1. NAME OF THE MEDICINAL PRODUCT

Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma

  1. QUALITATIVE AND QUANTITATIVE COMPOSITION

Each ml of solution contains
Olopatadine hydrochloride USP ……….1mg

Excipient(s) with known effect:

Benzalkonium chloride 0.1 mg/ml.

For the full list of excipients, see section 6.1.

  1. PHARMACEUTICAL FORM

Eye drops, solution (eye drops).

Clear, colourless solution.

  1. CLINICAL PARTICULARS

4.1 Therapeutic indications

Treatment of ocular signs and symptoms of seasonal allergic conjunctivitis.

4.2 Posology and method of administration

Posology

The dose is one drop of Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma in the conjunctival sac of the affected eye(s) twice daily (8 hourly). Treatment may be maintained for up to four months, if considered necessary.

Use in elderly

No dosage adjustment in elderly patients is necessary.

Paediatric patients

Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma may be used in paediatric patients three years of age and older at the same dose as in adults. The safety and efficacy of Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma in children aged under 3 years has not been established. No data are available.

Use in hepatic and renal impairment

Olopatadine in the form of eye drops (Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma) has not been studied in patients with renal or hepatic disease. However, no dosage adjustment is expected to be necessary in hepatic or renal impairment (see section 5.2).

Method of administration

For ocular use only.

After the bottle cap is removed, if the tamper evident snap collar is loose, remove before using the product. To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas, or other surfaces with the dropper tip of the bottle. Keep the bottle tightly closed when not in use.

In case of concomitant therapy with other topical ocular medicines, an interval of five minutes should be allowed between successive applications. Eye ointments should be administered last.

4.3 Contraindications

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

4.4 Special warnings and precautions for use

Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma is an antiallergic/antihistaminic agent and, although administered topically, is absorbed systemically. If signs of serious reactions or hypersensitivity occur, discontinue the use of this treatment.

Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma contains benzalkonium chloride which may cause eye irritation.

Benzalkonium chloride has also been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Close monitoring is required with frequent or prolonged use in dry eye patients, or in conditions where the cornea is compromised.

Contact lenses

Benzalkonium is known to discolour soft contact lenses. Avoid contact with soft contact lenses. Patients should be instructed to remove contact lenses prior to administration of the eye drop and wait at least15 minutes after instillation before re-inserting contact lenses.

4.5 Interaction with other medicinal products and other forms of interaction

No interaction studies with other medicinal products have been performed.

In vitro studies have shown that olopatadine did not inhibit metabolic reactions which involve cytochrome P-450 isozymes 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. These results indicate that olopatadine is unlikely to result in metabolic interactions with other concomitantly administered active substances.

4.6 Fertility, pregnancy and lactation

Pregnancy

There are no or limited amount of data from the use of ophthalmic olopatadine in pregnant women.

Studies in animals have shown reproductive toxicity following systemic administration (see section 5.3).

Olopatadine is not recommended during pregnancy and in women of childbearing potential not using contraception.

Breast-feeding

Available data in animals have shown excretion of olopatadine in milk following oral administration (for details see section 5.3).

A risk to the newborn/infants cannot be excluded.

Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma should not be used during breast-feeding.

Fertility

Studies have not been performed to evaluate the effect of topical ocular administration of olopatadine on human fertility.

4.7 Effects on ability to drive and use machines

Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma has no or negligible influence on the ability to drive and use machines.

As with any eye drop, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machinery.

4.8 Undesirable effects

Summary of safety profile

In clinical studies involving 1680 patients, Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma was administered one to four times daily in both eyes for up to four months as monotherapy or adjunctive therapy to loratadine 10 mg. Approximately 4.5% of patients can be expected to experience adverse reactions associated with the use of Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma; however, only 1.6% of patients discontinued from the clinical studies due to these adverse reactions. No serious ophthalmic or systemic adverse reactions related to Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma were reported in clinical studies. The most frequent treatment-related adverse reaction was eye pain, reported at an overall incidence of 0.7%.

