Simbrinza (brinzolamide/brimonidine tartrate)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Brinzolamide is a carbonic anhydrase inhibitor.
Brimonidine tartrate is a relatively selective alpha2-adrenergic agonist.
Brinzolamide is a carbonic anhydrase inhibitor. Similar to other carbonic anhydrase inhibitors (e.g., acetazolamide, dichlorphenamide, dorzolamide, methazolamide), brinzolamide is a nonbacteriostatic sulfonamide derivative. All these agents contain an unsubstituted sulfamyl group.
Brinzolamide is pharmacologically related to other carbonic anhydrase inhibitors. Although the exact mechanism of action by which carbonic anhydrase inhibitors lower intraocular pressure (IOP) has not been fully elucidated, fluorophotometric studies suggest that reduced aqueous humor formation is the principal effect. Topical brinzolamide can produce mean IOP reductions of about 16-19%.
Brinzolamide is a highly specific inhibitor of carbonic anhydrase II (CA-II), the main carbonic anhydrase isoenzyme involved in aqueous humor secretion. Inhibition of carbonic anhydrase in the ciliary process of the eye decreases the rate of aqueous humor secretion and IOP by slowing bicarbonate formation and reducing sodium and fluid transport.
Some systemic absorption occurs following topical administration of brinzolamide to the eye. Following long-term administration of topical brinzolamide, the drug accumulates in erythrocytes as a result of CA-II binding and exhibits a half-life in whole blood of approximately 111 days. In addition, the N-desethyl metabolite accumulates in erythrocytes as a result of binding to carbonic anhydrase.
However, sufficient CA-II activity remains so that adverse effects resulting from systemic carbonic anhydrase inhibition are not observed. Following topical application to the eye, plasma concentrations of both the parent drug and N-desethyl metabolite generally are below the quantitation limits of the assay. Brinzolamide is eliminated mainly in urine as unchanged drug; the N-desethyl metabolite also is recovered in urine along with lower concentrations of N-desmethoxypropyl and O-desmethyl metabolites.
Brimonidine, a relatively selective alpha2-adrenergic agonist, is structurally and pharmacologically related to apraclonidine and clonidine. In vitro pharmacologic studies indicate that the selectivity of brimonidine for alpha2- versus alpha1-adrenergic receptors is at least 10 or 28 times greater than that of clonidine or apraclonidine, respectively. Such selectivity of brimonidine for the alpha2-receptor may result in a reduced incidence of adverse pulmonary and cardiovascular effects.
Following topical application to the eye, brimonidine tartrate 0.2% reduces both elevated and normal intraocular pressure (IOP) in patients with or without glaucoma. Fluorophotometric studies in animals and humans suggest that brimonidine tartrate ophthalmic solution reduces IOP by decreasing aqueous humor production and increasing uveoscleral outflow. Peak ocular hypotensive effects occur 2-3 hours following topical administration of brimonidine tartrate ophthalmic solution.
Controlled studies in patients with primary open-angle glaucoma or ocular hypertension have demonstrated that the ocular hypotensive effect of brimonidine tartrate 0.1 or 0.15% ophthalmic solution is comparable to that of the 0.2% solution. When used at low dosages (i.e., brimonidine tartrate 0.025%) in individuals with normal IOP, the vasoconstrictive effects of the drug relieve ocular redness without altering IOP.
USES: This product contains two medications used to treat high pressure in the eye due to glaucoma (open-angle glaucoma-type) or a certain other eye disease (ocular hypertension). Lowering high pressure in the eye reduces the risk of vision loss, nerve damage, or blindness. This product contains brinzolamide and brimonidine.
These two medications work together to decrease the amount of fluid within the eye. Brinzolamide belongs to a class of drugs known as carbonic anhydrase inhibitors. Brimonidine belongs to a class of drugs known as alpha agonists.
This product is not recommended for use in children younger than 2 years of age due to an increased risk of serious side effects such as very slowed breathing. Ask the doctor or pharmacist for details.
