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Paraesthesia</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (&lt;1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Acne</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">1 (&lt;1%)</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Pain of skin</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr> <td class="Botrule Lrule Rrule Toprule">Vision blurred</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> <tr class="Last"> <td class="Botrule Lrule Rrule Toprule">Nasal congestion</td><td align="center" class="Botrule Lrule Rrule Toprule">2 (1%)</td><td align="center" class="Botrule Lrule Rrule Toprule">0</td> </tr> </tbody> </table></div>

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).

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

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.

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.

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.

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 ( 5.3) ].

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.

No information is available on overdose in adults with MIRVASO topical gel.

{ "type": "p", "children": [], "text": "No information is available on overdose in adults with MIRVASO topical gel." }

Oral overdoses of other alpha-2 adrenergic agonists have been reported to cause symptoms such as hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnoea, hypotonia, hypothermia, respiratory depression, and seizure.

{ "type": "p", "children": [], "text": "Oral overdoses of other alpha-2 adrenergic agonists have been reported to cause symptoms such as hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnoea, hypotonia, hypothermia, respiratory depression, and seizure." }

Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.

{ "type": "p", "children": [], "text": "Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained." }

MIRVASO (brimonidine) topical gel, 0.33% contains brimonidine tartrate, an alpha adrenergic agonist.

{ "type": "p", "children": [], "text": "MIRVASO (brimonidine) topical gel, 0.33% contains brimonidine tartrate, an alpha adrenergic agonist." }

The molecular formula of brimonidine tartrate is C 11H 10BrN 5• C 4H 6O 6. It has the following structural formula:

{ "type": "p", "children": [], "text": "The molecular formula of brimonidine tartrate is C\n \n 11H\n \n 10BrN\n \n 5• C\n \n 4H\n \n 6O\n \n 6. It has the following structural formula:\n\n " }

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.

{ "type": "p", "children": [], "text": "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.

{ "type": "p", "children": [], "text": "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." }

Brimonidine is a relatively selective alpha-2 adrenergic agonist. Topical application of MIRVASO topical gel may reduce erythema through direct vasoconstriction.

Absorption

The absorption of brimonidine from MIRVASO topical gel was evaluated in a clinical trial in 24 adult subjects with facial erythema associated with rosacea. All enrolled subjects received once daily topical application of MIRVASO topical gel 1 gram to the entire face for 29 days. Pharmacokinetic assessments were performed on Day 1, Day 15, and Day 29. The mean plasma maximum concentration (C max) and area under the concentration-time curve (AUC) were highest on Day 15, with C maxand AUC values (± standard deviation) of 46 ± 62 pg/mL and 417 ± 264 pg.hr/mL, respectively. The systemic drug exposure was slightly lower on Day 29 indicating no further drug accumulation.

Metabolism

Brimonidine is extensively metabolized by the liver.

Excretion

Urinary excretion is the major route of elimination of brimonidine and its metabolites.

Carcinogenesis

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.

Mutagenesis

Brimonidine tartrate was not mutagenic or clastogenic in a series of in vitroand in vivostudies, 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.

MIRVASO topical gel was evaluated for the treatment of moderate to severe, persistent (nontransient) facial erythema of rosacea in two randomized, double-blind, vehicle-controlled clinical trials, which were identical in design. The trials were conducted in 553 subjects aged 18 years and older who were treated once daily for 4 weeks with either MIRVASO topical gel or vehicle. Overall, 99% of subjects were Caucasian and 76% were female. Baseline disease severity was graded using a 5-point Clinical Erythema Assessment (CEA) scale and a 5-point Patient Self Assessment (PSA) scale, on which subjects scored either “moderate” or “severe” on both scales.

{ "type": "p", "children": [], "text": "MIRVASO topical gel was evaluated for the treatment of moderate to severe, persistent (nontransient) facial erythema of rosacea in two randomized, double-blind, vehicle-controlled clinical trials, which were identical in design. The trials were conducted in 553 subjects aged 18 years and older who were treated once daily for 4 weeks with either MIRVASO topical gel or vehicle. Overall, 99% of subjects were Caucasian and 76% were female. Baseline disease severity was graded using a 5-point Clinical Erythema Assessment (CEA) scale and a 5-point Patient Self Assessment (PSA) scale, on which subjects scored either “moderate” or “severe” on both scales." }

The primary efficacy endpoint in both pivotal trials was 2-grade Composite Success, defined as the proportion of subjects with a 2-grade improvement on both CEA and PSA measured at hours 3, 6, 9, and 12 on Day 29. Table 2 presents the efficacy results. In addition to Day 29, efficacy was evaluated on Day 15 and Day 1, and the results are presented in Figures 1 and 2 for Studies 1 and 2, respectively.

{ "type": "p", "children": [], "text": "The primary efficacy endpoint in both pivotal trials was 2-grade Composite Success, defined as the proportion of subjects with a 2-grade improvement on both CEA and PSA measured at hours 3, 6, 9, and 12 on Day 29. Table 2 presents the efficacy results. In addition to Day 29, efficacy was evaluated on Day 15 and Day 1, and the results are presented in Figures 1 and 2 for Studies 1 and 2, respectively." }

<div class="scrollingtable"><table border="1" cellpadding="4" cellspacing="0"> <caption> <span>Table 2: Summary of 2-grade Composite Success on Day 29</span> </caption> <col/> <col/> <col/> <col/> <col/> <tbody class="Headless"> <tr class="First"> <td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Success</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Study 1</span></td><td align="center" class="Botrule Lrule Rrule Toprule" colspan="2"><span class="Bold">Study 2</span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule"></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">MIRVASO Topical Gel <br/> (N=129) </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Vehicle Gel <br/> (N=131) </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">MIRVAO Topical Gel <br/> (N=148) </span></td><td align="center" class="Botrule Lrule Rrule Toprule"><span class="Bold">Vehicle Gel <br/> (N=145) </span></td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">Hour 3</td><td align="center" class="Botrule Lrule Rrule Toprule">31%</td><td align="center" class="Botrule Lrule Rrule Toprule">11%</td><td align="center" class="Botrule Lrule Rrule Toprule">25%</td><td align="center" class="Botrule Lrule Rrule Toprule">9%</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">Hour 6</td><td align="center" class="Botrule Lrule Rrule Toprule">30%</td><td align="center" class="Botrule Lrule Rrule Toprule">10%</td><td align="center" class="Botrule Lrule Rrule Toprule">25%</td><td align="center" class="Botrule Lrule Rrule Toprule">9%</td> </tr> <tr> <td align="center" class="Botrule Lrule Rrule Toprule">Hour 9</td><td align="center" class="Botrule Lrule Rrule Toprule">26%</td><td align="center" class="Botrule Lrule Rrule Toprule">10%</td><td align="center" class="Botrule Lrule Rrule Toprule">18%</td><td align="center" class="Botrule Lrule Rrule Toprule">11%</td> </tr> <tr class="Last"> <td align="center" class="Botrule Lrule Rrule Toprule">Hour 12</td><td align="center" class="Botrule Lrule Rrule Toprule">23%</td><td align="center" class="Botrule Lrule Rrule Toprule">9%</td><td align="center" class="Botrule Lrule Rrule Toprule">22%</td><td align="center" class="Botrule Lrule Rrule Toprule">10%</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table border=\"1\" cellpadding=\"4\" cellspacing=\"0\">\n<caption>\n<span>Table 2: Summary of 2-grade Composite Success on Day 29</span>\n</caption>\n<col/>\n<col/>\n<col/>\n<col/>\n<col/>\n<tbody class=\"Headless\">\n<tr class=\"First\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Success</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Study 1</span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\" colspan=\"2\"><span class=\"Bold\">Study 2</span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">MIRVASO Topical Gel \n <br/> (N=129)\n </span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Vehicle Gel \n <br/> (N=131)\n </span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">MIRVAO Topical Gel \n <br/> (N=148)\n </span></td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\"><span class=\"Bold\">Vehicle Gel \n <br/> (N=145)\n </span></td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">Hour 3</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">31%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">11%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">25%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">9%</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">Hour 6</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">30%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">10%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">25%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">9%</td>\n</tr>\n<tr>\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">Hour 9</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">26%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">10%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">18%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">11%</td>\n</tr>\n<tr class=\"Last\">\n<td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">Hour 12</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">23%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">9%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">22%</td><td align=\"center\" class=\"Botrule Lrule Rrule Toprule\">10%</td>\n</tr>\n</tbody>\n</table></div>" }

