Timolol Ophthalmic Solution USP 0.5% w/v Taj Pharma

1. NAME OF THE MEDICINAL PRODUCT

Timolol Ophthalmic Solution USP 0.25% w/v Taj Pharma
Timolol Ophthalmic Solution USP 0.5% w/v Taj Pharma

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

   a) Each ml of Ophthalmic Solution contains:
   Timolol maleate equivalent to
   2.5mg of Timolol USP……………………2.5mg

   b) Each ml of Ophthalmic Solution contains:
   Timolol maleate equivalent to
   5 mg of Timolol USP………………………5mg

Excipient with known effect

Each ml of Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma 2.5 mg/ml solution contains 12.72 mg phosphates.

For the full list of excipients, see section 6.1.

3. PHARMACEUTICAL FORM

Eye drops, solution.

Clear, colourless eye drops.

pH: 6.5-7.5

Osmolality: 270-330 mOsm/Kg

4. CLINICAL PARTICULARS

4.1 Therapeutic indications

Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma eye drops, solution is a beta-adrenoreceptor blocking agent used topically in the reduction of elevated intra-ocular pressure in various conditions.

Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma is indicated in adult patients with ocular hypertension; adult patients with chronic open-angle glaucoma including aphakic patients; some adult patients with secondary glaucoma.

4.2 Posology and method of administration

Adults

Posology

Recommended therapy is one drop of 2.5 mg/ml solution in the affected eye, once or twice (morning and evening) a day.

When using nasolacrimal occlusion or closing the eyelids for 2 minutes, the systemic absorption is reduced. This may result in a decrease in systemic adverse reactions and an increase in local activity.

If clinical response is not adequate, dose may be changed to one drop of 5 mg/ml solution in each affected eye, once or twice (morning and evening) a day. If needed, Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma may be used with other agent(s) for lowering intra-ocular pressure. The use of two topical beta-adrenergic blocking agents is not recommended (see section 4.4).

Intra-ocular pressure should be reassessed approximately four weeks after starting treatment because response to Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma may take a few weeks to stabilise.

Provided that the intra-ocular pressure is maintained at satisfactory levels, many patients can then be placed on once-a-day therapy of Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma.

Transfer from other agents

When another topical beta-blocking agent is being used, discontinue its use after a full day of therapy and start treatment with Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma the next day with one drop of 2.5 mg/ml Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma in each affected eye once or twice (morning and evening) a day. The dose may be increased to one drop of 5 mg/ml solution in each affected eye once or twice (morning and evening) a day if the response is not adequate.

When transferring a patient from a single anti-glaucoma agent other than a topical beta-blocking agent, continue the agent and add one drop of 2.5 mg/ml Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma in each affected eye once or twice (morning and evening) a day. On the following day, discontinue the previous agent completely and continue with Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma. If a higher dose of Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma is required, substitute to one drop of 5 mg/ml solution in each affected eye once or twice (morning and evening) a day.

Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma eye drops, solution is a sterile solution that does not contain a preservative.

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 as this could cause injury to the eye.

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.

Paediatric population

Due to limited data, timolol could only be recommended for use in primary congenital and primary juvenile glaucoma for a transitional period while a decision is made on a surgical approach and in case of failed surgery while awaiting further options.

Posology

Clinicians should strongly evaluate the risks and benefits when considering medical therapy with timolol in paediatric patients. A detailed medical history and examination to determine the presence of systemic abnormalities should precede the use of timolol.

No specific dose recommendation can be given as there is only limited clinical data (see also section 5.1).

However, if benefit outweighs the risk, it is recommended to use the lowest active agent concentration available once daily. If intra-ocular pressure (IOP) could not be sufficiently controlled, a careful up titration to a maximum of two drops of 5 mg/ml timolol eye drops solution daily per affected eye has to be considered. If applied twice daily, an interval of 12 hours should be preferred.

Furthermore, the patients, especially neonates, should be closely observed after the first dose for one to two hours in the office and closely monitored for ocular and systemic adverse reactions until surgery is performed.

