Azopt Information
Azopt (Brinzolamide) Indications And Usage
Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% is a carbonic anhydrase inhibitor indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
Azopt (Brinzolamide) Dosage And Administration
The recommended dose is 1 drop of Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% in the affected eye(s) three times daily. If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten (10) minutes apart.
Azopt (Brinzolamide) Dosage Forms And Strengths
Solution containing 10 mg/mL brinzolamide.
Azopt (Brinzolamide) Contraindications
Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% is contraindicated in patients who are hypersensitive to any component of this product.
Azopt (Brinzolamide) Drug Interactions
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 Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1%.
Azopt (Brinzolamide) Use In Specific Populations
Pregnancy Category CDevelopmental toxicity studies with brinzolamide in rabbits at oral doses of 1, 3, and 6 mg/kg/day (20, 62, and 125 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 (375 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 C-brinzolamide to pregnant rats, radioactivity was found to cross the placenta and was present in the fetal tissues and blood.
There are no adequate and well-controlled studies in pregnant women. Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
In a study of brinzolamide in lactating rats, decreases in body weight gain in offspring at an oral dose of 15 mg/kg/day (312 times the recommended human ophthalmic dose) were seen during lactation. No other effects were observed. However, following oral administration of C-brinzolamide to lactating rats, radioactivity was found in milk at concentrations below those in the blood and plasma.
It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1%, 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.
Azopt (Brinzolamide) 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.
Azopt (Brinzolamide) Description
Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 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 CHNOS, and its structural formula is:
Brinzolamide has a molecular weight of 383.5 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.
Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 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 Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% contains: brinzolamide 10 mg/mL. benzalkonium chloride 0.1 mg/mL. mannitol, carbomer 974P, tyloxapol, edetate disodium, sodium chloride, purified water, and hydrochloric acid and/or sodium hydroxide to adjust pH.
Azopt (Brinzolamide) Clinical Pharmacology
Carbonic anhydrase (CA) 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 (CA-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 intraocular pressure (IOP).
Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% contains brinzolamide, an inhibitor of carbonic anhydrase II (CA-II). Following topical ocular administration, brinzolamide inhibits aqueous humor formation and reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.
Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. Due to its affinity for CA-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 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 low and generally below assay quantitation limits (
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 Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% dosed to both eyes three times per day and simulates systemic drug and metabolite concentrations similar to those achieved with long-term topical dosing. RBC CA activity was measured to assess the degree of systemic CA inhibition. Brinzolamide saturation of RBC CA-II was achieved within 4 weeks (RBC concentrations of approximately 20 μM). N-Desethyl brinzolamide accumulated in RBCs to steady-state within 20-28 weeks reaching concentrations ranging from 6-30 μM. The inhibition of CA-II activity at steady-state was approximately 70-75%, which is below the degree of inhibition expected to have a pharmacological effect on renal function or respiration in healthy subjects.
Azopt (Brinzolamide) Clinical Studies
In two, three-month clinical studies, Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% dosed three times per day (TID) in patients with elevated intraocular pressure (IOP), produced significant reductions in IOPs (4 -5 mmHg). These IOP reductions are equivalent to the reductions observed with TRUSOPT* (dorzolamide hydrochloride ophthalmic solution) 2% dosed TID in the same studies.
In two clinical studies in patients with elevated intraocular pressure, Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% was associated with less stinging and burning upon instillation than TRUSOPT* 2%.
Azopt (Brinzolamide) How Supplied/storage And Handling
Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% is supplied in plastic DROP-TAINER® dispensers with a controlled dispensing-tip as follows:
5 mL NDC 0065-0275-05
10 mL NDC 0065-0275-10
15 mL NDC 0065-0275-15
Store Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1% at 4-30°C (39-86°F). Shake well before use.
Azopt (Brinzolamide) Patient Counseling Information
The preservative in Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1%, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of Azopt (Brinzolamide) ® (brinzolamide ophthalmic suspension) 1%, but may be reinserted 15 minutes after instillation.
©2000- 2009 Alcon, Inc.
Rx Only
U.S. Patent Nos: 5,240,923; 5,378,703; 5,461,081; 6,071,904.
*TRUSOPT is a registered trademark of Merck & Co., Inc.
ALCON LABORATORIES, INC.
Fort Worth, Texas 76134 USA
Azopt (Brinzolamide) Principle Display Panel
NDA 0065-0275-05
Alcon®
Azopt (Brinzolamide) ®
(brinzolamide ophthalmic suspension) 1%
5 mL Sterile