2-grade Composite Success: 2-grade improvement on CEA and 2-grade improvement on PSA.         

{ "type": "p", "children": [], "text": "2-grade Composite Success: 2-grade improvement on CEA and 2-grade improvement on PSA.         " }

MIRVASO (brimonidine) topical gel, 0.33% is a white to light yellow opaque gel, supplied in a laminated tube or pump with a child resistant cap in the following sizes:

{ "type": "p", "children": [], "text": "MIRVASO (brimonidine) topical gel, 0.33% is a white to light yellow opaque gel, supplied in a laminated tube or pump with a child resistant cap in the following sizes:" }

30 gram tube NDC0299-5980-30

{ "type": "p", "children": [], "text": "30 gram tube\n \n NDC0299-5980-30\n\n " }

30 gram pump NDC0299-5980-35

{ "type": "p", "children": [], "text": "30 gram pump\n \n NDC0299-5980-35\n\n " }

45 gram tube NDC0299-5980-45

{ "type": "p", "children": [], "text": "45 gram tube\n \n NDC0299-5980-45\n\n " }

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F and 86°F) [See USP Controlled Room Temperature]." }

See FDA-approved patient labeling (Patient Information and Instructions for Use)

{ "type": "p", "children": [], "text": "See FDA-approved patient labeling (Patient Information and Instructions for Use)" }

Patients using MIRVASO topical gel should receive the following information and instructions:

{ "type": "p", "children": [], "text": "Patients using MIRVASO topical gel should receive the following information and instructions:" }

{ "type": "ul", "children": [ "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." ], "text": "" }

Marketed by:

{ "type": "p", "children": [], "text": "Marketed by:" }

GALDERMA LABORATORIES, L.P., Fort Worth, Texas 76177 USA

{ "type": "p", "children": [], "text": "GALDERMA LABORATORIES, L.P., Fort Worth, Texas 76177 USA" }

Made in Canada.

{ "type": "p", "children": [], "text": "Made in Canada." }

All trademarks are the property of their respective owners.

{ "type": "p", "children": [], "text": "All trademarks are the property of their respective owners." }

P52849-2 or P51217-3

{ "type": "p", "children": [], "text": "P52849-2 or P51217-3" }

MIRVASO (Mer-VAY-soe) (brimonidine) topical gel

{ "type": "p", "children": [], "text": "\nMIRVASO (Mer-VAY-soe)\n\n(brimonidine)\n\ntopical gel\n\n" }

Important information:MIRVASO ®topical gel is for use on the face only. Do not use MIRVASO topical gel in your eyes, mouth, or vagina. Keep MIRVASO topical gel out of the reach of children. If anyone, especially a child, accidentally swallows MIRVASO topical gel, they may have serious side effects and need to be treated in a hospital. Get medical help right away if you, a child, or anyone else swallows MIRVASO topical gel and has any of these symptoms: • lack of energy, trouble breathing or stops breathing, a slow heart beat, confusion, sweating, restlessness, muscle spasms, or twitching.

{ "type": "p", "children": [], "text": "\nImportant information:MIRVASO\n \n ®topical gel is for use on the face only. Do not use MIRVASO topical gel in your eyes, mouth, or vagina. \n \nKeep MIRVASO topical gel out of the reach of children.\n\nIf anyone, especially a child, accidentally swallows MIRVASO topical gel, they may have serious side effects and need to be treated in a hospital. Get medical help right away if you, a child, or anyone else swallows MIRVASO topical gel and has any of these symptoms:\n\n• lack of energy, trouble breathing or stops breathing, a slow heart beat, confusion, sweating, restlessness, muscle spasms, or twitching.\n" }

What is MIRVASO topical gel? MIRVASO topical gel is a prescription medicine that is used on your skin (topical) to treat facial redness due to rosacea that does not go away (persistent) in adults who are 18 years of age or older.

{ "type": "p", "children": [], "text": "\nWhat is MIRVASO topical gel?\n MIRVASO topical gel is a prescription medicine that is used on your skin (topical) to treat facial redness due to rosacea that does not go away (persistent) in adults who are 18 years of age or older.\n\n " }

It is not known if MIRVASO topical gel is safe and effective in children.

{ "type": "p", "children": [], "text": "It is not known if MIRVASO topical gel is safe and effective in children." }

Who should not use MIRVASO topical gel?

{ "type": "p", "children": [], "text": "\nWho should not use MIRVASO topical gel?\n" }

Do not use MIRVASO topical gel if youhave had a serious allergic reaction to any of the ingredients in MIRVASO topical gel. See the end of this Patient Information leaflet for a list of ingredients in MIRVASO topical gel. See “What are the possible side effects of MIRVASO topical gel?”

