Brimonidine, a selective alpha-agonist, and brinzolamide, a carbonic anhydrase inhibitor, are combined together to decrease intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. Brimonidine; brinzolamide is available as fixed-dose ophthalmic drop that is administered as 1 drop three times daily, with the intent of reducing medication burden. The fixed dose combination resulted in a statistically significantly greater reduction in IOP (16.3-19.8 mm Hg) after 3 months of treatment than that of either brimonidine 0.2% (17.9-22.5 mm Hg; p < 0.001) or brinzolamide 1% (19.3-20.9 mm Hg; p < 0.002) administered as monotherapy in a clinical trial of 660 patients with either open-angle glaucoma or ocular hypertension. Brimonidine; brinzolamide (Simbrinza) was FDA-approved in April 2013.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
-Brimonidine; brinzolamide is administered topically to the eye. Shake well prior to use.
-If more than one ophthalmic drug is to be administered, the two drugs should be administered at least 5 minutes apart.
-Contact lenses should be removed prior to instilling brimonidine; brinzolamide; they can be reinserted after 15 minutes.
The most frequently reported adverse reactions in patients treated with brimonidine; brinzolamide occurring at an incidence of approximately 3 to 5% include blurred vision, ocular irritation, dysgeusia, xerophthalmia, and ocular allergy. Adverse reactions led to discontinuation of therapy in approximately 11% of patients.
There have been rare reports of bacterial keratitis associated with the use of multiple dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface. Contamination of ophthalmic preparations, like brimonidine; brinzolamide, can lead to severe ocular damage and possible blindness.
Headache (30% or less), fatigue/drowsiness (30% or less), dizziness (9% or less), asthenia (3 to 9%), insomnia (less than 3%), depression (less than 3%), anxiety (less than 3%), and syncope (less than 3%) have been reported during clinical trials of brimonidine and/or brinzolamide.
The following ocular-related adverse reactions have been reported during clinical studies of brimonidine and/or brinzolamide: foreign body sensation (30% or less), conjunctival hyperemia (30% or less), conjunctival follicles (30% or less), ocular pruritus (30% or less), corneal erosion/staining (3 to 9%), photophobia (3 to 9%), eyelid erythema (3 to 9%), conjunctival edema (3 to 9%), blepharedema (3 to 9%), conjunctival blanching (3 to 9%), visual impairment (3 to 9%), ocular pain (1 to 9%), blepharitis (1 to 9%), and ocular discharge (1 to 5%). The following adverse reactions were reported less frequently with either brimonidine or brinzolamide: lid crusting (less than 3%), ocular hemorrhage, (less than 3%), conjunctivitis (less than 1%), diplopia (less than 1%), ocular fatigue (less than 1%), keratoconjunctivitis (less than 1%), and keratopathy (less than 1%). Iritis, keratoconjunctivitis sicca, and miosis were reported during postmarketing use of brimonidine.
The potential for corneal edema is increased when brimonidine; brinzolamide is used in patients with low endothelial cell counts. Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium.
Contact dermatitis (1 to 5%) alopecia (less than 1%) and urticaria (less than 1%) were reported during clinical trials of brinzolamide and may occur during brimonidine; brinzolamide therapy.
Xerostomia (30% or less), upper respiratory symptoms (3 to 9%), rhinitis (1 to 5%), nasal dryness (less than 3%), dyspnea (less than 1%), and pharyngitis (less than 1%) were reported during clinical trials of brimonidine and/or brinzolamide.
Chest pain (unspecified) (less than 1%) was reported during clinical trials of brinzolamide. Hypertension (less than 3%) and palpitations/arrhythmia exacerbation (less than 3%) were reported during clinical trials of brimonidine. Bradycardia and sinus tachycardia have been reported during postmarketing use of brimonidine.
Gastrointestinal symptoms (3 to 9%), dyspepsia (less than 1%), diarrhea (less than 1%), and nausea (less than 1%) were reported during clinical trials of brimonidine and/or brinzolamide.
Hypertonia and kidney pain were reported at an incidence less than 1% in clinical trials of brinzolamide. Musculoskeletal pain was reported in 3 to 9% of patients in clinical trial of brimonidine.
Use brimonidine; brinzolamide with caution in patients with low endothelial cell counts; the potential for corneal edema is increased in these patients. Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium.
Brimonidine; brinzolamide is contraindicated in patients with hypersensitivity to either component. Also, brinzolamide is a chemical sulfonamide possessing a structure and pharmacologic activity distinct from the bacteriostatic sulfonamides. Rarely, sulfonamides of any type can produce allergic reactions, some of which may be severe. Use brimonidine; brinzolamide with caution, if at all, in patients with a history of sulfonamide hypersensitivity. Brinzolamide is absorbed systemically and may cause the same types of adverse reactions that are attributable to sulfonamides. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides. Sensitization may recur when a sulfonamide is re-administered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, brimonidine; brinzolamide should be discontinued immediately.