Generic name: brinzolamide/brimonidine tartrate
Pronunciation: (brin-ZOE-la-mide/bri-MON-i-deen)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Simbrinza
Indications
The following indications are listed for Simbrinza:
- Ocular Hypertension
- Open Angle Glaucoma
Also known as: Chronic Glaucoma, Compensated Glaucoma, Glaucoma Simplex, Increased Intraocular Pressure, Increased Iop, Open-Angle Glaucoma, Raised Intraocular Pressure, Simple Glaucoma.
Dosing
For the treatment of open-angle glaucoma or ocular hypertension in adults, the usual dosage of brinzolamide is 1 drop of a 1% ophthalmic suspension in the affected eye(s) 3 times daily.
If the target intraocular pressure (IOP) is not achieved, alternative or additional ocular hypotensive agents may be required. (See Uses: Ocular Hypertension and Glaucoma.) When brinzolamide is used in fixed combination with brimonidine tartrate, the usual adult dosage is 1 drop of an ophthalmic suspension containing brinzolamide 1% and brimonidine tartrate 0.2% in the affected eye(s) 3 times daily. Because of the potential for additive systemic effects, combined use of topical brinzolamide and an oral carbonic anhydrase inhibitor (e.g., acetazolamide, dichlorphenamide, methazolamide) is not recommended by the manufacturer.
Brimonidine tartrate is applied topically to the eye as an ophthalmic solution. Brimonidine tartrate also is commercially available in fixed combination with brinzolamide (as an ophthalmic suspension) and in fixed combination with timolol (as an ophthalmic solution) for topical application to the eye.
Although topical brimonidine has been administered twice daily as an ocular hypotensive agent in certain clinical studies, reductions in intraocular pressure (IOP) induced by the drug appear to diminish 8 hours following administration. Therefore, the manufacturers recommend administering brimonidine tartrate 0.1, 0.15, or 0.2% ophthalmic solution 3 times daily at intervals of approximately 8 hours. The fixed-combination ophthalmic suspension containing brinzolamide and brimonidine tartrate also is administered 3 times daily. However, when used in fixed combination with timolol, brimonidine is administered twice daily at intervals of approximately 12 hours. For self-medication for temporary relief of ocular redness, brimonidine tartrate 0.025% may be administered up to 4 times daily.
The fixed-combination ophthalmic suspension containing brinzolamide and brimonidine tartrate should be shaken well prior to use.
Care should be taken to avoid contamination of the dispensing container. (See Bacterial Keratitis under Cautions: Warnings/Precautions.)
Some brimonidine ophthalmic preparations contain benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to administration of each dose of these preparations, but may be reinserted 15 minutes after the dose. The manufacturer of brimonidine tartrate 0.025% ophthalmic solution states that contact lenses may be reinserted 10 minutes after the dose.
If the patient is receiving more than one topical ophthalmic preparation, the preparations should be administered at least 5 minutes apart.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
No formal drug interaction studies have been performed.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
Brinzolamide is contraindicated in patient with known hypersensitivity to the drug or any ingredient in the formulation.
Brimonidine is contraindicated in neonates and infants younger than 2 years of age. (See Pediatric Use under Warnings/Precautions: Specific Populations, in Cautions.) Brimonidine also is contraindicated in patients with known hypersensitivity to the drug or any ingredient in the formulation.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in approximately 1-10% of patients receiving brinzolamide include blurred vision, taste abnormality (bitter, sour, or unusual taste), blepharitis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular pruritus, and rhinitis.
Adverse effects reported in approximately 10-30% of patients receiving brimonidine tartrate 0.1-0.2% ophthalmic solution include oral dryness, ocular or conjunctival hyperemia, burning and stinging, allergic conjunctivitis, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, and ocular pruritus. In addition, corneal staining/erosion, photophobia, eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, ocular irritation, GI symptoms, hypertension, asthenia, conjunctival blanching, abnormal vision, visual disturbances, and muscular pain have been reported in approximately 3-9% of patients receiving brimonidine tartrate 0.1-0.2% ophthalmic solution.