{ "type": "p", "children": [], "text": "\nDo not use MIRVASO topical gel if youhave had a serious allergic reaction to any of the ingredients in MIRVASO topical gel. See the end of this Patient Information leaflet for a list of ingredients in MIRVASO topical gel.\n \n See “What are the possible side effects of MIRVASO topical gel?”\n" }

What should I tell my doctor before using MIRVASO topical gel? Before using MIRVASO topical gel, tell your doctor about all of your medical conditions including if you:

{ "type": "p", "children": [], "text": "\nWhat should I tell my doctor before using MIRVASO topical gel?\n\nBefore using MIRVASO topical gel, tell your doctor about all of your medical conditions including if you:\n" }

• have depression • have heart or blood vessel problems • have dizziness or blood pressure problems • have problems with blood circulation or have had a stroke • have dry mouth or Sjögren’s Syndrome • have skin tightening or scleroderma • have Raynaud’s phenomenon • have irritated skin or open sores • plan to have any laser procedures • are pregnant or plan to become pregnant. It is not known if MIRVASO topical gel will harm your unborn baby. • are breastfeeding. It is not known if MIRVASO topical gel passes into your breast milk. You and your doctor should decide if you will use MIRVASO topical gel or breastfeed. You should not do both.

{ "type": "p", "children": [], "text": "• have depression \n • have heart or blood vessel problems \n • have dizziness or blood pressure problems \n • have problems with blood circulation or have had a stroke \n • have dry mouth or Sjögren’s Syndrome \n • have skin tightening or scleroderma \n • have Raynaud’s phenomenon \n • have irritated skin or open sores \n • plan to have any laser procedures \n • are pregnant or plan to become pregnant. It is not known if MIRVASO topical gel will harm your unborn baby. \n • are breastfeeding. It is not known if MIRVASO topical gel passes into your breast milk. You and your doctor should decide if you will use MIRVASO topical gel or breastfeed. You should not do both.\n " }

Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, skin products, vitamins, and herbal supplements. Using MIRVASO topical gel with certain other medicines may affect each other and can cause serious side effects.

{ "type": "p", "children": [], "text": "\nTell your doctor about all the medicines you take, including prescription and over-the-counter medicines, skin products, vitamins, and herbal supplements. Using MIRVASO topical gel with certain other medicines may affect each other and can cause serious side effects.\n\n " }

How should I use MIRVASO topical gel?

{ "type": "p", "children": [], "text": "\nHow should I use MIRVASO topical gel?\n" }

See the detailed Instructions for Use that comes with your MIRVASO topical gel tube or pump for information about how to apply MIRVASO topical gel correctly.

{ "type": "p", "children": [], "text": "See the detailed Instructions for Use that comes with your MIRVASO topical gel tube or pump for information about how to apply MIRVASO topical gel correctly." }

• Use MIRVASO topical gel exactly as your doctor tells you.Do not use more MIRVASO topical gel than prescribed. Call your doctor if you are not sure. • You should not apply MIRVASO topical gel to irritated skin or open wounds. • MIRVASO topical gel is for use on your skin only. Do not use MIRVASO topical gel in your eyes, mouth, or vagina. Avoid contact with your lips and eyes.

{ "type": "p", "children": [], "text": "•\n \n Use MIRVASO topical gel exactly as your doctor tells you.Do not use more MIRVASO topical gel than prescribed. Call your doctor if you are not sure. \n • You should not apply MIRVASO topical gel to irritated skin or open wounds. \n • MIRVASO topical gel is for use on your skin only. Do not use MIRVASO topical gel in your eyes, mouth, or vagina. Avoid contact with your lips and eyes.\n\n " }

What are the possible side effects of MIRVASO topical gel?

{ "type": "p", "children": [], "text": "\nWhat are the possible side effects of MIRVASO topical gel?\n" }

MIRVASO topical gel may cause serious side effects, including:

{ "type": "p", "children": [], "text": "\nMIRVASO topical gel may cause serious side effects, including:\n" }

• See “Important information” at the beginning of this Patient Information leaflet.

{ "type": "p", "children": [], "text": "\n• See “Important information” at the beginning of this Patient Information leaflet.\n" }

• Problems with blood circulation.People who use MIRVASO topical gel can have problems with blood circulation, including a slow heart rate, low blood pressure, and dizziness. These problems may sometimes be serious and lead to hospitalization. See “What should I tell my doctor before using MIRVASO topical gel?”

{ "type": "p", "children": [], "text": "\n• Problems with blood circulation.People who use MIRVASO topical gel can have problems with blood circulation, including a slow heart rate, low blood pressure, and dizziness. These problems may sometimes be serious and lead to hospitalization. See “What should I tell my doctor before using MIRVASO topical gel?”\n\n " }

• Serious allergic (hypersensitivity) reactionshave happened in people who use MIRVASO topical gel. Stop using MIRVASO topical gel and go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of a serious allergic reaction including:

{ "type": "p", "children": [], "text": "•\n \n Serious allergic (hypersensitivity) reactionshave happened in people who use MIRVASO topical gel. Stop using MIRVASO topical gel and go to the nearest hospital emergency room right away if you have any of the following signs and symptoms of a serious allergic reaction including:\n\n " }

o swelling of your face, lips, tongue, or throat o hives o trouble breathing

{ "type": "p", "children": [], "text": "o swelling of your face, lips, tongue, or throat \n o hives \n o trouble breathing\n " }

The most common side effects of MIRVASO topical gel include:

{ "type": "p", "children": [], "text": "\nThe most common side effects of MIRVASO topical gel include:\n" }

• redness • flushing • burning sensation of the skin • skin reactions (contact dermatitis).

{ "type": "p", "children": [], "text": "• redness • flushing • burning sensation of the skin • skin reactions (contact dermatitis)." }

Skin redness is common after applying MIRVASO topical gel, and may be worse than before you applied it. You may also develop redness on areas of your face that were not affected by rosacea, as well as on your neck and chest.

{ "type": "p", "children": [], "text": "Skin redness is common after applying MIRVASO topical gel, and may be worse than before you applied it. You may also develop redness on areas of your face that were not affected by rosacea, as well as on your neck and chest." }

Skin flushing is common and may happen off and on after applying MIRVASO topical gel. In some cases, the flushing may be new, may happen more often, or you may have increased redness with flushing.

{ "type": "p", "children": [], "text": "Skin flushing is common and may happen off and on after applying MIRVASO topical gel. In some cases, the flushing may be new, may happen more often, or you may have increased redness with flushing." }

Pale colored skin or very white skin (excessive whitening) can happen at or outside the treated area.

{ "type": "p", "children": [], "text": "Pale colored skin or very white skin (excessive whitening) can happen at or outside the treated area." }

Tell your doctor if you get skin redness, flushing, and pale colored skin that is uncomfortable for you.

{ "type": "p", "children": [], "text": "Tell your doctor if you get skin redness, flushing, and pale colored skin that is uncomfortable for you." }

These are not all the possible side effects of MIRVASO topical gel.

{ "type": "p", "children": [], "text": "These are not all the possible side effects of MIRVASO topical gel." }

Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA-1088.

{ "type": "p", "children": [], "text": "Call your doctor for medical advice about side effects.  You may report side effects to FDA at 1-800-FDA-1088." }

General information about the safe and effective use of MIRVASO topical gel Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or doctor for information about MIRVASO topical gel that is written for health professionals. Do not use MIRVASO topical gel for a condition for which it was not prescribed. Do not give MIRVASO topical gel to other people, even if they have the same symptoms that you have. It may harm them.

