Mirvaso

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.

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 the reach of children.

5.4 Systemic Adverse Reactions of Alpha-2 Adrenergic Agonists

Postmarketing cases of bradycardia, hypotension (including orthostatic hypotension) and dizziness have been reported. Some cases required hospitalization. Some cases involved application of 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.

5.5 Local Vasomotor Adverse Reactions

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.

5.6 Hypersensitivity

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.