OLOPT/ OLOPT DS

OLOPT

Each ml contains:

Olopatadine Hydrochloride equ. to Olopatadine USP 0.1 % w/v

Benzalkonium Chloride Solution BP 0.02 % v/v (as preservative)

Water for Injections BP q.s.

 OLOPT – DS

Each ml contains:

Olopatadine Hydrochloride equ. to Olopatadine USP 0.2 % w/v

Benzalkonium Chloride Solution BP 0.02 % v/v (as preservative)

Water for Injections BP q.s.

 DESCRIPTION

A clear, colorless to almost colorless solution.

 PHARMACODYNAMIC

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 antagonizes 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 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.

PHARMACOKINETICS

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 8 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 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.

 THERAPEUTIC INDICATION

Treatment of ocular signs and symptoms of seasonal allergic conjunctivitis.

DOSAGE AND ADMINISTRATION

Posology

The dose is one drop of Olopatadine Eye drops, Solution 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.

Elderly

No dosage adjustment in elderly patients is necessary.

Paediatric population

Olopatadine 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 in children aged under 3 years has not been established. No data are available.

Hepatic and renal impairment

Olopatadine in the form of eye drops 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.

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.

INSTRUCTION FOR USE

Apply OLOPT & OLOPT-DS Eye Drops in the following way:

1. Wash your hands. Tilt your head back and look at the ceiling.
2. Gently pull the lower eyelid down until there is a small pocket.
3. Turn the bottle upside down and gently press the bottle to release drops into eyes that needs treatment.
4. Let go of the lower lid, and close your eye for 30 seconds.
5. To avoid contamination, do not let the tip of dropper touch your eye or anything else.
6. Replace and tighten the cap straight after use.

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 Eye drops, solution 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.

 CONTRAINDICATION

• Hypersensitivity to the active substance or to any of the excipients.

WARNING AND PRECAUTIONS

• Olopatadine 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 contains benzalkonium chloride which may cause eye irritation, especially if patients have dry eyes or disorders of the cornea (the clear layer at the front of the eye). If patients feel abnormal eye sensation, stinging or pain in the eye after using this medicine, seek medical attention immediately.
• 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.
• Benzalkonium chloride may be absorbed by soft contact lenses and may change the colour of the contact lenses. Patients should be instructed to remove contact lenses before using this medicine and put them back 15 minutes afterwards.

PREGNANCY, LACTATION, FERTILITY AND ABILITY TO DRIVE

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. 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.

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

Olopatadine Eye drops, solution 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.

Effects on ability to drive and use machines

Olopatadine Eye drops, solution 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.

DRUG 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.

ADVERSE EFFECTS

The frequency of adverse reactions documented during clinical trials is given. The frequency is defined as follows: Very Common (≥ 1/10); Common (≥ 1/100, <1/10); Uncommon (≥ 1/1,000, <1/100); Rare (≥ 1/10,000, <1/1,000); Very Rare (<1/10,000), not known (cannot be estimated from the available data).

PRESENTATION

OLOPT Eye Drops are supplied in 5 ml and OLOPT-DS are supplied in 2.5 ml and 5 ml sterilized opaque plastic container with nozzle and cap.

 STORAGE AND OTHER INFORMATION

Store at temperature between 4-25 °C.

Preserve from light and store in light resistant container. Keep this medicine out of the sight and reach of children. Do not touch the dropper tip or other dispensing tip to any surface since this may contaminate the solution. Use the solution within one month after opening the container.