{ "type": "p", "children": [], "text": "\nGeneral information about the safe and effective use of MIRVASO topical gel\n Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. You can ask your pharmacist or doctor for information about MIRVASO topical gel that is written for health professionals. Do not use MIRVASO topical gel for a condition for which it was not prescribed. Do not give MIRVASO topical gel to other people, even if they have the same symptoms that you have. It may harm them.\n\n " }

What are the ingredients in MIRVASO topical gel?

{ "type": "p", "children": [], "text": "\nWhat are the ingredients in MIRVASO topical gel?\n" }

Active ingredient: brimonidine Inactive ingredients: carbomer homopolymer type B, glycerin, methylparaben, phenoxyethanol, propylene glycol, purified water, sodium hydroxide, titanium dioxide.

{ "type": "p", "children": [], "text": "Active ingredient: brimonidine \n Inactive ingredients: carbomer homopolymer type B, glycerin, methylparaben, phenoxyethanol, propylene glycol, purified water, sodium hydroxide, titanium dioxide.\n " }

Marketed by: GALDERMA LABORATORIES, L.P., Fort Worth, TX 76177 USA

{ "type": "p", "children": [], "text": "Marketed by: GALDERMA LABORATORIES, L.P., Fort Worth, TX 76177 USA" }

Made in Canada.

{ "type": "p", "children": [], "text": "Made in Canada." }

This Patient Information has been approved by the U.S. Food and Drug Administration. Revised: Nov 2017

{ "type": "p", "children": [], "text": "This Patient Information has been approved by the U.S. Food and Drug Administration. \n Revised: Nov 2017\n " }

Instructions for Use MIRVASO (Mer-VAY-soe) (brimonidine)topical geltube

{ "type": "p", "children": [], "text": "\nInstructions for Use \n \nMIRVASO (Mer-VAY-soe) \n \n(brimonidine)topical geltube\n" }

Important:MIRVASO ®topical gel is for use on the face only. Do not use MIRVASO topical gel in your eyes, mouth, or vagina.

{ "type": "p", "children": [], "text": "\nImportant:MIRVASO\n \n ®topical gel is for use on the face only. Do not use MIRVASO topical gel in your eyes, mouth, or vagina.\n\n " }

Keep MIRVASO topical gel out of the reach of children. If anyone, especially a child, accidentally swallows MIRVASO topical gel, they may have serious side effects and need to be treated in a hospital. Get medical help right away if you, a child, or anyone else swallows MIRVASO topical gel and has any of these symptoms: • lack of energy, trouble breathing or stops breathing, a slow heart beat, confusion, sweating, restlessness, muscle spasms, or twitching.

{ "type": "p", "children": [], "text": "\nKeep MIRVASO topical gel out of the reach of children. \n \nIf anyone, especially a child, accidentally swallows MIRVASO topical gel, they may have serious side effects and need to be treated in a hospital. Get medical help right away if you, a child, or anyone else swallows MIRVASO topical gel and has any of these symptoms:\n\n• lack of energy, trouble breathing or stops breathing, a slow heart beat, confusion, sweating, restlessness, muscle spasms, or twitching.\n" }

Read and follow the steps below so that you use your tube of MIRVASO topical gel correctly: 1. Open the tube of MIRVASO topical gel by gently pressing down on the child resistant cap and twist in the direction of the arrow as shown below (counterclockwise). See Figures A and B. To avoid spilling, do not squeeze the tube while opening or closing.

{ "type": "p", "children": [], "text": "Read and follow the steps below so that you use your tube of MIRVASO topical gel correctly: \n 1. Open the tube of MIRVASO topical gel by gently pressing down on the child resistant cap and twist in the direction of the arrow as shown below (counterclockwise). See Figures A and B. To avoid spilling, do not squeeze the tube while opening or closing.\n " }

Figure A

{ "type": "p", "children": [], "text": "Figure A" }

Figure B

{ "type": "p", "children": [], "text": "Figure B" }

2. To apply MIRVASO topical gel to your face, squeeze a pea-sized amount of MIRVASO topical gel from the tube onto your fingertip. See Figure C.

{ "type": "p", "children": [], "text": "2. To apply MIRVASO topical gel to your face, squeeze a pea-sized amount of MIRVASO topical gel from the tube onto your fingertip. See Figure C." }

Figure C

{ "type": "p", "children": [], "text": "Figure C" }

3. Apply a pea-sized amount of MIRVASO topical gel onto each of the five areas of your face (forehead, chin,     nose, each cheek) 1 time each day. You will use a total of 5 pea-sized amounts of MIRVASO     topical gel. Spread the gel smoothly and evenly in a thin layer over your face.     Avoid contact with your eyes and lips. Do not apply MIRVASO topical gel to irritated skin or open wounds.

{ "type": "p", "children": [], "text": "3. Apply a pea-sized amount of MIRVASO topical gel onto each of the five areas of your face (forehead, chin, \n     nose, each cheek) 1 time each day. You will use a total of 5 pea-sized amounts of MIRVASO \n     topical gel. Spread the gel smoothly and evenly in a thin layer over your face. \n     Avoid contact with your eyes and lips. Do not apply MIRVASO topical gel to irritated skin or open wounds.\n " }

4. To close your MIRVASO topical gel tube, place the cap back on the tube. Gently press down on the child resistant cap and twist to the right (clockwise). See Figure D.

{ "type": "p", "children": [], "text": "4. To close your MIRVASO topical gel tube, place the cap back on the tube. Gently press down on the child resistant cap and twist to the right (clockwise). See Figure D." }

Figure D

{ "type": "p", "children": [], "text": "Figure D" }

5. Wash your hands right away after applying MIRVASO topical gel.

{ "type": "p", "children": [], "text": "5. Wash your hands right away after applying MIRVASO topical gel." }

How should I store MIRVASO topical gel?

{ "type": "p", "children": [], "text": "\nHow should I store MIRVASO topical gel?\n" }

• Store MIRVASO topical gel at room temperature between 68°F to 77°F (20°C to 25°C).

{ "type": "p", "children": [], "text": "• Store MIRVASO topical gel at room temperature between 68°F to 77°F (20°C to 25°C)." }

Keep MIRVASO topical gel and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep MIRVASO topical gel and all medicines out of the reach of children.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Marketed by: GALDERMA LABORATORIES, L.P. Fort Worth, TX 76177 USA Made in Canada. Revised: October 2015

{ "type": "p", "children": [], "text": "Marketed by: GALDERMA LABORATORIES, L.P. \n Fort Worth, TX 76177 USA \n Made in Canada. \n Revised: October 2015\n " }

Instructions for Use MIRVASO (Mer-VAY-soe) (brimonidine)topical gelPump

{ "type": "p", "children": [], "text": "\nInstructions for Use \n \nMIRVASO (Mer-VAY-soe) \n \n(brimonidine)topical gelPump\n" }

Important:MIRVASO ®topical gel is for use on the face only. Do not use MIRVASO topical gel in your eyes, mouth, or vagina.

