NDC 0078-0904 Simbrinza
Brinzolamide/brimonidine Tartrate Suspension/ Drops Ophthalmic

Product Information

What is NDC 0078-0904?

The NDC code 0078-0904 is assigned by the FDA to the product Simbrinza which is a human prescription drug product labeled by Novartis Pharmaceuticals Corporation. The generic name of Simbrinza is brinzolamide/brimonidine tartrate. The product's dosage form is suspension/ drops and is administered via ophthalmic form. The product is distributed in 2 packages with assigned NDC codes 0078-0904-38 1 bottle in 1 carton / 8 ml in 1 bottle, 0078-0904-98 1 bottle in 1 carton / 2.5 ml in 1 bottle. This page includes all the important details about this product, including active and inactive ingredients, pharmagologic classes, product uses and characteristics, UNII information, RxNorm crosswalk and the complete product label.

NDC Product Code0078-0904
Proprietary Name What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.
Simbrinza
Non-Proprietary Name What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.
Brinzolamide/brimonidine Tartrate
Product Type What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.
Human Prescription Drug
Dosage FormSuspension/ Drops - A suspension which is usually administered in a dropwise fashion.
Administration Route(s) What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.
  • Ophthalmic - Administration to the external eye.
Product Labeler Information What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.
Novartis Pharmaceuticals Corporation
Labeler Code0078
FDA Application Number What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.
NDA204251
Marketing Category What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.
NDA - A product marketed under an approved New Drug Application.
Start Marketing Date What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.
05-01-2013
End Marketing Date What is the End Marketing Date?
This is the date the product will no longer be available on the market. If a product is no longer being manufactured, in most cases, the FDA recommends firms use the expiration date of the last lot produced as the EndMarketingDate, to reflect the potential for drug product to remain available after manufacturing has ceased. Products that are the subject of ongoing manufacturing will not ordinarily have any EndMarketingDate. Products with a value in the EndMarketingDate will be removed from the NDC Directory when the EndMarketingDate is reached.
02-28-2023
Exclude Flag What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".
N
NDC Code Structure

What are the uses for Simbrinza?


Product Packages

NDC Code 0078-0904-38

Package Description: 1 BOTTLE in 1 CARTON / 8 mL in 1 BOTTLE

Price per Unit: $23.83508 per ML

NDC Code 0078-0904-98

Package Description: 1 BOTTLE in 1 CARTON / 2.5 mL in 1 BOTTLE

Product Details

What are Simbrinza Active Ingredients?

An active ingredient is the substance responsible for the medicinal effects of a product specified by the substance's molecular structure or if the molecular structure is not known, defined by an unambiguous definition that identifies the substance. Each active ingredient name is the preferred term of the UNII code submitted.

Simbrinza Active Ingredients UNII Codes

NDC to RxNorm Crosswalk

What is RxNorm? RxNorm is a normalized naming system for generic and branded drugs that assigns unique concept identifier(s) known as RxCUIs to NDC products.The NDC to RxNorm Crosswalk for this produdct indicates multiple concept unique identifiers (RXCUIs) are associated with this product:
  • RxCUI: 1421451 - brinzolamide 1 % / brimonidine tartrate 0.2 % Ophthalmic Suspension
  • RxCUI: 1421451 - brimonidine tartrate 2 MG/ML / brinzolamide 10 MG/ML Ophthalmic Suspension
  • RxCUI: 1421451 - brimonidine tartrate 0.2 % / brinzolamide 1 % Ophthalmic Suspension
  • RxCUI: 1421456 - SIMBRINZA 1 % / 0.2 % Ophthalmic Suspension
  • RxCUI: 1421456 - brimonidine tartrate 2 MG/ML / brinzolamide 10 MG/ML Ophthalmic Suspension [Simbrinza]

Simbrinza Inactive Ingredients UNII Codes

The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

Pharmacologic Class(es)

A pharmacologic class is a group of drugs that share the same scientifically documented properties. The following is a list of the reported pharmacologic class(es) corresponding to the active ingredients of this product.

