Brivex

Indications

Brivex is indicated for the treatment of Glaucoma & ocular hypertension

Adverse Effects

Most common adverse reactions occurring in approximately 3 to 5% of patients included blurred vision, eye irritation, dysgeusia (bad taste), dry mouth, eye allergy.

Drug Interactions

Brinzolamide:There is a potential additive effect of the known systemic effects of carbonic anhydrase inhibition in patients receiving both oral and topical carbonic anhydrase inhibitors. Rare instances of acid-base alterations have occurred with high-dose salicylate therapy Brimonidine: Antihypertensives/Cardiac Glycosides: Because Brimonidine may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with Brimonidine is advised CNS Depressants: Although specific drug interaction studies have not been conducted with Brimonidine, the possibility of an additive or potentiating effect with CNS depressants (alcohol, barbiturates, opiates, sedatives, or anesthetics) should be considered Tricyclic Antidepressants: 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, 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 Inhibitors: 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

Mechanism of Action

Brivex is comprised of two components: brinzolamide (carbonic anhydrase inhibitor) and brimonidine tartrate (alpha 2 adrenergic receptor agonist). Each of these two components decreases elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage. Brinzolamide inhibits carbonic anhydrase in the ciliary processes of the eye to decrease aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Brinzolamide has a peak ocular hypotensive effect occurring at 2 to 3 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. Brimonidine tartrate has a peak ocular hypotensive effect occurring at two hours post-dosing. The result is a reduction in intraocular pressure (IOP).

Pharmacokinetics

The half life of Brinzolamide in Brivex is 111 days, half life of Brimonidine in Brivex is 3 hours

Absorption, Distribution, Metabolism & Excretion

Brinzolamide Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its high affinity for CA-II, brinzolamide distributes extensively into the red blood cells (RBCs) and exhibits a long half-life in whole blood (mean of approximately 24 weeks). Binding to plasma proteins is not extensive (about 60%). Brinzolamide is eliminated primarily by renal excretion (approximately 60%). About 20% of the dose has been accounted for in urine as metabolite. Brimonidine 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

Drug Use in Pregnancy

Brimonidine: 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 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 should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus 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 brimonidine tartrate 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 Brinzolamide: There are no or limited amount of data from the use of ophthalmic brinzolamide in pregnant women. Studies in animals have shown reproductive toxicity following systemic administration