ANTI-GLAUCOMA

ALFAPRES-T / 5mL
APPATIM / 5mL
A-BRINZO
A-CARTEOL/5mL
ALFAPRES-TH / 5mL
APPACARPINE_HS
BIMPOST 0.1
BIMPOST/3mL
BIMPOST  PF/0.1
BIMPOST  PF/0.3
BIMPOST T
BRINZO B
DORZA/5mL
DORZA TPF
DORZA PF
DORZA T

ALFAPRES-T

ALFAPRES-T

Pack : 5 Ml Pack

DESCRIPTION:

Alphapres-T Eye Drops is a relatively selective alpha-2 adrenergic receptor agonist with a non-selective beta-adrenergic receptor inhibitor (topical intraocular pressure lowering agent).

COMPOSITION:

Composition: Each ML Contains:

• Timolol Maleate IP eqv. to Timolol......5 mg
• Brimonidine Tartrate IP..............1.5 mg
• Oxychloro Complex...........0.05 mg (As preservative)
• Aqueous Buffered vehicle.........q.s.

PACKAGING:

Primary packing - 5ml Opaque poly bottles White caps & Nozzles.
‍Secondary Packing - Labels, Cartons, Shrink Pack & Shipper box.

AVAILABILITY:

5ml of solution in White poly bottles with white caps & nozzles in properly sealed.

SHELF LIFE:

24 months from the date of manufacturing.

STORAGE:

Keep in a cool & dark place. Below 25ºC.Do not allow to Freeze.

USES:

This combination medication is used to treat high pressure inside the eye due to glaucoma (open-angle type) or other eye diseases (e.g., ocular hypertension). Lowering high pressure inside the eye helps to prevent blindness.

Indications And Usage:

Alphapres-T Eye Drops is an alpha-adrenergic receptor agonist with a beta-adrenergic receptor inhibitor indicated for the reduction of elevated intraocular pressure (IOP) in patients with glaucoma or ocular hypertension, who require adjunctive or replacement therapy due to inadequately controlled IOP; the IOP-lowering of Alphapres-T Eye Drops.

CONTRAINDICATIONS:

Alphapres-T Eye Drops are contraindicated in patients with hypersensitivity to any component of this medication, in patients receiving monoamine oxidase (MAO) inhibitor therapy, in patients with bronchospasm, bronchial asthma or patients with a history of bronchial asthma, or severe chronic obstructive pulmonary disease, in patients with sinus bradycardia, sick sinus syndrome, sinoatrial nodal block,second or third degree atrioventricular block not controlled with a pacemaker, overt cardiac failure or cardiogenic shock.

DOSAGE AND ADMINISTRATION:

The recommended dose is one drop of Alphapres-T Eye Drops in the affected eye(s) twice daily approximately 12 hours apart. If more than one topical ophthalmic product is to be used, the different products should be instilled at least 5 minutes apart.

SUPPLY:

One White Lupolene bottle packed with printed labeled in a unit carton and, Such 25 Carton Packed in a Shrink Sleeves. Such 12 shrinks packed in a shipper.

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Appatim

Appatim

Pack : 5ml Pack

DESCRIPTION:

Appatim Eye Drops (Timolol Maleate Eye Drops) is a non-selective beta-adrenergic receptor blocking agent. Its chemical name is (-)-1-(tert-butylamino)-3-[(4-morpholino-1,2,5-thiadiazol-3-yl)oxy]-2propanol maleate (1:1) (salt). Timolol maleate possesses an asymmetric carbon atom in its structure and is provided as the levo-isomer.

COMPOSITION:

Label Claim: Each ML Contains :

TimololMaleate IP

  • Equivalent to Timolol...........5 mg
  • Benzalkonium Chloride Solution IP......0.0002 Ml (As preservative)
  • Aqueous Buffered Vehicle............q.s.

PACKAGING:

Primary packing - 5ml Clear Poly bottles White caps & Nozzles.

Secondary Packing - Labels, Cartons, Shrink Pack & Shipper box.

AVAILABILITY:

5ml of solution in clear poly bottles with white caps & nozzles in properly sealed.

SHELF LIFE:

24 months from the date of manufacturing.

STORAGE:

Keep in a cool & dark place. Below 25ºC.Do not allow to Freeze.

CLINICAL PHARMACOLOGY:

Mechanism Of Action:

Timolol maleate is a beta1 and beta2 (non-selective) adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anesthetic (membrane-stabilizing) activity.

Beta-adrenergic receptor blockade reduces cardiac output in both healthy subjects and patients with heart disease. In patients with severe impairment of myocardial function, beta-adrenergic receptor blockade may inhibit the stimulatory effect of the sympathetic nervous system necessary to maintain adequate cardiac function.

Beta-adrenergic receptor blockade in the bronchi and bronchioles results in increased airway resistance from unopposed parasympathetic activity. Such an effect in patients with asthma or other bronchospastic conditions is potentially dangerous.

Appatim Eye Drops (Timolol Maleate Eye Drops), when applied topically on the eye, has the action of reducing elevated as well as normal intraocular pressure, whether or not accompanied by glaucoma. Elevated intraocular pressure is a major risk factor in the pathogenesis of glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous visual field loss and optic nerve damage.

The onset of reduction in intraocular pressure following administration of timolol maleate can usually be detected within one-half hour after a single dose. The maximum effect usually occurs in one to two hours and significant lowering of intraocular pressure can be maintained for periods as long as 24 hours with a single dose. Repeated observations over a period of one year indicate that the intraocular pressure-lowering effect of timolol maleate is well maintained.

The precise mechanism of the ocular hypotensive action of timolol maleate is not clearly established at this time. Tonography and fluorophotometry studies in man suggest that its predominant action may be related to reduced aqueous formation. However, in some studies a slight increase in outflow facility was also observed.

Pharmacokinetics:

In a study of plasma drug concentration in six subjects, the systemic exposure to timolol was determined following twice daily administration of timolol maleate ophthalmic solution 0.5%. The mean peak plasma concentration following morning dosing was 0.46 ng/mL and following afternoon dosing was 0.35ng/mL.

Clinical Studies:

In controlled multiclinic studies in patients with untreated intraocular pressures of 22 mmHg or greater, timolol maleate ophthalmic solution 0.25 percent or 0.5 percent administered twice a day produced a greater reduction in intraocular pressure than 1, 2, 3, or 4 percent pilocarpine solution administered four times a day or 0.5, 1, or 2 percent epinephrine hydrochloride solution administered twice a day. In these studies, timolol maleate was generally well tolerated and produced fewer and less\ severe side effects than either pilocarpine or epinephrine. A slight reduction of resting heart rate in some patients receiving timolol maleate (mean reduction 2.9 beats/minute standard deviation 10.2) was observed.

INDICATIONS AND USAGE:

Appatim Eye Drops (Timolol Maleate Eye Drops), is indicated in the treatment of elevated intraocular pressure in patients with ocular hypertension or open-angle glaucoma.

CONTRAINDICATIONS:

Appatim Eye Drops (Timolol Maleate Eye Drops) is contraindicated in patient with overt heart failure, cardiogenic shock, sinus bradycardia, second-or third-degree atrioventricular block, bronchial or history asthma or severe chronic obstructive pulmonary disease or hypersensitive to any component of this product.

WARNINGS :

In patients without a history of cardiac failure continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure.

Appatim Eye Drops (Timolol Maleate Eye Drops) should be discontinued at the first sign or symptom of cardiac failure.

Beta adrenergic blocking agent should be administrated with caution on patient subject to spontaneous hypoglycemic or to diabetic patient (especially those with liable diabetes ) who are receiving insulin or oral hypoglycemic agent. Patient suspected of developing thyrotoxicosis should be managed carefully to avoid except withdrawal of beta adrenergic blocking agent which might precipitate a thyroid strom. If irritation persists or increases on using Appatim Eye Drops (Timolol Maleate Eye Drops) ,discontinue the use and consult the physician.

If irriatation persists or increases on using Appatim Eye Drops (Timolol Maleate Eye Drops) ,discontinue the use and consult the physician.

DOSAGE AND ADMINISTRATION:

The recommended doses of Appatim Eye Drops (Timolol Maleate Eye Drops) is one drop two time a day or as directed by the physician.

SUPPLY:

Appatim Eye Drops (Timolol Maleate Eye Drops) is supplied in one clear polyethylene Bottle packed with printed labelled & cartons and Such 25 Carton Packed in a Shrink Sleeves & corrugated box.

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A-Brinzo

Brinzolamide Ophthalmic Suspension USP 1 %w/v

THIS LEAFLET CONTAINS IMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER FUTURE REFERENCE

DESCRIPTION:

A-Brinzo (Brinzolamide Ophthalmic Suspension USP 1 % w/v) contains a carbonic anhydrase inhibitor formulated for multidose topical ophthalmic use. Brinzolamide is described chemically as: (R)-(+)-4-Ethylamino-2-(3-methoxypropyl)-3,4-dihydro-2H-thieno [3,2-e]-1,2-thiazine-6-sulfonamide-1,1-dioxide.

COMPOSITION:

Each ML Contains :

• Brinzolamide USP       10 mg
• Stabilized Oxychloro Complex 0.005 % w/v
  (As preservative)
• Aqueous Buffered Vehicle                    q.s.
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INDICATION AND USAGE

A-Brinzo (Brinzolamide Ophthalmic Suspension USP 1 % w/v) is indicated in the treatment of elevated intra ocular pressure in patients with ocular hypertension or open-angle glaucoma.

CLINICAL PHARMACOLOGY

Mechanism of Action

Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. It catalyzes the reversible reaction involving the hydration of carbon dioxide and the dehydration of carbonic acid. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II(CA-II), found primarily in red blood cells (RBCs), but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor 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).

Pharmacokinetics

Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. 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). In humans, 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 ( < 10 ng/mL). Binding to plasma proteins is approximately 60%. Brinzolamide is eliminated predominantly in the urine as unchanged drug. N-Desethyl brinzolamide is also found in the urine along with lower concentrations of the N- desmethoxypropyl and O-desmethyl metabolites.

CONTRAINDICATIONS

A-Brinzo (Brinzolamide Ophthalmic Suspension USP 1 % w/v) is contraindicated in patients who are hypersensitive to any component of this product.

WARNINGS AND PRECAUTIONS

A-Brinzo (Brinzolamide Ophthalmic Suspension USP 1% w/v) 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 A- Brinzo (Brinzolamide Ophthalmic Suspension USP 1 % w/v). 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 preparation.

Nursing Mothers

In a study of brinzolamide in lactating rats, decreases in body weight gain in offspring at an oral dose of 15mg/kg/day (312 times the recommended human ophthalmic dose) were seen during lactation. No other effects were observed. However, following oral administration of 14C-brinzolamide 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 A-Brinzo (Brinzolamide Ophthalmic Suspension USP 1% w/v), 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.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

ADVERSE REACTIONS

The most frequently reported treatment-related adverse reactions were: dysgeusia (6.0%) (bitter or unusual taste) and temporary blurred vision (5.4%) upon instillation, lasting from a few seconds to a few minutes. These events occurred in approximately 5-10% of patients. Blepharitis, dermatitis, dry eye, foreign body sensation, headache, hyperemia, ocular discharge, ocular discomfort, ocular keratitis, ocular pain, ocular pruritus and rhinitis were reported at an incidence of 1- 5%.The following adverse reactions were reported at an incidence below1%: allergic reactions, alopecia, chest pain, conjunctivitis, diarrhea, dizziness, dry mouth, dyspnea, dyspepsia, eye fatigue, hypertonia, keratoconjunctivitis, keratopathy, kidney pain, lid margin crusting or sticky sensation, nausea, pharyngitis, tearing and urticaria.