* Please review the disclaimer below.

Simbrinza Product Label

FDA filings in the form of structured product labels are documents that include all published material associated whith this product. Product label information includes data like indications and usage generic names, contraindications, active ingredients, strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Label Table of Contents



1     Indications And Usage



SIMBRINZA (brinzolamide and brimonidine tartrate ophthalmic suspension) 1% and 0.2% is a fixed combination of a carbonic anhydrase inhibitor and an alpha-2 adrenergic receptor agonist indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.


2     Dosage And Administration



The recommended dose is one drop of SIMBRINZA in the affected eye(s) three times daily. Shake well before use. SIMBRINZA ophthalmic suspension may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart.


3     Dosage Forms And Strengths



Suspension containing 10 mg/mL brinzolamide and 2 mg/mL brimonidine tartrate.


4.1     Hypersensitivity



SIMBRINZA is contraindicated in patients who are hypersensitive to any component of this product.


4.2     Neonates And Infants (Under The Age Of Two Years)



SIMBRINZA is contraindicated in neonates and infants (under the age of two years) [see Use in Specific Populations (8.4)].


5.1     Sulfonamide Hypersensitivity Reactions



SIMBRINZA contains brinzolamide, a sulfonamide, and although administered topically is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of SIMBRINZA. Fatalities have occurred due to severe reactions to sulfonamides including Stevens-Johnson syndrome, toxic epidermal necrolysis, fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias. Sensitization may recur when a sulfonamide is re-administered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation [see Patient Counseling Information (17)].


5.2     Corneal Endothelium



Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. There is an increased potential for developing corneal edema in patients with low endothelial cell counts. Caution should be used when prescribing SIMBRINZA to this group of patients.


5.3     Severe Renal Impairment



SIMBRINZA has not been specifically studied in patients with severe renal impairment (CrCl less than 30 mL/min). Since brinzolamide and its metabolites are excreted predominantly by the kidney, SIMBRINZA is not recommended in such patients.


5.4     Acute Angle-Closure Glaucoma



The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. SIMBRINZA has not been studied in patients with acute angle-closure glaucoma.


5.5     Contact Lens Wear



The preservative in SIMBRINZA, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of SIMBRINZA but may be reinserted 15 minutes after instillation [see Patient Counseling Information (17)].


5.6     Severe Cardiovascular Disease



Brimonidine tartrate, a component of SIMBRINZA, has a less than 5% mean decrease in blood pressure two hours after dosing in clinical studies; caution should be exercised in treating patients with severe cardiovascular disease.


5.7     Severe Hepatic Impairment



Because brimonidine tartrate, a component of SIMBRINZA, has not been studied in patients with hepatic impairment, caution should be exercised in such patients.


5.8     Potentiation Of Vascular Insufficiency



Brimonidine tartrate, a component of SIMBRINZA, may potentiate syndromes associated with vascular insufficiency. SIMBRINZA should be used with caution in patients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangiitis obliterans.


5.9     Contamination Of Topical Ophthalmic Products After Use



There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers have been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient Counseling Information (17)].


6.1     Clinical Trials Experience



Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to the rates in the clinical trials of another drug and may not reflect the rates observed in practice.

SIMBRINZA

In two clinical trials of three months duration 435 patients were treated with SIMBRINZA, and 915 were treated with the two individual components. The most frequently reported adverse reactions in patients treated with SIMBRINZA occurring in approximately 3% to 5% of patients in descending order of incidence were blurred vision, eye irritation, dysgeusia (bad taste), dry mouth, and eye allergy. Rates of adverse reactions reported with the individual components were comparable. Treatment discontinuation, mainly due to adverse reactions, was reported in 11% of SIMBRINZA patients.

Other adverse reactions that have been reported with the individual components during clinical trials are listed below.