{ "type": "p", "children": [], "text": "\nImportant:MIRVASO\n \n ®topical gel is for use on the face only. Do not use MIRVASO topical gel in your eyes, mouth, or vagina.\n\n " }

Keep MIRVASO topical gel out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep MIRVASO topical gel out of the reach of children.\n" }

If anyone, especially a child, accidentally swallows MIRVASO topical gel, they may have serious side effects and need to be treated in a hospital. Get medical help right away if you, a child, or anyone else swallows MIRVASO topical gel and has any of these symptoms:

{ "type": "p", "children": [], "text": "\nIf anyone, especially a child, accidentally swallows MIRVASO topical gel, they may have serious side effects and need to be treated in a hospital. Get medical help right away if you, a child, or anyone else swallows MIRVASO topical gel and has any of these symptoms:\n" }

• lack of energy, trouble breathing or stops breathing, a slow heart beat, confusion, sweating, restlessness, muscle spasms, or twitching.

{ "type": "p", "children": [], "text": "\n• lack of energy, trouble breathing or stops breathing, a slow heart beat, confusion, sweating, restlessness, muscle spasms, or twitching.\n" }

Read and follow the steps below so that you use your MIRVASO topical gel correctly:

{ "type": "p", "children": [], "text": "Read and follow the steps below so that you use your MIRVASO topical gel correctly:" }

1. Push the cap down and turn it counter-clockwise until the cap can be removed. See Figures A and B. The clear sticker will break when opening for the first time. Note:when the cap is removed, the pump is not child-resistant.

{ "type": "p", "children": [], "text": "1. Push the cap down and turn it counter-clockwise until the cap can be removed. See Figures A and B. The clear sticker will break when opening for the first time. \n \nNote:when the cap is removed, the pump is not child-resistant.\n\n " }

Figure A

{ "type": "p", "children": [], "text": "Figure A" }

Figure B

{ "type": "p", "children": [], "text": "Figure B" }

Figure C

{ "type": "p", "children": [], "text": "Figure C" }

Before the first use, prime the pump by pressing down several times until the medicine is dispensed onto your fingertip.

{ "type": "p", "children": [], "text": "Before the first use, prime the pump by pressing down several times until the medicine is dispensed onto your fingertip." }

2. To apply MIRVASO topical gel to your face, dispense a pea-sized amount of MIRVASO topical gel from the pump onto your fingertip. See Figure C.

{ "type": "p", "children": [], "text": "2. To apply MIRVASO topical gel to your face, dispense a pea-sized amount of MIRVASO topical gel from the pump onto your fingertip. See Figure C." }

3. Apply a pea-sized amount of MIRVASO topical gel onto each of the five areas of your face (forehead, chin, nose, each cheek) 1 time each day. You will use a total of 5 pea-sized amounts of MIRVASO topical gel. Spread the gel smoothly and evenly in a thin layer over your face. Avoid contact with your eyes and lips. Do not apply MIRVASO topical gel to irritated skin or open wounds.

{ "type": "p", "children": [], "text": "3. Apply a pea-sized amount of MIRVASO topical gel onto each of the five areas of your face (forehead, chin, nose, each cheek) 1 time each day. You will use a total of 5 pea-sized amounts of MIRVASO topical gel. Spread the gel smoothly and evenly in a thin layer over your face. Avoid contact with your eyes and lips. Do not apply MIRVASO topical gel to irritated skin or open wounds." }

4. To close your MIRVASO topical gel pump, place the cap back on the pump. Push down and turn the cap to the right (clockwise) until it stops. This pump is child-resistant again. See Figure D.

{ "type": "p", "children": [], "text": "4. To close your MIRVASO topical gel pump, place the cap back on the pump. Push down and turn the cap to the right (clockwise) until it stops. This pump is child-resistant again. See Figure D." }

Figure D

{ "type": "p", "children": [], "text": "Figure D" }

5. Wash your hands right away after applying MIRVASO topical gel.

{ "type": "p", "children": [], "text": "5. Wash your hands right away after applying MIRVASO topical gel." }

How should I store MIRVASO topical gel?

{ "type": "p", "children": [], "text": "\nHow should I store MIRVASO topical gel?\n" }

• Store MIRVASO topical gel at room temperature between 68°F to 77°F (20°C to 25°C).

{ "type": "p", "children": [], "text": "• Store MIRVASO topical gel at room temperature between 68°F to 77°F (20°C to 25°C)." }

Keep MIRVASO topical gel and all medicines out of the reach of children.

{ "type": "p", "children": [], "text": "\nKeep MIRVASO topical gel and all medicines out of the reach of children.\n" }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Marketed by: GALDERMA LABORATORIES, L.P., Fort Worth, TX 76177 USA, Made in Canada Issued: November 2017 

{ "type": "p", "children": [], "text": "Marketed by: GALDERMA LABORATORIES, L.P., Fort Worth, TX 76177 USA, \n Made in Canada \n Issued: November 2017 \n " }

Rx Only NDC 0299-5980-35

{ "type": "p", "children": [], "text": "\nRx Only\n\nNDC 0299-5980-35\n" }

Mirvaso ® (brimonidine) topical gel, 0.33%* PUMP

{ "type": "p", "children": [], "text": "\nMirvaso\n \n ®\n (brimonidine) topical gel, 0.33%*\n \n \n PUMP\n\n " }

*Each gram of Mirvaso topical gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base

{ "type": "p", "children": [], "text": "*Each gram of Mirvaso topical gel contains 5 mg of brimonidine tartrate, equivalent to 3.3 mg of brimonidine free base" }

For Topical Use Only Keep Out of Reach of Children

{ "type": "p", "children": [], "text": "\nFor Topical Use Only \n Keep Out of Reach of Children\n \n" }

GALDERMA NET WT. 30 g

{ "type": "p", "children": [], "text": "GALDERMA \n NET WT. 30 g \n \n" }

Not for oral, ophthalmic or intravaginal use. To Open Pump:Push the cap down while turning it counter-clockwise to remove the cap. Usual Dosage:Apply a pea-size amount once daily to each of the five areas of the face (forehead, chin, nose, and each cheek) avoiding the eyes and lips. See package insert for complete prescribing information. Each gramcontains the activeingredient brimonidine tartrate 5mg with the inactiveingredients carbomer homopolymer type B, glycerin, methylparaben, phenoxyethanol, propylene glycol, purified water, sodium hydroxide, and titanium dioxide.

