Brinzolamide

Brinzolamide is an antihypertensive agent belonging to Carbonic Anhydrase Inhibitor.

Brinzolamide is a carbonic anhydrase inhibitor used for the reduction of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

Following topical ocular administration, Brinzolamide is absorbed into the systemic circulation. Time to peak plasma concentration and Duration of Action of Brinzolamide were found to be approximately 2 hours and 8-12 hours respectively. Brinzolamide distributes extensively into the RBCs and exhibits a long half-life in whole blood (approximately 111 days) and is approximately 60% bound to plasma proteins. Brinzolamide is eliminated predominantly in the urine as an unchanged drug. N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N-desmethoxypropyl and O-desmethyl metabolites.

Brinzolamide shows common side effects like Blurred vision, Discharge from the eye, dry eyes, redness, soreness, irritation, or pain of the eye or eyelid, skin rash, etc.

Brinzolamide is available in the form of Ophthalmic suspension.

Brinzolamide is available in India, the US, the UK, Canada, Europe, China, Italy, Spain, France, Japan, and Australia.

Brinzolamide belonging to the Carbonic Anhydrase Inhibitor acts as an antihypertensive agent.

Brinzolamide is a highly specific inhibitor of CA-II, which is the main CA isoenzyme involved in the secretion of aqueous humor. Inhibition of CA in the ciliary process of the eye slows the formation of bicarbonate and reduces sodium and fluid transport. This results in a reduction in the rate of aqueous humor secretion and intraocular pressure.

The onset of action of Brinzolamide is not clinically established.

The Duration of Action for Brinzolamide in the body is approximately 8-12 hours.

The Tmax was found within 2 hours following the administration of Brinzolamide.

Brinzolamide is available in the form of Ophthalmic suspension.

Ophthalmic Brinzolamide comes as a suspension (liquid) to instill in the eye. Brinzolamide eye drops are usually instilled in one drop three times a day.

Brinzolamide is a carbonic anhydrase inhibitor used for the reduction of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma. It works by reducing the production of fluid in your eyes and lowering eye pressure.

Brinzolamide is an antihypertensive agent belonging to Carbonic Anhydrase Inhibitor.

Brinzolamide Inhibits carbonic anhydrase, which in turn causes aqueous humor secretion to decrease. This effect reduces intraocular pressure.

Brinzolamide is approved for use in the following clinical indications

• Intraocular Hypertension

Brinzolamide is indicated for the management of elevated intraocular pressure in patients with ocular hypertension.

• Intraocular Hypertension or open-angle glaucoma

Brinzolamide is used for the management of open-angle glaucoma.

• Intraocular pressure

Ophthalmic: Instill 1 drop in affected eye(s) 3 times daily.

• Glaucoma (open-angle)

Adult

Ophthalmic: Instill 1 drop in the affected eye(s) 3 times daily.

Brinzolamide is available in various strengths 1% (10ml and 15ml).

Brinzolamide is available in the form of Ophthalmic suspension.

No information is available.

Brinzolamide is contraindicated in patients with

• Patients who are hypersensitive to any component of this product.

Off-label

• Hypersensitivity to sulfonamide.
• Severe renal impairment (CrCl <30 mL/minute); hyperchloremic acidosis.

• Sulfonamide Hypersensitivity Reactions

Brinzolamide (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 Brinzolamide (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 readministered irrespective of the route of administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.

• 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 Brinzolamide (brinzolamide ophthalmic suspension) 1% to this group of patients.

• Severe Renal Impairment

Brinzolamide (brinzolamide ophthalmic suspension) 1% has not been studied in patients with severe renal impairment (CrCl < 30 mL/min). Because BRINZOLAMIDE® (brinzolamide ophthalmic suspension) 1% and its metabolite are excreted predominantly by the kidney, Brinzolamide (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. Brinzolamide (brinzolamide ophthalmic suspension) 1% has not been studied in patients with acute angle-closure glaucoma.

• Contact Lens Wear

The preservative in Brinzolamide (brinzolamide ophthalmic suspension) 1%, benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during the instillation of Brinzolamide (brinzolamide ophthalmic suspension) 1%, but may be reinserted 15 minutes after instillation.

No information is available.

