- brimonidine tartrate
POM: Prescription only medicine
This information is intended for use by health professionals
Paediatric populationNo clinical studies have been performed in adolescents (12 to 17 years). Brimonidine eye drops shoud not be used in children aged below 12 years and are contraindicated in neonates and infants (less than 2 years of age) (see sections 4.3, 4.4 & 4.9). It is known that severe adverse reactions can occur in neonates. The safety and efficacy of brimonidine has not been established in children.
Adults including the elderly:One drop into the affected eye(s) twice daily, approximately 12 hours apart. No dosage adjustment is required in elderly patients. To reduce possible systemic absorption, it is recommended that the lachrymal sac be compressed at the medial canthus (punctul occlusion) for one minute immediately after the instillation of each drop. If more than one topical ophthalmic drug is to be administered, they should be instilled 5 to 15 minutes apart.
Patients with renal and hepatic impairment:Brimonidine eye drops have not been studied in patients with renal or hepatic impairment (see section 4.4).
Method of administration
Precautions to be taken before handling or administering the medicinal product
Paediatric populationChildren of 2 years of age and above, especially those in the 2 to 7 age range and/or weighing ≤20 kg, should be treated with caution and closely monitored due to the high incidence of somnolence (see section 4.8). Caution is required in treating patients with: - severe or unstable and uncontrolled cardiovascular disease. - depression - cerebral or coronary insufficiency - Raynaud's phenomenon - orthostatic hypotension - thromboangiitis obliterans The use of Brimonidine Eye Drops has not been studied in patients with hepatic or renal impairment, therefore, caution should be exercised when treating such patients.It is reported that some patients (12.7%) in clinical trials experienced ocular allergic type reaction with brimonidine eye drops (see section 4.8); if allergic reactions are apparent, treatment should be discontinued.Delayed ocular hypersensitivity reactions have been reported with Brimonidine Eye Drops, with some reported to be associated with an increase in IOP.The Brimonidine eye drops contain benzalkonium chloride as preservative, which may cause eye irritation. Remove contact lenses prior to application and wait at least 15minutes before reinserting. Known to discolour soft contact lenses.
Very common : ≥1 in 10.
Common : ≥1 in 100 and <1 in 10.
Uncommon : ≥1 in 1,000 and <1 in 100.
Rare : ≥1 in 10,000 and <1 in 1,000.
Very rare :
< 1 in 10,000.
Cardiac disorders:Uncommon: Palpitations/arrhythmias (including bradycardia and tachycardia).
Nervous system disorders:Very common: Headache, drowsiness. Common: Dizziness, abnormal taste. Very rare: Syncope
Eye disorders:Very common : Ocular irritation including allergic reactions (hyperaemia, burning, stinging, pruritis, foreign body sensation, conjunctival follicles); blurred vision, allergic blepharitis, allergic blepharoconjuctivitis, allergic conjunctivitis, ocular allergic reaction and follicular conjunctivitis.Common: Local irritation (eyelid hyperaemia and oedema, blepharitis, conjunctival oedema and discharge, ocular pain and tearing); photophobia; corneal erosion and staining; ocular dryness; conjunctival blanching; abnormal vision; conjunctivitis.Very rare : Iritis (anterior uveitis); miosis.
Respiratory, thoracic and mediastinal disorders:Common: Upper respiratory symptoms.Uncommon: Nasal dryness.Rare: Dyspnoea
Gastrointestinal disorders:Very common: Oral dryness.Common: Gastrointestinal symptoms.
Vascular disorders:Very rare: Hypertension, hypotension.
General disorders and administration site conditions:Very common: Fatigue.Common: Asthenia.
Immune system disorders:Uncommon: Systemic allergic reactions.
Psychiatric disorders:Uncommon: Depression.Very rare: Insomnia.The following adverse reactions have been identified during post-marketing use of Brimonidine eye drops in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made.