Brinzolamide 1%

In clinical trials of brinzolamide ophthalmic suspension 1%, the most frequently reported adverse reactions reported in 5% to 10% of patients were blurred vision and bitter, sour or unusual taste. Adverse reactions occurring in 1% to 5% of patients were blepharitis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular pruritus, and rhinitis.

The following adverse reactions were reported at an incidence below 1%: allergic reactions, alopecia, chest pain, conjunctivitis, diarrhea, diplopia, dizziness, dry mouth, dyspnea, dyspepsia, eye fatigue, hypertonia, keratoconjunctivitis, keratopathy, kidney pain, lid margin crusting or sticky sensation, nausea, pharyngitis, tearing, and urticaria.

Brimonidine Tartrate 0.2%

In clinical trials of brimonidine tartrate 0.2%, adverse reactions occurring in approximately 10% to 30% of the subjects, in descending order of incidence, included oral dryness, ocular hyperemia, burning and stinging, headache, blurring, foreign body sensation, fatigue/drowsiness, conjunctival follicles, ocular allergic reactions, and ocular pruritus.

Reactions occurring in approximately 3% to 9% of the subjects, in descending order included corneal staining/erosion, photophobia, eyelid erythema, ocular ache/pain, ocular dryness, tearing, upper respiratory symptoms, eyelid edema, conjunctival edema, dizziness, blepharitis, ocular irritation, gastrointestinal symptoms, asthenia, conjunctival blanching, abnormal vision, and muscular pain.

The following adverse reactions were reported in less than 3% of the patients: lid crusting, conjunctival hemorrhage, abnormal taste, insomnia, conjunctival discharge, depression, hypertension, anxiety, palpitations/arrhythmias, nasal dryness, and syncope.


6.2     Postmarketing Experience



The following reactions have been identified during postmarketing use of brimonidine tartrate ophthalmic solutions in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to brimonidine tartrate ophthalmic solutions, or a combination of these factors, include: bradycardia, hypersensitivity, iritis, keratoconjunctivitis sicca, miosis, nausea, skin reactions (including erythema, eyelid pruritus, rash, and vasodilation), and tachycardia.

Apnea, bradycardia, coma, hypotension, hypothermia, hypotonia, lethargy, pallor, respiratory depression, and somnolence have been reported in infants receiving brimonidine tartrate ophthalmic solutions [see Contraindications (4.2)].


7.1     Oral Carbonic Anhydrase Inhibitors



There is a potential for an additive effect on the known systemic effects of carbonic anhydrase inhibition in patients receiving an oral carbonic anhydrase inhibitor and brinzolamide ophthalmic suspension 1%, a component of SIMBRINZA ophthalmic suspension. The concomitant administration of SIMBRINZA and oral carbonic anhydrase inhibitors is not recommended.


7.2     High-Dose Salicylate Therapy



Carbonic anhydrase inhibitors may produce acid-base and electrolyte alterations. These alterations were not reported in the clinical trials with brinzolamide ophthalmic suspension 1%. However, in patients treated with oral carbonic anhydrase inhibitors, rare instances of acid-base alterations have occurred with high-dose salicylate therapy. Therefore, the potential for such drug interactions should be considered in patients receiving SIMBRINZA.


7.3     Central Nervous System Depressants



Although specific drug interaction studies have not been conducted with SIMBRINZA, the possibility of an additive or potentiating effect with central nervous system (CNS) depressants (alcohol, opiates, barbiturates, sedatives, or anesthetics) should be considered.


7.4     Antihypertensives/Cardiac Glycosides



Because brimonidine tartrate, a component of SIMBRINZA, may reduce blood pressure, caution in using drugs such as antihypertensives and/or cardiac glycosides with SIMBRINZA is advised.


7.5     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 SIMBRINZA 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.


7.6     Monoamine Oxidase Inhibitors



Monoamine oxidase inhibitors (MAOIs) may theoretically interfere with the metabolism of brimonidine tartrate and potentially result in an increased systemic side-effect such as hypotension. Caution is advised in patients taking MAOIs, which can affect the metabolism and uptake of circulating amines.


