Brimonidine

On August 26, 2013, the United States Food and Drug Administration (FDA) approved brimonidine (Mirvaso®) current gel, 0.33% * (Galderma Laboratories, Texas, USA) For Topical Treatment of Persistent Facial Treatment erythema Rosacea (redness) in adults over 18 years of age. It is not indicated for the treatment of inflammatory injuries (papules and pustules) of rosacea.

Although several medications are approved for the treatment of inflammatory rosacea, there is currently no approved medication that directly targets rosacea erythema, making it a key unmet medical need.

Brimonidine is the first and only FDA approved topical treatment specifically developed and indicated for facial erythema in rosacea.

Applied once a day, brimonidine works quickly to reduce rosacea redness and the beneficial effects last up to 12 hours.

Brimonidine is also available as eye drops to treat ocular hypertension or glaucoma.

How does brimonidine work?

• While the exact cause of rosacea erythema is not known, the erythema is presumed to result from deregulation at cutaneous vasomotor responses, leading to abnormal dilation of the face blood vessels about various stimuli.
• Research studies suggest the involvement of adrenergic receptors in the neurovascular regulatory pathway.
• Brimonidine is a relatively selective alpha-2 adrenergic agonist.
• Topical application of brimonidine gel can reduce erythema by constricting dilated facial blood vessels to reduce rosacea redness.

Link to key evidence from clinical trials on brimonidine

Dosage and administration

• Brimonidine is supplied as a gel for topical administration.
• It is recommended that you apply a pea-sized amount of the medication once a day to each of the five areas of the face: center forehead, chin, nose, and cheeks.
• The gel should be applied smoothly and evenly as a thin layer over the entire face, avoiding the eyes and lips.
• The gel should not be applied to irritated skin or open wounds.
• Hands should be thoroughly washed after applying topical gel.

What are the side effects of brimonidine?

In clinical trials, the most common Adverse reactions (occurring at a frequency ≥1%) including:

• erythema
• blush
• burning sensation on the skin
• Contact dermatitis

In the long-term study, where patients used topical brimonidine gel for up to 12 months, the most common adverse events including redness (10%), erythema (8%), rosacea (5%), nasopharyngitis (5%), burning sensation on the skin (4%), increased intraocular pressure (4%) and headache (4%).

Post-marketing reports suggest that flare-up of redness and rebound discomfort may be more common than clinical trials predicted.

Warnings and precautions

Worsening vascular insufficiency

Brimonidine topical gel should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenonorthostatic hypotensionthrombangiitis obliterans scleroderma/ /systemic sclerosisor Sjögren syndrome.

Severe heart disease

Alpha-2 adrenergic agonists can lower blood pressure. Brimonidine topical gel should be used with caution in patients with severe, unstable or uncontrolled cardiovascular disease.

Serious adverse reactions after oral intake.

Two young children experienced serious adverse reactions after an accident ingestion brimonidine topical gel. Adverse reactions experienced included lethargy, respiratory distress with apneic episodes (requiring intubation), breast bradycardiaconfusion psychomotor hyperactivity and diaphoresis. Both children were hospitalized overnight and discharged the next day without aftermath.

The pregnancy

There are no adequate and well-controlled studies on the use of topical brimonidine gel in pregnant women. It is not known if brimonidine is safe for breastfeeding mothers. In animal studies, brimonidine tartrate has been shown to be excreted in breast milk.

Children

Safety and effectiveness in pediatric patients have not been studied.

The elders

Clinical studies of the topical brimonidine gel did not include a sufficient number of subjects age 65 and older to determine whether they respond differently to younger subjects. One hundred and five subjects older than 65 years were included in clinical trials with topical brimonidine gel. No overall differences in safety or effectiveness were observed between subjects 65 years of age and younger adult subjects.

Drug interactions

Blood pressure and heart medications.

Alpha-2 agonists, as a class, can lower blood pressure. Patients in concomitant beta-blockers, antihypertensives and / or cardiac glycosides must be carefully monitored.

Central nervous system depressants

Although no specific drug interaction studies have been conducted with topical brimonidine gel, the possibility of an additive or potentiating effect with CNS Depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered.

Monoamine oxidase inhibitors

Monoamine oxidase (MAO) inhibitors may theoretically interfere with metabolism of brimonidine and can lead to increased systemic side effects, such as hypotension.