{ "type": "p", "children": [], "text": "Not for oral, ophthalmic or intravaginal use. \n \n\nTo Open Pump:Push the cap down while turning it counter-clockwise to remove the cap. \n \n\nUsual Dosage:Apply a pea-size amount once daily to each of the five areas of the face (forehead, chin, nose, and each cheek) avoiding the eyes and lips. See package insert for complete prescribing information. \n \n\nEach gramcontains the\n \n activeingredient brimonidine tartrate 5mg with the\n \n inactiveingredients carbomer homopolymer type B, glycerin, methylparaben, phenoxyethanol, propylene glycol, purified water, sodium hydroxide, and titanium dioxide.\n\n " }

Storage:Store at 20° to 25°C (68° to 77°F), excursions permitted between 15° and 30°C (59° and 86°F). [See USP Controlled Room Temperature].

{ "type": "p", "children": [], "text": "\nStorage:Store at 20° to 25°C (68° to 77°F), excursions permitted between 15° and 30°C (59° and 86°F). [See USP Controlled Room Temperature].\n\n " }

See bottom of carton for lot number and expiration date. All trademarks are the property of their respective owners.

{ "type": "p", "children": [], "text": "See bottom of carton for lot number and expiration date. \n \n All trademarks are the property of their respective owners. \n \n\n" }

Marketed by: GALDERMA LABORATORIES, L.P. Dallas, TX 75201 USA Made in Canada P52848-3

{ "type": "p", "children": [], "text": "Marketed by: \n GALDERMA LABORATORIES, L.P. \n Dallas, TX 75201 USA \n Made in Canada \n P52848-3\n " }

Brimonidine tartrate ophthalmic solution 0.1% or 0.15% is an alpha adrenergic receptor agonist indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

{ "type": "p", "children": [], "text": "Brimonidine tartrate ophthalmic solution 0.1% or 0.15% is an alpha adrenergic receptor agonist indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. " }

The recommended dose is one drop of brimonidine tartrate ophthalmic solution 0.1% or 0.15% in the affected eye(s) three times daily, approximately 8 hours apart. Brimonidine tartrate ophthalmic solution 0.1% or 0.15% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic product is to be used, the different products should be instilled at least 5 minutes apart.

{ "type": "p", "children": [], "text": "The recommended dose is one drop of brimonidine tartrate ophthalmic solution 0.1% or 0.15% in the affected eye(s) three times daily, approximately 8 hours apart. Brimonidine tartrate ophthalmic solution 0.1% or 0.15% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic product is to be used, the different products should be instilled at least 5 minutes apart. " }

Solution containing 1 mg/mL or 1.5 mg/mL brimonidine tartrate.

{ "type": "p", "children": [], "text": "Solution containing 1 mg/mL or 1.5 mg/mL brimonidine tartrate. " }

Brimonidine tartrate ophthalmic solution 0.1% and 0.15% is contraindicated in neonates and infants (under the age of 2 years).

Brimonidine tartrate ophthalmic solution 0.1% and 0.15% is contraindicated in patients who have exhibited a hypersensitivity reaction to any component of this medication in the past.

Brimonidine tartrate ophthalmic solution 0.1% and 0.15% may potentiate syndromes associated with vascular insufficiency. Brimonidine tartrate ophthalmic solution 0.1% and 0.15% should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis obliterans.

Although brimonidine tartrate ophthalmic solution had minimal effect on the blood pressure of patients in clinical studies, caution should be exercised in treating patients with severe cardiovascular disease.

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient Counseling Information (17)].

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

Adverse reactions occurring in approximately 10-20% of the subjects receiving brimonidine ophthalmic solution (0.1-0.2%) included: allergic conjunctivitis, conjunctival hyperemia, and eye pruritus. Adverse reactions occurring in approximately 5-9% included: burning sensation, conjunctival folliculosis, hypertension, ocular allergic reaction, oral dryness, and visual disturbance.

Adverse reactions occurring in approximately 1-4% of the subjects receiving brimonidine ophthalmic solution (0.1-0.2%) included: abnormal taste, allergic reaction, asthenia, blepharitis, blepharoconjunctivitis, blurred vision, bronchitis, cataract, conjunctival edema, conjunctival hemorrhage, conjunctivitis, cough, dizziness, dyspepsia, dyspnea, epiphora, eye discharge, eye dryness, eye irritation, eye pain, eyelid edema, eyelid erythema, fatigue, flu syndrome, follicular conjunctivitis, foreign body sensation, gastrointestinal disorder, headache, hypercholesterolemia, hypotension, infection (primarily colds and respiratory infections), insomnia, keratitis, lid disorder, pharyngitis, photophobia, rash, rhinitis, sinus infection, sinusitis, somnolence, stinging, superficial punctate keratopathy, tearing, visual field defect, vitreous detachment, vitreous disorder, vitreous floaters, and worsened visual acuity.

The following reactions were reported in less than 1% of subjects: corneal erosion, hordeolum, nasal dryness, and taste perversion.

The following reactions have been identified during postmarketing use of brimonidine tartrate ophthalmic solutions in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to brimonidine tartrate ophthalmic solutions, or a combination of these factors, include: bradycardia, depression, hypersensitivity, iritis, keratoconjunctivitis sicca, miosis, nausea, skin reactions (including erythema, eyelid pruritus, rash, and vasodilation), syncope, and tachycardia. Apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine tartrate ophthalmic solutions.

Because brimonidine tartrate ophthalmic solution 0.1% and 0.15% may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with brimonidine tartrate ophthalmic solution 0.1% and 0.15% is advised.

Although specific drug interaction studies have not been conducted with brimonidine tartrate ophthalmic solution 0.1% and 0.15%, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered.

Tricyclic antidepressants have been reported to blunt the hypotensive effect of systemic clonidine. It is not known whether the concurrent use of these agents with brimonidine tartrate ophthalmic solution 0.1% and 0.15% in humans can lead to resulting interference with the IOP lowering effect. Caution is advised in patients taking tricyclic antidepressants which can affect the metabolism and uptake of circulating amines.

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.

Pregnancy Category B: Teratogenicity studies have been performed in animals.

Brimonidine tartrate was not teratogenic when given orally during gestation days 6 through 15 in rats and days 6 through 18 in rabbits. The highest doses of brimonidine tartrate in rats (2.5 mg/kg/day) and rabbits (5.0 mg/kg/day) achieved AUC exposure values 360- and 20-fold higher, or 260- and 15-fold higher, respectively, than similar values estimated in humans treated with brimonidine tartrate ophthalmic solution 0.1% or 0.15%, 1 drop in both eyes three times daily.

There are no adequate and well-controlled studies in pregnant women; however, in animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent. Because animal reproduction studies are not always predictive of human response, brimonidine tartrate ophthalmic solution 0.1% and 0.15% should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

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 brimonidine tartrate ophthalmic solution 0.1% and 0.15% 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.

