Olodrops

INSTRUCTIONS for medical use of the medicinal product OLODROPS (OLODROPS)

Composition:

Active substance: olopatadine;

1 ml of solution contains olopatadine hydrochloride equivalent to olopatadine 1 mg;

Excipients: benzalkonium chloride, sodium chloride, anhydrous sodium hydrogen phosphate, hydrochloric acid diluted, sodium hydroxide, water for injections.

Pharmaceutical form. Eye drops.

Main physicochemical characteristics: clear, colorless solution.

Pharmacotherapeutic group.

Agents for ophthalmological use. Anti-inflammatory and antiallergic agents.

ATC code S01GX09.

Pharmacological Properties

Pharmacodynamics

Olopatadine is a potent, selective anti-allergic/antihistamine agent with multiple distinct mechanisms of action. It inhibits the release of histamine (the primary mediator of allergic reactions in humans) and prevents histamine-induced cytokine release from human conjunctival epithelial cells. In vitro studies indicate that the drug acts on conjunctival mast cells, suppressing the release of inflammatory mediators. It has been observed that topical ophthalmic administration of olopatadine in patients with patent nasolacrimal ducts reduces nasal signs and symptoms commonly associated with seasonal allergic conjunctivitis. The drug does not cause clinically significant changes in pupil diameter.

Preclinical data obtained from standard safety, pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity studies revealed no hazard to humans.

Animal studies showed delayed development in puppies nursed by dams that received systemic olopatadine treatment at doses exceeding the maximum recommended dose for human ophthalmic use. Olopatadine was detected in the milk of lactating rats following oral administration.

Pharmacokinetics

Olopatadine is systemically absorbed, as with other topically applied medicinal products. However, systemic absorption following topical administration is low, with plasma concentrations ranging from below the lower limit of quantification (<0.5 ng/mL) to 1.3 ng/mL. These concentrations are 50 to 200 times lower than those achieved after oral administration of well-tolerated doses of the drug. Pharmacokinetic studies following oral administration showed that the elimination half-life of olopatadine in plasma is approximately 8–12 hours, with the drug being primarily excreted by the kidneys. Approximately 60–70% of the administered dose was recovered in urine as unchanged active substance. Two metabolites, mono-desmethyl and N-oxide, were detected in urine at low concentrations.

Since olopatadine is excreted in urine primarily as unchanged active substance, its pharmacokinetics are altered in renal impairment. Peak plasma concentrations in patients with severe renal insufficiency (mean creatinine clearance of 13 mL/min) were 2 to 3 times higher than in healthy adult volunteers. In patients undergoing hemodialysis after receiving a 10 mg oral dose, plasma olopatadine concentrations were significantly lower on dialysis days compared to non-dialysis days, suggesting that olopatadine is removed during hemodialysis.

Comparative pharmacokinetic studies following a 10 mg oral dose in young individuals (mean age 21 years) and elderly individuals (mean age 74 years) showed no significant differences in plasma concentrations, protein binding, or urinary excretion of unchanged drug and metabolites.

Pharmacokinetic studies of olopatadine following oral administration in patients with severe renal insufficiency have been conducted. Results indicate that somewhat higher plasma concentrations of olopatadine can be expected in this patient population. However, since plasma concentrations following topical ophthalmic administration of olopatadine are 50 to 200 times lower than those achieved with well-tolerated oral doses, dosage adjustment is not required for elderly individuals or patients with renal impairment. Hepatic metabolism is not a major route of elimination for the drug; therefore, dosage adjustment is not necessary in patients with hepatic impairment.

Clinical characteristics.

Indications.

Treatment of seasonal allergic conjunctivitis.

Contraindications.

Hypersensitivity to olopatadine or to any of the excipients of the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Studies on olopatadine interaction with other medicinal products have not been conducted.

In vitro studies have shown that olopatadine does not inhibit metabolic reactions of cytochrome P450 isoenzymes 1A2, 2C8, 2C9, 2C19, 2D6, 2E1, and 3A4. These results indicate that olopatadine does not cause metabolic interactions with other active substances when used concomitantly.

If other ophthalmic agents are used, see section "Administration and dosage".

Special precautions for use

Olodrops is a topical antiallergic/antihistamine agent that is systemically absorbed. The drug should be discontinued at the first signs of serious reactions or increased sensitivity.

Olodrops contains benzalkonium chloride, which may cause eye irritation.

It has also been reported that benzalkonium chloride may lead to punctate keratopathy and/or toxic ulcerative keratopathy. Patients with dry eye syndrome or corneal damage who use the product frequently or for prolonged periods should be carefully monitored.

Contact lenses

Benzalkonium chloride is known to discolor contact lenses. Contact with soft contact lenses should be avoided. Patients should be advised to remove contact lenses before instilling the drops and to wait at least 15 minutes after instillation before reinserting the lenses.

