Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma

1. NAME OF THE MEDICINAL PRODUCT

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of suspension contains:
Brinzolamide USP……………………10mg
(1% w/v)

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Eye drops, suspension.

White to off-white suspension.

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmais indicated to decrease elevated intraocular pressure in:

• Ocular hypertension
• Open-angle glaucoma

as monotherapy in adult patients unresponsive to beta-blockers or in adult patients in whom beta-blockers are contraindicated, or as adjunctive therapy to beta-blockers or prostaglandin analogues (see also section 5.1).

4.2 Posology and method of administration

Posology

When used as monotherapy or adjunctive therapy, the recommended dose is one drop of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma in the conjunctival sac of the affected eye(s) twice daily. Some patients may have a better response with one drop three times a day.

Special populations

Elderly population

No dose adjustment in elderly patients is necessary.

Patients with hepatic and renal impairment

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Parma has not been studied in patients with hepatic impairment and is therefore not recommended in such patients.

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmahas not been studied in patients with severe renal impairment (creatinine clearance < 30 ml/min) or in patients with hyperchloraemic acidosis. Since Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmaand its main metabolite are excreted predominantly by the kidney, Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmais therefore contra-indicated in such patients (see also section 4.3).

Paediatric population

The efficacy and safety of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmain infants, children and adolescents aged 0 to 17 years has not been established. Currently available data are described in sections 4.8 and 5.1. Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmais not recommended for use in infants, children and adolescents.

Method of administration

For ocular use.

Nasolacrimal occlusion or gently closing the eyelid after instillation is recommended. This may reduce the systemic absorption of medicinal products administered via the ocular route and result in a decrease in systemic side effects.

Instruct the patient to shake the bottle well before use. To prevent contamination of the dropper tip and suspension, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle. Remove contact lenses prior to application and wait at least 15 minutes before reinsertion. Instruct patients to keep the bottle tightly closed when not in use.

When substituting another ophthalmic antiglaucoma agent with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma, discontinue the other agent and start the following day with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma.

If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart. Eye ointments should be administered last.

If a dose is missed, treatment should be continued with the next dose as planned. The dose should not exceed one drop in the affected eye(s) three times daily.

4.3 Contraindications

• Hypersensitivity to the active substance or any of the excipients listed in section 6.1
• Known hypersensitivity to sulfonamides (see also section 4.4).
• Severe renal impairment.
• Hyperchloraemic acidosis.

4.4 Special warnings and precautions for use

Systemic effects

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmais a sulfonamide inhibitor of carbonic anhydrase and, although administered topically, is absorbed systemically. The same types of adverse reactions that are attributable to sulfonamides may occur with topical administration. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation.

Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors. Use with caution in patients with risk of renal impairment because the possible risk of metabolic acidosis (see section 4.2).

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmahas not been studied in pre-term infants (less than 36 weeks gestational age) or those less than 1 week of age. Patients with significant renal tubular immaturity or abnormalities should only receive Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmaafter careful consideration of the risk benefit balance because of the possible risk of metabolic acidosis.

Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination. Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is absorbed systemically and therefore this may occur with topical administration.

Concomitant therapy

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 Ophthalmic Suspension USP 1% w/v Taj Parma The concomitant administration of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmaand oral carbonic anhydrase inhibitors has not been studied and is not recommended (see also section 4.5).

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Parma was primarily evaluated in concomitant administration with timolol during adjunctive glaucoma therapy. Additionally the IOP-reducing effect of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmaas adjunctive therapy to the prostaglandin analogue travoprost has been studied. No long term data are available on the use of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmaas adjunctive therapy to travoprost (see also section 5.1).

There is limited experience with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma in the treatment of patients with pseudoexfoliative glaucoma or pigmentary glaucoma. Caution should be used in treating these patients and close monitoring of intraocular pressure (IOP) is recommended. Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma has not been studied in patients with narrow-angle glaucoma and its use is not recommended in these patients.