Brimonidine tartrate ophthalmic solution 0.1% and 0.15% is contraindicated in children under the age of 2 years [see Contraindications (4.1)]. During postmarketing surveillance, apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine. The safety and effectiveness of brimonidine tartrate have not been studied in children below the age of 2 years.

In a well-controlled clinical study conducted in pediatric glaucoma patients (ages 2 to 7 years) the most commonly observed adverse reactions with brimonidine tartrate ophthalmic solution 0.2% dosed three times daily were somnolence (50-83% in patients ages 2 to 6 years) and decreased alertness. In pediatric patients 7 years of age (>20 kg), somnolence appears to occur less frequently (25%). Approximately 16% of patients on brimonidine tartrate ophthalmic solution discontinued from the study due to somnolence. 

No overall differences in safety or effectiveness have been observed between elderly and other adult patients.

Brimonidine tartrate ophthalmic solution 0.1% and 0.15% has not been studied in patients with hepatic impairment.

Brimonidine tartrate ophthalmic solution 0.1% and 0.15% has not been studied in patients with renal impairment. The effect of dialysis on brimonidine pharmacokinetics in patients with renal failure is not known.

Very limited information exists on accidental ingestion of brimonidine in adults; the only adverse reaction reported to date has been hypotension. Symptoms of brimonidine overdose have been reported in neonates, infants, and children receiving brimonidine tartrate ophthalmic solution 0.1% and 0.15% as part of medical treatment of congenital glaucoma or by accidental oral ingestion [see Use in Specific Populations (8.4)]. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.

{ "type": "p", "children": [], "text": "Very limited information exists on accidental ingestion of brimonidine in adults; the only adverse reaction reported to date has been hypotension. Symptoms of brimonidine overdose have been reported in neonates, infants, and children receiving brimonidine tartrate ophthalmic solution 0.1% and 0.15% as part of medical treatment of congenital glaucoma or by accidental oral ingestion [see Use in Specific Populations (8.4)]. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained. " }

Brimonidine tartrate ophthalmic solution 0.1% or 0.15%, sterile, is a relatively selective alpha-2 adrenergic receptor agonist (topical intraocular pressure lowering agent).

{ "type": "p", "children": [], "text": "Brimonidine tartrate ophthalmic solution 0.1% or 0.15%, sterile, is a relatively selective alpha-2 adrenergic receptor agonist (topical intraocular pressure lowering agent). " }

The structural formula of brimonidine tartrate is:

{ "type": "p", "children": [], "text": "The structural formula of brimonidine tartrate is:" }

5-Bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate; MW= 442.24

{ "type": "p", "children": [], "text": "5-Bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate; MW= 442.24" }

In solution, brimonidine tartrate ophthalmic solution 0.1% and 0.15% has a clear, greenish-yellow color. It has an osmolality of 250-350 mOsmol/kg and a pH of 7.4-8.0 (0.1%) or 6.9-7.4 (0.15%).

{ "type": "p", "children": [], "text": "In solution, brimonidine tartrate ophthalmic solution 0.1% and 0.15% has a clear, greenish-yellow color. It has an osmolality of 250-350 mOsmol/kg and a pH of 7.4-8.0 (0.1%) or 6.9-7.4 (0.15%)." }

Brimonidine tartrate appears as an off-white to pale-yellow powder and is soluble in both water (0.6 mg/mL) and in the product vehicle (1.4 mg/mL) at pH 7.7.

{ "type": "p", "children": [], "text": "Brimonidine tartrate appears as an off-white to pale-yellow powder and is soluble in both water (0.6 mg/mL) and in the product vehicle (1.4 mg/mL) at pH 7.7. " }

Each mL of brimonidine tartrate ophthalmic solution 0.1% and 0.15% contains the active ingredient brimonidine tartrate 0.1% (1 mg/mL) or 0.15% (1.5 mg/mL) with the inactive ingredients sodium carboxymethylcellulose; sodium borate; boric acid; sodium chloride; potassium chloride; calcium chloride; magnesium chloride; PURITE® 0.005% (0.05 mg/mL) as a preservative; purified water; and hydrochloric acid and/or sodium hydroxide to adjust pH.

{ "type": "p", "children": [], "text": "Each mL of brimonidine tartrate ophthalmic solution 0.1% and 0.15% contains the active ingredient brimonidine tartrate 0.1% (1 mg/mL) or 0.15% (1.5 mg/mL) with the inactive ingredients sodium carboxymethylcellulose; sodium borate; boric acid; sodium chloride; potassium chloride; calcium chloride; magnesium chloride; PURITE® 0.005% (0.05 mg/mL) as a preservative; purified water; and hydrochloric acid and/or sodium hydroxide to adjust pH." }

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.

Absorption

After ocular administration of either a 0.1% or 0.2% solution, plasma concentrations peaked within 0.5 to 2.5 hours and declined with a systemic half-life of approximately 2 hours.

Distribution

The protein binding of brimonidine has not been studied.

Metabolism

In humans, brimonidine is extensively metabolized by the liver.

Excretion

Urinary excretion is the major route of elimination of brimonidine and its metabolites. Approximately 87% of an orally-administered radioactive dose of brimonidine was eliminated within 120 hours, with 74% found in the urine.

No compound-related carcinogenic effects were observed in either mice or rats following a 21-month and 24-month study, respectively. In these studies, dietary administration of brimonidine tartrate at doses up to 2.5 mg/kg/day in mice and 1 mg/kg/day in rats achieved 150 and 120 times or 90 and 80 times, respectively, the plasma Cmax drug concentration in humans treated with one drop of brimonidine tartrate ophthalmic solution 0.1% or 0.15% into both eyes 3 times per day, the recommended daily human dose.

Brimonidine tartrate was not mutagenic or clastogenic in a series of in vitro and in vivo studies including the Ames bacterial reversion test, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, and three in vivo studies in CD-1 mice: a host-mediated assay, cytogenetic study, and dominant lethal assay.

Reproduction and fertility studies in rats with brimonidine tartrate demonstrated no adverse effect on male or female fertility at doses which achieve up to approximately 125 and 90 times the systemic exposure following the maximum recommended human ophthalmic dose of brimonidine tartrate ophthalmic solution 0.1% or 0.15%, respectively. 

Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Brimonidine tartrate has the action of lowering intraocular pressure with minimal effect on cardiovascular and pulmonary parameters.

{ "type": "p", "children": [], "text": "Elevated IOP presents a major risk factor in glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Brimonidine tartrate has the action of lowering intraocular pressure with minimal effect on cardiovascular and pulmonary parameters." }

Clinical studies were conducted to evaluate the safety, efficacy, and acceptability of brimonidine tartrate ophthalmic solution 0.15% compared with brimonidine tartrate ophthalmic solution 0.2% administered three-times-daily in patients with open-angle glaucoma or ocular hypertension. Those results indicated that brimonidine tartrate ophthalmic solution 0.15% is comparable in IOP lowering effect to brimonidine tartrate ophthalmic solution 0.2%, and effectively lowers IOP in patients with open-angle glaucoma or ocular hypertension by approximately 2-6 mmHg.