DOSAGE AND ADMINISTRATION

Shake well before use. The recommended dose is 1 drop of A-Brinzo (Brinzolamide Ophthalmic Suspension USP 1 % w/v) in the affected eye(s) three times daily. A-Brinzo (Brinzolamide Ophthalmic Suspension USP 1 % w/v) may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.

STORAGE

Preserve in tight containers. Store at a temperature between 4°C and 30°C.Do not allow to freeze.

SHELF LIFE

24   Months  

HOW SUPPLIED

A-Brinzo / 5 mL (Brinzolamide Ophthalmic Suspension USP 1 % w/v) is supplied in 5 mL sterile poly bottle.
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A-Brinzo

A-CARTEOL EYE DROPS

(Carteolol Hydrochloride Ophthalmic SolutionUSP 2% w/v)

THIS LEAFLET CONTAINS IMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER FUTURE REFERENCE

DESCRIPTION:

A-CARTEOL Eye Drops (Carteolol Hydrochloride Ophthalmic Solution USP 2% w/v) is a nonselective beta-adrenoceptor blocking agent for ophthalmic use.

The chemical name for carteolol hydrochloride is (±)-5-[3-[(1,1-dimethylethyl) amino]-2- hydroxypropoxy]-3,4-dihydro-2(1H)-quinolinone monohydrochloride. Structural formula: C16H24N2O3HCI
Mol. Wt.                    : 328.84
pH                             : 6.0 - 8.0

IINE

COMPOSITION:

Each ML Contains :

• Carteolol Hydrochloride USP 20mg
• Stabilized Oxychloro
  Complex 0.005 % w/v
  (As preservative)
• Sterile Aqueous  Vehicle                    q.s.
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CLINICAL PHARMACOLOGY

Carteolol is a nonselective beta-adrenergic blocking agent with associated intrinsic sympathomimetic activity and without significant membrane-stabilizing activity.Carteolol Hydrochloride reduces normal and elevated intraocular pressure (IOP) whether or not accompanied by glaucoma. The exact mechanism of the ocular hypotensive effect of beta-blockers has not been definitely demonstrated. In general, beta-adrenergic blockers reduce cardiac output in patients in good and poor cardio vascular health. In patients with severe impairment of myocardial function, beta- blockers may inhibit the sympathetic stimulation necessary to maintain adequate cardiac function. Beta-adrenergic blockers may also increase airway resistance in the bronchi and bronchioles due to unopposed parasympathetic activity. Given topically twice daily in controlled domestic clinical trials ranging from 1.5 to 3 months, Carteolol Hydrochloride produced a median percent reduction of IOP 22%to 25%. No significant effects were noted on corneal sensitivity, tear secretion, or pupil size.

INDICATIONS AND USAGE

A-CARTEOL EyeDrops (Carteolol Hydrochloride Ophthalmic Solution USP 2% w/v) has been shown to be effective in lowering intraocular pressure and may be used in patients with chronic open-angle glaucoma and intraocular hypertension. It maybe used alone or in combination with other intraocular pressure lowering medications.

CONTRAINDICATIONS

Carteolol is contraindicated in those individuals with bronchial asthma or with a history of bronchial asthma, or severe chronic obstructive pulmonary disease (see WARNINGS); sinus bradycardia; second- and third-degree atrioventricular block; overt cardiac failure (see WARNINGS); cardiogenic shock; or hyper sensivity to any component of this product.

WARNINGS

Carteolol has not been detected in plasma following ocular instillation. However, as with other topically applied ophthalmic preparations, Carteolol maybe absorbed systemically. The same adverse reactions found with systemic administration of beta-adrenergic blocking agents may occur with topical administration. For example, severe respiratory reactions and cardiac reactions, including death due to bronchospasm in patients with asthma, and rarely death in association with cardiac failure, have been reported with topical application of beta- adrenergic blocking agents (see CONTRAINDICATIONS).
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Cardiac Failure: Sympathetic stimulation may be essential for support of the circulation in individuals with diminished myocardial contractility, and its inhibition by beta-adrenergic receptor blockade may precipitate more severe failure. In Patients Without a History of Cardiac Failure: Continued depression of the myocardium with beta-blocking agents over a period of time can, in some cases, lead to cardiac failure. At the first sign or symptom of cardiac failure, Carteolol Hydrochloride should be discontinued.
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 Non-Allergic Bronchospasm: In patients with non-allergic bronchospasm or with a history of non-allergic bronchospasm (e.g., chronic bronchitis, emphysema), Carteolol Hydrochloride Ophthalmic Solution should be administered with caution since it may block bronchodilation produced by endogenous and exogenous catecholamine stimulation of beta2 receptors. 

‍Major Surgery: The necessity or desirability of withdrawal of beta-adrenergic blocking agents prior to major surgery is controversial. Beta-adrenergic receptor blockade impairs the ability of the heart to respond to beta-adrenergically mediated reflex stimuli. This may augment the risk of general anesthesia in surgical procedures. Some patients receiving beta-adrenergic receptor blocking agents have been subject to protracted severe hypotension during anesthesia. For these reasons, in patients undergoing elective surgery, gradual withdrawal of beta-adrenergic receptor blocking agents may be appropriate. If necessary during surgery, the effects of beta-adrenergic blocking agents may be reversed by sufficient doses of such agonists as isoproterenol, dopamine, dobutamine or levarterenol (see OVERDOSAGE).

‍DiabetesMellitus: Beta-adrenergic blocking agents should be administered with caution in patients subject to spontaneous hypoglycemia or to diabetic patients (especially those with labile diabetes) who are receiving insulin or oral hypoglycemic agents. Beta-adrenergic receptor blocking agents may mask the signs and symptoms of acute hypoglycemia. Thyrotoxicosis: Beta-adrenergic blocking agents may mask certain clinical signs (e.g.,tachycardia) of hyperthyroidism. Patients suspected of developing thyrotoxicosis should be managed carefully to avoid abrupt withdrawal of beta-adrenergic blocking agents which might precipitate a thyroid storm.

PRECAUTIONS

General

A-CARTEOL Eye Drops (Carteolol Hydrochloride Ophthalmic Solution USP 2% w/v) should be used with caution in patients with known hypersensitivity to other beta-adrenoceptor blocking agents.Use with caution in patients with known diminished pulmonary function. In patients with angle-closure glaucoma, the immediate objective of treatment is to reopen the angle. This requires constricting the pupil with a miotic. Carteolol has little or no effect on the pupil. When Carteolol is used to reduce elevated intraocular pressure in angle-closure glaucoma, it should be used with a miotic and not alone

Information to the Patient

For topical use only. To prevent contaminating the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use. Protect from light.

Risk from Anaphylactic Reaction

While taking beta-blockers, patients with a history of atopy or a history of severe anaphylactic reaction to a variety of allergens may be more reactive to repeated accidental, diagnostic or therapeutic challenge with such allergens. Such patients may be unresponsive to the usual doses of epinephrine used to treat anaphylactic reactions.

Muscle Weakness

Beta-adrenergic blockade has been reported to potentiate muscle weakness consistent with certain myasthenic symptoms(e.g., diplopia, ptosis and generalized weakness).

Drug Interactions

A-CARTEOL Eye Drops (Carteolol Hydrochloride Ophthalmic Solution USP 2% w/v) should be used with caution in patients who are receiving a beta-adrenergic blocking agent orally, because of the potential for additive effects on systemic beta-blockade. Close observation of the patient is recommended when a beta-blocker is administered to patients receiving catecholamine-depleting drugs such as reserpine, because of possible additive effects and the production of hypotension and/or marked bradycardia, which may produce vertigo, syncope, or postural hypotension.

Carcinogenesis,   Mutagenesis,   Impairment   of   Fertility  Carteolol hydrochloride did not produce carcinogenic effects at doses up to 40 mg/kg/day in two-year oral rat and mouse studies. Test of mutagenicity, including the Ames Test, recombinant (rec)-assay, in vivo cytogenetics and dominant lethal assay demonstrated no evidence for mutagenic potential. Fertility of male and female rats and male and female mice was unaffected by administration of carteolol hydrochloride dosages up to 150 mg/kg/day.

Pregnancy

Teratogenic Effects
‍PregnancyCategory C:  Carteolol hydrochloride increased resorptions and decreased fetal weights in rabbits and rats at maternally toxic doses approximately 1052 and 5264 times the maximum recommended human oral dose (10 mg/70 kg/day), respectively. A dose-related increase in wavy ribs was noted in the developing rat fetus when pregnant females received daily doses of approximately 212 times the maximum recommended human oral dose. No such effects were noted in pregnant mice subjected to up to 1052 times the maximum recommended human oral dose. There are no adequate and well-controlled studies in pregnant women. A-CARTEOL Eye Drops (Carteolol Hydrochloride Ophthalmic Solution USP2% w/v) 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, although in animal studies carteolol has been shown to be excreted in breast milk. Caution should be exercised when A-CARTEOL Eye Drops (Carteolol Hydrochloride Ophthalmic Solution USP 2% w/v) is administered to nursing mothers.

 Pediatric Use: Safety and effectiveness in pediatric patients have not been established.

ADVERSE REACTIONS

The following adverse reactions have been reported in clinical trials with Carteolol Hydrochloride Ophthalmic Solution.

Ocular:  Transient eye irritation, burning, tearing, conjunctival hyperemia and edema occurred in about 1 of 4 patients. Ocular symptoms including blurred and cloudy vision, photophobia, decreased night vision, and ptosis and ocular signs including blepharoconjunctivitis, abnormal corneal staining, and corneal sensitivity occurred occasionally.

‍Systemic: As is characteristic of nonselective adrenergic blocking agents, Carteolol may cause bradycardia and decreased blood pressure (See WARNINGS). The following systemic events have occasionally been reported with the use of A-CARTEOL Eye Drops (Carteolol Hydrochloride Ophthalmic Solution USP 2% w/v): cardiac arrhythmia, heart palpitation, dyspnea, asthenia, headache, dizziness, insomnia, sinusitis, and taste perversion.
The following additional adverse reactions have been reported with ophthalmic use of beta1 and beta2(nonselective) adrenergic receptor blocking agents:
Body As a Whole: Headache
Cardiovascular: Arrhythmia,
syncope,heart block, cerebralvascular accident, cerebralischemia, congestive heartfailure, palpitation (see WARNINGS).
Digestive: Nausea
Psychiatric: Depression
‍Skin: Hypersensitivity, including localized and generalized rash
‍Respiratory:Bronchospasm (predominantlyin patients with pre-existing bronchospasticdisease), respiratory failure(see WARNINGS)
‍Endocrine: Masked symptomsof hypoglycemia in insulin-dependent diabetics(see WARNINGS)
Special Senses:Signs and symptoms ofkeratitis, blepharoptosis, visual disturbancesincluding refractive changes(due to withdrawal of miotic therapy in some cases),diplopia, ptosis.
Other reactions associated with the oral use of nonselective adrenergic receptor blocking agents should be considered potentialeffects with ophthalmic use of these agents.