Method of administration

To limit potential adverse reactions only one drop should be instilled per dosing time.

Systemic absorption of topically administered β-blockers can be reduced by nasolacrimal occlusion and by keeping the eyes closed as long as possible (e.g. for 3 – 5 minutes) after instillation of drops. See also sections 4.4 and 5.2.

Duration of treatment

For a transient treatment in the paediatric population.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

As with all products containing beta-receptor blocking agents, Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma is contraindicated in patients with:

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

4.4 Special warnings and precautions for use

Like other topically applied ophthalmic agents, timolol is absorbed systemically. Due to beta-adrenergic component, timolol, the same types of cardiovascular, pulmonary and other adverse reactions seen with systemic beta-adrenergic blocking agents may occur. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. To reduce the systemic absorption, see section 4.2.

Other beta-blocking agents

The effect on intra-ocular pressure or the known effects of systemic beta-blockade may be potentiated when timolol is given to patients already receiving a systemic beta-blocking agent. The response of these patients should be closely observed. The use of two topical beta-adrenergic blocking agents is not recommended (see section 4.5).

In patients with closed-angle glaucoma, Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma should be used in combination with miotics, as the immediate purpose of the treatment is to reopen the chamber angle which requires a constriction of the pupil. Timolol has little or no effect on the pupil.

Choroidal detachment

Choroidal detachment has been reported with administration of aqueous suppressant therapy (e.g. timolol, acetazolamide) after filtration procedures.

Anaphylactic reactions

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 challenge with such allergens and may be unresponsive to the usual doses of adrenaline used to treat anaphylactic reactions.

Cardiac disorders

In patients with cardiovascular diseases (e.g. coronary heart disease, Prinzmetal’s angina and cardiac failure) and hypotension therapy with beta-blockers should be critically assessed and the therapy with other active substances should be considered. Patients with cardiovascular diseases should be watched for signs of deterioration of these diseases and of adverse reactions.

Due to its negative effect on conduction time, beta-blockers should only be given with caution to patients with first degree heart block.

Vascular disorders

Patients with severe peripheral circulatory disturbance/disorders (i.e. severe forms of Raynaud’s disease or Raynaud’s syndrome) should be treated with caution.

Respiratory disorders

Respiratory reactions, including death due to bronchospasm in patients with asthma, have been reported following administration of some ophthalmic beta-blockers.

Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma should be used with caution in patients with mild/moderate chronic obstructive pulmonary disease (COPD) and only if the potential benefit outweighs the potential risk.

Hypoglycaemia/diabetes

Beta-blockers should be administered with caution in patients subject to spontaneous hypoglycaemia or to patients with labile diabetes, as beta-blockers may mask the signs and symptoms of acute hypoglycaemia.

Beta-blockers may also mask the signs of hyperthyroidism.

Corneal diseases

Ophthalmic beta-blockers may induce dryness of eyes. Patients with corneal diseases should be treated with caution.

Surgical anaesthesia

Beta-blocking ophthalmological preparations may block systemic beta-agonist effects e.g. of adrenaline. The anaesthesiologist should be informed when the patient is receiving timolol.

Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma should also be used with great care in connection with the following diseases and conditions:

• Myasthenia: Beta-adrenergic blocking may potentiate muscle weakness corresponding to certain myasthenia symptoms (e.g. diplopia, ptosis, general weakening).
• Untreated pheochromocytoma.
• Metabolic acidosis.
• Large surgical procedures: It is recommended to gradually decrease the use of adrenergic beta-blocking medicinal products prior to the procedure in order to avoid the reflex stimuli of the beta-blockers on the heart and thus lessen the risk of hypotension and cardiac arrest during the anaesthesia.
• Intermittent claudication.
• Severely reduced kidney function. With dialysis patients, pronounced drop in blood pressure has been observed.

Patients with a history of contact hypersensitivity to silver should not use this product as dispensed drops may contain traces of silver.

Timolol has not been studied in patients using contact lenses.

Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma should not be used while using soft contact lenses. The lenses should only be inserted 15 minutes after the drip.