Tabulated list of adverse reactions

The following adverse reactions have been reported during clinical studies and post-marketing data and are classified according to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1000)very rare (<1/10,000) or not known (cannot be estimated from the available data). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

System Organ ClassificationFrequencyAdverse Reactions
Infections and infestationsUncommonrhinitis
Immune system disordersNot knownhypersensitivity, swelling face
Nervous system disordersCommonheadache, dysgeusia
Uncommondizziness, hypoaesthesia
Not knownsomnolence
Eye disordersCommoneye pain, eye irritation, dry eye, abnormal sensation in eyes
Uncommoncorneal erosion, corneal epithelium defect, corneal epithelium disorder, punctate keratitis, keratitis, corneal staining, eye discharge, photophobia, vision blurred, visual acuity reduced, blepharospasm, ocular discomfort, eye pruritus, conjunctival follicles, conjunctival disorder, foreign body sensation in eyes, lacrimation increased, erythema of eyelid, eyelid oedema, eyelid disorder, ocular hyperaemia
Not knowncorneal oedema, eye oedema, eye swelling, conjunctivitis, mydriasis, visual disturbance, eyelid margin crusting
Respiratory, thoracic, and mediastinal disordersCommonnasal dryness
Not knowndyspnoea, sinusitis
Gastrointestinal disordersNot knownnausea, vomiting,
Skin and subcutaneous tissue disordersUncommondermatitis contact, skin burning sensation, dry skin
Not knowndermatitis, erythema
General disorders and administration site conditionsCommonfatigue
Not knownasthenia, malaise

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

No data are available in humans regarding overdose by accidental or deliberate ingestion. Olopatadine has a low order of acute toxicity in animals. Accidental ingestion of the entire contents of a bottle of Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma would deliver a maximum systemic exposure of 5 mg olopatadine. This exposure would result in a final dose of 0.5 mg/kg in a 10 kg infant, assuming 100% absorption.

Prolongation of the QTc interval in dogs was observed only at exposures considered sufficiently in excess of the maximum human exposure indicating little relevance to clinical use. A 5 mg oral dose was administered twice-daily for 2.5 days to 102 young and elderly male and female healthy volunteers with no significant prolongation of QTc interval compared to placebo. The range of peak steady-state olopatadine plasma concentrations (35 to 127 ng/ml) seen in this study represents at least a 70-fold safety margin for topical olopatadine with respect to effects on cardiac repolarisation.

In the case of overdose, appropriate monitoring and management of the patient should be implemented.

  1. PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: ophthalmologicals; decongestant and antiallergics; other antiallergics,
Olopatadine is a potent selective antiallergic/antihistaminic agent that exerts its effects through multiple distinct mechanisms of action. It antagonises histamine (the primary mediator of allergic response in humans) and prevents histamine induced inflammatory cytokine production by human conjunctival epithelial cells. Data from in vitro studies suggest that it may act on human conjunctival mast cells to inhibit the release of pro-inflammatory mediators. In patients with patent nasolacrimal ducts, topical ocular administration of Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma was suggested to reduce the nasal signs and symptoms that frequently accompany seasonal allergic conjunctivitis. It does not produce a clinically significant change in pupil diameter.

5.2 Pharmacokinetic properties

Absorption

Olopatadine is absorbed systemically, as are other topically administered medicinal products. However, systemic absorption of topically applied olopatadine is minimal with plasma concentrations ranging from below the assay quantitation limit (<0.5 ng/ml) up to 1.3 ng/ml. These concentrations are 50-to 200-fold lower than those following well tolerated oral doses.

Elimination

From oral pharmacokinetic studies, the half-life of olopatadine in plasma was approximately eight to 12 hours, and elimination was predominantly through renal excretion. Approximately 60-70% of the dose was recovered in the urine as active substance. Two metabolites, the mono-desmethyl and the N-oxide, were detected at low concentrations in the urine.

Since olopatadine is excreted in urine primarily as unchanged active substance, impairment of renal function alters the pharmacokinetics of olopatadine with peak plasma concentrations 2.3-fold greater in patients with severe renal impairment (mean creatinine clearance of 13.0 ml/min) compared to healthy adults. Following a 10 mg oral dose in patients undergoing haemodialysis (with no urinary output), plasma olopatadine concentrations were significantly lower on the haemodialysis day than on the non-haemodialysis day suggesting olopatadine can be removed by haemodialysis.