OVERDOSAGE

No specific information on emergency treatment of overdosage in humans is available. Should accidental ocular overdosage occur, flush eye(s) with water or normal saline. The most common effects expected with overdosage of a beta-adrenergic blocking agent are bradycardia, bronchospasm, congestive heart failure and hypotension.
In case of ingestion, treatment with A-CARTEOL Eye Drops (Carteolol Hydrochloride Ophthalmic Solution USP 2% w/v) should be discontinued and gastric lavage considered. The patient should be closely observed and vital signs carefully monitored. The prolonged effects of carteolol must be considered when determining the duration of corrective therapy. On the basis of the pharmacologic profile, the following additional measures should be considered          as          appropriate:
‍Symptomatic Sinus Bradycardia or Heart Block: Administer atropine. If there is no response to vagal blockade, administer isoproterenol cautiously.
‍Bronchospasm: Administer a beta2-stimulating agent such as isoproterenol and/or a theophylline derivative.
Congestive Heart Failure: Administer diuretics and digitalis glycosides as necessary. Hypotension: Administer vasopressors such as intravenous dopamine, epinephrine or norepinephrine bitartrate.

DOSAGE AND ADMINISTRATION

The usual dose is one drop of A-CARTEOL Eye Drops (Carteolol Hydrochloride Ophthalmic Solution USP 2% w/v) in the affected eye(s) twice a day. If the patient's IOP is not at a satisfactory level on this regimen, concomitant therapy with pilocarpine and other miotics, and/or epinephrine or dipivefrin, and/or systemically administered carbonic anhydrase inhibitors, such as acetazolamide, can be instituted.

SHELF LIFE

24 Months

STORAGE

Keep in a cool & dark place. Store below 30°C. Do not allow to freeze.

HOW SUPPLIED

A-CARTEOL EYEDROPS (Carteolol  Hydrochloride Ophthalmic Solution USP 2% w/v) is supplied in 5 mL poly bottle. 
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A-Carteol

Alfapres-TH/5mL EYE DROPS

( Brimonidine Tartrate & Timolol Eye Drops)

THIS LEAFLET CONTAINS IMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER FUTURE REFERENCE

DESCRIPTION:

ALFAPRES-TH (Brimonidine Tartrate& Timolol Eye Drops) is a relatively selective alpha- 2   adrenergic agonist for ophthalmic use.
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COMPOSITION:

Each ML Contains :

• Brimonidine Tartrate IP                         2 mg
• Timolol Maleate IP
   eq.  to  Timolol                                       5 mg
   Benzalkonium Chloride
    Solution IP      0.005 % w/v
  (As preservative)
• Isotonic  Aqueous  Vehicle                    q.s.
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STORAGE

Keep in a cool & dark place.
Store   Below   25ºC.
Do not allow to Freeze.

INDICATION

ALFAPRES-TH ophthalmic solution is indicated for the control of intraocular pressure(IOP) in patients with chronic open-angle glaucoma or ocular hypertension who are stabilized on the individual components given at the same dosages.

DOSAGE AND ADMINISTRATION

The recommended dose is one drop of ALFPRES-TH in the affected eye(s) twice daily, approximately 12 hours apart.

HOW SUPPLIED

ALFAPRES-TH (Brimonidine Tartrate& Timolol Eye Drops ) Sterile solution is available in 5 mL Poly bottle.

SHELF LIFE

24 months

PACKAING

Primary packing- 5ml Opaque poly bottles White caps & Nozzles
Secondary Packing- Labels, Cartons, Shrink Pack & Shipper box
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Alfapres-TH

APPACARPINE HS 2% w/v

(Pilocarpine Eye Drops IP 2% w/v)

THIS LEAFLET CONTAINS IMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER FUTURE REFERENCE

DESCRIPTION:

Appacarpine HS 2% w/v (Pilocarpine Eye Drops IP 2% w/v) belongs to a group of medicine called miotics. It is used in the treatment of glaucoma and other eye conditions. It lowers the high pressure inside the eye and helps prevent vision loss and nerve damage.

COMPOSITION:

Each ML Contains :

• Pilocarpine Nitrate IP                        20 mg
• Chlorbutol   IP                                      5mg
   (As preservative)
• Aqueous  Vehicle                               q.s.
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INDICATION AND USAGE

Appacarpine HS 2% w/v (Pilocarpine Eye Drops IP 2% w/v) contains a miotic agent. It is used to make the pupil of the eye smaller. Your doctor or eye specialist may use it to:
•    Reverse the effects of eye drops which cause the pupil to enlarge.
•   Treat high pressure of liquid inside the eye (glaucoma) in emergency situation.
This medicine is indicated for children, adults and the elderly.

CLINICAL PHARMACOLOGY

Pharmacodynamic properties
Pharmacotherapeutic group:   parasympathomimetics, ATC code: S01EB01
‍
Pilocarpine is a direct acting parasympathomimetic drug. It duplicates the muscarinic effect of acetyl choline, but not its nicotinic effects. Consequently, Pilocarpinestimulates the smooth muscle and secretary glands but does not affect the striated muscle.

Paediatric population
‍There are literature reports of the ocular use of Pilocarpine in concentrations up to 2% in patients aged 1 month and older. However, information on the dose and strength used is limited. Safety data do not suggest any significant safety issues in children, or any difference between the safety profiles of Pilocarpine in children and adults.

Pharmacokinetic properties
Pilocarpine has a low ocular bioavailability when topically applied and this has been attributed to extensive pre-corneal drug loss in conjunction with the resistance to normal corneal penetration. Further, Pilocarpine appears to bind to the eye pigments from which it is gradually released to the muscles. Inactivation of Pilocarpine in the eye is thought to occur by a hydrolyzing enzyme. The amount of this enzyme is not changed by the prolonged use of Pilocarpine by glaucoma patients, nor is it changed in patients poorly controlled by glaucoma therapy
‍
‍Preclinical   safety   data
There are no preclinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

CONTRAINDICATIONS

Conditions where pupillary constriction is undesirable e.g.acute iritis, anterior uveitis and some forms of secondary glaucoma.                                                                       Patients with soft contact lenses should not use this preparation. Hypersensitivity to the active substance or to any of the excipients

WARNINGS AND PRECAUTIONS

Systemic reactions rarely occur when treating chronic simple glaucoma at normal doses. However, in the treatment of acute closed-angle glaucoma the possibility of systemic reactions must be considered because of the higher doses given. Caution is particularly advised in patients with acute heart failure, bronchial asthma, peptic ulceration, hypertension, urinary tract obstruction, Parkinson's disease and corneal abrasions.

Retinal detachments have been caused in susceptible individuals and those with pre-existing retinal disease, therefore, fundus examination is advised in all patients prior to the initiation of therapy. 

Patients with chronic glaucoma on long-term Pilocarpine therapy should have regular monitoring of intraocular pressure and visual fields. 

Systemic absorption may be reduced by compressing the lacrimal sac at the medial canthus for one minute during and following the instillation of the drops. (This blocks the passage of the drops via the naso-lacrimal duct to the wide absorptive area of the nasal and pharyngeal mucosa. It is especially advisable in children.)

Interaction with other medicinal products and other forms of interaction 
‍
Although clinically not proven, the miotic effects of Pilocarpine may be antagonised by long-term topical or systemic corticosteroid therapy, systemic anticholinergics, antihistamines, pethidine, sympathomimetics or tricyclic antidepressants. Concomitant administration of two miotics is not recommended because of inter-drug antagonism and the risk that unresponsiveness may develop to both drugs.

Fertility, pregnancy and lactation
Safety for use in pregnancy and lactation has not been established, therefore, use only when clearly indicated.
‍
Effects on ability to drive and use machines
Causes difficulty with dark adaptation, therefore, caution is necessary when night driving and when hazardous tasks are undertaken in poor illumination. May cause accommodation spasm. Patients should be advised not to drive or use machinery if vision is not clear. 
Overdose
If accidentally ingested, induce emesis or perform gastric lavage. Observe for signs of toxicity (salivation, lacrimation, sweating, bronchial spasm, cyanosis, nausea, vomiting and diarrhoea)

ADVERSE REACTIONS

Adverse drug reactions from clinical trials are listed by MedDRA system organ class. Within each system organ class, the adverse drug reactions are ranked by frequency, with the most frequent reactions first. In addition, the corresponding frequency category for each adverse drug reaction is based on 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), not known (cannot be estimated from the available data).

System Organ Class

Frequency

Undesirable Effect

Eye disorders

Not Known
























Not known

‍

Burning, Itching, Smarting, Blurring of vision, ciliary spasm, conjunctival vascular congestion, induced myopia, sensitisation of the lids and conjunctiva, reduced visual  acity in poor illumination, lens  changes with chronic use,  increased papillary block, retinal detachments and vitreous haemorrhages.



Lacrimation

Nervous System disorders

Not Known





Not Known

Browache and headache(especially in younger patients who have just started therapy).


Sweating,Salivation
‍

Cardiac Disorders

Not Known

Bradycardia

Vascular Disorders

Not Known

Hypotension

Respiratory, Thoracicand mediastinal disorders

Not Known

Pulmonary oedema, bronchial spasm

Gastrointestinal Disorders

Not Known

nausea, vomiting and diarrhoea

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme,

DOSAGE AND ADMINISTRATION

Adults (including the elderly) Instil dropwise into the eye according to the recommended dosage. To induce miosis, one or two drops should be used. In cases of emergency treatment of acute narrow-angle glaucoma, one drop should be used every five minutes until miosis is achieved. Pediatric population Based on the infrequency of reports of adverse events in children, and the extensive experience of use of Pilocarpine in childhood glaucoma, concentrations of up to 2% may be safely used in children. Treatment should be started with the lowest available dose and concentration in patients under 18 years of age. Depending on clinical response and tolerability, the dose may be increased up to the maximum recommended adult dosage of the 2% Pilocarpine eye drop solution. Directly after administration of any dose, the lacrimal punctum should be occluded for one minute with a finger to limit systemic exposure.

STORAGE

Store protected from light and moisture. Store below 25°C. Do not allow to Freeze

SHELF LIFE

24 Months

HOW SUPPLIED:

Appacarpine HS 2% w/v (Pilocarpine Eye Drops IP 2% w/v) supplied in 5 mL sterile poly bottle.
‍

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Appacarpine HS

BIMPOST 0.1

(Bimatoprost Ophthalmic Solution 0.01% w/v)

THIS LEAFLET CONTAINS IMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER FUTURE REFERENCE

DESCRIPTION:

BIMPOST 0.1 (Bimatoprost Ophthalmic Solution0.01%w/v) is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is (Z)-7[(1R,2R,3R,5S)-3,5-Dihydroxy-2-[(1E,3S)-3- hydroxy-5-phenyl-1-pentenyl]cyclopentyl] 5-N-ethylheptenamide, and its molecular weight is415.58. Its molecular formula is C25H37NO4.