Paediatric population

Timolol solutions should generally be used cautiously in young glaucoma patients (see also section 5.2).

It is important to notify the parents of potential adverse reactions so they can immediately discontinue the medicinal therapy (see section 4.8). Signs to look for are, for example, coughing and wheezing.

Because of the possibility of apnoea and Cheyne-Stokes breathing, the medicinal product should be used with extreme caution in neonates, infants and toddlers. A portable apnoea monitor may also be helpful for neonates on timolol.

4.5 Interaction with other medicinal products and other forms of interaction

No specific interaction studies with other medicinal products have been performed with timolol maleate.

Cases of mydriasis have been reported with simultaneous use of ophthalmological beta-blockers and adrenalin. Even though timolol administered by itself has little or no effect on the size of the pupil, close ophthalmological monitoring is advised.

Potentiated systemic beta-blockade (e.g. decreased heart rate, depression) has been reported during combined treatment with CYP2D6 inhibitors (e.g. quinidine; fluoxetine, paroxetine) and timolol.

There is a potential for additive effects resulting in hypotension and/or marked bradycardia when ophthalmic beta-blockers solution is administered concomitantly with oral calcium-channel blockers, beta-adrenergic blocking agents, antiarrhythmics (including amiodarone), digitalis glycosides, parasympathomimetics, guanethidine.

Oral beta-adrenergic blocking agents may exacerbate the rebound hypertension which can follow the withdrawal of clonidine.

Timolol potentiates the effect of other medicinal products with effect on the bulbous tension.

Beta-blockers may increase the hypoglycaemic effect of insulin and oral anti-diabetic medicinal products and mask signs and symptoms of hypoglycaemia (see section 4.4).

If more than one ophthalmic medicinal product is used, at least 5 minutes have to pass between using the different eye drops.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no adequate data for the use of timolol in pregnant women. Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma should not be used during pregnancy unless clearly necessary. To reduce the systemic absorption, see section 4.2.

Epidemiological studies have not revealed malformative effects but show a risk for intra uterine growth retardation when beta-blockers are administered by the oral route. In addition, signs and symptoms of beta-blockade (e.g. bradycardia, hypotension, respiratory distress and hypoglycaemia) have been observed in the neonate when beta-blockers have been administered until delivery. If Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma is administered until delivery, the neonate should be carefully monitored during the first days of life.

Breast-feeding

Beta-blockers are excreted in breast milk. However, at therapeutic doses of timolol maleate in eye drops it is not likely that sufficient amounts would be present in breast milk to produce clinical symptoms of beta-blockade in the infant. To reduce the systemic absorption, see section 4.2.

Fertility

Non-clinical data do not show any effects of timolol on male or female fertility.

4.7 Effects on ability to drive and use machines

Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma has minor influence on the ability to drive and use machines. While driving vehicles or operating different machines, it should be taken into account that occasionally visual disturbances may occur including refractive changes, diplopia, ptosis, frequent episodes of mild and transient blurred vision and occasional episodes of dizziness or fatigue.

4.8 Undesirable effects

Summary of the safety profile

Like other topically applied ophthalmic medicinal products, timolol is absorbed into the systemic circulation. This may cause similar undesirable effects as seen with systemic beta-blocking agents. Incidence of systemic ADRs after topical ophthalmic administration is lower than for systemic administration. The mentioned adverse reactions include reactions set within the group of ophthalmological beta-blockers.

The most common adverse reactions are burning or biting sensations after instillation, which occurs in approx. 13% of the patients.

Tabulated summary of adverse reactions

The following adverse reactions are classified according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), or very rare (<1/10,000).

Additional adverse reactions have been seen with ophthalmic beta-blockers and may potentially occur with Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma.

Cases of corneal calcification have been reported very rarely in association with the use of phosphate-containing eye drops in some patients with significantly damaged corneas.

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.

4.9 Overdose

Symptoms of overdose are similar to those seen with systemic beta adrenergic blocking agents such as dizziness, headache, shortness of breath, bradycardia, bronchospasm, cardiac arrest, acute cardiovascular insufficiency and hypotension (see section 4.8).

