AZOPT EYE DROPS

Indications

• Glaucoma
• Ocular hypertension
• Primary glaucoma
• Secondary glaucoma

Dosage

Children: For children, apply 1 drop into the affected eye(s) twice daily; may increase frequency if necessary.

Adults: Instill 1 drop into the affected eye(s) three times daily.

Mechanism of action

Brinzolamide inhibits the enzyme carbonic anhydrase, which decreases the production of aqueous humor in the eye, thereby lowering intraocular pressure.

Pharmacodynamics

By reducing the secretion of bicarbonate ions, brinzolamide decreases the osmotic gradient and reduces fluid movement into the aqueous humor, leading to decreased intraocular pressure.

Pharmacokinetics

Brinzolamide is administered topically as an eye drop. Systemic absorption can occur, but it is generally limited. The drug is metabolized in the liver and excreted primarily in urine. Its half-life varies, but significant systemic exposure is rare with topical use.

Contra-indications

• History of sulfonamide hypersensitivity
• Hyperchloraemic acidosis
• Renal tubular immaturity or abnormality

Adverse effects

• Eye discomfort
• Vision disorders
• Bitter taste
• Angioedema
• Bronchospasm
• Dizziness
• Dry mouth
• Dyspnoea
• Epistaxis
• Local reaction
• Pain
• Arrhythmias
• Asthenia
• Severe cutaneous adverse reactions
• Chest discomfort
• Cough
• Depression
• Diarrhoea
• Throat irritation
• Urolithiasis

Precautions

• Monitor blood count and plasma electrolyte concentrations with prolonged use
• Chronic corneal defects
• History of intra-ocular surgery
• History of renal calculi
• Systemic absorption follows topical application

Pregnancy

Manufacturer advises avoid, especially in first trimester (toxicity in animal studies).

Breast-feeding

Amount too small to be harmful; use only if benefit outweighs risk.

Storage

Store in a cool, dry place away from light.

Formulations

• Topical eye drops

Mechanism of action

Brinzolamide is a highly specific, reversible, non-competitive inhibitor of carbonic anhydrases (CA), the enzymes catalyzing the reversible reaction of water and carbon dioxide (CO2) to form bicarbonate ions. Although there are 7 isoforms of CA in human tissues, brinzolamide has the highest affinity to CA II. Brinzolamide and its active metabolites were not found to displace any known ligands in vitro from their respective receptors or enzymes commonly involved in producing side effects or ancillary pharmacology, thus explaining brinzolamide's high order of safety.

Pharmacodynamics

Inhibition of carbonic anhydrase II (CA-II) in the ciliary process of the eye slows the formation of bicarbonate and thus fluid flow, lowering intraocular pressure (IOP). The IOP-reducing effect of brinzolamide as adjunctive therapy to the prostaglandin analog travoprost was studied. Following a 4-week run-in with travoprost, patients with an IOP ≥19 mmHg were randomized to receive added treatment with brinzolamide or timolol. An additional decrease in mean diurnal IOP of 3.2 to 3.4 mmHg for the brinzolamide group and 3.2 to 4.2 mmHg for the timolol group were observed. There was an overall higher incidence of non-serious ocular adverse reactions, mainly related to signs of local irritation, in the brinzolamide/travoprost groups. The events were mild and did not affect the overall discontinuation rates in the studies. A clinical trial was conducted with brinzolamide in 32 pediatric patients less than 6 years of age, diagnosed with glaucoma or ocular hypertension. Some patients were naive to IOP therapy whilst others were on other IOP-lowering medicinal product(s). Those who had been on previous IOP medicinal products were not required to discontinue their IOP medicinal product(s) until the initiation of monotherapy with brinzolamide. Among patients who were naive to IOP therapy (10 patients), the efficacy of brinzolamide was similar to that seen previously in adults, with mean IOP reductions from baseline ranging up to 5 mmHg. Among patients who were on topical IOP-lowering medicinal products (22 patients), mean IOP increased slightly from baseline in the brinzolamide group.