COMPOSITION:

Each ML Contains :

•Bimatoprost                 0.1 mg
• Benzalkonium Chloride SolutionIP     0.2 mg
   (As preservative)
• Aqueous Buffered Vehicle                                                   q.s.
‍

CLINICAL PHARMACOLOGY

Mechanism of Action Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

NONCLINICAL TOXICOLOGY

Carcinogenesis,   Mutagenesis,   Impairment  of   Fertility Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavageat doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times the recommended human exposure based on blood AUC levels respectively) for 104 weeks

Bimatoprost was not mutagenic or clastogenicin the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (at least 103 times the recommended human exposure based on blood AUC levels).

Pregnancy                                                                                                                          Pregnancy Category C Teratogenic effects: In embryo/fetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of Bimatoprost which achieved at least 33 or 97 times, respectively, the maximum intended human exposure based on blood AUC levels. At doses at least 41 times the maximum intended human exposure based on blood AUC levels, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup body weights were reduced. There are no adequate and well- controlled studies of BIMPOST0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) administration in pregnant women. Because animal reproductive studies are not always predictive of human response BIMPOST 0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v)should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus. Nursing Mothers It is not known whether BIMPOST 0.1(Bimatoprost Ophthalmic Solution 0.01%w/v) is excreted in human milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when BIMPOST 0.1 (Bimatoprost Ophthalmic Solution0.01%w/v) is administered to a nursing woman.

Pediatric Use
  Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

OVERDOSAGE

No information is available on over dosage in humans. If overdose with BIMPOST 0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) occurs, treatment should be symptomatic. In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 is at least 70 times higher than the accidental dose of one bottle of BIMPOST 0.1 for a 10 kg child.

ADVERSE REACTIONS

Clinical Studies Experience: Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In clinical studies with BIMPOST 0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) the most common adverse event was conjunctival hyperemia (range 25% – 45%). Approximately 0.5% to 3% of patients discontinued therapy due to conjunctival hyperemia with 0.01%Bimatoprost Ophthalmic Solutions. Other common events (>10%) included growth of eyelashes, and ocular pruritus.

CONTRAINDICATIONS:

None

WARNINGS AND PRECAUTIONS

Pigmentation
Bimatoprost Ophthalmic Solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue(eyelid) and eyelashes. Pigmentation is expectedto increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of Bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment.

DOSAGE AND ADMINISTRATION:

The recommended dosage is one drop in the affected eye(s) once daily in the evening. BIMPOST0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v)should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect. Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to12 hours.

STORAGE:

Store in dry place at a temperature not exceeding 25°C.
Do not allow to Freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

BIMPOST 0.1 / 3mL (Bimatoprost Ophthalmic Solution0.01%w/v) is supplied in 5 mL sterile poly bottle
‍

Aod address

BIMPOST 0.1

BIMPOST ®

(Bimatoprost Ophthalmic Solution 0.03% w/v)

DESCRIPTION:

BIMPOST (Bimatoprost Ophthalmic Solution 0.03%w/v) is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is (Z)-7 [(1R,2R,3R,5S)-3,5-Dihydroxy-2- [(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl] 5-N-ethylheptenamide, and its molecular weight is 415.58. Its molecular formula is C25H37NO4.

COMPOSITION:

Each ML Contains :

•Bimatoprost                  0.3 mg
• Benzalkonium Chloride Solution  USP                 0.1 mg
   (As preservative)
• Aqueous Buffered Vehicle                                                   q.s.
‍

CLINICAL PHARMACOLOGY

Mechanism of Action Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believedto lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

NONCLINICAL TOXICOLOGY

Carcinogenesis,   Mutagenesis,   Impairment  of   Fertility Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times the recommended human exposure based on blood AUC levels respectively) for 104 weeks

Bimatoprost was not mutagenic or clastogenicin the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (at least 103 times the recommended human exposure based on blood AUC levels).

Pregnancy                                                                                                                          Pregnancy Category C Teratogenic effects: In embryo/fetal developmental studies in pregnant mice and rats, abortionwas observed at oral doses of Bimatoprost which achieved at least33 or 97 times, respectively, the maximum intended human exposure based on blood AUC levels. At doses at least 41 times the maximum intended human exposure based on blood AUC levels, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup body weights were reduced. There are no adequate and well-controlled studies of BIMPOST0.01% and 0.03% (Bimatoprost Ophthalmic Solution) administration in pregnant women. Because animal reproductive studies are not always predictive of human response BIMPOST should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers
It is not known whether BIMPOST is excreted in human milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when BIMPOST is administered to a nursing woman.

Pediatric Use
Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

OVERDOSAGE

No information is available on over dosage in humans. If overdose with BIMPOST 0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) occurs, treatment should be symptomatic. In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 is at least 70 times higher than the accidental dose of one bottle of BIMPOST 0.1 for a 10 kg child.

ADVERSE REACTIONS

Clinical Studies Experience: Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. In clinical studies with BIMPOST 0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) the most common adverse event was conjunctival hyperemia (range 25% – 45%). Approximately 0.5% to 3% of patients discontinued therapy due to conjunctival hyperemia with 0.01%Bimatoprost Ophthalmic Solutions. Other common events (>10%) included growth of eyelashes, and ocular pruritus.

CONTRAINDICATIONS:

None

WARNINGS AND PRECAUTIONS

Pigmentation
Bimatoprost Ophthalmic Solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue(eyelid) and eyelashes. Pigmentation is expectedto increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of Bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment.

DOSAGE AND ADMINISTRATION:

The recommended dosage is one drop in the affected eye(s) once daily in the evening. BIMPOST (Bimatoprost Ophthalmic Solution 0.03% w/v) should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect. Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

STORAGE:

Keep  in   a  cool   &   dark  place.
Store below 30°C. Do not allow to freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

BIMPOST (BimatoprostOphthalmic Solution 0.03%w/v) is supplied in one Polethylene Bottle packed with printed labelled & cartons And Such 25 Carton Packed in a Shrink Sleeves & corrugated box.
‍

Aod address

BIMPOST 3mL

BIMPOST PF-0.1

(Bimatoprost Ophthalmic Solution 0.01% w/v)

THIS LEAFLET CONTAINS IMPORTANTPRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLYAND RETAIN FOR FURTHER FUTURE REFERENCE.

DESCRIPTION:

BIMPOST PF-0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is (Z)-7 [(1R,2R,3R,5S)-3,5-Dihydroxy-2- [(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl] 5-N-ethylheptenamide, and its molecular weight is 415.58.Its molecular formula is C25H37NO4.

COMPOSITION:

Each ML Contains :

•Bimatoprost             0.1 mg
• Aqueous Buffered Vehicle                                                   q.s.
‍

CLINICAL PHARMACOLOGY

Mechanism of Action Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

NONCLINICAL TOXICOLOGY

Carcinogenesis,   Mutagenesis,   Impairment  of   Fertility Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times the recommended human exposure based on blood AUC levels respectively) for 104 weeks

Bimatoprost was not mutagenic or clastogenicin the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (at least 103 times the recommended human exposure based on blood AUC levels).

Pregnancy                                                                                                                         Pregnancy Category C Teratogenic effects: In embryo/fetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of Bimatoprost which achieved at least 33 or 97 times, respectively, the maximum intended human exposure based on blood AUC levels. At doses at least 41 times the maximum intended human exposure based on blood AUC levels, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup body weights were reduced. There are no adequate and well- controlled studies of BIMPOST PF-0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) administration in pregnant women. Because animal reproductive studies are not always predictive of human response BIMPOST PF-0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v)should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers
It is not known whether BIMPOST PF-0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) is excreted inhuman milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when BIMPOST PF-0.1 (Bimatoprost Ophthalmic Solution0.01%w/v) is administered to a nursing woman.

Pediatric Use
Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

OVERDOSAGE

No information is available on over dosage in humans. If overdose with BIMPOST PF-0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) occurs, treatment should be symptomatic. In oral(by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 is at least70 times higher than the accidental dose of one bottle of BIMPOST PF-0.1for a 10 kg child.

ADVERSE REACTIONS

Clinical Studies Experience: Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. 

In clinical studies with BIMPOST PF-0.1(Bimatoprost Ophthalmic Solution 0.01%w/v) the most common adverse event was conjunctival hyperemia (range 25% – 45%). Approximately 0.5% to 3% of patients discontinued therapy due to conjunctival hyperemia with 0.01%Bimatoprost Ophthalmic Solutions. Other common events (>10%) included growth of eyelashes, and ocular pruritus.

CONTRAINDICATIONS:

None

WARNINGS AND PRECAUTIONS

Pigmentation
Bimatoprost Ophthalmic Solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue(eyelid) and eyelashes. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of Bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment.

DOSAGE AND ADMINISTRATION:

The recommended dosage is one drop in the affected eye(s) once daily in the evening. BIMPOST PF-0.1 (Bimatoprost Ophthalmic Solution 0.01%w/v) should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect. Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

STORAGE:

Store in dry place at a temperature not exceeding 25°C.
Do not allow to Freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

BIMPOST PF-0.1 / 3mL (Bimatoprost Ophthalmic Solution 0.01%w/v)is supplied in 5 mL sterile poly bottle.
‍

Aod address

BIMPOST PF_0.1

BIMPOST PF-0.3 Eye Drops

      Preservative Free

 (Bimatoprost Ophthalmic Solution)

DESCRIPTION:

BIMPOST PF-0.3 Bimatoprost Ophthalmic Solution) is a synthetic prostamide analog with ocular hypotensive activity. Its chemical name is (Z)-7 [(1R,2R,3R,5S)-3,5-Dihydroxy-2- [(1E,3S)-3-hydroxy-5-phenyl-1-pentenyl]cyclopentyl] 5-N-ethylheptenamide, and its molecular weight is 415.58. Its molecular formula is C25H37NO4.

COMPOSITION:

Each ML Contains :

•Bimatoprost             0.3 mg
 • Aqueous Buffered Vehicle                                                   q.s.
‍

CLINICAL PHARMACOLOGY

Mechanism of Action Bimatoprost, a prostaglandin analog, is a synthetic structural analog of prostaglandin with ocular hypotensive activity. It selectively mimics the effects of naturally occurring substances, prostamides. Bimatoprost is believed to lower intraocular pressure (IOP) in humans by increasing outflow of aqueous humor through both the trabecular meshwork and uveoscleral routes. Elevated IOP presents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss.

NONCLINICAL TOXICOLOGY

Carcinogenesis,   Mutagenesis,   Impairment  of   Fertility Bimatoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 2 mg/kg/day and 1 mg/kg/day respectively (at least 192 and 291 times the recommended human exposure based on blood AUC levels respectively) for 104 weeks

Bimatoprost was not mutagenic or clastogenicin the Ames test, in the mouse lymphoma test, or in the in vivo mouse micronucleus tests. Bimatoprost did not impair fertility in male or female rats up to doses of 0.6 mg/kg/day (at least 103 times the recommended human exposure based on blood AUC levels).