8.1     Pregnancy



Pregnancy Category C: Developmental toxicity studies with brinzolamide in rabbits at oral doses of 1, 3, and 6 mg/kg/day (20, 60, and 120 times the recommended human ophthalmic dose) produced maternal toxicity at 6 mg/kg/day and a significant increase in the number of fetal variations, such as accessory skull bones, which was only slightly higher than the historic value at 1 and 6 mg/kg. In rats, statistically decreased body weights of fetuses from dams receiving oral doses of 18 mg/kg/day (180 times the recommended human ophthalmic dose) during gestation were proportional to the reduced maternal weight gain, with no statistically significant effects on organ or tissue development. Increases in unossified sternebrae, reduced ossification of the skull, and unossified hyoid that occurred at 6 and 18 mg/kg were not statistically significant. No treatment-related malformations were seen. Following oral administration of 14C-brinzolamide to pregnant rats, radioactivity was found to cross the placenta and was present in the fetal tissues and blood.

Developmental toxicity studies performed in rats with oral doses of 0.66 mg brimonidine base/kg revealed no evidence of harm to the fetus. Dosing at this level resulted in a plasma drug concentration approximately 100 times higher than that seen in humans at the recommended human ophthalmic dose. In animal studies, brimonidine crossed the placenta and entered into the fetal circulation to a limited extent.

There are no adequate and well-controlled studies in pregnant women. SIMBRINZA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.


8.3     Nursing Mothers



In a study of brinzolamide in lactating rats, decreases in body weight gain in offspring at an oral dose of 15 mg/kg/day (150 times the recommended human ophthalmic dose) were observed during lactation. No other effects were observed. However, following oral administration of 14C-brinzolamide to lactating rats, radioactivity was found in milk at concentrations below those in the blood and plasma. In animal studies, brimonidine was excreted in breast milk.

It is not known whether brinzolamide and brimonidine tartrate are excreted in human milk following topical ocular administration. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from SIMBRINZA, 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.


8.4     Pediatric Use



The individual component, brinzolamide, has been studied in pediatric glaucoma patients 4 weeks to 5 years of age. The individual component, brimonidine tartrate, has been studied in pediatric patients two to seven years old. Somnolence (50% to 83%) and decreased alertness was seen in patients two to six years old. SIMBRINZA is contraindicated in children under the age of two years [see Contraindications (4.2)].


8.5     Geriatric Use



No overall differences in safety or effectiveness have been observed between elderly and adult patients.


10     Overdosage



Although no human data are available, electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur following an oral overdose of brinzolamide. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.

Very limited information exists on accidental ingestion of brimonidine in adults; the only adverse event reported to date has been hypotension. Symptoms of brimonidine overdose have been reported in neonates, infants, and children receiving brimonidine as part of medical treatment of congenital glaucoma or by accidental oral ingestion. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.


11     Description



SIMBRINZA is a fixed combination of a carbonic anhydrase inhibitor and an alpha-2 adrenergic receptor agonist.

Brinzolamide is described chemically as: (R)-(+)-4-Ethylamino-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno [3,2-e]-1,2-thiazine-6-sulfonamide-1,1- dioxide. Its empirical formula is C12H21N3O5S3, and its structural formula is:

Brinzolamide has a molecular weight of 383.5 g/mol. It is a white powder, which is insoluble in water, very soluble in methanol and soluble in ethanol.

Brimonidine tartrate is described chemically as: 5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate. Its empirical formula of C11H10BrN5 – C4H6O6 and its structural formula is:

Brimonidine tartrate has a molecular weight of 442.2 g/mol. It is a white to yellow powder that is soluble in water (34 mg/mL) at pH 6.5.

SIMBRINZA is supplied as a sterile, aqueous suspension which has been formulated to be readily suspended following shaking. It has a pH of approximately 6.5 and an osmolality of approximately 270 mOsm/kg.