The possible role of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma on corneal endothelial function has not been investigated in patients with compromised corneas (particularly in patients with low endothelial cell count). Specifically, patients wearing contact lenses have not been studied and careful monitoring of these patients when using Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is recommended, since carbonic anhydrase inhibitors may affect corneal hydration and wearing contact lenses might increase the risk for the cornea. Careful monitoring of patients with compromised corneas such as patients with diabetes mellitus or corneal dystrophies is recommended.

Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmacontains benzalkonium chloride, close monitoring is required with frequent or prolonged use in dry eye patients, or in conditions where the cornea is compromised.

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharmahas not been studied in patients wearing contact lenses. Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma contains benzalkonium chloride which may cause eye irritation and is known to discolour soft contact lenses. Contact with soft contact lenses is to be avoided. Patients must be instructed to remove contact lenses prior to the application of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Parma and wait at least 15 minutes after instillation of the dose before reinsertion.

Potential rebound effects following cessation of treatment with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma have not been studied; the IOP-lowering effect is expected to last for 5-7 days.

Paediatric population

The safety and efficacy of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma in infants, children and adolescents aged 0 to 17 years has not been established and its use is not recommended in infants, children or adolescents.

4.5 Interaction with other medicinal products and other forms of interaction

Specific interaction studies with other medicinal products have not been performed with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma. In clinical studies, Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma was used concomitantly with prostaglandin analogues and timolol ophthalmic preparations without evidence of adverse interactions. Association between Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma and miotics or adrenergic agonists has not been evaluated during adjunctive glaucoma therapy.

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is a carbonic anhydrase inhibitor and, although administered topically, is absorbed systemically. Acid-base disturbances have been reported with oral carbonic anhydrase inhibitors. The potential for interactions must be considered in patients receiving Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma.

The cytochrome P-450 isozymes responsible for metabolism of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma include CYP3A4 (main), CYP2A6, CYP2C8 and CYP2C9. It is expected that inhibitors of CYP3A4 such as ketoconazole, itraconazole, clotrimazole, ritonavir and troleandomycin will inhibit the metabolism of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma by CYP3A4. Caution is advised if CYP3A4 inhibitors are given concomitantly. However, accumulation of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is unlikely as renal elimination is the major route. Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is not an inhibitor of cytochrome P-450 isozymes.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of ophthalmic Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma in pregnant women. Studies in animals have shown reproductive toxicity following systemic administration (see also section 5.3).

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

It is unknown whether Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma/metabolites are excreted in human milk following topical ocular administration. Animal studies have shown the excretion of minimal levels of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma in breast milk following oral administration.

A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma therapy taking in to account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

Fertility

Animal studies with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma demonstrated no effect on fertility. Studies have not been performed to evaluate the effect of topical ocular administration of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma on human fertility.

4.7 Effects on ability to drive and use machines

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma has a minor influence on the ability to drive and use machines.

Temporary blurred vision or other visual disturbances, may affect the ability to drive or use machines (see also section 4.8). If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machines.

Oral carbonic anhydrase inhibitors may impair the ability to perform tasks requiring mental alertness and/or physical coordination (see also section 4.4 and section 4.8).

4.8 Undesirable effects

Summary of the safety profile

In clinical studies involving 2732 patients treated with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma as monotherapy or adjunctive therapy to timolol maleate 5 mg/ml, the most frequently reported treatment-related adverse reactions were: dysgeusia (6.0%) (bitter or unusual taste, see description below) and temporary blurred vision (5.4%) upon instillation, lasting from a few seconds to a few minutes (see also section 4.7).

Tabular list of adverse reactions

The following adverse reactions have been reported with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma 10mg/ml eye drops, suspension and are classified according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000), or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The adverse reactions were obtained from clinical trials and postmarketing spontaneous reports.

