AZOPT® (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 C₁₂H₂₁N₃O₅S₃, 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 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 ophthalmic suspension) 1% contains 10 mg brinzolamide. Inactive ingredients are mannitol, carbomer 974P, tyloxapol, edetate disodium, sodium chloride, hydrochloric acid and/or sodium hydroxide (to adjust pH), and purified water. Benzalkonium chloride 0.01 % is added as a preservative.

Last updated on RxList: 5/13/2008

AZOPT® (brinzolamide ophthalmic suspension) 1% is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Shake well before use. The recommended dose is 1 drop of AZOPT® (brinzolamide ophthalmic suspension) 1% in the affected eye(s) three times daily.

AZOPT® (brinzolamide ophthalmic suspension) 1% may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.

AZOPT® (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

Storage: Store AZOPT® (brinzolamide ophthalmic suspension) 1% at 4-30°C (39-86°F).

ALCON LABORATORIES, INC. Fort Worth, Texas 76134 USA. FDA Rev date: 9/28/2006 

Last updated on RxList: 5/13/2008

In clinical studies of AZOPT® (brinzolamide ophthalmic suspension) 1%, the most frequently reported adverse events associated with AZOPT® (brinzolamide ophthalmic suspension) 1% were blurred vision and bitter, sour or unusual taste. These events occurred in approximately 5-10% of patients. Blepharitis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular pruritus and rhinitis were reported at an incidence of 1-5%.

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.

AZOPT® (brinzolamide ophthalmic suspension) 1% contains a carbonic anhydrase inhibitor. Acid-base and electrolyte alterations were not reported in the clinical trials with brinzolamide. However, in patients treated with oral carbonic anhydrase inhibitors, rare instances of drug interactions have occurred with high-dose salicylate therapy. Therefore, the potential for such drug interactions should be considered in patients receiving AZOPT® (brinzolamide ophthalmic suspension) 1%.

Last updated on RxList: 5/13/2008

AZOPT® (brinzolamide ophthalmic suspension) 1% 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 AZOPT® (brinzolamide ophthalmic suspension) 1%. 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 re-administered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.

General

Carbonic anhydrase activity has been observed in both the cytoplasm and around the plasma membranes of the corneal endothelium. The effect of continued administration of AZOPT® (brinzolamide ophthalmic suspension) 1% on the corneal endothelium has not been fully evaluated.

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. AZOPT® (brinzolamide ophthalmic suspension) 1% has not been studied in patients with acute angle-closure glaucoma. AZOPT® (brinzolamide ophthalmic suspension) 1% has not been studied in patients with severe renal impairment (CrCl < 3O mL/min). Because AZOPT® (brinzolamide ophthalmic suspension) 1% and its metabolite are excreted predominantly by the kidney, AZOPT® (brinzolamide ophthalmic suspension) 1% is not recommended in such patients. AZOPT® (brinzolamide ophthalmic suspension) 1% has not been studied in patients with hepatic impairment and should be used with caution in such patients. 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 AZOPT® (brinzolamide ophthalmicsuspension) 1%. The concomitant administration of AZOPT® (brinzolamide ophthalmic suspension) 1% and oral carbonic anhydrase inhibitors is not recommended.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity data on brinzolamide are not available. The 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. 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 (375 times the recommended human ophthalmic dose).

Pregnancy

Teratogenic Effects: Pregnancy Category C. Developmental 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 ¹⁴C-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 ophthalmic suspension) 1% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

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 (312 times the recommended human ophthalmic dose) were seen 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.

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 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.

Pediatric Use

A three-month controlled clinical study was conducted in which AZOPT® (brinzolamide ophthalmic suspension) 1% 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 AZOPT®. IOP-lowering efficacy was not demonstrated in this study in which the mean decrease in elevated IOP was between 0 and 2 mmHg. Five out of 32 patients demonstrated an increase in corneal diameter of one millimeter.

Geriatric Use

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

Last updated on RxList: 5/13/2008

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 ophthalmic suspension) 1% is contraindicated in patients who are hypersensitive to any component of this product.

Last updated on RxList: 5/13/2008

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 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 ( < 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 AZOPT® (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. In two, three-month clinical studies, AZOPT® (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 ophthalmic suspension) 1% was associated with less stinging and burning upon instillation than TRUSOPT* 2%.

