NDC 68682-464 Brinzolamide


NDC Product Code 68682-464

NDC CODE: 68682-464

Proprietary Name: Brinzolamide 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.

Non-Proprietary Name: Brinzolamide 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.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • Brinzolamide is used to treat high pressure inside the eye due to glaucoma (open angle-type) or other eye diseases (e.g., ocular hypertension). Lowering high pressure inside the eye helps to prevent blindness. This medication works by decreasing the amount of fluid within the eye. It belongs to a class of drugs known as carbonic anhydrase inhibitors.

NDC Code Structure

NDC 68682-464-10

Package Description: 1 BOTTLE, PLASTIC in 1 CARTON > 10 mL in 1 BOTTLE, PLASTIC

NDC 68682-464-15

Package Description: 1 BOTTLE, PLASTIC in 1 CARTON > 15 mL in 1 BOTTLE, PLASTIC

NDC Product Information

Brinzolamide with NDC 68682-464 is a a human prescription drug product labeled by Oceanside Pharmaceuticals.. The generic name of Brinzolamide is brinzolamide. The product's dosage form is suspension/ drops and is administered via ophthalmic form.

Dosage Form: Suspension/ Drops - A suspension which is usually administered in a dropwise fashion.

Product Type: Human Prescription Drug 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.

Brinzolamide Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

Inactive Ingredient(s)

About the Inactive Ingredient(s)
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.

  • WATER (UNII: 059QF0KO0R)

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.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Carbonic Anhydrase Inhibitor - [EPC] (Established Pharmacologic Class)
  • Carbonic Anhydrase Inhibitors - [MoA] (Mechanism of Action)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Oceanside Pharmaceuticals.
Labeler Code: 68682
FDA Application Number: ANDA204884 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.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. 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.

Start Marketing Date: 08-25-2021 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2022 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO 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".

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Brinzolamide Product Label Images

Brinzolamide Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Brinzolamide ophthalmic suspension is a carbonic anhydrase inhibitor indicated in the treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma.

2 Dosage And Administration

The recommended dose is one drop of brinzolamide ophthalmic suspension in the affected eye(s) 3 times daily. Brinzolamide 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 10 minutes apart.

3 Dosage Forms And Strengths

Ophthalmic suspension containing brinzolamide 10 mg/mL (1%).

4 Contraindications

Brinzolamide ophthalmic suspension is contraindicated in patients who are hypersensitive to any component of this product.

5.1 Sulfonamide Hypersensitivity Reactions

Brinzolamide ophthalmic suspension is a sulfonamide and although administered topically, it is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of brinzolamide ophthalmic suspension. Fatalities have occurred, although rarely, 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 readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.

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 brinzolamide ophthalmic suspension to this group of patients.

5.3 Severe Renal Impairment

Brinzolamide ophthalmic suspension has not been studied in patients with severe renal impairment [creatinine clearance (CrCl) less than 30 mL/min]. Because brinzolamide ophthalmic suspension and its metabolite are excreted predominantly by the kidney, brinzolamide ophthalmic suspension 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. Brinzolamide ophthalmic suspension has not been studied in patients with acute angle-closure glaucoma.

5.5 Risk Of Contamination

Avoid allowing the tip of the dispensing container to contact the eye or surrounding structures or other surfaces, since the product can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from contaminated solutions.

5.6 Contact Lens Wear

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

6.1 Clinical Trials Experience

Because clinical trials 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.In clinical studies of brinzolamide ophthalmic suspension, 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.

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. The concomitant administration of brinzolamide ophthalmic suspension 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. 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 brinzolamide ophthalmic suspension.

8.1 Pregnancy

Risk SummaryThere are no adequate and well-controlled studies in pregnant women to inform drug-associated risk.In reproductive toxicity studies, brinzolamide administered orally to rats induced fetal toxicity at 375-times the recommended human ophthalmic dose (RHOD) based on mg/kg. In rabbits, no fetal toxicity was observed following oral administration (see Data).The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4%, and of miscarriage is 15% to 20%, of clinically recognized pregnancies.DataAnimal DataEmbryo-fetal studies were conducted in pregnant rats administered 0, 2, 6, or 18 mg/kg/day brinzolamide by oral gavage on gestation days 6 to 17, to target the period of organogenesis. Decreased fetal body weight with reduced skeletal ossification were observed at 18 mg/kg/day (375 times the RHOD based on mg/kg). The no-observed-adverse-effect-level (NOAEL) for fetal toxicity was 6 mg/kg/day (125 times the RHOD). Decreased maternal weight gain was observed at 18 mg/kg/day. The NOAEL for maternal toxicity was 6 mg/kg/day (125 times the RHOD). Embryo-fetal studies were conducted in pregnant rabbits administered 0, 1, 3, or 6 mg/kg/day of brinzolamide by oral gavage on gestation days 6 to 18, to target the period of organogenesis. No treatment-related fetal effects were observed at any dose. The NOAEL for fetal toxicity was 6 mg/kg/day (125 times the RHOD based on mg/kg). Maternal weight loss during pregnancy was observed at 3 mg/kg/day (63 times the RHOD) and above. The NOAEL for maternal toxicity was 1 mg/kg/day (21 times the RHOD).A peri-/postnatal study was conducted in rats administered brinzolamide by oral gavage from gestation day 16 through lactation day 20. Decreased pup body weight was observed at 15 mg/kg/day (313 times the RHOD based on mg/kg). The NOAEL for developmental toxicity was 5 mg/kg/day (104 times the RHOD). 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.

8.2 Lactation

Risk SummaryThere are no data on the presence of brinzolamide in human milk, the effects on the breastfed infant, or the effects on milk production. Brinzolamide has been detected in the milk of lactating rats.The development and health benefits of breastfeeding should be considered along with the mother’s clinical need for brinzolamide ophthalmic suspension and any potential adverse effects on the breast-fed child from brinzolamide ophthalmic suspension.