Description of selected adverse events

Dysgeusia (bitter or unusual taste in the mouth following instillation) was the most frequently reported systemic adverse reaction associated with the use of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma during clinical studies. It is likely caused by passage of the eye drops in the nasopharynx via the nasolacrimal canal. Nasolacrimal occlusion or gently closing the eyelid after instillation may help reduce the incidence of this effect (see also section 4.2).

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is a sulfonamide inhibitor of carbonic anhydrase with systemic absorption. Gastrointestinal, nervous system, haematological, renal and metabolic effects are generally associated with systemic carbonic anhydrase inhibitors. The same type of adverse reactions that are attributable to oral carbonic anhydrase inhibitors may occur with topical administration.

No unexpected adverse reactions have been observed with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma when used as adjunctive therapy to travoprost. The adverse reactions seen with the adjunctive therapy have been observed with each active substance alone.

Paediatric population

In small short-term clinical trials, approximately 12.5% of paediatric patients were observed to experience adverse reactions, the majority of which were local, non-serious ocular reactions such as conjunctival hyperaemia, eye irritation, eye discharge, and lacrimation increased (see also section 5.1).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important.

4.9 Overdose

No case of overdose has been reported.

Treatment should be symptomatic and supportive. Electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur. Serum electrolyte levels (particularly potassium) and blood pH levels must be monitored.

5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antiglaucoma preparations and miotics, carbonic anhydrase inhibitors, ATC code: S01EC04.

Mechanism of action

Carbonic anhydrase (CA) is an enzyme found in many tissues of the body, including the eye. Carbonic anhydrase catalyses the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid.

Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humour secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. The result is a reduction in intraocular pressure (IOP) which is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma, an inhibitor of carbonic anhydrase II (CA-II), the predominant iso-enzyme in the eye, with an in vitro IC50 of 3.2 nM and a Ki of 0.13 nM against CA-II.

Clinical efficacy and safety

The IOP-reducing effect of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma as adjunctive therapy to the prostaglandin analogue 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 Ophthalmic Suspension USP 1% w/v Taj Pharma or timolol. An additional decrease in mean diurnal IOP of 3.2 to 3.4 mmHg for the Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma 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 Ophthalmic Suspension USP 1% w/v Taj Pharma/travoprost groups. The events were mild and did not affect the overall discontinuation rates in the studies (see also section 4.8).

Paediatric population

A clinical trial was conducted with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma in 32 paediatric 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 product(s) were not required to discontinue their IOP medicinal product(s) until initiation of monotherapy with Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma.

Among patients who were naive to IOP therapy (10 patients), the efficacy of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma 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 product(s) (22 patients), mean IOP increased slightly from baseline in the Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma group.

5.2 Pharmacokinetic properties

Absorption, distribution and biotransformation

Following topical ocular administration, Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is absorbed into the systemic circulation. Due to its high affinity for CA-II, Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma distributes extensively into the red blood cells (RBCs) and exhibits a long half-life in whole blood (mean of approximately 24 weeks). In humans, the metabolite N-desethylBrinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is formed, which also binds to CA and accumulates in RBCs. This metabolite binds mainly to CA-I in the presence of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma. In plasma, both Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma and N-desethylBrinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma concentrations are low and generally below assay quantitation limits (<7.5 ng/ml). Binding to plasma proteins is not extensive (about 60%).

Elimination

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma is eliminated primarily by renal excretion (approximately 60%). About 20% of the dose has been accounted for in urine as metabolite. Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma and N-desethylBrinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma are the predominant components in the urine along with trace levels (<1%) of the N-desmethoxypropyl and O-desmethyl metabolites.

Pharmacokinetic/pharmacodynamic relationship

In an oral pharmacokinetic study, healthy volunteers received 1 mg capsules of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma twice daily for up to 32 weeks and RBC CA activity was measured to assess the degree of systemic CA inhibition.

Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma saturation of RBC CA-II was achieved within 4 weeks (RBC concentrations of approximately 20 μM). N-DesethylBrinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma accumulated in RBCs to steady state within 20-28 weeks reaching concentrations ranging from 6-30 μM. The inhibition of total RBC CA activity at steady state was approximately 70-75%.