Adverse effects reported in approximately 1-4% of patients receiving brimonidine tartrate 0.025% ophthalmic solution include decreased visual acuity, conjunctival or ocular hyperemia, dry eye, instillation site pain, and headache.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of topical ophthalmic brinzolamide have not been established in children. A 3-month controlled clinical trial in 32 pediatric patients 4 weeks to 5 years of age failed to demonstrate intraocular pressure (IOP)-lowering efficacy of twice-daily topical administration of brinzolamide 1%. Patients were not required to discontinue their current IOP-lowering therapy until initiation of monotherapy with brinzolamide. The mean decrease in elevated IOP with brinzolamide therapy was 0-2 mm Hg. An increase in corneal diameter of 1 mm was observed in 5 patients.
Safety and efficacy of topical brimonidine tartrate for the treatment of open-angle glaucoma or ocular hypertension in pediatric patients younger than 2 years of age have not been established. Because potentially serious adverse effects, including apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence, have been reported in infants treated with topical brimonidine tartrate, use of the drug is contraindicated in infants younger than 2 years of age. In a well-controlled clinical study in children 2-7 years of age with glaucoma who received brimonidine tartrate 0.2% ophthalmic solution 3 times daily, the most commonly observed adverse effects were somnolence and decreased mental alertness; approximately 16% of these children discontinued therapy because of somnolence. The incidence of somnolence generally appeared to be age and weight related, occurring in 50-83% of children 2-6 years of age and 25% of those 7 years of age who weighed more than 20 kg.
The individual components of brinzolamide and brimonidine tartrate fixed-combination ophthalmic suspension have been studied in pediatric patients 4 weeks to 5 years of age (brinzolamide) and 2-7 years of age (brimonidine).
Safety and efficacy of brimonidine tartrate and timolol fixed-combination ophthalmic solution in pediatric patients 2-16 years of age have been established based on evidence from adequate and well-controlled studies of the fixed combination in adults and additional data from a study evaluating the individually administered drugs (brimonidine tartrate 0.2% administered 3 times daily as an adjunct to timolol therapy) in children 2-7 years of age with glaucoma.
Safety and efficacy of brimonidine tartrate 0.025% ophthalmic solution for self-medication for relief of ocular redness due to minor irritation have not been established in children younger than 5 years of age. Safety and efficacy in pediatric patients 5 years of age or older are supported by evidence from controlled clinical trials in adults and additional data from a safety study that included both adults and pediatric patients 5 years of age or older.
Following oral administration of radiolabeled brinzolamide in rats, radioactivity crossed the placenta and was detected in fetal circulation and tissues. In studies in rats, no drug-related malformations or effects on organ or tissue development were observed, and reductions in fetal body weight were proportional to reductions in maternal weight gain. In developmental toxicity studies in rabbits, a slight increase in the number of fetal variations (e.g., accessory skull bones) was observed.
There are no adequate and well-controlled studies of brinzolamide to date in pregnant women. Brinzolamide should be used during pregnancy only if potential benefits to the woman justify the potential risk to the fetus.
In studies in animals, brimonidine crossed the placenta and entered the fetal circulation to a limited extent; no evidence of teratogenicity was observed. There are no adequate and well-controlled studies of brimonidine to date in pregnant women. Brimonidine should be used during pregnancy only if potential benefits to the woman justify the potential risk to the fetus.
Brinzolamide is distributed into milk in rats following oral administration. It is not known whether brinzolamide is distributed into human milk following topical application to the eye. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
Brimonidine is distributed into milk in animals. It is not known whether brimonidine is distributed into human milk following topical application to the eye. A decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.
No overall differences in safety and efficacy of topical ophthalmic brinzolamide have been observed between geriatric patients and younger adults.
No substantial differences in safety and efficacy have been observed between geriatric patients and younger adults.
ICD codes
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Last reviewed · Source: First Databank (FDB) drug data
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