Brimonidine; brinzolamide should be used cautiously in patients with mild to moderate renal impairment. Brimonidine; brinzolamide has not been studied in patients with severe renal impairment (CrCl < 30 mL/min) and is not recommended in such patients because brinzolamide and its metabolites are excreted predominantly by the kidney. Severe renal impairment may limit the metabolism of brinzolamide.
Use brimonidine; brinzolamide with caution in patients with hepatic disease. The brimonidine component has not been studied in these patients.
Brimonidine; brinzolamide has not been studied in patients with acute closed-angle glaucoma. Management of patients with acute closed-angle glaucoma requires therapeutic interventions in addition to ocular hypotensive agents.
Brimonidine; brinzolamide is contraindicated in neonates, infants, and children < 2 years. Additionally, when the individual component brimonidine was studied in children 2 to 7 years of age, somnolence (50 to 83%) and decreased alertness were seen in children 2 to 6 years of age.
Brimonidine has minimal effects on blood pressure and other cardiopulmonary hemodynamics; however, brimonidine, brinzolamide should be used with caution in patients with severe cardiac disease.
Brimonidine; brinzolamide contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of brimonidine; brinzolamide but may be reinserted after 15 minutes.
Brimonidine; brinzolamide should be used with caution in patients with Raynaud's phenomenon, thromboangiitis obliterans (Buerger's disease), depression, cerebral or coronary insufficiency and orthostatic hypotension. Brimonidine may potentiate syndromes associated with vascular insufficiency.
Brimonidine; brinzolamide is classified in FDA pregnancy category C. There are no adequate and well-controlled studies in pregnant women. According to the manufacturer, brimonidine; brinzolamide should be used during pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.
According to the manufacturer, a decision should be made whether to discontinue nursing or to discontinue brimonidine; brinzolamide, taking into account the importance of the drug to the mother. It is not known whether brimonidine; brinzolamide is excreted in breast milk. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
For the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension:
Ophthalmic dosage:
Adults, Adolescents, and Children >=2 years: Instill 1 drop into the affected eye(s) 3 times daily. If more than one ophthalmic drug is being used, separate administration by at least 5 minutes.
Maximum Dosage Limits:
-Adults
3 drops/day per affected eye.
-Geriatric
3 drops/day per affected eye.
-Adolescents
3 drops/day per affected eye.
-Children
>= 2 years: 3 drops/day per affected eye.
< 2 years: Use is contraindicated.
-Infants
Use is contraindicated.
-Neonates
Use is contraindicated.
Patients with Hepatic Impairment Dosing
Brimonidine; brinzolamide has not been studied in patients with hepatic impairment; use caution in treating these patients.
Patients with Renal Impairment Dosing
CrCl >= 30 mL/min: No dosage adjustment is necessary.
CrCl < 30 mL/min: Use is not recommended.
*non-FDA-approved indication
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Acetaminophen; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Acetaminophen; Hydrocodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Acetaminophen; Oxycodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Alfentanil: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Alprazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Amitriptyline: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Amobarbital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Aspirin, ASA; Oxycodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Barbiturates: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Belladonna; Opium: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Benzhydrocodone; Acetaminophen: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Benzodiazepines: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Butalbital; Acetaminophen: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Butalbital; Acetaminophen; Caffeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists. (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists. (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Cardiac glycosides: (Minor) Alpha-agonists as a class, may reduce heart rate and blood pressure. Although ophthalmic brimonidine administration generally does not have clinically significant effects on pulse and blood pressure, it should be used with caution with cardiac glycosides.
Celecoxib; Tramadol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Chlordiazepoxide: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Chlordiazepoxide; Amitriptyline: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines. (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Chlordiazepoxide; Clidinium: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Chlorpheniramine; Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Chlorpheniramine; Hydrocodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Clomipramine: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Clonazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Clorazepate: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Codeine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Codeine; Guaifenesin: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Codeine; Phenylephrine; Promethazine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Codeine; Promethazine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Desipramine: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Diazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Digoxin: (Minor) Alpha-agonists as a class, may reduce heart rate and blood pressure. Although ophthalmic brimonidine administration generally does not have clinically significant effects on pulse and blood pressure, it should be used with caution with cardiac glycosides.