8.4 Pediatric Use

A 3-month controlled clinical study was conducted in which brinzolamide ophthalmic suspension was dosed only twice a day in pediatric patients 4 weeks to 5 years of age. Patients were not required to discontinue their IOP-lowering medication(s) until initiation of monotherapy with brinzolamide ophthalmic suspension. IOP-lowering efficacy was not demonstrated in this study in which the mean decrease in elevated IOP was between 0 mmHg and 2 mmHg. Five out of 32 patients demonstrated an increase in corneal diameter of one millimeter.

8.5 Geriatric Use

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

10 Overdosage

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

11 Description

Brinzolamide ophthalmic suspension USP, 1% contains a carbonic anhydrase inhibitor formulated for multidose topical ophthalmic use. 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 and a melting point of about 131°C. It is a white powder, which is insoluble in water, very soluble in methanol and soluble in ethanol. Brinzolamide ophthalmic suspension USP, 1% is supplied as a sterile, aqueous suspension of brinzolamide which has been formulated to be readily suspended and slow settling, following shaking. It has a pH of approximately 7.5 and an osmolality of 300 mOsm/kg.Each mL of brinzolamide ophthalmic suspension USP, 1% contains: Active ingredient: brinzolamide 10 mg. Preservative: Benzalkonium chloride 0.1 mg. Inactives: carbomer 974P, edetate disodium, mannitol, sodium chloride, tyloxapol, water for injection, with hydrochloric acid and/or sodium hydroxide to adjust pH.

12.1 Mechanism Of Action

Carbonic anhydrase is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II, found primarily in red blood cells (RBCs), but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in IOP.Brinzolamide ophthalmic suspension contains brinzolamide, an inhibitor of carbonic anhydrase II. Following topical ocular administration, brinzolamide inhibits aqueous humor formation and reduces elevated IOP. Elevated IOP is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.

12.3 Pharmacokinetics

Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its affinity for carbonic anhydrase II, brinzolamide distributes extensively into the 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 carbonic anhydrase and accumulates in RBCs. This metabolite binds mainly to carbonic anhydrase I in the presence of brinzolamide. In plasma, both parent brinzolamide and N-desethyl brinzolamide concentrations are low and generally below assay quantitation limits (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.An oral pharmacokinetic study was conducted in which healthy volunteers received 1 mg capsules of brinzolamide twice per day for up to 32 weeks. This regimen approximates the amount of drug delivered by topical ocular administration of brinzolamide ophthalmic suspension dosed to both eyes 3 times per day and simulates systemic drug and metabolite concentrations similar to those achieved with long-term topical dosing. Red blood cell carbonic anhydrase activity was measured to assess the degree of systemic carbonic anhydrase inhibition. Brinzolamide saturation of RBC carbonic anhydrase II was achieved within 4 weeks (RBC concentrations of approximately 20 mcM). N-Desethyl brinzolamide accumulated in RBCs to steady-state within 20 to 28 weeks reaching concentrations ranging from 6 to 30 mcM. The inhibition of carbonic anhydrase II activity at steady state was approximately 70% to 75%, which is below the degree of inhibition expected to have a pharmacological effect on renal function or respiration in healthy subjects.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

CarcinogenesisBrinzolamide 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 2 year studies. Brinzolamide was not carcinogenic in male mice or female rats dosed orally for up to 2 years. The carcinogenicity appears secondary to kidney and urinary bladder toxicity. These levels of exposure cannot be achieved with topical ophthalmic dosing in humans. MutagenesisThe following tests for mutagenic potential 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. Impairment of FertilityIn 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 (375 times the RHOD based on mg/kg).

14 Clinical Studies

In two, 3-month clinical studies, brinzolamide ophthalmic suspension dosed 3 times per day in patients with elevated IOP, produced significant reductions in IOPs (4 mmHg to 5 mmHg). These IOP reductions are equivalent to the reductions observed with dorzolamide hydrochloride ophthalmic solution, 2% dosed 3 times per day in the same studies.In 2 clinical studies in patients with elevated IOP, brinzolamide ophthalmic suspension was associated with less stinging and burning upon instillation than dorzolamide hydrochloride ophthalmic solution, 2%.

16 How Supplied/Storage And Handling

Brinzolamide ophthalmic suspension USP, 1% is supplied in natural, round boston, LDPE bottles with an extended controlled drop tip LLDPE tip as follows:10 mL NDC 68682-464-1015 mL NDC 68682-464-15Storage and HandlingStore brinzolamide ophthalmic suspension USP, 1% at 4° to 30°C (39° to 86°F). Shake well before use. After opening, brinzolamide ophthalmic suspension USP, 1% can be used until the expiration date on the bottle.

17 Patient Counseling Information

Sulfonamide Hypersensitivity ReactionsAdvise 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 VisionVision may be temporarily blurred following dosing with brinzolamide ophthalmic suspension. Advise patients to exercise care in operating machinery or driving a motor vehicle.Avoiding Contamination of the ProductInstruct patients to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures or other surfaces, since the product 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.Intercurrent Ocular ConditionsAdvise 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 multi-dose container.Concomitant Topical Ocular TherapyIf more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.Contact Lens WearThe preservative in brinzolamide ophthalmic suspension, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of brinzolamide ophthalmic suspension, but may be reinserted 15 minutes after instillation.Distributed by:Oceanside Pharmaceuticals, a division of Bausch Health US, LLC Bridgewater, NJ 08807 USA© 2021 Bausch Health Companies Inc. or its affiliates9671502 (Folded)9671602 (Flat)

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