Olopatadine

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT OLOPATADINE

Composition:

Active substance: olopatadine (olopatadine);

1 ml of the preparation contains 1 mg of olopatadine;

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

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear solution, colorless to light yellow.

Pharmacotherapeutic group. Agents for use in ophthalmology. 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 antagonizes the release of histamine (the primary mediator of allergic reactions in humans) and prevents histamine-induced stimulation of cytokine production by human conjunctival epithelial cells. In vitro studies indicate that the drug acts on mast cells of the human conjunctiva, inhibiting the release of inflammatory mediators. It has been observed that topical ophthalmic administration of the drug 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.

Standard safety studies, including pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity studies, revealed no risk to humans.

Delayed puppy development was observed in pups nursed by females receiving systemic doses of olopatadine exceeding the maximum recommended dose for human ophthalmic use. Olopatadine was detected in the milk of lactating rats after oral administration.

Pharmacokinetics.

Olopatadine is systemically absorbed, as are other locally applied medicinal agents. However, with topical application, systemic absorption of olopatadine is minimal, and plasma concentrations range from below the limit of quantification (< 0.5 ng/mL) to 1.3 ng/mL. These concentrations are 50–200 times lower than those achieved after oral administration of well-tolerated doses of the drug.

The elimination half-life of olopatadine in plasma after oral administration is approximately 8–12 hours, and the drug is primarily excreted by the kidneys. Approximately 60–70% of the administered dose is 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 predominantly as unchanged active substance, its pharmacokinetics are altered in renal impairment. Peak plasma concentrations in patients with severe renal impairment (mean creatinine clearance of 13 mL/min) are 2–3 times higher than in healthy adult volunteers. In patients undergoing hemodialysis after 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.

After oral administration of a 10 mg dose, no significant differences in plasma concentrations, protein binding, or urinary excretion of unchanged drug and metabolites were observed between young and elderly individuals.

Following oral administration to patients with severe renal impairment, somewhat higher plasma concentrations may be expected. However, since plasma concentrations after topical ophthalmic administration of olopatadine are 50–200 times lower than those achieved with well-tolerated oral doses, dosage adjustment is not required for elderly patients or patients with renal impairment. Hepatic metabolism is not a major elimination pathway 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 the interaction of the drug with other medicinal products have not been conducted.

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

Special precautions for use

The drug is an antiallergic/antihistamine agent intended for topical use, but it is systemically absorbed. The drug should be discontinued at the first signs of serious reactions or hypersensitivity.

It has also been reported that benzalkonium chloride may cause punctate keratopathy and/or toxic ulcerative keratopathy. Patients with dry eye syndrome or corneal damage who use the drug 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 applying the drug and to wait at least 15 minutes after instillation before reinserting the contact lenses.

Use during pregnancy or breastfeeding

Pregnancy

Data on the ophthalmic use of olopatadine in pregnant women are lacking or limited in number. Reproductive toxicity has been observed in animals following systemic administration (see section "Pharmacological properties"). Olopatadine is not recommended for use in pregnant women or in women of reproductive potential who are not using contraceptive measures.

Breastfeeding

After oral administration in animals, olopatadine was excreted into animal milk (see "Pharmacological properties" for details). A risk to newborns/infants cannot be excluded. The drug should not be used during breastfeeding.

Reproductive function

No studies have been conducted to evaluate the effect of olopatadine on human reproductive function following topical ophthalmic administration.

Ability to influence reaction speed when driving or operating machinery

The drug has no or negligible influence on the ability to drive or operate machinery. However, as with any eye drops, 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.

Dosage and Administration

For ophthalmic use only.

One drop of the medicinal product should be administered into the conjunctival sac of the affected eye(s) twice daily (with an 8-hour interval). If necessary, treatment may continue for up to 4 months.

Use in elderly patients.

No dosage adjustment is required for this patient population.

Use in children and adolescents.

The medicinal product can be used in pediatric practice in children aged 3 years and older at the same dosage as in adults. Safety and efficacy of the medicinal product in children under 3 years of age have not been established. Data in this age group are lacking.

Use in hepatic or renal impairment.

Studies with olopatadine in the form of eye drops have not been conducted in patients with hepatic or renal impairment. However, no dosage adjustment is necessary in patients with hepatic or renal impairment (see section "Pharmacokinetics").

To prevent contamination of the dropper tip and the contents of the bottle, care should be taken not to touch the eyelids, surrounding areas, or other surfaces with the tip of the dropper cap. The bottle should be tightly closed after each use.

If more than one ophthalmic medicinal product is used locally, the interval between their administration should be at least 5 minutes. Ophthalmic ointments should be applied last.

Children.

The medicinal product can be used in children aged 3 years and older at the same dosage as in adults.

Overdose.

There are no data on overdose in humans following accidental or intentional ingestion. Olopatadine showed a low level of acute toxicity in animals. Accidental ingestion of the entire contents of one bottle of the medicinal product would result in a maximum systemic exposure of 5 mg of olopatadine. This exposure could occur at a final dose of 0.5 mg/mL in a child weighing 10 kg assuming 100% absorption.

Prolongation of the QT interval in dogs was observed only at doses substantially exceeding the maximum human dose, indicating a low likelihood of QT prolongation during clinical use. In healthy volunteers, young adults, and elderly individuals receiving 5 mg of the medicinal product orally twice daily for 2.5 days, a slight increase in QT interval was observed compared to placebo. Peak plasma concentrations of olopatadine (ranging from 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 case of overdose, appropriate patient evaluation and treatment should be initiated.

Adverse reactions.

During clinical trials, olopatadine was administered once to four times daily in both eyes for up to four months either as monotherapy or as add-on therapy to loratadine 10 mg. Adverse effects associated with olopatadine use were observed in approximately 4.5% of patients; however, only 1.6% of patients discontinued clinical trials due to these adverse effects. No serious ophthalmological or systemic adverse events related to the use of the drug were reported during clinical trials. The most common adverse effect with olopatadine use was ocular pain, occurring at a frequency of 0.7%.

The adverse reactions listed below were observed during clinical trials and in the post-marketing period and are classified by 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 frequency not known (cannot be estimated from available data). Within each group, adverse reactions are listed in order of decreasing severity.

In patients with significant corneal involvement, very rare cases of corneal calcification have 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, according to current legislation, any suspected adverse reactions to the medicinal product occurring in patients during therapy.

Reporting adverse reactions after medicinal product registration is of significant importance. It enables ongoing monitoring of the benefit-risk profile of the medicinal product. Medical and pharmaceutical personnel, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy of the medicinal product via the Automated Information System for Pharmacovigilance at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

The shelf life of the medicinal product after opening the container is no more than 4 weeks.

Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 5 ml in a bottle with a dropper cap in a box.

Prescription status. Prescription only.

Manufacturer. Limited Liability Company "FARMEKS GROUP".

Manufacturer's address and place of business.

100, Shevchenka Street, Boryspil, Kyiv region, 08301, Ukraine.