{ "type": "p", "children": [], "text": "Clinical studies were conducted to evaluate the safety, efficacy, and acceptability of brimonidine tartrate ophthalmic solution 0.15% compared with brimonidine tartrate ophthalmic solution 0.2% administered three-times-daily in patients with open-angle glaucoma or ocular hypertension. Those results indicated that brimonidine tartrate ophthalmic solution 0.15% is comparable in IOP lowering effect to brimonidine tartrate ophthalmic solution 0.2%, and effectively lowers IOP in patients with open-angle glaucoma or ocular hypertension by approximately 2-6 mmHg." }

A clinical study was conducted to evaluate the safety, efficacy, and acceptability of brimonidine tartrate ophthalmic solution 0.1% compared with brimonidine tartrate ophthalmic solution 0.2% administered three-times-daily in patients with open-angle glaucoma or ocular hypertension. Those results indicated that brimonidine tartrate ophthalmic solution 0.1% is equivalent in IOP lowering effect to brimonidine tartrate ophthalmic solution 0.2%, and effectively lowers IOP in patients with open-angle glaucoma or ocular hypertension by approximately 2-6 mmHg.

{ "type": "p", "children": [], "text": "A clinical study was conducted to evaluate the safety, efficacy, and acceptability of brimonidine tartrate ophthalmic solution 0.1% compared with brimonidine tartrate ophthalmic solution 0.2% administered three-times-daily in patients with open-angle glaucoma or ocular hypertension. Those results indicated that brimonidine tartrate ophthalmic solution 0.1% is equivalent in IOP lowering effect to brimonidine tartrate ophthalmic solution 0.2%, and effectively lowers IOP in patients with open-angle glaucoma or ocular hypertension by approximately 2-6 mmHg." }

Brimonidine tartrate ophthalmic solution 0.1% and 0.15% is supplied sterile, in teal opaque plastic LDPE bottles and tips, with purple high impact polystyrene (HIPS) caps as follows:

{ "type": "p", "children": [], "text": "Brimonidine tartrate ophthalmic solution 0.1% and 0.15% is supplied sterile, in teal opaque plastic LDPE bottles and tips, with purple high impact polystyrene (HIPS) caps as follows:" }

0.1%

{ "type": "p", "children": [], "text": "\n0.1%\n" }

5 mL in 10 mL bottle         NDC 82182-321-0510 mL in 10 mL bottle       NDC 82182-321-1015 mL in 15 mL bottle       NDC 82182-321-15

{ "type": "p", "children": [], "text": "5 mL in 10 mL bottle         NDC 82182-321-0510 mL in 10 mL bottle\n\t\t     \n\tNDC 82182-321-1015 mL in 15 mL bottle\n\t\t     \n\tNDC 82182-321-15" }

0.15% 5 mL in 10 mL bottle         NDC 82182-773-0510 mL in 10 mL bottle       NDC 82182-773-1015 mL in 15 mL bottle       NDC 82182-773-15

{ "type": "p", "children": [], "text": "\n0.15%\n5 mL in 10 mL bottle\n\t\t     \n\t  NDC 82182-773-0510 mL in 10 mL bottle\n\t\t     \n\tNDC 82182-773-1015 mL in 15 mL bottle\n\t\t     \n\tNDC 82182-773-15 " }

Storage: Store at 15o-25oC (59o-77oF).

{ "type": "p", "children": [], "text": "\nStorage: Store at 15o-25oC (59o-77oF). " }

Patients should be instructed that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions (5.3)]. Always replace the cap after using. If solution changes color or becomes cloudy, do not use. Do not use the product after the expiration date marked on the bottle.

{ "type": "p", "children": [], "text": "Patients should be instructed that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions (5.3)]. Always replace the cap after using. If solution changes color or becomes cloudy, do not use. Do not use the product after the expiration date marked on the bottle." }

Patients also should be advised that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician's advice concerning the continued use of the present multidose container.

{ "type": "p", "children": [], "text": "Patients also should be advised that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician's advice concerning the continued use of the present multidose container. " }

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.

{ "type": "p", "children": [], "text": "If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart." }

As with other similar medications, brimonidine tartrate ophthalmic solution 0.1% and 0.15% may cause fatigue and/or drowsiness in some patients. Patients who engage in hazardous activities should be cautioned of the potential for a decrease in mental alertness.

{ "type": "p", "children": [], "text": "As with other similar medications, brimonidine tartrate ophthalmic solution 0.1% and 0.15% may cause fatigue and/or drowsiness in some patients. Patients who engage in hazardous activities should be cautioned of the potential for a decrease in mental alertness. " }

Distributed by: AbbVie Inc.North Chicago, IL 60064

{ "type": "p", "children": [], "text": "Distributed by: AbbVie Inc.North Chicago, IL 60064" }

© 2024 AbbVie. All rights reserved.PACIFIC PHARMA and its design and PURITE are trademarks of Allergan, Inc., an AbbVie company.

{ "type": "p", "children": [], "text": "© 2024 AbbVie. All rights reserved.PACIFIC PHARMA and its design and PURITE are trademarks of Allergan, Inc., an AbbVie company." }

20086912R1

{ "type": "p", "children": [], "text": "20086912R1" }

PACIFICPHARMANDC 82182-773-05BRIMONIDINETARTRATEophthalmicsolution, 0.15%5 mLsterileRx only

{ "type": "p", "children": [], "text": "PACIFICPHARMANDC 82182-773-05BRIMONIDINETARTRATEophthalmicsolution, 0.15%5 mLsterileRx only \n" }

PACIFICPHARMANDC 82182-773-10BRIMONIDINETARTRATEophthalmicsolution, 0.15%10 mLsterileRx only

{ "type": "p", "children": [], "text": "PACIFICPHARMANDC 82182-773-10BRIMONIDINETARTRATEophthalmicsolution, 0.15%10 mLsterileRx only \n" }

PACIFICPHARMANDC 82182-773-15BRIMONIDINETARTRATEophthalmicsolution, 0.15%15 mLsterileRx only

{ "type": "p", "children": [], "text": "PACIFICPHARMANDC 82182-773-15BRIMONIDINETARTRATEophthalmicsolution, 0.15%15 mLsterileRx only" }

PACIFICPHARMANDC: 82182-321-05 BRIMONIDINE TARTRATE ophthalmicsolution, 0.1% 5 mL sterileRx only

{ "type": "p", "children": [], "text": "PACIFICPHARMANDC: 82182-321-05\nBRIMONIDINE TARTRATE\nophthalmicsolution, 0.1%\n5 mL\nsterileRx only" }