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Azopt (Brinzolamide) - Warnings and Precautions

 
 



WARNINGS

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.

PRECAUTIONS

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 < 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. 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 ophthalmic suspension) 1%. The concomitant administration of AZOPT® (brinzolamide ophthalmic suspension) 1% and oral carbonic anhydrase inhibitors is not recommended.

Information For Patients

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.

Drug Interactions

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%.

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.

Page last updated: 2008-05-19

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