Each mL of SIMBRINZA contains: Active ingredients: brinzolamide 10 mg, brimonidine tartrate 2 mg (equivalent to 1.32 mg as brimonidine free base); Preservative: benzalkonium chloride 0.03 mg; Inactive ingredients: boric acid, carbomer 974P, mannitol, propylene glycol, purified water, sodium chloride, and tyloxapol. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH.


12.1     Mechanism Of Action



SIMBRINZA is comprised of two components: brinzolamide (carbonic anhydrase inhibitor) and brimonidine tartrate (alpha-2 adrenergic receptor agonist). Each of these two components decreases elevated IOP. Elevated IOP is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. The higher the level of IOP, 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 two to three 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 IOP.


12.3     Pharmacokinetics



Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its affinity for CA-II, brinzolamide distributes extensively into the red blood cells (RBCs) and exhibits a long half-life in whole blood (approximately 111 days). In humans, the metabolite N-desethyl brinzolamide is formed, which also binds to CA and accumulates in RBCs. This metabolite binds mainly to CA-I in the presence of brinzolamide. In plasma, both parent brinzolamide and N-desethyl brinzolamide concentrations are less than 10 ng/mL. Binding to plasma proteins is approximately 60%. Brinzolamide is eliminated predominantly 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.

After ocular administration of a 0.2% solution of brimonidine tartrate, plasma concentrations peaked within one to four hours and declined with a systemic half-life of approximately three hours. In humans, systemic metabolism of brimonidine is extensive. It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites. Approximately 87% of an orally-administered radioactive dose was eliminated within 120 hours, with 74% found in the urine.

In humans, a study was conducted to evaluate the pharmacokinetics of the fixed combination of brinzolamide and brimonidine tartrate 1% and 0.2% ophthalmic suspension. Healthy volunteers were randomly assigned to receive twice or three times a day either the fixed combination, or either of its individual components, brinzolamide or brimonidine. Subjects who were assigned to the brinzolamide alone or combination arms were administered oral brinzolamide capsules for two weeks prior to beginning dosing with the topical ocular suspension. The results demonstrate that the systemic plasma exposure (area under the curve [AUC)] and Cmax) to brinzolamide and brimonidine in humans is similar after dosing with the fixed combination to that observed following dosing with the individual components.


13.1     Carcinogenesis, Mutagenesis, Impairment Of Fertility



Brinzolamide caused urinary bladder tumors in female mice at oral doses of 10 mg/kg/day and in male rats at oral doses of 8 mg/kg/day in two year studies. Brinzolamide was not carcinogenic in male mice or female rats dosed orally for up to two years. The carcinogenicity appears secondary to kidney and urinary bladder toxicity. These levels of exposure cannot be achieved with topical ophthalmic dosing in humans.

The following tests for mutagenic potential of brinzolamide were negative: (1) in vivo mouse micronucleus assay; (2) in vivo sister chromatid exchange assay; and (3) Ames E. coli test. The in vitro mouse lymphoma forward mutation assay was negative in the absence of activation, but positive in the presence of microsomal activation. In this assay, there was no consistent dose-response relationship to the increased mutation frequency and cytotoxicity likely contributed to the high mutation frequency. Carbonic anhydrase inhibitors, as a class, are not mutagenic and the weight of evidence supports that brinzolamide is consistent with the class. In reproduction studies of brinzolamide in rats, there were no adverse effects on the fertility or reproductive capacity of males or females at doses up to 18 mg/kg/day (180 times the recommended human ophthalmic dose).

Brimonidine tartrate was not carcinogenic in either a 21-month mouse or 24-month rat study. In these studies, dietary administration of brimonidine tartrate at doses up to 2.5 mg/kg/day in mice and 1 mg/kg/day in rats resulted in plasma drug concentrations 80 and 120 times higher than the human plasma drug level at the recommended clinical dose, respectively. Brimonidine tartrate was not mutagenic or cytogenic in a series of in vitro and in vivo studies including the Ames test, chromosomal aberration assay in Chinese Hamster Ovary (CHO) cells, a host-mediated assay and cytogenic studies in mice, and a dominant lethal assay. In reproductive studies performed in rats with oral doses of 0.66 mg brimonidine base/kg (approximately 100 times the plasma drug concentration level seen in humans following multiple ophthalmic doses), fertility was not impaired.