If overdose occurs, the following measures should be considered:

1. Administration of activated charcoal, if the preparation has been taken orally. Studies have shown that timolol maleate cannot be removed by haemodialysis.
2. Symptomatic bradycardia: atropine sulphate, 0.25 to 2 mg intravenously, should be used to induce vagal blockade. If bradycardia persists, intravenous isoprenaline hydrochloride should be administered cautiously. In refractory cases, the use of a cardiac pacemaker may be considered.
3. Hypotension: a sympathomimetic pressor agent such as dopamine, dobutamine or noradrenaline should be used. In refractory cases, the use of glucagon has been reported to be useful.
4. Bronchospasm: isoprenaline hydrochloride should be given. Concomitant therapy with aminophylline may be considered.
5. Acute cardiac failure: conventional therapy with digitalis, diuretics and oxygen should be instituted immediately. In refractory cases, the use of intravenous aminophylline is recommended. This may be followed, if necessary, by glucagon, which has been reported useful.
6. Heart block (second- or third-degree): isoprenaline hydrochloride or a pacemaker should be used.

   5. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Ophthalmologicals, antiglaucoma preparations and miotics, beta-blocking agents.

Mechanism of action

Timolol Ophthalmic Solution USP 0.25% w/v / 0.5% w/v Taj Pharma (timolol-maleate) is a non-selective beta-receptor blocker without beta-stimulating effect or significant membrane stabilizing local anaesthetic effect.

Pharmacodynamic effects

The pressure-reducing effect of timolol-maleate is more likely due to reduced influx of chamber fluid than an increased outflow, however, it is still unclear whether the pressure effect is a pure beta-blocking effect. The medicinal product does not influence blood pressure and heart rate.

Clinical efficacy and safety

Clinical studies show that timolol eye drops lower the intra-ocular pressure in glaucomatous eyes. No or insignificant changes in pupil size or visual acuity have been observed.

Paediatric population

There is only very limited data available on the use of timolol (2.5 mg/ml, 5 mg/ml twice daily one drop) in the paediatric population. In one small, double-masked, randomized, published clinical study conducted for a treatment period of up to 12 weeks on 105 children (n=71 on timolol) aged 12 days – 5 years the data have shown to some extent evidence, that timolol in the indication primary congenital and primary juvenile glaucoma is effective in short-term treatment.

5.2 Pharmacokinetic properties

Absorption

The onset of reduction in intra-ocular pressure can be detected within one-half hour after a single dose. The maximum effect occurs in one or two hours; significant lowering of IOP can be maintained for as long as 24 hours with a single dose.

In some cases, a decreased therapeutic effect has been observed in long-term treatment.

Paediatric population

As already confirmed by adult data, 80% of each eye drop passes through the nasolacrimal system where it may be rapidly absorbed into the systemic circulation via the nasal mucosa, conjunctiva, nasolacrimal duct, oropharynx and gut or the skin from tear overflow.

Due to the fact that the blood volume in children is smaller than that in adults a higher circulation concentration has to be taken into account. In addition, neonates have immature metabolic enzyme pathways and it may result in an increase in elimination half-life and potentiating adverse events.

Limited data show that plasma timolol levels in children after 2.5 mg/ml greatly exceed those in adults after 5 mg/ml, especially in infants and are presumed to increase the risk of adverse reactions such as bronchospasm and bradycardia.

5.3 Preclinical safety data

No adverse ocular reactions were observed in rabbits and dogs administered timolol topically in studies lasting one and twelve months.

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

6. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Disodium phosphate dodecahydrate, Sodium dihydrogen phosphate dehydrate, Sodium hydroxide (For pH adjustment), Water for injection

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

30 months

After first opening, the product may be stored for a maximum of 28 days. No special storage conditions are required.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions. For storage conditions after first opening of the medicinal product, see section 6.3.

6.5 Nature and contents of container

White opaque 11 ml LDPE bottle and white Novelia nozzle (HDPE and silicone) with a white HDPE cap.

