Treatment of ocular signs and symptoms of seasonal allergic conjunctivitis.

Posology

The dose is one drop of PATANOL 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

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

PATANOL 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.

PATANOL 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

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

Olopatadine was found not to be teratogenic in rats and rabbits. However, rats treated at 600 mg/kg/day, or 93,750 times the MROHD and rabbits treated at 400 mg/kg/day, or 62,500 times the MROHD, during organogenesis showed a decrease in live fetuses. There are, however, 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.

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

Breast-feeding

Olopatadine has been identified in the milk of nursing rats following oral administration. 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 PATANOL (olopatadine hydrochloride ophthalmic solution) 0.1% is administered to a nursing mother.

A risk to the new born/infants cannot be excluded.

PATANOL 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.

PATANOL 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.

Summary of safety profile

In clinical studies involving 1680 patients, PATANOL 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 PATANOL; 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 PATANOL 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.

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.

To report any side effect(s):

·         Saudi Arabia

-          Saudi Food and Drug Authority National Pharmacovigilance Center (NPC):

o Fax: +966112057662

o Call NPC at +966-11-2038222, Exts: 2317-2356-2340.

o Toll free phone: 8002490000

o SFDA call center: 19999

o E-mail: npc.drug@sfda.gov.sa

o Website: https://ade.sfda.gov.sa

-          Patient Safety Department Novartis Consulting AG - Saudi Arabia:

o Toll Free Number: 8001240078

o Phone: +966112658100

o Fax: +966112658107

o Email: adverse.events@novartis.com

•    Other GCC States:

-  Please contact the relevant competent authority.

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 PATANOL 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.

Pharmacotherapeutic Group:  ophthalmologicals; decongestant and antiallergics; other antiallergics.

ATC code: S01GX 09

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 PATANOL was suggested to reduce the nasal signs and symptoms that frequently accompany seasonal allergic conjunctivitis.  It does not produce a clinically

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. 

Comparison of Olopatadine plasma concentration after topical ocular dosing and oral dosing

*1: AUC_0-6

*2: Not calculated because of insufficiency of samples

*3: AUC_0-12 mean estimates from Day 12

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 PATANOL 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.

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.

Benzalkonium chloride

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 medicinal products.

Store below 30ºC.

Do not use this medicine after the expiry date, which is stated on the packaging.

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

Low density polyethylene (LDPE) DROP-TAINER® bottle with LDPE dispensing plug and polypropylene closure.

8 mL bottle containing 5 mL solution

Carton contains 1 bottle.

No special requirements.