Doxepin: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Estazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Eszopiclone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Fentanyl: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Flurazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Homatropine; Hydrocodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Hydrocodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Hydrocodone; Ibuprofen: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Hydromorphone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Ibuprofen; Oxycodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Imipramine: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Isocarboxazid: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Levorphanol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Linezolid: (Moderate) Use brimonidine with caution with MAOIs because they can affect the metabolism and uptake of circulating amines. Linezolid is an antibiotic that is also a reversible, non-selective inhibitor of MAO. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Lorazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Meperidine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Meprobamate: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Methadone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Methohexital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Midazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Monoamine oxidase inhibitors: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Morphine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Morphine; Naltrexone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Nortriptyline: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Oliceridine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Opiate Agonists: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Oxazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Oxycodone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Oxymorphone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Pentobarbital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Perphenazine; Amitriptyline: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Phenelzine: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Phenobarbital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Primidone: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Protriptyline: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Quazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Rasagiline: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Remifentanil: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Remimazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Secobarbital: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including barbiturates.
Selegiline: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Sufentanil: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Tapentadol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Temazepam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Tramadol: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Tramadol; Acetaminophen: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of opiate agonists.
Tranylcypromine: (Moderate) Use caution during concurrent administration of brimonidine and monoamine oxidase inhibitors (MAOIs). MAOIs can affect the metabolism and uptake of circulating amines. MAOIs may theoretically interfere with the metabolism of brimonidine resulting in increased systemic side effects like hypotension.
Triazolam: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of the anxiolytics, sedatives, and hypnotics including benzodiazepines.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Trimipramine: (Moderate) Tricyclic antidepressants have been reported to decrease the antihypertensive effects of systemic clonidine. It is not known whether tricyclic antidepressants will affect the IOP-lowering efficacy of brimonidine eye solution. There are no data concerning the levels of systemic catecholamines after ophthalmic administration of brimonidine; however, monitor patients carefully who are taking brimonidine and tricyclic antidepressants.
Zaleplon: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Zolpidem: (Moderate) Based on the sedative effects of brimonidine in individual patients, brimonidine administration has potential to enhance the CNS depressants effects of anxiolytics, sedatives, and hypnotics.
Brimonidine and brinzolamide both decrease elevated intraocular pressure (IOP). Reduction of elevated or normal IOP occurs irrespective of the presence of glaucoma.
-Brimonidine: Brimonidine is a potent, selective alpha-2-agonist that is 1000-fold more selective for the alpha-2 versus the alpha-1 receptor. When brimonidine is compared to clonidine and apraclonidine, it is 7-12 and 23-32 times, respectively, more selective for the alpha-2 receptor. Brimonidine decreases IOP, without causing mydriasis, by reducing aqueous humor production and increasing uveoscleral aqueous humor outflow. Brimonidine has been shown to be neuroprotective to the optic nerve in animal studies.
-Brinzolamide: Brinzolamide inhibits carbonic anhydrase II (CA-II). Carbonic anhydrase catalyzes the reversible reaction involving hydration of carbon dioxide and dehydration of carbonic acid. Many body tissues contain carbonic anhydrase; CA-II is an isozyme that plays a key role in controlling aqueous humor production and pressure in the eye. Carbonic anhydrase II is found in the ciliary body of the eye and works by decreasing bicarbonate ion concentrations in ocular fluid. This results in decreased aqueous humor secretion and subsequently a reduction in IOP. Carbonic anhydrase II is also present in red blood cells and other cells that secrete hydrogen or hydrogen compounds. Brinzolamide appears to have no clinically significant biochemical or hematologic effects when administered topically to the eye.
Brimonidine; brinzolamide ophthalmic suspension is administered topically to the eye.
-Brimonidine: Brimonidine is extensively metabolized by the liver and is eliminated in the urine.
-Brinzolamide: In the systemic circulation, brinzolamide distributes extensively into erythrocytes and exhibits a long half-life in whole blood (about 111 days) due to its affinity for carbonic anhydrase type II (CA-II). Approximately 60% of brinzolamide in plasma is protein bound. Brinzolamide is metabolized to N-desethyl brinzolamide which also binds to carbonic anhydrase and accumulates in erythrocytes. In the presence of brinzolamide, this metabolite mainly binds to CA-I. Plasma concentrations of both brinzolamide and the metabolite are low and generally below the level of assay detection (< 10 ng/mL). Brinzolamide is eliminated primarily in the urine as unchanged drug. N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N-desmethoxypropyl and O-desmethyl metabolites.
-Route-Specific Pharmacokinetics
Other Route(s)
Ophthalmic Route
The systemic plasma exposure (AUC and Cmax) to brimonidine and brinzolamide is similar after dosing with the fixed combination to that observed following dosing with the individual components.
-Brimonidine: Following ophthalmic administration of brimonidine 0.2%, the Tmax occurred in 1-4 hours with a systemic half-life of 3 hours. The time to peak ocular hypotensive effect on IOP is about 2 hours.
-Brinzolamide: Following ophthalmic administration, brinzolamide is absorbed into the systemic circulation. The time to peak ocular hypotensive effect is 2-3 hours.