Studies comparing the pharmacokinetics of 10 mg oral doses of olopatadine in young (mean age 21 years) and elderly (mean age 74 years) showed no significant differences in the plasma concentrations (AUC), protein binding or urinary excretion of unchanged parent drug and metabolites.

A renal impairment study after oral dosing of olopatadine has been performed in patients with severe renal impairment. The results indicate that a somewhat higher plasma concentration can be expected with Olopatadine Hydrochloride Ophthalmic Solution 0.1% w/v Taj Pharma in this population. Since plasma concentrations following topical ocular dosing of olopatadine are 50-to 200-fold lower than after well-tolerated oral doses, dose adjustment is not expected to be necessary in the elderly or in the renally impaired population. Liver metabolism is a minor route of elimination. Dose adjustment is not expected to be necessary with hepatic impairment.

5.3 Preclinical safety data

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

Studies in animals have shown reduced growth of nursing pups of dams receiving systemic doses of olopatadine well in excess of the maximum level recommended for human ocular use. Olopatadine has been detected in the milk of nursing rats following oral administration.

  1. PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Benzalkonium chloride, sodium chloride, disodium phosphate dodecahydrate, hydrochloric acid (to adjust pH), sodium hydroxide (to adjust pH), purified water

6.2 Incompatibilities

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.

6.3 Shelf life

3 years.

Shelf-life after first opening

Discard four weeks after first opening.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

5 ml opaque low density polyethylene bottles with polypropylene screw caps (DROP-TAINER).

Cartons containing 1 or 3 bottles. Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

  1. 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

OLOPATADINE HYDROCHLORIDE
OPHTHALMIC SOLUTION
0.1% W/V
TAJ PHARMA

PACKAGE LEAFLET: INFORMATION FOR THE USER

Olopatadine

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

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

WHAT IS IN THIS LEAFLET

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

    1. WHAT OLOPATADINE HYDROCHLORIDE IS AND WHAT IT IS USED FOR

Olopatadine Hydrochloride is used for the treatment of signs and symptoms of seasonal allergic conjunctivitis.

Allergic conjunctivitis. Some materials (allergens) like pollens, house dust or animal fur may cause allergic reactions resulting in itching, redness as well as swelling of the surface of your eye.

Olopatadine Hydrochloride is a medicine for treatment of allergic conditions of the eye. It works by reducing the intensity of the allergic reaction.

  1. WHAT YOU NEED TO KNOW BEFORE YOU USE OLOPATADINE HYDROCHLORIDE DO NOT USE OLOPATADINE HYDROCHLORIDE
  • If you are allergic (hypersensitive) to olopatadine or any of the other ingredients of this medicine (listed in section 6).
  • You should not use OLOPATADINE HYDROCHLORIDE if you are breast-feeding.

Warnings and precautions

Talk to your doctor or pharmacist before using Olopatadine Hydrochloride.

You should remove contact lenses that are in your eyes before using Olopatadine Hydrochloride.

Children

Do not use Olopatadine Hydrochloride in children under the age of 3 years. Do not give this medicine to children under the ages of 3 years because there is no data to indicate that it is safe and work in children under

3 years.

Other medicines and Olopatadine Hydrochloride

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

If you are using other eye drops or eye ointment medicines, leave at least 5 minutes between each medicine. Eye ointments should be administered last.

Pregnancy, breast-feeding and fertility

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

You should not use Olopatadine Hydrochloride if you are breast-feeding, ask your doctor for advice before using this medicine.

Driving and using machines

You may find that your vision is blurred for a time just after you use Olopatadine Hydrochloride. Do not drive or use machines until this has worn off.

Olopatadine Hydrochloride contains Benzalkonium chloride

This medicine contains 0.5 mg benzalkonium chloride in each 5 ml which is equivalent to 0.1 mg/ml.

The preservative in Olopatadine Hydrochloride, benzalkonium chloride, may be absorbed by soft contact lenses and may change the colour of the contact lenses. You should remove contact lenses before using this medicine and put them back 15 minutes afterwards. Benzalkonium chloride may also cause eye irritation, especially if you have dry eyes or disorders of the cornea (the clear layer at the front of the eye). If you feel abnormal eye sensation, stinging or pain in the eye after using this medicine, talk to your doctor.