Last updated on RxList: 1/29/2005

AZOPT® (brinzolamide ophthalmic suspension) 1% is a sulfonamide and although administered topically, it is absorbed

systemically; therefore, the same types of adverse reactions attributable to sulfonamides may occur with topical administration.

Patients should be advised 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).

Vision may be temporarily blurred following dosing with AZOPT® (brinzolamide ophthalmic suspension) 1%. Care should be exercised in operating machinery or driving a motor vehicle.

Patients should be instructed 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.

Patients should also be advised 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.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart. The preservative in AZOPT® (brinzolamide ophthalmic suspension) 1%, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of AZOPT® (brinzolamide ophthalmic suspension) 1%, but may be reinserted 15 minutes after instillation.

Last updated on RxList: 5/13/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

BRINZOLAMIDE SUSPENSION - OPHTHALMIC

(brin-ZOHL-uh-mide)

COMMON BRAND NAME(S): Azopt

USES: 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.

HOW TO USE: Apply this medication in the affected eye(s), usually one drop 3 times a day or as directed by your doctor. Shake the bottle well before using.

To apply eye drops, wash your hands first. To avoid contamination, do not touch the dropper tip or let it touch your eye or any other surface.

The preservative in this product may be absorbed by contact lenses. If you wear contact lenses, remove them before using your eye drops. Wait at least 15 minutes after each dose before putting your lenses back in.

Tilt your head back, look upward, and pull down the lower eyelid to make a pouch. Hold the dropper directly over your eye and place one drop into the pouch. Look downward and gently close your eyes for 1 to 2 minutes. Place one finger at the corner of your eye (near the nose) and apply gentle pressure. This will prevent the medication from draining out. Try not to blink and do not rub your eye. Repeat these steps for your other eye if so directed.

Do not rinse the dropper. Replace the dropper cap after each use.

If you are using another kind of eye medication (e.g., drops or ointments), wait at least 10 minutes before applying other medications. Use eye drops before eye ointments to allow the eye drops to enter the eye.

Use this medication regularly in order to get the most benefit from it. Remember to use it at the same times each day. It is important to continue using brinzolamide even if you feel well. Most people with glaucoma or high pressure in the eye do not feel sick.

SIDE EFFECTS: Temporary blurred vision, bitter/sour/unusual taste in your mouth, dry eyes, temporary discomfort/itching/redness of the eye, feeling as if something is in your eye, eye discharge, and headache may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Seek immediate medical attention if you have any of these rare but very serious side effects: eye or eyelid swelling/pain, stomach/side/back pain, persistent nausea or vomiting, yellowing eyes/skin, dark urine, easy bruising or bleeding, unusual tiredness, signs of infection (e.g., fever, chills, persistent sore throat), chest pain.

A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using brinzolamide, tell your doctor or pharmacist if you are allergic to it; or to sulfa drugs or the preservative benzalkonium chloride; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: other eye conditions, kidney problems, liver disease.

If you develop an eye infection or injury, or have eye surgery, check with your doctor about whether you should continue to use your current bottle of brinzolamide. You may be advised to start using a new bottle.

Use caution while engaging in activities requiring clear vision such as driving or using machinery because your vision may be temporarily blurred or unstable after applying this drug.

This medication should be used only when clearly needed during pregnancy. Discuss the risks and benefits with your doctor.

It is not known whether this drug passes into breast milk. Because of the potential risk to the infant, breast-feeding while using this drug is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your healthcare professionals (e.g., doctor or pharmacist) may already be aware of any possible drug interactions and may be monitoring you for it. Do not start, stop or change the dosage of any medicine before checking with them first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: oral carbonic anhydrase inhibitors (e.g., acetazolamide, methazolamide), high doses of aspirin or related salicylates (e.g., high doses used for arthritis), topiramate.

Low-dose aspirin, as prescribed by your doctor for specific medical reasons such as heart attack or stroke prevention (usually at dosages of 81-325 milligrams per day), should be continued. Consult your doctor or pharmacist for more details.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US national poison hotline at 1-800-222-1222. Canadian residents should call their local poison control center directly. This medicine may be harmful if swallowed.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., eye exams) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store between 39-86 degrees F (4-30 degrees C) away from light and moisture. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.