Eye disordersIridocyclitis (anterior uveitis)Eyelid pruritusSkin and subcutaneous tissue disordersSkin reaction including erythema, face oedema, pruritus, rash and vasodilationIn cases where brimonidine has been used as part of the medical treatment of congenital glaucoma, symptoms of brimonidine overdose such as loss of consciousness, hypotension, hypotonia, bradycardia, hypothermia, cyanosis apnoea, lethargy, somnolence, pallor and respiratory depression have been reported in neonates and infants receiving brimonidine (see section 4.3).In a 3 month, phase 3 study in children aged 2 to 7 years with glaucoma, inadequately controlled by beta-blockers, a high prevalence of somnolence (55%) was reported with brimonidine eye drops as adjunctive treatment. In 8% of children, this was severe and ledto discontinuation of treatment in 13%. The incidence of somnolence decreased with increasing age, being least in the 7-year-old age group (25%), but was more affected by weight, occurring more frequently in those children weighing ≤20 kg (63%) compared to those weighing >20 kg (25%) (See section 4.4)Reporting of suspected adverse reactionsReporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to: www.mhra.gov.uk/yellowcard
Ophthalmic overdose (Adults):
In those cases received, the events reported have generally been those already listed as adverse reactions
Systemic overdose resulting from accidental ingestion (Adults):There is very limited information regarding accidental ingestion of brimonidine in adults. The only adverse event reported to date was hypotension. It was reported that the hypotensive episode was followed by rebound hypertension. Treatment of oral overdose includes supportive and symptomatic therapy; patient's airways should be maintained. Oral overdoses of other alpha-2-agonists have been reported to cause symptoms such as hypotension, asthenia, vomiting, lethargy, sedation, bradycardia, arrhythmias, miosis, apnoea, hypotonia, hypothermia, respiratory depression and seizure Paediatric population Reports of serious adverse effects following inadvertent ingestion of brimonidine eye drops have been published/reported. The subjects experienced symptoms of CNS depression, typically temporary coma or low level of consciousness, lethargy, somnolence, hypotonia, bradycardia, hypothermia, pallor, respiratory depression and apnoea, and required admission to intensive care with intubation if indicated. All subjects were reported to have made a full recovery, usually within 6-24 hours. .
a) General characteristics:It is reported that after ocular administration of a 0.2% solution twice daily for 10 days, plasma concentrations are low (mean Cmax 0.06 ng/ml). There is a slight accumulation in the blood after multiple instillations (twice daily for 10 days). AUC0-12h at steady stated is reported as 0.31 nghr/ml, compared to 0.23 nghr/ml after the initial dose. The mean apparent half-life in the systemic circulation was approximately 3 hours in humans after topical dosing. Plasma protein binding of brimonidine after topical dosing in humans is approximately 29%.Brimonidine binds reversibly to melanin in ocular tissues, in vitro and in vivo. It is reported that following 2 weeks of ocular instillation, the concentrations of brimonidine in iris, ciliary body and choroid-retina were 3- to 17-fold higher than those after a single dose. Accumulation does not occur in the absence of melanin.The significance of melanin binding in humans is unclear, however, no significant ocular adverse reaction was found during biomicroscopic examination of eyes in patients treated with brimonidine eye drops for up to one year, nor was significant ocular toxicity found during a one year ocular safety study in monkeys given approximately 4 times the recommended dose.Following oral administration to man, brimonidine is well absorbed and rapidly eliminated. The major part of the dose (around 75%) is excreted as metabolites in urine within 5 days; no unchanged drug was detected in urine. In-vitro studies, using animal and human liver, indicate that the metabolism is mediated largely by aldehyde oxidase and cytochrome P450. Hence, the systemic elimination seems to be primarily hepatic metabolism.
Kinetics profile:No great deviation from dose proportionality for plasma Cmax and AUC has been observed following a single topical dose of 0.08%, 0.2% and 0.5%.
b) Characteristics in patients:The Cmax, AUC, and apparent half-life of brimonidine are similar in the elderly (subjects 65 years or older) after a single dose compared with young adults, indicating that its systemic absorption and elimination are not affected by age.Based on data from a 3 months clinical study, which included elderly patients, it is reported that systemic exposure to brimonidine was very low.