Subjects with moderate renal impairment (creatinine clearance of 30-60 ml/minute) were administered 1 mg of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma twice daily orally for up to 54 weeks. Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma RBC concentration ranged from about 20 to 40 μM by week 4 of treatment. At steady-state, Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma and its metabolite RBC concentrations ranged from 22.0 to 46.1 and 17.1 to 88.6 μM, respectively.

N-desethylBrinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma RBC concentrations increased and total RBC CA activity decreased with decreasing creatinine clearance but Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma RBC concentrations and CA-II activity remained unchanged. In subjects with the highest degree of renal impairment inhibition of total CA activity was greater although it was inferior to 90% at steady-state.

In a topical ocular study, at steady-state, Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma RBC concentrations were similar to those found in the oral study, but levels of N-desethylBrinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma were lower. Carbonic anhydrase activity was approximately 40-70% of predose levels.

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, and carcinogenic potential.

Developmental toxicity studies in rabbits with oral doses of Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma of up to 6 mg/kg/day (125 times the recommended human ophthalmic dose) revealed no effect on foetal development despite significant maternal toxicity. Similar studies in rats resulted in slightly reduced ossification of skull and sternebrae of foetuses of dams receiving Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma at doses of 18 mg/kg/day (375 times the recommended human ophthalmic dose), but not 6 mg/kg/day. These findings occurred at doses that caused metabolic acidosis with decreased body weight gain in dams and decreased foetal weights. Dose-related decreases in foetal weights were observed in pups of dams receiving Brinzolamide Ophthalmic Suspension USP 1% w/v Taj Pharma orally ranging from a slight decrease (about 5-6%) at 2 mg/kg/day to nearly 14% at 18 mg/kg/day. During lactation, the no adverse effect level in the offspring was 5 mg/kg/day.

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Benzalkonium chloride,

Mannitol, Carbomer, Disodium edetate, Sodium chloride, Water, purified, Hydrochloric acid/sodium hydroxide (for pH adjustment)

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

2 years (unopened)

After opening: 4 weeks

6.4 Special precautions for storage

Keep the bottle in the outer carton.

6.5 Nature and contents of container

5 ml (LDPE) bottle, containing 5 ml of Eye Drops, Suspension, with a (LDPE) insert dropper and a (HDPE) cap.

Pack sizes:

1 x 5 ml bottle packed in a single carton

3 x 5 ml bottles packed in a single carton

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements

7. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com

BRINZOLAMIDE
OPHTHALMIC SUSPENSION USP
1% W/V
TAJ PHARMA

PACKAGE LEAFLET: INFORMATION FOR THE USER

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor or pharmacist.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. See section 4.

WHAT IS IN THIS LEAFLET

1. What brinzolamide is and what it is used for
2. What you need to know before you use brinzolamide
3. How to use brinzolamide
4. Possible side effects
5. How to store brinzolamide
6. Contents of the pack and other information

   1. WHAT BRINZOLAMIDE IS AND WHAT IT IS USED FOR

Brinzolamide contains brinzolamide which belongs to a group of medicines called carbonic anhydrase inhibitors. It reduces pressure within the eye.

Brinzolamide eye drops are used to treat high pressure in the eye. This pressure can lead to an illness called glaucoma.

If the pressure in the eye is too high, it can damage your sight.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE BRINZOLAMIDE

Do not use brinzolamide

• if you have severe kidney problems.
• if you are allergic to brinzolamide. or any of the other ingredients of this medicine (listed in section 6).
• if you are allergic to medicines called sulphonamides. Examples include medicines used to treat diabetes and infections and also diuretics (water tablets). Brinzolamide may cause the same allergy.
• if you have too much acidity in your blood (a condition called hyperchloraemic acidosis).

If you have further questions, ask your doctor for advice.