  1. HOW TO USE OLOPATADINE HYDROCHLORIDE

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

The recommended dose is one drop in the eye or eyes, twice a day, morning and evening.

Use this much unless your doctor tells you to do differently. Only use Olopatadine Hydrochloride in both eyes if your doctor told you to. Use it for as long as your doctor told you to.

Olopatadine Hydrochloride should only be used as an eye drop. TURN THE PAGE FOR MORE ADVICE.

Now turn over.

How to use Olopatadine Hydrochloride (continued)

  • Get the Olopatadine Hydrochloride bottle and a mirror.
  • Wash your hands.
  • Take the bottle and twist off the cap.
  • After cap is removed, if the tamper evident snap collar is loose, remove before using the product.

Hold the bottle, pointing down, between your thumb and middle finger.

  • Tilt your head back. Pull down your eyelid with a clean finger, until there is a ‘pocket’ between the eyelid and your eye. The drop will go in here (picture 1).
  • Bring the bottle tip close to the eye. Use the mirror if it helps.
  • Don’t touch your eye or eyelid, surrounding areas or other surfaces with the dropper. It could infect the drops left in the bottle.
  • Gently press on the base of the bottle to release one drop of Olopatadine Hydrochloride at a time.
  • Don’t squeeze the bottle, it is designed so that just a gentle press on the bottom is needed (picture 2).
  • If you use drops in both eyes, repeat the steps for your other eye.
  • Put the bottle cap back on firmly immediately after use.

If a drop misses your eye, try again.

If you use more Olopatadine Hydrochloride than you should

Rinse it all out with warm water. Do not put in any more drops until it’s time for your next regular dose.

If you forget to use Olopatadine Hydrochloride

Use a single drop as soon as you remember, and then go back to your regular dosing routine. However, if it is almost time for your next dose, skip the missed dose before going back to your regular dosing routine. Do not use a double dose to make up for the one missed.

If you stop using Olopatadine Hydrochloride

Do not stop using this medicine without first speaking to your doctor.

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

  1. POSSIBLE SIDE EFFECTS

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following side effects have been seen with Olopatadine Hydrochloride:

Common (may affect up to 1 in 10 people)

Effects in the eye:

Eye pain, eye irritation, dry eye, abnormal eye sensation, eye discomfort.

General side effects

Headache, fatigue, dry nose, bad taste.

Uncommon (may affect up to 1 in 100 people)

Effects in the eye

Blurred, reduced, or abnormal vision, corneal disorder, eye surface inflammation with or without surface damage, inflammation or infection of the conjunctiva, eye discharge, sensitivity to light, increased tear production, itchy eye, redness of the eye, eyelid abnormality, itching, redness, swelling, or crusting of the eyelid.

General side effects

Abnormal or decreased sensation, dizziness, runny nose, dry skin, skin inflammation.

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

Effects in the eye

Eye swelling, corneal swelling, change in pupil size.

General side effects

Shortness of breath, increased allergic symptoms, facial swelling, drowsiness, generalized weakness, nausea, vomiting, sinus infection, skin redness and itching.

In very rare cases, some patients with severe damage to the clear layer at the front of the eye (the cornea) have developed cloudy patches on the cornea due to calcium build-up during treatment.

Reporting of side effects

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

  1. HOW TO STORE OLOPATADINE HYDROCHLORIDE

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 bottle and the box after ‘EXP’. The expiry date refers to the last day of the month.

This medicine does not require any special storage conditions.

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

Do not throw away 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          CONTENT OF THE PACK AND OTHER INFORMATION WHAT OLOPATADINE HYDROCHLORIDE CONTAINS

Each ml of solution contains
Olopatadine hydrochloride USP ……….1mg

The other ingredients are benzalkonium chloride, sodium chloride, disodium phosphate dodecahydrate, hydrochloric acid and/or sodium hydroxide and purified water.

What Olopatadine Hydrochloride looks like and contents of the pack

Olopatadine Hydrochloride is a clear and colourless liquid (a solution) supplied in a pack containing either one 5 ml bottle or three 5 ml plastic bottles with screw caps.

Not all pack sizes may be marketed.

  1. 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