Simbrinza®
Brinzolamide 1% / Brimonidine 0.2% · ophthalmic suspension
Antiglaucoma
Approved uses
Elevated IOP in open-angle glaucoma or ocular hypertension
1 drop in the affected eye(s) TID; shake well before use
Peak IOP lowering comes 2 to 3 hours after a dose, holding mean IOP near 16 to 20 mm Hg.
Add-on to a prostaglandin analog when that monotherapy is insufficient
1 drop TID alongside the once-daily prostaglandin analog; separate drops by at least 5 minutes
Adds a 3.4 mm Hg drop beyond a prostaglandin alone, taking mean diurnal IOP to 17.1 mm Hg at 6 weeks.
OFF-LABELNot in the FDA label for this product
Elevated IOP on prostaglandin analog monotherapy
1 drop BID alongside the once-daily prostaglandin analog
RCT · n=188 · no TID arm
Phase 4 randomized double-masked trial, 96 patients on BID fixed combination plus prostaglandin analog versus 92 on vehicle plus prostaglandin analog for 6 weeks: least squares mean diurnal IOP change -5.59 mmHg (95% CI -6.2 to -5.0) versus -2.15 mmHg (95% CI -2.7 to -1.6), treatment difference -3.44 mmHg (95% CI -4.2 to -2.7, P below 0.001). Ocular adverse events 21.1% versus 8.7%; the trial did not compare BID against the labeled TID regimen.
Contraindications
- Hypersensitivity to any component of this product
- Neonates and infants under 2 years of age
Available FormsOphthalmic suspension, 8 mL in a 10 mL bottle, brinzolamide 1% (10 mg/mL), brimonidine tartrate 0.2% (2 mg/mL)
Mechanism of ActionFixed combination of a carbonic anhydrase inhibitor and an alpha-2 adrenergic agonist: brinzolamide inhibits carbonic anhydrase in the ciliary processes to slow bicarbonate formation and cut aqueous secretion, while brimonidine both reduces aqueous production and increases uveoscleral outflow. Peak ocular hypotensive effect is 2 to 3 hours post-dose for brinzolamide and 2 hours for brimonidine.
Warnings & Precautions
- Sulfonamide hypersensitivity: Brinzolamide is a systemically absorbed sulfonamide; fatalities have occurred from Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia and other blood dyscrasias. Discontinue immediately if signs appear; sensitization can recur on re-exposure by any route.
- Corneal endothelium: Higher risk of corneal edema with low endothelial cell counts.
- Somnolence in young children: 50% to 83% with decreased alertness in ages 2 to 6 on the brimonidine component.
- Vascular insufficiency: Caution with depression, cerebral or coronary insufficiency, Raynaud's phenomenon, orthostatic hypotension, thromboangiitis obliterans; the brimonidine component may potentiate these syndromes.
- Severe cardiovascular disease: Brimonidine produced a mean blood pressure decrease of less than 5% at 2 hours; caution.
- Severe renal impairment: Not recommended below CrCl 30 mL/min; brinzolamide and its metabolite are renally cleared.
- Severe hepatic impairment: Brimonidine not studied in hepatic impairment; caution.
- Oral carbonic anhydrase inhibitors: Additive systemic carbonic anhydrase inhibition; concomitant use not recommended.
- MAO inhibitors: May theoretically interfere with brimonidine metabolism and increase systemic effects such as hypotension; caution advised.
- Tricyclic antidepressants: Reported to blunt the hypotensive effect of systemic clonidine; the effect on IOP lowering is unknown, caution advised.
- CNS depressants, antihypertensives, cardiac glycosides: Additive or potentiating effect possible with alcohol, opiates, barbiturates, sedatives or anesthetics; blood pressure may fall further with antihypertensives or cardiac glycosides.
- Fatigue and drowsiness: Class effect; reduced mental alertness matters for driving and hazardous activities.
- Soft contact lenses: Benzalkonium chloride is absorbed; remove lenses at instillation, reinsert 15 minutes later.
- Acute angle-closure glaucoma: Not studied; management requires intervention beyond ocular hypotensive agents.
- Bacterial keratitis: Reported from contaminated multi-dose containers, mostly in eyes with concurrent corneal disease or epithelial disruption.
Common Side Effects
- Ocular: Blurred vision, eye irritation, eye allergy, each approximately 3% to 5% in the fixed-combination trials.
- Systemic: Dysgeusia (bad taste) and dry mouth, each approximately 3% to 5%.
- Discontinuation: 11% of fixed-combination patients, mainly for adverse reactions, across two 3-month trials (n=435).
- Brinzolamide component: Blurred vision and bitter, sour or unusual taste 5% to 10%; blepharitis, dry eye, foreign body sensation, hyperemia, ocular discharge, discomfort, keratitis, pain, pruritus 1% to 5%.
- Brimonidine component: Oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue and drowsiness, conjunctival follicles, ocular allergy, pruritus 10% to 30%.
- Postmarketing ocular: Iritis, miosis, keratoconjunctivitis sicca reported with brimonidine.
- Postmarketing systemic: Stevens-Johnson syndrome and toxic epidermal necrolysis with brinzolamide; bradycardia, tachycardia, hypersensitivity with brimonidine.
- Infants: Apnea, bradycardia, hypotension, hypothermia, lethargy, respiratory depression, somnolence reported with brimonidine drops.
Pregnancy & LactationPregnancy: No adequate and well-controlled studies in pregnant women; use only if the potential benefit justifies the potential risk to the fetus. Oral brinzolamide in rabbits produced maternal toxicity at 120 times the ophthalmic dose and an increase in fetal variations such as accessory skull bones at 20 and 120 times, only slightly above the historical value.
Lactation: Excretion in human milk after topical ocular use is unknown; brimonidine is excreted in animal milk and radioactivity appeared in rat milk after oral brinzolamide. Weigh discontinuing nursing against discontinuing the drug.
Pediatric UseContraindicated under age 2.