Pack sizes: 1 or 2 bottles of 5 ml solution in a card box.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

Any unused medicinal product or waste material should be disposed of in accordance with local requirements.

7. MANUFACTURED IN INDIA BY:

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

TIMOLOL
OPHTHALMIC SOLUTION USP
0.25% W/V / 0.5% W/V
TAJ PHARMA

PACKAGE LEAFLET: INFORMATION FOR THE USER

Timolol

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

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

Important information about the administration of this product

Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma eye drops are contained within a novel multidose eye drop bottle, which allows for the solution not to contain any preservatives. Due to the design of the container, administration with these eye drops is not the same as standard eye drop bottles.

• Prior to first use, practice using the drops away from the eye. Slowly squeeze the bottle to deliver one drop in the air to get used to the pressure and time required to deliver one drop.
• Please note that there might be a few seconds delay between squeezing and the drop coming out. Do not squeeze too hard, or more than one drop may come out.
• After use and prior to recapping, the bottle should be shaken once in a downwards direction, without touching the dropper tip, in order to remove any residual liquid on the tip. This is necessary in order to ensure delivery of subsequent drops.
• If more than one type of eye drop is used, leave at least 5 minutes between administrations of each eye drop solution.

Please read the full instructions on the correct use of this product in Section 3 of the leaflet (‘‘How to use Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma’’), before using these eye drops.

WHAT IS IN THIS LEAFLET

1. What Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma is and what it is used for
2. What you need to know before you use Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma
3. How to use Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma
4. Possible side effects
5. How to store Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma
6. Contents of the pack and other information

   1. WHAT TIMOLOL OPHTHALMIC SOLUTION USP 0.25% & 0.5% W/V TAJ PHARMA IS AND WHAT IT IS USED FOR

Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma contains a substance called timolol which belongs to a group of medicines called beta-blockers.

Timolol lowers the pressure in your eye(s). It is used to treat chronic open-angle and secondary glaucoma, when the pressure in the eye is raised, in adults.

Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma eye drops, solution is a sterile solution that does not contain a preservative.

2. WHAT YOU NEED TO KNOW BEFORE YOU USE TIMOLOL OPHTHALMIC SOLUTION USP 0.25% & 0.5% W/V TAJ PHARMA

Do not use Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma if:

• You are allergic to timolol, beta-blockers or any of the other ingredients of this medicine (listed in section 6).
• You have now or have had in the past respiratory problems such as asthma, severe chronic obstructive bronchitis (severe lung disease which may cause wheeziness, difficulty in breathing and/or long-standing cough).
• You have a slow heartbeat, heart failure or disorders of heart rhythm (irregular heartbeats).
• You have “cardiogenic shock” – a serious heart condition caused by very low blood pressure, which may result in the following symptoms: dizziness and lightheadedness, fast pulse rate, white skin, sweating, restlessness, loss of consciousness.

If you are not sure whether you should use Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma talk to your doctor or pharmacist.

Warnings and precautions

Talk to your doctor before using Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma if you have now or have had in the past:

• Coronary heart disease (symptoms can include chest pain or tightness, breathlessness or choking), heart failure.
• Closed-angle glaucoma, a condition in which the pressure inside your eye becomes too high.
• Low blood pressure.
• Disturbances of heart rate such as slow heartbeat.
• Breathing problems, asthma or chronic obstructive pulmonary disease.
• Poor blood circulation disease (such as Raynaud’s disease or Raynaud’s syndrome).
• Diabetes as timolol may mask signs and symptoms of low blood sugar.
• overactivity of the thyroid gland as timolol may mask signs and symptoms.
• Muscle weakness.
• Tumor of the adrenal gland (pheochromocytoma).
• Blood and body fluid abnormality (metabolic acidosis).
• Pain in the legs when walking due to poor circulation in the legs (claudication).
• Reduced kidney function.
• You wear soft contact lenses. Timolol has not been studied in patients wearing contact lenses. If you wear contact lenses, you should consult your doctor before using Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma.

