Brimonidine (Topical) (Onreltea)

1. Health Canada Product Monograph — Brimonidine (Topical)

• Onreltea gel 0.33% is indicated for the topical treatment of facial erythema of rosacea in adults 18 years of age or older.
• It treats persistent background redness. It has no effect on visible telangiectatic blood vessels or on inflammatory papules/pustules, and its use for flushing episodes themselves is based only on limited case-report and consensus evidence.

• There are no adequate, well-controlled studies of Onreltea in pregnant women, and animal studies showed brimonidine crosses the placenta to a limited extent.
• Use during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.

• It is not known whether topical brimonidine is excreted into human milk.
• Because of the potential for serious adverse reactions in a nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the drug's importance to the mother.

• Over 100 patients aged 65 and older were included in Phase 3 trials, with no overall difference in safety or effectiveness compared with younger adults.

• Contraindicated in children under 2 years of age because of serious systemic safety risks with accidental ingestion.
• Not recommended in children and adolescents 2 to 18 years of age; safety concerns related to systemic absorption have been identified in the 2-to-12-year age group, and safety/effectiveness have not been established under age 18.

• Once daily application. Start with a small amount of gel (less than the maximum) for at least 1 week, then increase gradually based on tolerability and response.
• Apply a small, pea-sized amount to each of 5 areas of the face (forehead, chin, nose, each cheek), for a maximum total of about 1 g daily, avoiding the eyes, eyelids, lips, mouth, and inside of the nose.
• Do not apply to irritated skin, open wounds, or skin recently treated with laser therapy.
• Wash hands immediately after applying. Cosmetics may be applied afterward.
• Redness reduction begins within about 30 minutes, with peak effect around 3 hours; contact the prescriber if there is no improvement within 5 days.
• Do not exceed the recommended dose or frequency -- the safety of higher doses or repeated daily application has not been assessed.
• If a dose is missed, apply at the next scheduled time; do not double up.

If overdose is suspected, seek emergency medical attention immediately or contact your regional Poison Control Centre without delay.

• No adult overdose data are available for topical Onreltea. Oral overdose of other alpha-2 agonists has caused hypotension, weakness, vomiting, lethargy, sedation, bradycardia, arrhythmias, pinpoint pupils, apnea, low muscle tone, hypothermia, respiratory depression, and seizure.
• Accidental ingestion by young children has caused lethargy, respiratory distress with apnea requiring intubation, slow heart rate, confusion, agitation, and sweating -- keep out of reach of children and seek emergency care immediately if ingested.
• Treatment of oral overdose is supportive; contact your regional Poison Control Centre for any suspected overdose.

• Redness (erythema), itching (pruritus), flushing, and a skin-burning sensation are the most commonly reported effects, each occurring in roughly 1 to 3% of patients; these are usually transient and mild to moderate.
• Eyelid swelling, dry mouth, feeling hot, coldness of skin, alcohol-induced flushing, headache, tingling (paraesthesia), nasal congestion or stinging, acne, dermatitis, dry skin, skin discomfort or irritation, facial swelling, and hives have also been reported.

Serious side effects require immediate discussion with the prescriber or emergency care.

• Aggravated (rebound) erythema and flushing -- can be more severe than the redness present before treatment; most cases occur within the first 2 weeks and resolve after stopping. See Use with caution below.
• Uncommon: facial swelling, hives, dizziness.
• Rare: angioedema, slow heart rate (bradycardia), low blood pressure (including on standing).
• Seek medical attention for facial or throat swelling, difficulty breathing, widespread hives, fainting, or a very slow heartbeat.

• Rebound erythema: some patients experience worsening redness and flushing, at times spreading beyond the original treatment area (including the neck and chest) or occurring with a new pattern, typically within the first 2 weeks of use. If this occurs, stop treatment; cooling, an NSAID, or an antihistamine may help symptoms. If restarting after a break for aggravated erythema, test on a small area of skin for at least a day before resuming full-face application.
• Do not exceed the labelled dose or frequency of application.
• Not for oral, ophthalmic, or intravaginal use, and should not be applied close to the eyes.
• Use with caution in patients with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, thromboangiitis obliterans, scleroderma, or Sjogren's syndrome, since systemic alpha-2 agonist effects can be potentiated.
• Use with caution in severe, unstable, or uncontrolled cardiovascular disease, since alpha-2 agonists can lower blood pressure.
• Not studied in renal or hepatic impairment -- use caution.
• Contains methylparahydroxybenzoate, which may cause a (possibly delayed) allergic reaction, and propylene glycol, which may cause skin irritation.

• Hypersensitivity to brimonidine tartrate or any component of the formulation.
• Children under 2 years of age.

• No formal drug-drug interaction studies have been conducted.
• Possible additive or potentiating effect with CNS depressants (alcohol, barbiturates, opioids, sedatives, anesthetics).
• Caution with monoamine oxidase inhibitors, which may theoretically increase systemic side effects such as hypotension.
• Caution with drugs affecting the metabolism/uptake of circulating amines (e.g., chlorpromazine, methylphenidate, reserpine) and with other adrenergic receptor agonists/antagonists (e.g., isoprenaline, prazosin).
• Caution when combined with other systemic alpha-adrenergic agonists, beta-blockers, other antihypertensives, or cardiac glycosides, given the class effect of lowering blood pressure.

• None established; this is a topical product with minimal systemic absorption when used as directed.

• Apply once daily; there is no meal-related timing requirement since this is a topical product.

• Store at room temperature (15°C to 30°C). Protect from freezing. Keep out of the reach of children -- accidental ingestion has caused serious reactions in young children.

• Onreltea gel reduces the persistent facial redness of rosacea when applied once daily; it does not treat bumps/pimples or visible blood vessels.
• Redness reduction starts within about 30 minutes and peaks around 3 hours, then wears off -- this is expected, not a sign the medication has stopped working.
• Watch for redness or flushing that comes back worse than before treatment (rebound erythema), especially in the first 2 weeks -- stop the gel and contact your pharmacist or doctor if this happens.
• Use only a pea-sized amount on each of the 5 face areas (forehead, chin, nose, both cheeks); more is not more effective and has not been shown to be safe.
• Keep this medication away from children -- swallowing it has caused serious reactions requiring hospitalization.