Included as part of the PRECAUTIONS section.
Sulfonamide Hypersensitivity Reactions
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
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.
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.
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.
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.
Carcinogenesis, Mutagenesis, Impairment Of Fertility
Brinzolamide 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. 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).
In two, three-month clinical studies, AZOPT®
(brinzolamide ophthalmic suspension) 1% dosed three times per day in patients
with elevated intraocular pressure (IOP), produced significant reductions in
IOPs (4 to 5 mmHg). These IOP reductions are equivalent to the reductions
observed with TRUSOPT* (dorzolamide hydrochloride ophthalmic solution) 2% dosed
three times per day 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%.
Use In Specific Populations
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
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 14Cbrinzolamide 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.
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.
No overall differences in safety or effectiveness have
been observed between elderly and younger patients.