If you have a history of contact hypersensitivity to silver, you should not use this product.

Tell your doctor before you have an operation that you are using Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma as timolol may change the effects of some medicines used during anaesthesia.

If you suspect that Timolol Ophthalmic Solution USP 0.25% & 0.5%  w/v Taj Pharma is causing an allergic reaction or hypersensitivity (for example, skin rash or redness and itching of the eye) contact your doctor immediately.

Children and adolescents

Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma should generally be used with caution in young patients. In newborns, infants and toddlers Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma should be used with extreme caution. If coughing, wheezing, abnormal breathing or abnormal pauses in breathing (apnoea) occur, the use of the medicine should be stopped immediately. Contact your doctor as soon as possible. A portable apnoea monitor may also be helpful.

Other medicines and Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma

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

Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma can affect or be affected by other medicines you are using, including other eye drops for the treatment of glaucoma.

Tell your doctor if you are using or intend to use medicines to lower blood pressure, heart medicine or medicines to treat diabetes.

It is important to tell your doctor before using Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma if you are taking one or more of the following medicines:

• Eye drops containing adrenaline.
• A calcium antagonist, such as nifedipine, verapamil or diltiazem, often used to treat high blood pressure, angina, an abnormal heartbeat or Raynaud’s syndrome.
• Guanethidine, a medicine often used to treat high blood pressure.
• Parasympathomimetic medicine, which may have been prescribed to help you pass urine. Parasympathomimetics are also a particular type of medicine which is sometimes used to help restore normal movements through the bowel.
• Digoxin, a medicine used to relieve heart failure or treat abnormal heartbeat.
• Quinidine, used to treat heart conditions and some types of malaria.
• Antidepressants known as fluoxetine and paroxetine.
• Antiarrhythmics (including amiodarone).
• Clonidine, a medicine used to treat high blood pressure.
• Other beta-blockers taken by mouth or used as eye drops, because they belong to the same group of medicines as Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma and could have an additive effect.
• Insulin and other oral anti-diabetic medicines.

Pregnancy and breast-feeding

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

Use in pregnancy

Do not use Timolol Ophthalmic Solution USP 0.25% & 0.5%  w/v Taj Pharma if you are pregnant unless your doctor considers it necessary.

Use in breast-feeding

Do not use Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma if you are breast-feeding. Timolol may get into your milk.

Driving and using machines

There are possible side effects associated with Timolol Ophthalmic Solution USP 0.25% & 0.5%  w/v Taj Pharma, such as dizziness, tiredness and changes in your eyesight, such as blurred vision, drooping of the upper eyelid (making the eye stay half closed), double vision which may affect your ability to drive and/or operate machinery.

Do not drive and/or operate machinery until you feel well and your vision is clear.

Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma contains phosphate buffer

Each ml of Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma 2.5mg/ml solution contains 12.72mg phosphates.

Each ml of Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma 5mg/ml solution contains 11.78mg phosphates.

If you suffer from severe damage to the clear layer at the front of the eye (the cornea), phosphates may cause in very rare cases cloudy patches on the cornea due to calcium build-up during treatment.

3. HOW TO USE TIMOLOL OPHTHALMIC SOLUTION USP 0.25% & 0.5% W/V TAJ PHARMA

Always use this medicine exactly as your doctor has told you. Check with your doctor or pharmacist if you are not sure. The doctor will decide how many drops you should take each day and how long you should use them.

The recommended dose is one drop in the affected eye(s) once or twice (one in the morning and one in the evening) each day.

Do not change your recommended dose without talking to your doctor.

Do not allow the tip of the bottle to touch the eye or areas around the eye. It could cause injury to your eye. The eye drops solution may become contaminated with bacteria that can cause eye infections leading to serious damage of the eye, even loss of vision.

To avoid possible contamination of the bottle, keep the tip of the bottle away from contact with any surface.