14     Clinical Studies



Two clinical trials of three months duration were conducted in patients with open-angle glaucoma or ocular hypertension to compare the IOP-lowering effect of SIMBRINZA dosed three times daily to individually administered 1% brinzolamide three times daily and 0.2% brimonidine tartrate three times daily. Mean IOP values at baseline are presented in Table 1.

Table 1. Mean (SD) Intraocular Pressure Values at Baseline
Abbreviation: SD, standard deviation.
SIMBRINZABrinzolamideBrimonidine
Study 1(n = 209)(n = 224)(n = 216)
8 AM26.9 (2.63)27.1 (2.64)27.0 (2.56)
10 AM25.3 (2.76)25.4 (2.74)25.4 (2.78)
3 PM23.7 (2.98)23.8 (3.24)24.0 (3.27)
5 PM23.2 (3.08)23.6 (3.39)23.7 (3.30)
Study 2(n = 218)(n = 229)(n = 232)
8 AM27.2 (2.75)27.2 (2.72)27.3 (2.73)
10 AM25.8 (3.09)26.0 (3.20)25.8 (3.02)
3 PM24.4 (3.67)24.4 (3.58)24.0 (3.39)
5 PM24.1 (3.71)24.2 (3.86)23.7 (3.58)

The IOP-lowering effect of SIMBRINZA ophthalmic suspension was 1 to 3 mmHg greater than monotherapy with either 1% brinzolamide or 0.2% brimonidine tartrate throughout the duration of the trials. Least Square Mean IOP (mmHg) and the results at Week 2, Week 6, and Month 3 for each study are provided in Table 2.

Table 2. Mean IOP (mmHg) by Treatment Group and Treatment Difference in Mean IOPa
Abbreviations: CI, confidence interval (95% CI); IOP, intraocular pressure.
aBased on the Intent-to-Treat Population defined as all patients who received study drug and completed at least 1 on-therapy study visit.
bThe estimates are based on least square means derived from a linear mixed model that accounts for correlated IOP measurements within patient; Treatment difference is SIMBRINZA minus individual component.
SIMBRINZABrinzolamideBrimonidine
Study 1(N = 209)(N = 224)(N = 216)
MeanMeanDifference (95% CI)bMeanDifference (95% CI)b
Week 2
8 AM20.422.0-1.6 (-2.3, -0.9)22.4-2.0 (-2.7, -1.3)
10 AM17.120.5-3.4 (-4.1, -2.7)19.4-2.3 (-3.0, -1.6)
3 PM18.420.4-1.9 (-2.6, -1.3)20.6-2.2 (-2.9, -1.5)
5 PM16.619.7-3.2 (-3.9, -2.5)18.4-1.9 (-2.6, -1.2)
Week 6
8 AM20.421.9-1.5 (-2.2, -0.8)22.6-2.3 (-3.0, -1.6)
10 AM17.520.2-2.7 (-3.4, -2.0)19.5-2.0 (-2.7, -1.3)
3 PM18.920.2-1.2 (-1.9, -0.5)21.1-2.1 (-2.8, -1.4)
5 PM17.019.7-2.6 (-3.3, -1.9)18.6-1.5 (-2.2, -0.8)
Month 3
8 AM20.521.6-1.1 (-1.8, -0.4)23.3-2.8 (-3.5, -2.1)
10 AM17.220.4-3.2 (-3.9, -2.5)19.7-2.5 (-3.2, -1.8)
3 PM18.720.4-1.8 (-2.5, -1.1)21.3-2.6 (-3.3, -1.9)
5 PM17.020.0-3.0 (-3.7, -2.3)18.8-1.8 (-2.5, -1.1)
Study 2(N = 218)(N = 229)(N = 232)
Week 2
8 AM20.522.2-1.7 (-2.4, -1.0)22.8-2.4 (-3.1, -1.7)
10 AM17.420.7-3.3 (-4.0, -2.6)19.2-1.8 (-2.5, -1.2)
3 PM18.720.5-1.7 (-2.4, -1.1)21.1-2.3 (-3.0, -1.6)
5 PM16.520.1-3.6 (-4.3, -2.9)18.3-1.8 (-2.4, -1.1)
Week 6
8 AM20.721.9-1.2 (-1.9, -0.5)23.2-2.5 (-3.2, -1.8)
10 AM17.420.5-3.1 (-3.8, -2.4)19.7-2.3 (-3.0, -1.6)
3 PM19.320.2-0.8 (-1.5, -0.2)21.2-1.9 (-2.6, -1.2)
5 PM16.919.9-3.0 (-3.7, -2.3)18.5-1.7 (-2.4, -1.0)
Month 3
8 AM21.122.0-1.0 (-1.7, -0.3)23.2-2.2 (-2.9, -1.5)
10 AM18.020.8-2.8 (-3.5, -2.1)19.9-1.9 (-2.6, -1.2)
3 PM19.520.7-1.2 (-1.9, -0.5)21.5-2.0 (-2.7, -1.3)
5 PM17.220.4-3.2 (-3.9, -2.5)18.9-1.7 (-2.4, -1.0)

