SIMBRINZA
Classes
Other Miotics-Antiglaucoma Combinations
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.
Adverse Reactions
visual impairment / Early / 3.0-9.0
corneal erosion / Delayed / 3.0-9.0
ocular hemorrhage / Delayed / 0-3.0
arrhythmia exacerbation / Early / 0-3.0
keratitis / Delayed / 0-1.0
keratoconjunctivitis / Early / 0-1.0
bradycardia / Rapid / Incidence not known
conjunctival hyperemia / Early / 0-30.0
blepharitis / Early / 1.0-9.0
edema / Delayed / 3.0-9.0
erythema / Early / 3.0-9.0
photophobia / Early / 3.0-9.0
blurred vision / Early / 3.0-5.0
contact dermatitis / Delayed / 1.0-5.0
depression / Delayed / 0-3.0
hypertension / Early / 0-3.0
palpitations / Early / 0-3.0
conjunctivitis / Delayed / 0-1.0
keratopathy / Delayed / 0-1.0
dyspnea / Early / 0-1.0
chest pain (unspecified) / Early / 0-1.0
hypertonia / Delayed / 0-1.0
iritis / Delayed / Incidence not known
corneal edema / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
fatigue / Early / 0-30.0
headache / Early / 0-30.0
drowsiness / Early / 0-30.0
foreign body sensation / Rapid / 0-30.0
ocular pruritus / Rapid / 0-30.0
xerostomia / Early / 0-30.0
dizziness / Early / 0-9.0
asthenia / Delayed / 3.0-9.0
blepharedema / Early / 3.0-9.0
ocular pain / Early / 1.0-9.0
musculoskeletal pain / Early / 3.0-9.0
dysgeusia / Early / 3.0-5.0
xerophthalmia / Early / 3.0-5.0
ocular irritation / Rapid / 3.0-5.0
ocular discharge / Delayed / 1.0-5.0
rhinitis / Early / 1.0-5.0
insomnia / Early / 0-3.0
anxiety / Delayed / 0-3.0
syncope / Early / 0-3.0
nasal dryness / Early / 0-3.0
diplopia / Early / 0-1.0
urticaria / Rapid / 0-1.0
alopecia / Delayed / 0-1.0
pharyngitis / Delayed / 0-1.0
dyspepsia / Early / 0-1.0
nausea / Early / 0-1.0
diarrhea / Early / 0-1.0
miosis / Early / Incidence not known
Common Brand Names
SIMBRINZA
Dea Class
Rx
Description
Combines a selective alpha-agonist (brimonidine) and a carbonic anhydrase inhibitor (brinzolamide) into a single ophthalmic preparation
Used for the treatment of open-angle glaucoma or ocular hypertension
Fixed-dose combination produces statistically significant greater reduction in IOP than brimonidine or brinzolamide monotherapy
Dosage And Indications
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.
Dosing Considerations
Brimonidine; brinzolamide has not been studied in patients with hepatic impairment; use caution in treating these patients.
CrCl >= 30 mL/min: No dosage adjustment is necessary.
CrCl < 30 mL/min: Use is not recommended.
Drug Interactions
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
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.
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.
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.
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.
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.
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.
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.
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.
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.
How Supplied
Brinzolamide, Brimonidine/Brinzolamide, Brimonidine Tartrate Ophthalmic Susp: 1-0.2%
Maximum Dosage
3 drops/day per affected eye.
3 drops/day per affected eye.
3 drops/day per affected eye.
>= 2 years: 3 drops/day per affected eye.
< 2 years: Use is contraindicated.
Use is contraindicated.
Use is contraindicated.
Mechanism Of Action
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.
Pharmacokinetics
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.
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.
Pregnancy And Lactation
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.