Instructions for use

Before instillation of the eye drops:

• Wash your hands before opening the bottle.
• Do not use this medicine if you notice that the tamper-proof seal on the bottle neck is broken before you first use it.
• At the first use, after cap removal, without positioning the eyedropper above the eye, slowly squeeze the bottle to deliver one drop in the air to get used to the pressure and time required to deliver one drop. In case of difficulties of delivering one drop at a time, this step might be repeated.
• Choose the position that you find most comfortable for the instillation of the drops (you can sit down, lie on your back, or stand in front of a mirror).

Instillation:

1. Hold the bottle directly below the cap and turn the cap to open the bottle. Do not touch anything with the tip of the bottle to avoid contamination of the solution.
2. Tilt your head backwards and hold the bottle above your eye.
3. Pull the lower eyelid down and look up. Squeeze the bottle gently in the middle and let a drop fall into your eye. Please note that there might be a few seconds delay between squeezing and the drop coming out. Do not squeeze too hard.

If you are not sure how to administer your medicine, ask your doctor, pharmacist or nurse.

4. Blink a few times so that the drop spreads over the eye.
5. After using Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma, press a finger into the corner of your eye, by the nose for 2 minutes. This helps to stop the eye drops getting into the rest of your body.
6. Follow the instructions 2-5 for dropping also into the other eye.
7. After use and prior to recapping, the bottle should be shaken once in a downwards direction, without touching the dropper tip, in order to remove any residual liquid on the tip. This is necessary in order to ensure delivery of subsequent drops.

There might remain a small amount of solution in the bottle at the end. This is accounted for by an overfill of all bottles ensuring that 5ml solution can always be dispensed.

Do not use the eye drops for longer than 28 days after first opening the bottle.

Use in children and adolescents

Before your child starts to use Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma, your child’s doctor will have carried out a detailed medical examination and decided whether or not this medicine is suitable. Your child, especially a newborn, should be closely monitored for one to two hours after the first dose and carefully monitored for any signs of side effects.

Method of administration for use in children and adolescents

One drop only of Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma should be instilled into the affected eye(s) each time. Follow the “Instructions for use” above when administering the eye drops.

Duration of treatment for use in children and adolescents

Your child’s doctor will decide for how long the eye drops will be needed.

If you use more Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma than you should

If you put too many drops in your eye or swallow any of the drops, you may:

• have a headache.
• Feel dizzy or light-headed.
• Have difficulty breathing.
• Have chest pain.
• Feel that your heart rate has slowed down.

If this happens, contact your doctor immediately.

If you forget to use Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma

It is important to take Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma as prescribed by your doctor.

• If you miss a dose, use the drops as soon as possible.
• If it is almost time for the next dose, skip the missed dose and take the next dose at the usual time.
• Do not take a double dose to make up for a forgotten dose.

If you stop using Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma

If you want to stop using this medicine talk to your doctor first. If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS

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

You can usually carry on taking the drops, unless the effects are serious. If you are worried, talk to a doctor or pharmacist. Do not stop using Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma without speaking to your doctor.

Serious side effects

See your doctor immediately if you notice any of the following side effects for which you may need urgent medical treatment:

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

• Severe sudden life-threatening allergic reaction with sudden rash, swelling beneath the skin that can occur in areas such as the face and limbs, and can obstruct the airway which may cause difficulty breathing or swallowing, and fainting (within minutes to hours) due to hypersensitivity (anaphylactic reaction).
• Paralysis, speech disorders, loss of consciousness due to reduced blood supply to the brain, interference with the blood supply to the brain which may lead to a stroke.
• Changes in the rhythm or speed of the heartbeat, congestive heart failure (heart disease with shortness of breath and swelling of the feet and legs due to fluid build-up), a type of heart rhythm disorder, heart attack, heart failure.
• Difficulty breathing, shortness of breath, wheezing, cough.
• Very slow pulse.
• Sudden decreased vision after surgery for glaucoma.
• Rash on the face, kidney inflammation, fever, joint and muscle pain due to connective tissue disease. A condition called lupus (systemic lupus erythematosus).
• Increases in signs and symptoms of myasthenia gravis (a muscle disorder which causes muscle weakness and fatigue of the eye muscles and/or of the muscles used in swallowing, chewing and breathing).
• Raynaud’s phenomenon (white, “dead” fingers and toes).
• Limping and leg pain when walking because there is a reduced blood supply to your legs.
• In men, a condition which affects your penis called Peyronie’s disease. The signs may be abnormal curve, pain or hardening of the tissue of your penis.

