Treatment of ocular signs and symptoms of seasonal allergic conjunctivitis.

Posology

The dose is one drop of iPAT 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.

Pediatric patients

iPAT may be used in pediatric patients three years of age and older at the same dose as in adults. The safety and efficacy of iPAT 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 (iPAT) 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.

iPAT is an anti-allergic/antihistaminic agent and, although administered topically, is absorbed systemically. If signs of serious reactions or hypersensitivity occur, discontinue the use of this treatment.

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.

Pregnancy

No adequate and well controlled studies in pregnant women. Because animal studies are not always predictive of human responses, this drug should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the embryo or fetus.

Breast-feeding

It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in the human breast milk. Nevertheless, caution should be exercised when iPAT ophthalmic solution is administered to a nursing mother.

Fertility

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

iPAT 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.

Like all medicines, this medicine can cause side effects, although not everybody gets them. The following undesirable effects were assessed to be treatment-related and are classified according to the following convention: very common (>1/10), common (>1/100 to < 1/10), uncommon (>1/1,000 to 1/10,000 to < 1/1000), or very rare (<1/10,000). Within each frequency grouping, undesirable effects are presented in decreasing order of seriousness. Infections and infestations

Uncommon: rhinitis Nervous system disorders

Common: headache, dysgeusia

Uncommon: dizziness, hypoaesthesia

Eye disorders

Common: eye pain, eye irritation, dry eye, abnormal sensation in eyes

Uncommon: corneal erosion, corneal epithelium defect, corneal epithelium disorder, punctuate keratitis, keratitis, corneal staining, eye discharge, photophobia, vision blurred , visual acuity reduced, belpharospasm, ocular discomfort, eye pruritus, conjunctival follicles, conjunctival disorder, foreign body sensation in eyes, lacrimation increased, eyelids pruritus, erythema of eyelid, eyelid oedema, eyelid disorder, conjunctival hyperaemia, ocular hyperaemia Respiratory, thoracic, and mediastinal disorders

Common: nasal dryness

Skin and subcutaneous tissue disorders

Uncommon: dermatitis contact, skin burning sensation, dry skin

General disorders and administration site conditions

Common: fatigue

Not known (cannot be estimated from the available data): the frequency at which these events occur is not known and cannot be estimated based upon the available data.

Ocular: corneal oedema, conjunctivitis, eye oedema, eye swelling, mydriasis, visual disturbance, eyelid margin crusting.

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 iPAT 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 repolarization.

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

Pharmacotherapeutic Group: ophthalmologicals; decongestant and anti-allergics; other antiallergics.

ATC code: S01GX 09

Olopatadine is a potent selective anti-allergic/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 iPAT 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.

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 monodesmethyl 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 2.3fold 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 hemodialysis (with no urinary output), plasma olopatadine concentrations were significantly lower on the hemodialysis day than on the non-hemodialysis day suggesting olopatadine can be removed by hemodialysis.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 iPAT 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.

Not applicable

Sodium phosphate dibasic

Sodium chloride

HCl (1M)

Highly purified water

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

Do not store above 30 o C.

A new patented technology was used in order to make our product a multi does & preservative free; PureFLow® technology which is used to avoid the need for preservative by not allowing contaminated air to enter the bottle keeping product sterile. Primary bottle is LDPE.

None