Pregnancy                                                                      Pregnancy Category C Teratogenic effects: In embryo/fetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of Bimatoprost which achieved at least 33 or 97 times, respectively, the maximum intended human exposure based on blood AUC levels. At doses at least 41 times the maximum intended human exposure based on blood AUC levels, the gestation length was reduced in the dams, the incidence of dead fetuses, late resorptions, peri- and postnatal pup mortality was increased, and pup body weights were reduced. There are no adequate and well- controlled studies of BIMPOST PF-0.3 (Bimatoprost Ophthalmic Solution ) administration in pregnant women. Because animal reproductive studies are not always predictive of human response BIMPOST PF-0.3 should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers
It is not known whether BIMPOST PF-0.3  is excreted inhuman milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. Because many drugs are excreted in human milk, caution should be exercised when BIMPOST PF-0.3 is administered to a nursing woman.

Pediatric Use
Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

OVERDOSAGE

No information is available on over dosage in humans. If overdose with BIMPOST PF-0.3 (Bimatoprost Ophthalmic Solution ) occurs, treatment should be symptomatic. In oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 is at least70 times higher than the accidental dose of one bottle of BIMPOST PF-0.3 for a 10 kg child.

ADVERSE REACTIONS

Clinical Studies Experience: Because clinical studies are conducted under widely varyingconditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice. 

In clinical studies with BIMPOST PF-0.3 (Bimatoprost Ophthalmic Solution ) the most common adverse event was conjunctival hyperemia (range 25% – 45%). Approximately 0.5% to 3% of patients discontinued therapy due to conjunctival hyperemia with 0.03% Bimatoprost Ophthalmic Solutions. Other common events (>10%) included growth of eyelashes, and ocular pruritus.

CONTRAINDICATIONS:

None

WARNINGS AND PRECAUTIONS

Pigmentation
Bimatoprost Ophthalmic Solution has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris, periorbital tissue(eyelid) and eyelashes. Pigmentation is expected to increase as long as bimatoprost is administered. The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After discontinuation of Bimatoprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are not known. Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment.

DOSAGE AND ADMINISTRATION:

The recommended dosage is one drop in the affected eye(s) once daily in the evening. BIMPOST PF-0.3 (Bimatoprost Ophthalmic Solution ) should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the intraocular pressure lowering effect. Reduction of the intraocular pressure starts approximately 4 hours after the first administration with maximum effect reached within approximately 8 to 12 hours.

STORAGE:

Store in dry place at a temperature not exceeding 30°C.
Do not allow to Freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

BIMPOST PF-0.3 / 3mL (Bimatoprost Ophthalmic Solution ) is supplied in 5 mL sterile poly bottle.
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Aod address

BIMPOST PF_0.3

BIMPOST - T

(Bimatoprost & Timolol Eye Drops)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION:

BIMPOST-T (Bimatoprost & Timolol Eye Drops) is used in the treatment of glaucoma and ocular hypertension. Bimatoprost is a prostaglandin analogue while Timolol is a beta blocker. They work by decreasing the production of aqueous humour (fluid in the eye), thereby lowering the increased eye pressure. It may also be used as an eye solutionto help hypotrichosis, a condition of the eye lashes where hair growth is deficient.

COMPOSITION:

Each ML Contains :

•Bimatoprost             0.3 mg
•Timolol Maleate USP
 Eq. to Timolol                         5.0mg
• Aqueous Buffered Vehicle                                     q.s.
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INDICATION

BIMPOST-T (Bimatoprost & Timolol Eye Drops) contains two different active substances (Bimatoprost and Timolol) that both reduce pressure in the eye. Bimatoprost belongs to a group of medicines called prostamides, a prostaglandin analogue. Timolol belongs to a group of medicines called beta-blockers. 
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Your eye contains a clear, watery liquid that feeds the inside of the eye. Liquid is constantly being drained out of the eye and new liquid is made to replace this. If the liquid cannot drain out quickly enough, the pressure inside the eye builds up and could eventually damage your sight (an illness called glaucoma). BIMPOST-T (Bimatoprost & Timolol Eye Drops) works by reducing the production of liquid and also increasing the amount of liquid that is drained. This reduces the pressure inside the eye. 
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BIMPOST-T (Bimatoprost & Timolol Eye Drops) are used to treat high pressure in the eye in adults, including the elderly. This high pressure can lead to glaucoma. Your doctor will prescribe you BIMPOST-T (Bimatoprost & Timolol Eye Drops) when other eye drops containing beta-blockers or prostaglandin analogues have not worked sufficiently on their own.

CLINICAL PHARMACOLOGY

Pharmacodynamic properties
‍Pharmacotherapeutic group: Ophthalmological,– Beta-Blocking Agents.

Mechanism of action
BIMPOST-T (Bimatoprost & Timolol Eye Drops) consists of two active substances: Bimatoprost and Timolol Maleate. These two components decrease elevated intraocular pressure (IOP) by complementary mechanisms of action and the combined effect results in additional IOP reduction compared to either compound administered alone. BIMPOST-T (Bimatoprost &Timolol Eye Drops) has a rapid onset of action. Bimatoprost is a potent ocular hypotensive active substance . It is a synthetic prostamide, structurally related to prostaglandin F2α (PGF2α) that does not act through any known prostaglandin receptors. Bimatoprost selectively mimics the effects of newly discovered biosynthesised substances called prostamides. The prostamide receptor, however, has not yet been structurally identified. The mechanism of action by which bimatoprost reduces intraocular pressure in man is by increasing aqueous humour outflow through the trabecular meshwork and enhancing uveoscleral outflow. Timolol Maleate is a beta1 and beta2 non-selective adrenergic receptor blocking agent that does not have significant intrinsic sympathomimetic, direct myocardial depressant, or local anaesthetic (membrane-stabilising) activity. Timolol Maleate lowers IOP by reducing aqueous humour formation. The precise mechanism of action is not clearly established, but inhibition of the increased cyclic AMP synthesis caused by endogenous beta-adrenergic stimulation is probable. 
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Clinical effects
The IOP-lowering effect of BIMPOST-T  (Bimatoprost & Timolol Eye Drops) is non-inferior to that achieved by adjunctive therapy of bimatoprost (once daily) and timolol (twice daily).
Existing literature data for BIMPOST-T (Bimatoprost &Timolol Eye Drops) suggest that evening dosing may be more effective in IOP lowering than morning dosing. However, consideration should be given to the likelihood of compliance when considering either morning or evening dosing.

Paediatric population
The safety and efficacy of BIMPOST-T (Bimatoprost & Timolol Eye Drops) in children aged 0 to 18 years has not been established.

DOSAGE AND ADMINISTRATION

The correct dosage will depend on the condition being treated and the individual patient. Strictly follow all instructions given by your doctor. Never self-medicate or adjust your dose yourself. When treating glaucoma, the usually dose is 1 drop per day administered to the affected eye. When used to treat hypotrichosis it must be administered using a single-use applicator which can be bought. Application is fairly easy, simply drop the solution onto the applicator and brush across the base of the eyelash. Use a new applicator for each eye, throwing the used applicator away each time.

CONTRAINDICATIONS

- - Reactive airway disease including bronchial asthma or a history of bronchial asthma, severe chronic obstructive pulmonary disease.
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--  Sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block, not controlled with pace-maker. Overt cardiac failure, cardiogenic shock.

WARNINGS AND PRECAUTIONS


Like other topically applied ophthalmic medicinal products, the active substances (TimololMaleate/ Bimatoprost) in BIMPOST-T (Bimatoprost & Timolol Eye Drops) may be absorbed systemically. No enhancement of the systemic absorption of the individual active substances has been observed. Due to the beta-adrenergic component, Timolol, the same types of cardiovascular, pulmonary and other adverse reactions as seen with systemic beta-blockers may occur. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration.

COMMON SIDE EFFECTS

Eye pain, Stinging sensation, Foreign body sensation, Itching, Irritation, Burning sensationin eye, Darkening of eyelashes, Change in color of iris.

ADVERSE REACTIONS

The adverse reactions reported in clinical studies using BIMPOST-T (Bimatoprost & Timolol Eye Drops) were limited to those earlier reported for either of the single active substances bimatoprost and timolol. No new adverse reactions specific for BIMPOST-T (Bimatoprost &Timolol Eye Drops) have been observed in clinical studies.

The majority of adverse reactions reported in clinical studies using BIMPOST-T (Bimatoprost & Timolol Eye Drops) were ocular, mild in severity and none were serious. Based on 12-monthclinical data, the most commonly reported adverse reaction was conjunctival hyperaemia (mostly trace to mild and thought to be of a non-inflammatory nature) in approximately 26% of patients and led to discontinuation in 1.5% of patients.

STORAGE:

Store in dry place at a temperature not exceeding 30°C.
Do not allow to Freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

BIMPOST-T / 3mL (Bimatoprost & Timolol Eye Drops)  sterile solution is supplied in 5 mL Poly bottle.
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Aod address

BIMPOST T

BRINZO B Eye Drops

(Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION:

Brinzo-B Eye Drops(Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) is a fixed combination of a carbonic anhydrase inhibitor and an alpha 2 adrenergic receptor agonist.Brinzolamide is describedchemically as: (R)-(+)-4- Ethylamino-2-(3-methoxypropyl)-3,4dihydro-2H- thieno [3,2-e]-1,2-thiazine-6-sulfonamide-1,1- dioxide.Its empirical formulais C12H21N3O5S3, and its structural formula is:
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Brinzo B


Brinzolamide has a molecularweight of 383.5. It is a white powder, which is insolublein water, very soluble in methanol and soluble in ethanol. Brimonidinetartrate is described chemically as: 5-bromo-6-(2-imidazolidinylideneamino) quinoxaline L-tartrate. Its empirical formula of C11H10BrN5 – C4H6O6, and its structural formulais :

Brinzo B


Brimonidine tartrate has a molecular weight of 442.2.It is a white to yellow powderthat is solublein water (34 mg/mL) at pH 6.0 to 7.5. Brinzo-B Eye Drops (Brinzolamide & Brimonidine TartrateOphthalmic Suspension) is supplied as a sterile, aqueous suspension which hasbeen formulated to be readily suspended following shaking. It has a pH of approximately 6.5 and an osmolality of approximately 270 mOsm/kg.

