Carbonic anhydrase inhibitors

Azopt

Approved 1 Apr 1998EyeSuspension/drops

Indications

AZOPT is a carbonic anhydrase inhibitor indicated in the treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. AZOPT is a carbonic anhydrase inhibitor indicated for the treatment of elevated intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma. ( 1 )

Contraindications

AZOPT is contraindicated in patients who are hypersensitive to any component of this product. Hypersensitivity to any component of this product. ( 4 )

Warnings and precautions

Sulfonamide hypersensitivity reactions. ( 5.1 )
Corneal edema may occur in patients with low endothelial cell counts. ( 5.2 )

5.1Sulfonamide Hypersensitivity Reactions

AZOPT 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. Fatalities have occurred, although rarely, due to severe reactions to sulfonamides, including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), fulminant hepatic necrosis, agranulocytosis, aplastic anemia, and other blood dyscrasias.

Sensitization may recur when a sulfonamide is readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation immediately.

5.2Corneal 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 to this group of patients.

5.3Severe Renal Impairment

AZOPT has not been studied in patients with severe renal impairment [creatinine clearance (CrCl) less than 30 mL/min]. Because AZOPT and its metabolite are excreted predominantly by the kidney, AZOPT is not recommended in such patients.

At a glance

Brand name: Azopt
Active substance: brinzolamide
Drug class: Carbonic anhydrase inhibitors
Route: Eye
Dosage form: Suspension/drops
Applicant: Sandoz
Status: Prescription
FDA approval: 1 Apr 1998
Application: NDA020816-001
RxCUI: 194882

Indications

Warnings and precautions

Sulfonamide hypersensitivity reactions. ( 5.1 )
Corneal edema may occur in patients with low endothelial cell counts. ( 5.2 )

5.1Sulfonamide Hypersensitivity Reactions

5.2Corneal Endothelium

5.3Severe Renal Impairment

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

There are no adequate and well-controlled studies in pregnant women to inform drug-associated risk. In reproductive toxicity studies, brinzolamide administered orally to rats induced fetal toxicity at 375 times the recommended human ophthalmic dose (RHOD) based on mg/kg. In rabbits, no fetal toxicity was observed following oral administration (see Data) . The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4%, and of miscarriage is 15% to 20%, of clinically recognized pregnancies.

Data Animal Data Embryo-fetal studies were conducted in pregnant rats administered 0, 2, 6, or 18 mg/kg/day brinzolamide by oral gavage on gestation days 6 to 17, to target the period of organogenesis. Decreased fetal body weight with reduced skeletal ossification were observed at 18 mg/kg/day (375 times the RHOD based on mg/kg). The no-observed-adverse-effect-level (NOAEL) for fetal toxicity was 6 mg/kg/day (125 times the RHOD).

Decreased maternal weight gain was observed at 18 mg/kg/day. The NOAEL for maternal toxicity was 6 mg/kg/day (125 times the RHOD). Embryo-fetal studies were conducted in pregnant rabbits administered 0, 1, 3, or 6 mg/kg/day of brinzolamide by oral gavage on gestation days 6 to 18, to target the period of organogenesis. No treatment-related fetal effects were observed at any dose. The NOAEL for fetal toxicity was 6 mg/kg/day (125 times the RHOD based on mg/kg).

Maternal weight loss during pregnancy was observed at 3 mg/kg/day (63 times the RHOD) and above. The NOAEL for maternal toxicity was 1 mg/kg/day (21 times the RHOD). A peri-/postnatal study was conducted in rats administered brinzolamide by oral gavage from gestation day 16 through lactation day 20. Decreased pup body weight was observed at 15 mg/kg/day (313 times the RHOD based on mg/kg). The NOAEL for developmental toxicity was 5 mg/kg/day (104 times the RHOD).

Following oral administration of 14 C-brinzolamide to pregnant rats, radioactivity was found to cross the placenta and was present in the fetal tissues and blood.

Azopt

Indications

Contraindications

Warnings and precautions

5.1Sulfonamide Hypersensitivity Reactions

5.2Corneal Endothelium

5.3Severe Renal Impairment

At a glance

Two medicines in one question?

Azopt

Indications

Contraindications

Warnings and precautions

5.1Sulfonamide Hypersensitivity Reactions

5.2Corneal Endothelium

5.3Severe Renal Impairment

At a glance

Two medicines in one question?

5.4Acute Angle-Closure Glaucoma

5.5Risk of Contamination

5.6Contact Lens Wear

Interactions

7.1Oral Carbonic Anhydrase Inhibitors

7.2High-Dose Salicylate Therapy

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information