AZOPT brinzolamide suspension/ drops
Alcon Laboratories, Inc.
AZOPT? (brinzolamide ophthalmic suspension) 1% contains 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 C12 H21 N3 O5 S3
Brinzolamide has molecular weight of 383.5 and melting point of about 131?C. It is white powder, which is insoluble in water, very soluble in methanol and soluble in ethanol.
AZOPT? (brinzolamide ophthalmic suspension) 1% is supplied as sterile, aqueous suspension of brinzolamide which has been formulated to be readily suspended and slow settling, following shaking. It has pH of approximately 7.5 and an osmolality of 300 mOsm/kg.
Each mL of AZOPT? (brinzolamide ophthalmic suspension) 1% contains: Active ingredient: brinzolamide 10 mg. Preservative: Benzalkonium chloride 0.1 mg. Inactives: mannitol, carbomer 974P, tyloxapol, edetate disodium, sodium chloride, purified water, with hydrochloric acid and/or sodium hydroxide to adjust pH.
Mechanism of Action
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 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 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 major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss.
INDICATIONS AND USAGE
AZOPT? (brinzolamide ophthalmic suspension) 1% is carbonic anhydrase inhibitor indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.
2 DOSAGE AND ADMINISTRATION
The recommended dose is one 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 (10) minutes apart.
3 DOSAGE FORMS AND STRENGTHS
Solution containing 10 mg/mL brinzolamide.
4 CONTRAINDICATIONS
AZOPT? (brinzolamide ophthalmic suspension) 1% is contraindicated in patients who are hypersensitive to any component of this product.
5 WARNINGS AND PRECAUTIONS
5.1 Sulfonamide Hypersensitivity Reactions
AZOPT? (brinzolamide ophthalmic suspension) 1% is 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 sulfonamide is re-administered 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 AZOPT? (brinzolamide ophthalmic suspension) 1% to this group of patients.
5.3 Severe Renal Impairment
AZOPT? (brinzolamide ophthalmic suspension) 1% has not been studied in patients with severe renal impairment (CrCl 30 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.
5.4 Acute Angle-Closure Glaucoma
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.
5.5 Contact Lens Wear
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.
6 ADVERSE REACTIONS
6.1 Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice.
In clinical studies of AZOPT? (brinzolamide ophthalmic suspension) 1%, the most frequently reported adverse reactions reported in to 10% of patients were blurred vision and bitter, sour or unusual taste. Adverse reactions occurring in 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 DRUG INTERACTIONS
7.1 Oral Carbonic Anhydrase Inhibitors
There is 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 ophthalmic suspension) 1%. The concomitant administration of AZOPT? (brinzolamide ophthalmic suspension) 1% 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 AZOPT? (brinzolamide ophthalmic suspension) 1%.
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Pregnancy Category C
PATIENT COUNSELING info.
17.1 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.
17.2 Temporary Blurred Vision
Vision may be temporarily blurred following dosing with AZOPT? (brinzolamide ophthalmic suspension) 1%. Advise patients to exercise care in operating machinery or driving motor vehicle.
17.3 Avoiding Contamination of the Product
Instruct 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.
17.4 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.
17.5 Concomitant Topical Ocular Therapy
If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.
17.6 Contact Lens Wear
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.