COMPOSITION:

Each ML Contains :

•Brinzolamide   USP   1 % w/v
•Brimonidine Tartrate USP                             0.2% w/v
 Stabilized Oxychloro Complex 0.005% w/v
(As preservative)
• Sterile Aqueous Vehicle                                  q.s.
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INDICATIONS AND USAGE

Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) is a fixed combination of a carbonic anhydrase inhibitor and an alpha 2 adrenergic receptor agonist indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.
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CLINICAL PHARMACOLOGY


Mechanism of action
Brinzo -B Eye Drops is comprised of two components: Brinzolamide (carbonic anhydrase inhibitor) and Brimonidine tartrate (alpha 2 adrenergic receptor agonist).Each of these two components decreases elevated intraocular pressure. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage. Brinzolamide inhibits carbonic anhydrase in the ciliary processes of the eye to decrease aqueous humor secretion, presumably by slowing the formation of bicarbonate ions with subsequent reduction in sodium and fluid transport. Brinzolamide has a peak ocular hypotensive effect occurring at 2 to 3 hours post-dosing. Fluorophotometric studies in animals and humans suggest that brimonidine tartrate has a dual mechanism of action by reducing aqueous humor production and increasing uveoscleral outflow. Brimonidine tartrate has a peak ocular hypotensive effect occurring at two hours post-dosing. The result is a reduction in intraocular pressure(IOP).
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Pharmacokinetics
‍Following topical ocular administration, brinzolamide is absorbed into the systemic circulation. 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). In humans, 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 <10 ng/mL. Binding to plasma proteins is approximately 60%. Brinzolamide is eliminated predominantly in the urine as unchanged drug. N-Desethylbrinzolamide is also found in the urine along with lower concentrations of the Ndesmethoxypropyl and O-desmethyl metabolites. After ocular administration of a 0.2% solution of brimonidine tartrate, plasma concentrations peaked within 1 to 4hours and declined with a systemic half-life of approximately 3 hours. In humans, systemic metabolism of brimonidine is extensive. It is metabolized primarily by the liver. Urinary excretion is the major route of elimination of the drug and its metabolites. Approximately 87% of anorally-administered radioactive dose was eliminated within 120 hours, with 74%found in the urine. In humans, a study was conducted to evaluate the pharmacokinetics of the fixed combination of brinzolamide / brimonidine tartrate 1%/0.2% ophthalmic suspension. Healthy volunteers were randomly assigned to receive twice or three times a day either the fixed combination, or either of its individual components, brinzolamide or brimonidine. Subjects who were assigned to the brinzolamide alone or combination arms were administered oral brinzolamide capsules for two weeks prior to beginning dosing with the topical ocular suspension. The results demonstrate that the systemic plasma exposure (AUC and Cmax) to brinzolamide and brimonidine in humans is similar after dosing with the fixed combination to that observed following dosing with the individual components.

DOSAGE AND ADMINISTRATION

The recommended dose isone drop of Brinzo-B Eye Drops (Brinzolamide & Brimonidine TartrateOphthalmic Suspension) in the affectedeye(s) three times daily. Shake well before use. Brinzo-B Eye Drops (Brinzolamide &Brimonidine Tartrate Ophthalmic Suspension) may be used concomitantly with other topicalophthalmic drug productsto lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs shouldbe administered at least five(5) minutes apart.

CONTRAINDICATIONS

Brinzo-B Eye Drops(Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) is contraindicated in the following patients:
-- Patients with hypersensitivity to brinzolamide, brimonidine, or to any ingredient in the formulation or component of the container (for a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph).
--Hypersensitivity to sulfonamides
--Patients receiving monoamine oxidase (MAO) inhibit or therapy
-- Patients on antidepressants that affect noradrenergic transmission
--Patients with severe renal impairmentŸ  Patients with hyperchloroaemic acidosis
--Neonates and infants under the age of 2 years

WARNINGS AND PRECAUTIONS


Brinzo-B Eye Drops (Brinzolamide& Brimonidine Tartrate Ophthalmic Suspension) contains Brinzolamide,  a  sulfonamide,  and  although  administered  topically  is absorbed systemically. Therefore, the same types of adverse reactions that are attributable to sulfonamides may occur with topical administration of Brinzo-B Eye Drops (Brinzolamide & Brimonidine  Tartrate  Ophthalmic  Suspension).  Fatalities  have  occurred 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 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 Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) to this group of patients.
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Severe Renal Impairment
‍Brinzo-B Eye Drops(Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) has not been specifically studied in patients with severe renal impairment (CrCl< 30 mL/min). Since brinzolamide and its metabolite are excreted predominantly by the kidney, Brinzo-B Eye Drops (Brinzolamide& Brimonidine Tartrate Ophthalmic Suspension)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. Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) has not been studied in patients with acute angle- closure glaucoma. Contact Lens Wear The preservative in Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension), benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of Brinzo-B Eye Drops(Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) but may be reinserted 15 minutes after instillation. Severe Cardiovascular Disease Brimonidine tartrate, a component of Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic  Suspension),  has  a  less  than  5%  mean  decrease  in blood pressure 2 hours after dosing in clinical studies; caution should be exercised in treating patients with severe cardiovascular disease. Severe Hepatic Impairment Because brimonidine tartrate, a component of Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension), has not been studied in patients with hepatic impairment, caution should be exercised in such patients.
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Acute Angle-Closure Glaucoma
‍The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) has not been studied in patients with acute angle- closure glaucoma.

Contact Lens Wear
The preservative in Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension), benzalkonium chloride, may be absorbed by soft contact lenses. Contact lenses should be removed during instillation of Brinzo-B Eye Drops(Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) but may be reinserted 15 minutes after instillation.

Severe Cardiovascular Disease
Brimonidine tartrate, a component of Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic  Suspension),  has  a  less  than  5%  mean  decrease  in blood pressure 2 hours after dosing in clinical studies; caution should be exercised in treating patients with severe cardiovascular disease.

Severe Hepatic Impairment
Because brimonidine tartrate, a component of Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension), has not been studied in patients with hepatic impairment, caution should be exercised in such patients.

Potentiation of Vascular Insufficiency
Brimonidine tartrate, a component of Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension), may potentiate syndromes associated with vascular insufficiency. Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) should be used with caution inpatients with depression, cerebral or coronary insufficiency, Raynaud’s phenomenon, orthostatic hypotension, or thromboangitis obliterans.
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 Contamination   of  Topical   Ophthalmic   Products  After  Use
There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers have been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface.
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ADVERSE REACTIONS

Clinical Studies Experience
Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice. Brinzo-B Eye Drops(Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) In two clinical trials of 3 months duration 435patients were treated with Brinzo-B Eye Drops(Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension), and 915 were treated with the two individual components. The most frequently reported adverse reactions in patients treated with Brinzo-B Eye Drops (Brinzolamide& Brimonidine Tartrate Ophthalmic Suspension) occurring in approximately 3 to 5% of patients in descending order of incidence were blurred vision, eye irritation, dysgeusia(bad taste), dry mouth, and eye allergy. Rates of adverse reactions reported with the individual components were comparable. Treatment discontinuation, mainly due to adverse reactions, was reported in11% of Brinzo-B Eye Drops (Brinzolamide &Brimonidine Tartrate Ophthalmic Suspension) patients.

OVERDOSAGE

Although no human data are available, electrolyte imbalance, development of an acidotic state, and possible nervous system effects may occur following an oral overdose of brinzolamide. Serum electrolyte levels(particularly potassium) and blood pH levels should be monitored. Very limited information exists on accidental ingestion of brimonidine in adults; the only adverse event reported to date has been hypotension. Symptoms of brimonidine overdose have been reported in neonates, infants, and children receiving brimonidine as part of medical treatment of congenital glaucoma or by accidental oral ingestion. Treatment of an oral overdose includes supportive and symptomatic therapy; a patent airway should be maintained.

STORAGE:

Store below 30°C. Protected from light & moisture.
Do not allow to freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

Brinzo-B Eye Drops (Brinzolamide & Brimonidine Tartrate Ophthalmic Suspension) is a sterile solution supplied in a 5 mL poly bottle.
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BRINZO B Eye Drops

DORZA/5mL

(Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION:

Dorza (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) is used in the treatment of increased pressure in the eye and open-angle glaucoma, a condition which may lead to eventual vision loss.

COMPOSITION:

Each ML Contains :

•DorzolamideHydrochloride IP
  eq. to Dorzolamide    20 mg
•Benzalkonium Chloride
  SolutionIP  0.075 mg
  (As    Preservative)
•AqueousVehicle                                   q.s.
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INDICATIONS AND USAGE

'Dorzolamide' is indicated:
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• As adjunctive therapy to beta-blockers,
• As monotherapy in patients unresponsive to beta-blockers or in whom beta-blockers are contraindicated, In the treatment ofelevated intra-ocular pressure in:
•Ocular hypertension,
•Open angle glaucoma,
•Pseudoexfoliative glaucoma.

CLINICAL PHARMACOLOGY


Pharmacodynamic properties
Pharmacotherapeutic group: Antiglaucoma preparations and miotics, Carbonic Anhydrase Inhibitors, dorzolamide,
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‍Mechanism of  action: Carbonic anhydrase(CA) is an enzyme found in many tissues of the body including the eye. In humans, carbonic anhydrase exists as a number of isoenzymes, the most active being carbonic anhydrase II (CA-II)found primarily in red blood cells (RBCs) but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion. The result is a reduction in intra-ocular pressure(IOP).
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Dorza (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) contains dorzolamide hydrochloride, a potent inhibitor of human carbonic anhydrase II. Following topical ocular administration, dorzolamide reduces elevated intra-ocular pressure, whether or not associated with glaucoma. Elevated intra-ocular pressure is a major risk factor in the pathogenesis of optic nerve damage and visual-field loss. Dorzolamide does not cause pupillary constriction and reduces intra-ocular pressure without side effects such as night blindness, accommodative spasm. Dorzolamide has minimal or no effect on pulse rate or blood pressure. Topically applied beta-adrenergic blocking agents also reduce IOP by decreasing aqueous humor secretion but by a different mechanism of action. Studies have shown that when dorzolamide is added to a topical beta-blocker, additional reduction in IOP is observed; this finding is consistent with the reported additive effects of beta-blockers and oral carbonic anhydrase inhibitors.
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Pharmacokinetic properties:
Unlike oral carbonic anhydrase inhibitors, topical administration of dorzolamide hydrochloride allows for the active substance to exert its effects directly in the eye at substantially lower doses and therefore with less systemic exposure. In clinical trials, this resulted in a reduction in IOP without the acid-base disturbances or alterations in electrolytes characteristic of oral carbonic anhydrase inhibitors.

CONTRAINDICATIONS

Dorzolamide has not been studied in patients with severe renal impairment (CrCl < 30 ml/min)or with hyper chloraemic acidosis. Because dorzolamide and its metabolites are excreted predominantly by the kidney, dorzolamide is therefore contra-indicated in such patients

WARNINGS AND PRECAUTIONS

 Dorzolamide has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients. 

The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Dorzolamide has not been studied in patients with acute
angle-closure glaucoma.
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Dorzolamide contains a sulphonamido group, which also occurs in sulphonamides and although administered topically, is absorbed systemically. Therefore the same types of adverse reactions that are attributable to sulphonamides may occur with topical administration, including severe reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation. Therapy with oral carbonican hydrase inhibitors has been associated
urolithiasis as a result of acid-base disturbances, especially in patients with a prior history of renal calculi. Although no acid-base disturbances have been observed with Dorzolamide, urolithiasis has been reported infrequently. Because Dorzolamide is a topical carbonic anhydrase inhibitor that is absorbed systemically, patients with a prior history of renal calculi may be at increased risk of urolithiasis while using Dorzolamide.