Other side effects

Common (may affect up to 1 in 10 people)

• Blurred vision, signs and symptoms of eye irritation (e.g. burning, stinging, itching, tearing, redness), inflammation of the eyelid, inflammation of the surface of the eye, irritation or pain in the eye, dry eyes, decreased corneal (layer at the front of the eye) sensitivity, corneal erosion (damage to the front layer of the eyeball), feeling of a foreign object in the eye, secretion
• Headache, dizziness

Uncommon (may affect up to 1 in 100 people)

• Fainting, general weakness, fatigue
• Depression
• Abnormal vision
• Nausea, indigestion

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

• General allergic reactions including localized and generalized rash, itchiness
• Double vision, drooping of the upper eyelid (making the eye stay half closed) and separation of one of the layers within the eyeball after surgery to reduce the pressure in the eye
• Low blood pressure
• Chest pain, palpitations, oedema (fluid build-up)
• Difficulty sleeping (insomnia), nightmares, memory loss
• Decreased sex drive
• Diarrhoea, dry mouth
• Hair loss, skin rash with white silvery coloured appearance (psoriasiform rash) or worsening of psoriasis
• Ringing sound in the ears
• Unusual sensations like tingling or pins and needles
• Cold hands and feet

Like other medicines applied into eyes, timolol is absorbed into the blood. This may cause similar side effects as seen with intravenous and/or oral beta-blocking agents. Incidence of side effects after topical ophthalmic administration is lower than when medicines are, for example, taken by mouth or injected. The following additional side effects were seen within the class of beta-blockers when used for treating eye conditions:

• Low blood glucose levels
• Corneal erosion (damage to the front layer of the eyeball), tearing and redness in the eyes
• Heart failure
• Severe allergic reactions with swelling and difficulty breathing
• Skin rash and itching
• Taste disturbances, abdominal pain, vomiting
• Muscle pain not caused by exercise
• Sexual dysfunction

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse.

This includes any possible side effects not listed in this leaflet.

5. HOW TO STORE TIMOLOL OPHTHALMIC SOLUTION USP 0.25% & 0.5% W/V TAJ PHARMA

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiry date which is stated on the carton and the bottle after EXP. The expiry date refers to the last day of that month.

This medicine does not require any special storage conditions.

Do not use the eye drops for longer than 28 days after first opening the bottle. Write down the date you opened the bottle in the space on the bottle label and box.

Make sure the bottle is properly closed.

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

6. CONTENTS OF THE PACK AND OTHER INFORMATION

What Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma contains

The active substance is timolol. Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma is available in two strengths:

a) Each ml of Ophthalmic Solution contains:
Timolol maleate equivalent to
5 mg of Timolol USP……………………2.5mg

b) Each ml of Ophthalmic Solution contains:
Timolol maleate equivalent to
5 mg of Timolol USP………………………5mg

The other ingredients are: sodium dihydrogen phosphate dihydrate, disodium phosphate dodecahydrate, sodium hydroxide (for pH adjustment), water for injections.

What Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma looks like and contents of the pack

Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma 2.5mg/ml eye drops, solution is presented as a clear, colourless aqueous solution in a white opaque 11ml LDPE bottle and white Novelia nozzle (HDPE and silicone) with a white HDPE cap.

Timolol Ophthalmic Solution USP 0.25% & 0.5% w/v Taj Pharma 5mg/ml eye drops, solution is presented as a clear, colourless aqueous solution in a white opaque 11ml LDPE bottle and white Novelia nozzle (HDPE and silicone) with a white HDPE cap.

Pack sizes: 1 or 2 bottles of 5ml solution in a cardboard box.

Not all pack sizes may be marketed.

7. MANUFACTURED IN INDIA BY:

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