Use during pregnancy or breastfeeding

Pregnancy

Data on the ophthalmic use of olopatadine in pregnant women are lacking or limited in number. Animal studies have shown reproductive toxicity following systemic administration. Olopatadine is not recommended for use in pregnant women or in women of childbearing potential who are not using contraception.

Breastfeeding

Animal studies have shown that olopatadine passes into breast milk after oral administration. A risk to newborns/infants cannot be excluded. Olopatadine should not be used during breastfeeding.

Reproductive function

Studies evaluating the effect of olopatadine on human reproductive function following topical ophthalmic administration have not been conducted.

Ability to affect reaction speed when driving or operating machinery

Olodrops has no or negligible influence on the ability to drive or operate machinery. However, as with other ophthalmic solutions, transient blurred vision or other visual disturbances may affect the ability to drive or operate machinery. If blurred vision occurs after instillation, patients should wait until vision clears before driving or operating machinery.

Method of Administration and Dosage

For ophthalmic use only. Use as directed by a physician.

Instill 1 drop of Olodrops into the conjunctival sac of the affected eye(s) twice daily (morning and evening). If necessary, treatment may continue for up to 4 months.

• Wash hands before instillation.
• Take the dropper bottle and unscrew the protective cap.
• After removing the cap, if the safety ring around the dropper rotates freely, remove it before instillation.
• Hold the bottle, pointing downwards, between the index and middle fingers.
• Tilt the head backward. Gently pull down the eyelid with a clean finger to create a "pocket" between the eyelid and the eye. Direct the drop into this pocket (Figure 1).
• Bring the tip of the dropper close to the eye. For convenience, perform this step in front of a mirror.
• Do not touch the dropper tip to the eye, eyelid, surrounding areas, or any other surfaces. This may contaminate the remaining solution in the bottle.
• Gently press the bottom of the bottle to release one drop of Olodrops at a time.
• Do not squeeze the bottle; it is designed so that only light pressure on the bottom is required (Figure 2).
• If instillation into both eyes is required, repeat the process for the other eye.
• Immediately after use, securely screw the cap back onto the bottle. Keep the dropper bottle tightly closed between uses.

If more than one ophthalmic product is required, the interval between instillations should be at least 5 minutes. Ophthalmic ointments should be administered last.

Use in Elderly Patients

No dose adjustment is necessary for this patient group.

Use in Children and Adolescents

Olopatadine may be used in pediatric patients (children aged 3 years and older) at the same dosage as in adults. The safety and efficacy of Olodrops in children under 3 years of age have not been established. Data for this age group are lacking.

Use in Hepatic and Renal Impairment

Studies with olopatadine ophthalmic solution in patients with hepatic or renal impairment have not been conducted. However, no dose adjustment is considered necessary in cases of hepatic or renal impairment.

Children. Use in children aged 3 years and older.

Overdose

Overdose is unlikely with topical administration. In case of excessive exposure, rinse the eyes with lukewarm water.

There are no data on overdose in humans following accidental or intentional ingestion. Accidental ingestion of the entire contents of an Olodrops bottle would result in a maximum systemic exposure of 5 mg of olopatadine. This could result in systemic effects at a dose of 0.5 mg/kg in a 10-kg child assuming 100% absorption.

In a study involving 102 healthy volunteers, including young men and women as well as elderly individuals, who received 5 mg of the drug orally twice daily for 2.5 days, a slight prolongation of the QT interval was observed compared to placebo. In this study, peak plasma concentrations of olopatadine (35 to 127 ng/mL) were at least 70 times higher than those achieved with topical olopatadine administration, with regard to effects on cardiac repolarization.

In the event of overdose, appropriate diagnostic measures and symptomatic treatment should be initiated.

Adverse reactions.

The most common adverse effect observed during the use of the medicinal product was ocular pain with an incidence rate of 0.7%. The adverse reactions listed below were reported during clinical studies and in the post-marketing period and were classified according to frequency: very common (≥1/10), common (>1/100, <1/10), uncommon (>1/1000, ≤1/100), rare (>1/10000, ≤1/1000), very rare (≤1/10000), or not known (cannot be estimated from available data). Within each frequency category, adverse reactions are listed in order of decreasing severity.

In patients with significant corneal involvement, corneal calcification has very rarely been reported with the use of ophthalmic solutions containing phosphates.

Reporting of suspected adverse reactions for registered medicinal products is very important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are requested to report any suspected adverse reactions that occur in patients during treatment.

Shelf life. 3 years.

Shelf life after first opening of the container: 28 days.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C, in a place inaccessible to children.

Packaging. 5 ml in a dropper bottle; 1 dropper bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer. Micro Labs Limited.

Manufacturer's address and place of business.
Plot Nos. 113-116, Phase 4, K.I.A.D.B. Industrial Area, Bommansandra, Bangalore, India.