Warnings and precautions

Talk to your doctor or pharmacist before using brinzolamide:

• if you have kidney or liver problems.
• if you have dry eyes or cornea problems.
• if you are taking other sulphonamide medicines.

Children and adolescents

Brinzolamide is not to be used by infants, children or adolescents under 18 of years of age unless advised by your doctor.

Other medicines and brinzolamide

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines.

If you are taking another carbonic anhydrase inhibitor (acetazolamide or dorzolamide, see section 1 ‘What brinzolamide is and what it is used for’), talk to your doctor.

Pregnancy and breast-feeding

If you are pregnant or breast-feeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine.

Women who may become pregnant are advised to use effective contraception during brinzolamide treatment. The use of brinzolamide is not recommended during pregnancy or breast-feeding. Do not use brinzolamide unless clearly indicated by your doctor.

Ask your doctor or pharmacist for advice before taking any medicine.

Driving and using machines

Do not drive or use machines until your vision is clear. You may find that your vision is blurred for a time just after using brinzolamide.

Brinzolamide may impair the ability to perform tasks requiring mental alertness and/or physical coordination. If affected, take care when driving or using machines.

Brinzolamide contains benzalkonium chloride

Brinzolamide contains a preservative (benzalkonium chloride) which may cause eye irritation and is known to discolour soft contact lenses. Contact with soft contact lenses should be avoided. If you wear contact lenses you should remove them prior to the application of brinzolamide and wait at least 15 minutes after instillation of the dose before putting your lenses back in.

3. HOW TO USE BRINZOLAMIDE

Always use this medicine exactly as your doctor or pharmacist has told you. Check with your doctor or pharmacist if you are not sure.

Only use brinzolamide for your eyes. Do not swallow or inject.

The recommended dose is

1 drop in the affected eye or eyes, twice a day -morning and night.

Use this much unless your doctor told you to do something different. Only use brinzolamide in both eyes if your doctor told you to. Use it for as long as your doctor told you to.

How to use

• Get the brinzolamide bottle and a mirror
• Wash your hands
• Shake the bottle and twist off the cap. After the cap is removed, if tamper evident snap collar is loose, remove before using the product.
• Hold the bottle, pointing down, between your thumb and middle finger
• Tilt your head back. Pull down your eyelid with a clean finger, until there is a ‘pocket’ between the eyelid and your eye. The drop will go in here (picture 1)
• Bring the bottle tip close to the eye. Use the mirror if it helps
• Do not touch your eye or eyelid, surrounding areas or other surfaces with the dropper.
  It could infect the drops
• Gently press on the base of the bottle to release one drop of brinzolamide at a time.
• Do not squeeze the bottle:it is designed so that a gentle press on the bottom is all that it needs (picture 2).
• After using brinzolamide, press a finger to the corner of your eye, by the nose (picture 3) for at least 1 minute. This helps to stop brinzolamide getting into the rest of the body.
• If you take drops in both eyes, repeat the steps for your other eye.
• Put the bottle cap back on firmly immediately after use.
• Use up one bottle before opening the next bottle.

If a drop misses your eye, try again.

If you are using other eye drops, leave at least 5 minutes between putting in brinzolamide and the other drops. Eye ointments should be administered last.

If you use more brinzolamide than you should

If you get too much in your eyes, rinse it all out with warm water. Do not put in any more drops until it’s time for your next regular dose.

If you forget to use brinzolamide

Use a single drop as soon as you remember, and then go back to your regular routine. Do not use a double dose to make up for a forgotten dose.

If you stop using brinzolamide

If you stop using brinzolamide without speaking to your doctor, the pressure in your eye will not be controlled which could lead to loss of sight.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everyone gets them.

The following side effects have been seen with brinzolamide.

Common side effects (may affect up to 1 in 10 people)

• Effects in the eye:blurred vision, eye irritation, eye pain, eye discharge, itchy eye, dry eye, abnormal eye sensation, redness of the eye.
• General side effects:bad taste.