‍Paediatric population
‍Dorzolamide has not been studied inpatients less than 36 weeks gestational age and less than 1 week of age. Patients with significant renal tubular immaturity should only received orzolamide after careful consideration of the risk benefit balance because of the possible risk of metabolic acidosis.
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Fertility, pregnancy and lactation
‍Pregnancy
‍Dorzolamide should not be used during pregnancy. There are no or limited amount of data from the use of Dorzolamide in pregnant women. In rabbits, Dorzolamide produced teratogenic effects at maternotoxic doses (see section5.3)

‍Breast-feeding
‍It is unknown whether Dorzolamide/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of dorzolamide/metabolites in milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Dorzolamide therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman. A risk to the newborns/infants cannot be excluded.

ADVERSE REACTIONS

Dorza (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) was evaluated in more than 1400 individuals in controlled and uncontrolled clinical studies. In long-term studies of 1108 patients treated with Dorza (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) as monotherapy or as adjunctive therapy with an ophthalmic beta-blocker, the most frequent cause of discontinuation (approximately 3%) from treatment with Dorza (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) was drug-related ocular adverse reactions, primarily conjunctivitis and lid reactions.

DOSAGE AND ADMINISTRATION

When used as monotherapy, the dose is one drop of Dorzolamide in the conjunctival sac of the affected eye(s),three times daily.
When used as adjunctive therapy with an ophthalmic beta-blocker, the dose is one drop of Dorzolamide in the conjunctival sac of the affected eye(s), two times daily.
When substituting Dorzolamide for another ophthalmic anti- glaucoma agent, discontinue the other agent after proper dosing on one day, and start Dorzolamide on the next day. If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart. The dosage and duration of the treatment should be as recommended by the doctor. If one dose is missed, treatment should continue with the next dose as normal. Patients should be instructed to wash their hands before use and avoid allowing the tip of the bottle to come into contact with the eye or surrounding structures. Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. Patients should be informed of the correct handling of the containers.

STORAGE:

Preserve in tight containers protected from light, at controlled room temperature.
Do not allow to freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

Dorza / 5mL (Dorzolamide Hydrochloride Ophthalmic Solution USP2% w/v) sterile solution is supplied in 5 mL Poly bottle.
‍

DORZA/5mL

DORZA TPF

(Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION:

Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP) is the combination of a topical carbonic anhydrase inhibitor and a topical beta- adrenergic reoeptor blocking agent. 

Dorzolamide Hydrochloride is described chemically as: (4S-trans)-4- (ethylamino)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-2- suIfonamide 7,7-d ioxide monohydrochloride. Dorzolamide Hydrochloride USP is optically active. 

Timolol Maleate is described chemically as: (-)-1-(tert-butyIamino)-3- [(4-morphoIino-1,2,5-thiadiazoI-3-yl)oxy]-2-propanolmaleate (1:1) (salt). Timolol Maleate USP possesses an asymmetric carbon atom in its structure and is provided as the levo-isomer.

COMPOSITION:

Each ML Contains :

Dorzolamide Hydrochloride  USP
eq. to Dorzolamide            2% w/v
Timolol Maleate USP
eq. to Timolol                      0.5% w/v
Water for Injections                  q.s.

INDICATIONS AND USAGE

Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP) is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insu9iciently responsive to beta-blockers (failed to achieve target IOP determined after multiple measurements over time). The IOP-lowering of Dorza- TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP) administered twice a day was slightly less than that seen with the concomitant administration of 0.5% Timolol administered twice a day and 2% Dorzolamide administered three times a day.

CLINICAL PHARMACOLOGY


Mechanism of Action Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and  Timolol Maleate Ophthalmic Solution USP) is comprised of two components: Dorzolamide hydrochloride and timolol maleate. Each of these two components decreases elevated intraocular pressure, whether or not associated with glaucoma, by reducing aqueous humor secretion. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage.

Pharmacokinetics

Dorzolamide Hydrochloride
‍When topically applied, Dorzolamide reaches the systemic circulation. To assess the potential for systemic carbonic anhydrase inhibition following topical administration, drug and metabolite concentrations in RBCs and plasma and carbonic anhydrase inhibition in RBCs were measured. Dorzolamide accumulates in RBCs during chronic dosing as a result of binding to CA-II. The parent drug forms a single N-desethyl metabolite, which inhibits CA-II less potently than the parent drug but also inhibits CA-I. The metabolite also accumulates in RBCs where it binds primarily to CA-I. Plasma concentrations of Dorzolamide and metabolite are generally below the assay limit of quantitation (15nM). Dorzolamide binds moderately to plasma proteins (approximately33%).

Dorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine. After dosing is stopped, Dorzolamide washes out of RBCs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months. 

To simulate the systemic exposure after long-term topical ocular administration, Dorzolamide was given orally to eight healthy subjects for up to 20 weeks. The oral dose of 2 mg twice daily closely approximates the amount of drug delivered by topical ocular administration of Dorzolamide 2% three times daily. Steady state was reached within 8 weeks. The inhibition of CA-II and total carbonic anhydrase activities was below the degree of inhibition anticipated to be necessary for a pharmacological effect on renal function and respiration in healthy individuals. 

‍Timolol Maleate 
‍In a study of plasma drug concentrations in six subjects, the systemic exposure to timolol was determined following Mice daily topical administration of Timolol Maleate Ophthalmic Solution 0.5%. The mean peak plasma concentration following morning dosing was 0.46 ng/mL.

CONTRAINDICATIONS

Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP) is contraindicated in patients with:
•Hypersensitivity to the active substances or to any of the excipients I
• Reactive airway disease, including bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease.
‍
•Sinus bradycardia, sick sinus syndrome, sino-atrial block, seoond- or third-degree atrioventricular block not controlled with a pacemaker, overt cardiac failure, cardiogenic shock
‍
.•  Severe renal impairment (CrCI < 30mI/min) or hyperchloraemic acidosis.

The above are based on the components and are not unique to the combination. 

Sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block, not controlled with pace-maker. Overt cardiac failure, cardiogenic shock.

WARNINGS AND PRECAUTIONS

Do not take Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP) if you are allergic to Dorza-TPF Eye Drops(Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP) or any of its ingredients. Before taking Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP), let your doctor know if you have a history of eye infection, allergies, closed-angle glaucoma, thyroid diseases, asthma, chronic obstructive pulmonary disease (COPD), heart, liver, and kidney diseases, diabetes, high or low blood pressure, depression, Raynaud's phenomenon (numbness in various parts of the body), and slow heartbeats that make you faint. Regular monitoring of blood sugars as it may mask the signs and symptoms of acute hypoglycaemia. It is unsafe to use Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP)during breastfeeding since Timolol can pass into breast milk and harm a nursing baby. Let your doctor know if you use other over-the-counter medications, herbal and vitamin supplements before taking Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP).

OVERDOSE

 No data are available in humans in regard to overdose by accidental or deliberate ingestion of Dorza-TPF Eye Drops (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP).
‍
‍Svmotoms There have been reports of inadvertent overdoses with Timolol maleate ophthalmic solution resulting in systemic effects similar to those seen with systemic beta adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest. The most common signs and symptoms to be expected with overdoses of Dorzolamide are electrolyte imbalance, development of an acidosis state, and possibly central nervous system effects. 
Only limited information is available with regard to human overdose by accidental or deliberate ingestion of Dorzolamide hydrochloride. With oral ingestion, somnolence has been reported. With topical application the following have been reported: nausea, dizziness, headache, fatigue, abnormal dreams, and dysphagia.
‍
‍Treatment' Treatment should be symptomatic and supportive. Serum electrolyte levels (particularly potassium)and blood pH levels should be monitored. Studies have shown that timolol does not dialyse readily.

DOSAGE AND ADMINISTRATION

The dose is one drop in the conjunctival sae of the affected eye(s)two times daily. If another topical ophthalmic agent is being used, Dorzolamide / Timolol and the other agent should be administered at least ten minutes apart.Patients should be instructed to wash their hands before use and avoid allowing the tip of the container to come into contact with the eye or surrounding structures. Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.W hen using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity. Paediatric population: Efficacy in paediatric patients has not been established. Safetyin paediatric patients below the age of two years has not been established.

STORAGE:

Preserve in tight containers protected from light, at controlled room temperature. Do not allow to freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

Dorza-TPF Eye Drops / 5mL (Dorzolamide Hydrochloride and Timolol Maleate Ophthalmic Solution USP) sterile solution is supplied in 5 mL Poly bottle.

Aod address

DORZA TPF

DORZA-PF Eye Drops

(Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION:

 Dorza-PF (Dorzolamide Hydrochloride Ophthalmic Solution USP 2%w/v) is used in the treatment of increased pressure in the eye and open-angle glaucoma, a condition which may lead to eventual vision loss.

COMPOSITION:

Each ML Contains :

Dorzolamide  Hydrochloride    USP
eq. to Dorzolamide                   2% w/v
Sterile Aqueous Vehicle             q.s.

INDICATION AND USAGE

'Dorzolamide' is indicated:

- As adjunctive therapy to beta-blockers,
- As monotherapy in patients unresponsive to beta-blockers are contraindicated, In the treatment of elevated in:
- Ocular hypertension.,
- Open angle glaucoma,
- Pseudoexfoliative glaucoma.
‍

CLINICAL PHARMACOLOGY

Pharmacodynamic properties:
Pharmacotherapeutic group: Antiglaucoma preparations and miotics, Carbonic Anhydrase Inhibitors, dorzolamide, 
‍Mechanism of  action:
Carbonic anhydrase (CA) is an enzyme found in many tissues of the body including the eye. In humans, carbonic anhydrase exists as a number of iso enzymes, the most active being carbonic anhydrase II (CA-II) found primarily in red blood cells(RBCs) but also in other tissues. Inhibition of carbonic anhydrase in the ciliary processes of the eye decreases aqueous humor secretion. The result is a reduction in intra-ocular pressure(IOP). 

Dorza-PF (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) contains dorzolamide hydrochloride, a potent inhibitor of human  carbonic  anhydrase  II.  Following  topical  ocular administration, dorzolamide reduces elevated intra-ocular pressure, whether or not associated with glaucoma. Elevated intra-ocular pressure is a major risk factor in the pathogenesis of optic nerve damage and visual-field loss. Dorzolamide does not cause pupillary constriction and reduces intra-ocular pressure without side effects such as night blindness, accommodative spasm. Dorzolamide has minimal or no effect on pulse rate or blood pressure. 

Topically applied beta-adrenergic blocking agents also reduce IOP by decreasing aqueous humor secretion but by a different mechanism of action. Studies have shown that when dorzolamide is added to a topical beta-blocker, additional reduction in IOP is observed; this finding is consistent with the reported additive effects of beta-blockers and oral carbonic anhydrase inhibitors.

 Pharmacokinetic properties:
Unlike oral carbonic anhydrase inhibitors, topical administration of dorzolamide hydrochloride allows for the active substance to exert its effects directly in the eye at substantially lower doses and therefore with less systemic exposure. In clinical trials, this resulted in a reduction in IOP without the acid-base disturbances or alterations in electrolytes characteristic of oral carbonic anhydrase inhibitors.

