OPATANOL 1mg / ml ophthalmic drops solution medication leaflet

Opatanol 1 mg/mL eye drops, solution

One mL of solution contains 1 mg olopatadine (as hydrochloride).

Benzalkonium chloride 0.1 mg/ml.

Disodium phosphate dodecahydrate (E339) 12.61 mg/ml (equivalent to 3.34 mg/ml of phosphates).

For the full list of excipients, see section 6.1.

Eye drops, solution (eye drops).

Clear, colourless solution.

Treatment of ocular signs and symptoms of seasonal allergic conjunctivitis.

The dose is one drop of Opatanol 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.

Opatanol may be used in paediatric patients three years of age and older at the same dose as in adults.

The safety and efficacy of Opatanol in children aged under 3 years has not been established. No dataare available.

Use in hepatic and renal impairment

Olopatadine in the form of eye drops (Opatanol) has not been studied in patients with renal or hepaticdisease. However, no dosage adjustment is expected to be necessary in hepatic or renal impairment(see section 5.2).

For ocular use only.

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

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

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

Opatanol is an antiallergic/antihistaminic agent and, although administered topically, is absorbedsystemically. If signs of serious reactions or hypersensitivity occur, discontinue the use of thistreatment.

Opatanol contains benzalkonium chloride which may cause eye irritation.

Benzalkonium chloride has also been reported to cause punctate keratopathy and/or toxic ulcerativekeratopathy. Close monitoring is required with frequent or prolonged use in dry eye patients, or inconditions 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 waitat least15 minutes after instillation before re-inserting contact lenses.

No interaction studies with other medicinal products have been performed.

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

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 (seesection 5.3).

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

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.

Opatanol should not be used during breast-feeding.

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

Opatanol 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 todrive or use machines. If blurred vision occurs at instillation, the patient must wait until the visionclears before driving or using machinery.

In clinical studies involving 1680 patients, Opatanol was administered one to four times daily in botheyes for up to four months as monotherapy or adjunctive therapy to loratadine 10 mg. Approximately4.5% of patients can be expected to experience adverse reactions associated with the use of Opatanol;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 Opatanol were reported in clinicalstudies. The most frequent treatment-related adverse reaction was eye pain, reported at an overallincidence of 0.7%.

The following adverse reactions have been reported during clinical studies and post-marketing dataand 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, adversereactions are presented in order of decreasing seriousness.

System Organ Classification Frequency Adverse Reactions

Infections and infestations Uncommon rhinitis

Immune system disorders Not known hypersensitivity, swelling face

Common headache, dysgeusia

Nervous system disorders Uncommon dizziness, hypoaesthesia

Not known somnolence

Common eye pain, eye irritation, dry eye, abnormalsensation in eyes

Uncommon corneal erosion, corneal epitheliumdefect, corneal epithelium disorder,punctate keratitis, keratitis, cornealstaining, eye discharge, photophobia,vision blurred, visual acuity reduced,blepharospasm, ocular discomfort, eye

Eye disorderspruritus, conjunctival follicles,conjunctival disorder, foreign bodysensation in eyes, lacrimation increased,erythema of eyelid, eyelid oedema, eyeliddisorder, ocular hyperaemia

Not known corneal oedema, eye oedema, eyeswelling, conjunctivitis, mydriasis, visualdisturbance, eyelid margin crusting

Respiratory, thoracic, and Common nasal drynessmediastinal disorders Not known dyspnoea, sinusitis

Gastrointestinal disorders Not known nausea, vomiting,

Uncommon dermatitis contact, skin burning sensation,

Skin and subcutaneous tissuedry skindisorders

Not known dermatitis, erythema

General disorders and Common fatigueadministration site conditions Not known asthenia, malaise

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

Reporting suspected adverse reactions after authorisation of the medicinal product is important. Itallows continued monitoring of the benefit/risk balance of the medicinal product. Healthcareprofessionals are asked to report any suspected adverse reactions via the national reporting systemlisted in Appendix V.

No data are available in humans regarding overdose by accidental or deliberate ingestion. Olopatadinehas a low order of acute toxicity in animals. Accidental ingestion of the entire contents of a bottle of

Opatanol would deliver a maximum systemic exposure of 5 mg olopatadine. This exposure wouldresult 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 inexcess of the maximum human exposure indicating little relevance to clinical use. A 5 mg oral dosewas administered twice-daily for 2.5 days to 102 young and elderly male and female healthyvolunteers with no significant prolongation of QTc interval compared to placebo. The range of peaksteady-state olopatadine plasma concentrations (35 to 127 ng/ml) seen in this study represents at leasta 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 beimplemented.

Pharmacotherapeutic group: ophthalmologicals; decongestant and antiallergics; other antiallergics,

ATC code: S01GX 09

Olopatadine is a potent selective antiallergic/antihistaminic agent that exerts its effects throughmultiple distinct mechanisms of action. It antagonises histamine (the primary mediator of allergicresponse in humans) and prevents histamine induced inflammatory cytokine production by humanconjunctival epithelial cells. Data from in vitro studies suggest that it may act on human conjunctivalmast cells to inhibit the release of pro-inflammatory mediators. In patients with patent nasolacrimalducts, topical ocular administration of Opatanol was suggested to reduce the nasal signs and symptomsthat frequently accompany seasonal allergic conjunctivitis. It does not produce a clinically significantchange in pupil diameter.

Olopatadine is absorbed systemically, as are other topically administered medicinal products.

However, systemic absorption of topically applied olopatadine is minimal with plasma concentrationsranging from below the assay quantitation limit (<0.5 ng/ml) up to 1.3 ng/ml. These concentrations are50-to 200-fold lower than those following well tolerated oral doses.

From oral pharmacokinetic studies, the half-life of olopatadine in plasma was approximately eight to12 hours, and elimination was predominantly through renal excretion. Approximately 60-70% of thedose 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 renalfunction alters the pharmacokinetics of olopatadine with peak plasma concentrations 2.3-fold greaterin patients with severe renal impairment (mean creatinine clearance of 13.0 ml/min) compared tohealthy adults. Following a 10 mg oral dose in patients undergoing haemodialysis (with no urinaryoutput), plasma olopatadine concentrations were significantly lower on the haemodialysis day than onthe non-haemodialysis day suggesting olopatadine can be removed by haemodialysis.

Studies comparing the pharmacokinetics of 10 mg oral doses of olopatadine in young (mean age21 years) and elderly (mean age 74 years) showed no significant differences in the plasmaconcentrations (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 severerenal impairment. The results indicate that a somewhat higher plasma concentration can be expectedwith Opatanol in this population. Since plasma concentrations following topical ocular dosing ofolopatadine are 50-to 200-fold lower than after well-tolerated oral doses, dose adjustment is notexpected to be necessary in the elderly or in the renally impaired population. Liver metabolism is aminor route of elimination. Dose adjustment is not expected to be necessary with hepatic impairment.

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

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

Sodium chloride

Disodium phosphate dodecahydrate (E339)

Hydrochloric acid (E507) (to adjust pH)

Sodium hydroxide (E524) (to adjust pH)

Purified water

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

3 years.

Shelf-life after first opening

Discard four weeks after first opening.

This medicinal product does not require any special storage conditions.

5 ml opaque low density polyethylene bottles with polypropylene screw caps.

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

No special requirements.

Novartis Europharm Limited

Vista Building

Elm Park, Merrion Road

Dublin 4

Ireland

EU/1/02/217/001-002

Date of first authorisation: 17 May 2002

Date of latest renewal: 22 May 2007

Detailed information on this medicinal product is available on the website of the European Medicines

Agency http://www.ema.europa.eu.