Figures 1 and 2 present the mean of individual subject IOP changes from baseline at Week 2, Week 6, and at Month 3 based on the observed data for the intent-to-treat population.

Figure 1.  Mean IOP Change from Baseline (Study 1)

Figure 2.  Mean IOP Change from Baseline (Study 2)


16     How Supplied/Storage And Handling



SIMBRINZA is supplied in white low density polyethylene (LDPE) DROP-TAINER® bottles with a natural LDPE dispensing-tip and light green polypropylene cap as follows:

8 mL in a 10 mL bottle NDC 0078-0904-38

Storage and Handling

Store SIMBRINZA at 2°C to 25°C (36 to 77°F).


17     Patient Counseling Information



Sulfonamide Reactions

Advise patients that if serious or unusual ocular or systemic reactions or signs of hypersensitivity occur, they should discontinue the use of the product and consult their physician [see Warnings and Precautions (5.1)].

Temporary Blurred Vision

Vision may be temporarily blurred following dosing with SIMBRINZA. Care should be exercised in operating machinery or driving a motor vehicle.

Effect on Ability to Drive and Use Machinery

As with other drugs in this class, SIMBRINZA may cause fatigue and/or drowsiness in some patients. Caution patients who engage in hazardous activities of the potential for a decrease in mental alertness.

Avoiding Contamination of the Product

Instruct patients that ocular solutions, if handled improperly or if the tip of the dispensing container contacts the eye or surrounding structures, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions (5.9)]. Always replace the cap after using. If solution changes color or becomes cloudy, do not use. Do not use the product after the expiration date marked on the bottle.

Intercurrent Ocular Conditions

Advise patients that if they have ocular surgery or develop an intercurrent ocular condition (e.g., trauma or infection), they should immediately seek their physician's advice concerning the continued use of the present multidose container.

Concomitant Topical Ocular Therapy

If more than one topical ophthalmic drug is being used, the drugs should be administered at least five minutes apart [see Dosage and Administration].

Contact Lens Wear

The preservative in SIMBRINZA, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of SIMBRINZA, but may be reinserted 15 minutes after instillation.


DROP-TAINER is a trademark of Alcon.

©Novartis

Distributed by:
Novartis Pharmaceuticals Corporation
East Hanover, NJ 07936

T2019-124


Principal Display Panel



NDC 0078-0904-38

SIMBRINZA®

(brinzolamide 1% and brimonidine tartrate 0.2% ophthalmic suspension

8 mL

Sterile

Rx Only

FOR TOPICAL OPHTHALMIC USE ONLY

NOVARTIS


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