CONTRAINDICATIONS

Dorzolamide has not been studied in patients with severe renal impairment (CrCl < 30 ml/min) or with hyperchloraemic acidosis. Because dorzolamide and its metabolites are excreted predominantly by the kidney, dorzolamide is therefore contra-indicated in such patients

WARNINGS AND PRECAUTIONS

Dorzolamide has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients. The management of patients with acute angle-closure glaucoma requires therapeutic interventions in addition to ocular hypotensive agents. Dorzolamide has not been studied in patients with acute
angle-closure glaucoma. Dorzolamide contains a sulphonamido group, which also occurs in sulphonamides and although administered topically, is absorbed systemically. Therefore the same types of adverse reactions that are attributable to sulphonamides may occur with topical administration, including severe reactions such as Stevens-Johnson syndrome and toxic epidermal necrolysis. If signs of serious reactions or hypersensitivity occur, discontinue the use of this preparation. Therapy with oral carbonic anhydrase inhibitors has been associated with urolithiasis as a result of acid-base disturbances, especially in patients with a prior history of renal calculi. Although no acid-base disturbances have been observed with Dorzolamide, urolithiasis has been reported infrequently. Because Dorzolamide is a topical carbonic anhydrase inhibitor that is absorbed systemically, patients with a prior history of renal calculi may be at increased risk of urolithiasis while using Dorzolamide.

 Paediatric population
‍Dorzolamide has not been studied inpatients less than 36 weeks gestational age and less than 1 week of age. Patients with significant renal tubular immaturity should only receive dorzolamide after careful consideration of the risk benefit balance because of the possible risk of metabolic acidosis.

Fertility, pregnancy and lactation
‍Pregnancy
‍Dorzolamide should not be used during pregnancy. There are no or limited amount of data from the use of Dorzolamide in pregnant women. In rabbits, Dorzolamide produced teratogenic effects at maternotoxic doses.

‍Breast-feeding
‍It is unknown whether Dorzolamide/metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of dorzolamide/metabolites in milk. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Dorzolamide therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.A risk to the newborns/infants cannot be excluded.

ADVERSE REACTIONS

Dorza-PF (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) was evaluated in more than 1400 individuals in controlled and uncontrolled clinical studies. In long-term studies of 1108 patients treated with Dorza-PF (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) as monotherapy or as adjunctive therapy with an ophthalmic beta-blocker, the most frequent cause of discontinuation (approximately 3%) from treatment with Dorza-PF (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) was drug-related ocular adverse reactions, primarily conjunctivitis and lid reactions.

DOSAGE AND ADMINISTRATION

 When used as monotherapy, the dose is one drop of Dorzolamide in the conjunctival sac of the affected eye(s),three times daily. When used as adjunctive therapy with an ophthalmic beta-blocker, the dose is one drop of Dorzolamide in the conjunctival sac of the affected eye(s), two times daily.W hen substituting Dorzolamide for another ophthalmic anti- glaucoma agent, discontinue the other agent after proper dosing on one day, and start Dorzolamide on the next day.

If more than one topical ophthalmic drug is being used, the drugs should be administered at least ten minutes apart.

The dosage and duration of the treatment should be as recommended by the doctor.

 If one dose is missed, treatment should continue with the next dose as normal.

Patients should be instructed to wash their hands before use and avoid allowing the tip of the bottle to come into contact with the eye or surrounding structures. 

Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. 

Patients should be informed of the correct handling of the containers.

STORAGE:

Preserve in tight containers protected from light, at controlled room temperature. Do not allow to freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

Dorza-PF / 5mL (Dorzolamide Hydrochloride Ophthalmic Solution USP 2% w/v) sterile solution is supplied in 5 mL poly bottle.
‍

Aod address

DORZA PF

DORZA-T Eye Drops
‍

(Dorzolamide and Timolol Eye Drops IP)

THIS LEAFLET CONTAINSIMPORTANT PRODUCT USE AND SAFETY INFORMATION, PLEASE READ CAREFULLY AND RETAIN FOR FURTHER REFERENCE.

DESCRIPTION:

Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP) is the combination of a topical carbonic anhydrase inhibitor and a topical beta-adrenergic receptor blocking agent. 

Dorzolamide Hydrochloride is described chemically as: (4S-trans)-4- (ethylamino)-5,6-dihydro-6-methyl-4H-thieno[2,3-b]thiopyran-2- sulfonamide 7,7-dioxide monohydrochloride. Dorzolamide Hydrochloride USP is optically active. 

Timolol Maleate is described chemically as: (-)-1-(tert-butylamino)-3- [(4-morpholino-1,2,5-thiadiazol-3-yl)oxy]-2-propanol maleate (1:1) (salt). Timolol Maleate USP possesses an asymmetric carbon atom in its structure and is provided as the levo-isomer.

COMPOSITION:

Each ML Contains :

Dorzolamide Hydrochloride   IP
eq. to Dorzolamide                   2% w/v
Timolol Maleate IP
eq. to Timolol                         0.5% w/v
Benzalkonium Chloride
Solution IP                             0.02% v/v
(As Preservative)
Water for Injections IP                     q.s.

INDICATION AND USAGE

Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP) is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension who are insufficiently responsive to beta-blockers (failed to achieve target IOP determined after multiple measurements over time). The IOP-lowering of Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP) administered twice a day was slightly less than that seen with the concomitant administration of 0.5% Timolol administered twice a day and 2% Dorzolamide administered three times a day.
‍

CLINICAL PHARMACOLOGY

Mechanism of Action Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP) is
comprised of two components: Dorzolamide hydrochloride and timolol maleate. Each of these two components decreases elevated intraocular pressure, whether or not associated with glaucoma, by reducing aqueous humor secretion. Elevated intraocular pressure is a major risk factor in the pathogenesis of optic nerve damage and glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of glaucomatous field loss and optic nerve damage.

‍Pharmacokinetics
‍Dorzolamide Hydrochloride
‍When topically applied, Dorzolamide reaches the systemic circulation. To assess the potential for systemic carbonic anhydrase inhibition following topical administration, drug and metabolite concentrations in RBCs and plasma and carbonic anhydrase inhibition in RBCs were measured. Dorzolamide accumulates in RBCs during chronic dosing as a result of binding to CA-II. The parent drug forms a single N-desethyl metabolite, which inhibits CA- II less potently than the parent drug but also inhibits CA-I. The metabolite also accumulates in RBCs where it binds primarily to CA-I. Plasma concentrations of Dorzolamide and metabolite are generally below the assay limit of quantitation (15nM).Dorzolamide binds moderately to plasma proteins(approximately 33%).

Dorzolamide is primarily excreted unchanged in the urine; the metabolite also is excreted in urine. After dosing is stopped, Dorzolamide washes out of RBCs nonlinearly, resulting in a rapid decline of drug concentration initially, followed by a slower elimination phase with a half-life of about four months. To simulate the systemic exposure after long-term topical ocular administration, Dorzolamide was given orally to eight healthy subjects for up to 20 weeks. The oral dose of 2 mg twice daily closely approximates the amount of drug delivered by topical ocular administration of Dorzolamide 2% three times daily. Steady state was reached within 8 weeks. The inhibition of CA-II and total carbonic anhydrase activities was below the degree of inhibition anticipated to be necessary for a pharmacological effect on renal function and respiration in healthy individuals.
‍
Timolol   Maleate
 In a study of plasma drug concentrations in six subjects, the systemic exposure to timolol was determined following twice daily topical administration of Timolol Maleate Ophthalmic Solution 0.5%. The mean peak plasma concentration following morning dosing was 0.46 ng/mL.

CONTRAINDICATIONS

Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP) is contraindicated in patients with:

• Hypersensitivity to the active substances or to any of the excipients .
• Reactive airway disease, including bronchial asthma or a history of bronchial asthma, or severe chronic obstructive pulmonary disease.
•Sinus bradycardia, sick sinus syndrome, sino-atrial block, second-or third-degree atrioventricular block not controlled with a pacemaker, overt cardiac failure, cardiogenic shock
.• Severe renal impairment (CrCl < 30ml/min) or hyperchloraemic acidosis.
‍
The above are based on the components and are not unique to the combination. 

Sinus bradycardia, sick sinus syndrome, sino-atrial block, second or third degree atrioventricular block, not controlled with pace-maker. Overt cardiac failure, cardiogenic shock.

WARNINGS AND PRECAUTIONS

Do not take Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP) if you are allergic to Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP) or any of its ingredients. Before taking Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP), let your doctor know if you have a history of eye infection, allergies, closed-angle glaucoma, thyroid diseases, asthma, chronic obstructive pulmonary disease (COPD), heart, liver, and kidney diseases, diabetes, high or low blood pressure, depression, Raynaud's phenomenon(numbness in various parts of the body),and slow heartbeats that make you faint. Regular monitoring of blood sugars as it may mask the signs and symptoms of acute hypoglycaemia. It is unsafe to use Dorza-T Eye Drops(Dorzolamide and Timolol Eye Drops IP) during breastfeeding since Timolol can pass into breastmilk and harm a nursing baby. Let your doctor know if you use other over-the-counter medications, herbal and vitamin supplements before taking Dorza-T Eye Drops (Dorzolamide and Timolol Eye Drops IP).

OVERDOSE

No data are available in humans in regard to overdose by accidental or deliberate ingestion of Dorza-T Eye Drops(Dorzolamide and Timolol Eye Drops IP).

Symptoms
There have been reports of inadvertent overdoses with Timolol maleate ophthalmic solution resulting in systemic effects similar to those seen with systemic beta adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, and cardiac arrest. The most common signs and symptoms to be expected with overdoses of Dorzolamide are electrolyte imbalance, development of an acidosis state, and possibly central nervous system effects. 

Only limited information is available with regard to human overdose by accidental or deliberate ingestion of Dorzolamide hydrochloride. With oral ingestion, somnolence has been reported. With topical application the following have been reported: nausea, dizziness, headache, fatigue, abnormal dreams, and dysphagia.

Treatment          
Treatment should be symptomatic and supportive. Serum electrolyte levels (particularly potassium) and blood pH levels should be monitored. Studies have shown that timolol does not dialyse readily.

DOSAGE AND ADMINISTRATION

 The dose is one drop in the conjunctival sac of the affected eye(s) two times daily. 
If another topical ophthalmic agent is being used, Dorzolamide / Timolol and the other agent should be administered at least ten minutes apart.
Patients should be instructed to wash their hands before use and avoid allowing the tip of the container to come into contact with the eye or surrounding structures. 
Patients should also be instructed that ocular solutions, if handled improperly, can become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions. When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic side effects and an increase in local activity.
‍Pediatric   population:
‍Efficacy in pediatric patients has not been established. Safety in pediatric patients below the age of two years has not been established.


STORAGE:

Keep in a cool & dark place. Store below 30°C. Do not allow to freeze.

SHELF LIFE

24 Months

HOW SUPPLIED:

Dorza-T Eye Drops / 5mL (Dorzolamide and Timolol Eye Drops IP) sterile solution is supplied in 5 mL Poly bottle.
‍

Aod address

DORZA T

APPASAMY ASSOCIATES (P) LTD,No.20, SBI Officer's colony,
1st Street, Arumbakkam, Chennai - 600 106, Tamil Nadu, India.
Call: +91 6382758855 /  +91 9381216555
E-mail : info@appasamy.com

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