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 Brinzolamide (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.

Pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant the use of the drug in pregnant women despite potential risks.

No information is available.

Common Adverse effects

• Hyperemia, headache, Dermatitis, Dysgeusia, Blurred vision, blepharitis, eye discharge, eye discomfort, eye pain, eye pruritus, keratitis, xerophthalmia, and Rhinitis.

Rare Adverse effects

• Alopecia, asthenopia, chest pain, conjunctivitis, corneal disease, crusting of the eyelid, diarrhea, diplopia, dizziness, dyspepsia, dyspnea, hypersensitivity reaction, hypertonia, keratoconjunctivitis, lacrimation, nausea, pharyngitis, renal pain, urticaria, xerostomia.

• Oral Carbonic Anhydrase Inhibitors

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

• 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 Brinzolamide (brinzolamide ophthalmic suspension) 1%.

• Alpha-/Beta-Agonists (Indirect-Acting)

Carbonic Anhydrase Inhibitors may increase the serum concentration of Alpha-/Beta-Agonists (Indirect-Acting).

• Amantadine

Carbonic Anhydrase Inhibitors may increase the serum concentration of Amantadine.

• Carbonic Anhydrase Inhibitors

May enhance the adverse/toxic effect of other Carbonic Anhydrase Inhibitors. The development of acid-base disorders with concurrent use of ophthalmic and oral carbonic anhydrase inhibitors has been reported. Management: Avoid concurrent use of different carbonic anhydrase inhibitors if possible. Monitor patients closely for the occurrence of kidney stones and with regard to the severity of metabolic acidosis.

The common side effect of Brinzolamide include the following

Common

• Blurred vision, Discharge from the eye, dry eyes, redness, soreness, irritation, or pain of the eye or eyelid, skin rash.

Rare

• Chest pain, cough, crusting in the corner of the eye, difficulty with swallowing, dizziness, double vision, excessive muscle tone, eye redness, irritation, or pain, fast heartbeat, hives, itching, swelling, or other signs of eye or eyelid irritation, kidney pain, muscle stiffness, muscle tension or tightness, puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue, seeing double, shortness of breath, sore throat, tightness in the chest, unusual tiredness or weakness, wheezing.

• Pregnancy

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 on pregnant women. Brinzolamide (brinzolamide ophthalmic suspension) 1% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

• Nursing Mothers

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 brinzolamide (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 brinzolamide (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 brinzolamideIOP-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

Although no human data are available, electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur following oral administration of an overdose. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored.

Pharmacodynamic

Used in the treatment of glaucoma, brinzolamide inhibits aqueous humor formation and reduces elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. Brinzolamide can decrease intraocular pressure by approximately 16-19% in patients with elevated intraocular pressure.

Pharmacokinetics

• Absorption

Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. The time to peak plasma concentration of Brinzolamide was found to be approximately 2 hours. The Duration of Action for Brinzolamide in the body is approximately 8-12 hours.

• Distribution

Due to its affinity for CA-II, brinzolamide distributes extensively into the RBCs and exhibits a long half-life in whole blood (approximately 111 days). Brinzolamide is approximately 60% bound to plasma proteins.

• Metabolism and Excretion

The metabolite N-desethyl brinzolamide is formed, which also binds to CA and accumulates in RBCs. This metabolite binds mainly to CA-I in the presence of brinzolamide. In plasma, both parent brinzolamide and Ndesethyl brinzolamide concentrations are low and generally below assay quantitation limits (<10ng/ml). Brinzolamide is eliminated predominantly in the urine as an unchanged drug. N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N-desmethoxypropyl and O-desmethyl metabolites.

• https://www.accessdata.fda.gov/drugsatfda_docs/label/2015/020816s019lbl.pdf
• https://www.rxlist.com/Brinzolamide-drug.htm#side_effects
• https://reference.medscape.com/drug/Brinzolamide-brinzolamide-343595
• https://www.drugs.com/sfx/brinzolamide-ophthalmic-side-effects.html
• https://go.drugbank.com/drugs/DB01194
• https://www.uptodate.com/contents/brinzolamide-drug-information#F142314
• https://www.syrianclinic.com/med/en/ProfDrugs/Brinzolamidepd.html#pharmacokinetics