Uncommon side effects (may affect up to 1 in 100 people)

• Effects in the eye:sensitivity to light inflammation or infection of the conjunctiva, eye swelling, eyelid itching, redness or swelling, growth on surface of eye, increased pigmentation of the eye, tired eyes, eyelid crusting, or increased tear production.
• General side effects:decreased or reduced heart function, palpitations, decreased heart rate, difficulty breathing, shortness of breath, cough, decreased red blood cell count in blood, increased chlorine level in blood, dizziness, drowsiness, difficulty with memory, depression, nervousness, generalized weakness, fatigue, feeling abnormal, pain, shaking, decreased sex drive, male sexual difficulty, cold symptoms, chest congestion, sinus infection, throat irritation, throat pain, abnormal or decreased sensation in mouth, inflammation of the lining of the oesophagus, abdominal pain, nausea, vomiting, upset stomach, frequent bowel movements, diarrhoea, intestinal gas, digestive disorder, kidney pain, muscle pain, muscle spasms, back pain, nose bleeds, runny nose, stuffy nose, sneezing, rash, abnormal skin sensation, itching, headache, dry mouth.

Rare side effects (may affect up to 1 in 1,000 people)

• Effects in the eye:corneal swelling, double or reduced vision, abnormal vision, decreased eye sensation, swelling around the eye, increased pressure in eye, damage to the optic nerve.
• General side effects:memory impairment, drowsiness, chest pain, upper respiratory tract congestion, sinus congestion, nasal congestion, dry nose, ringing in ears, hair loss, generalized itching, feeling jittery, irritability, irregular heart rate, body weakness, difficulty sleeping.

Not known (frequency cannot be estimated from the available data):

• Effects in the eye:eyelid abnormality, visual disturbance, corneal disorder, eye allergy, decreased growth or number of eyelashes.
• General side effects:increased allergic symptoms, decreased sensation, tremor, loss or decrease in taste, decreased blood pressure, increased blood pressure, increased heart rate, joint pain, asthma, pain in extremity, skin redness, inflammation, or itching, abnormal liver blood tests, swelling of the extremities, frequent urination, decreased appetite.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet.

5. HOW TO STORE BRINZOLAMIDE

Keep out of the sight and reach of children.

Do not use brinzolamide after the expiry date which is stated on the bottle and box after “EXP”. The expiry date refers to the last day of the month.

This medicine does not require any special storage conditions.

You must throw away a bottle four weeks after you first opened it, to prevent infections. Write down the date you opened each bottle in the space below and in the space on the bottle label and box.

For a pack containing a single bottle, write only one date.

Opened (1):

Opened (2):

Opened (3):

Do not throw away any medicines via wastewater or household waste. Ask your pharmacist how to throw away medicines you no longer use. These measures will help protect the environment.

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What brinzolamide contains

The active substance is brinzolamide 10mg/ml. The other ingredients are: benzalkonium chloride solution 50%, carbomer 974P, disodium edetate, mannitol (E421), Poloxamer 407, water for injection and sodium chloride. Tiny amounts of sodium hydroxide are added to keep acidity levels (pH levels) normal.

What brinzolamide looks like and the contents of the pack

Brinzolamide is a milky liquid (a suspension) supplied in a pack containing 1, 3 or 6 plastic (dropper container) bottles with a screw cap which includes 5 ml white homogenous suspension. The following pack sizes are available: outer cartons containing 1 x 5 ml, 3 x 5 ml

Not all pack sizes may be marketed.

7. MANUFACTURED IN INDIA BY:

TAJ PHARMACEUTICALS LTD.
Mumbai, India
Unit No. 214.Old Bake House,
Maharashtra chambers of  Commerce Lane,
Fort, Mumbai – 400001
at:Gujarat, INDIA.
Customer Service and Product Inquiries:
1-800-TRY-FIRST (1-800-222-434 & 1-800-222-825)
Monday through Saturday 9:00 a.m. to 7:00 p.m. EST
E-mail: tajgroup@tajpharma.com