Pallada

INSTRUCTION FOR MEDICAL USE OF MEDICINAL PRODUCT PALLADA (PALLADA)

Composition:

Active substance: olopatadine;

1 ml of solution contains olopatadine (as hydrochloride) 1 mg;

Excipients: benzalkonium chloride, sodium dihydrogen phosphate anhydrous, sodium chloride, sodium hydroxide or dilute hydrochloric acid, water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: 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 counteracts 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 olopatadine acts on mast cells of the human conjunctiva, inhibiting 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. It 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 suckled 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 following oral administration.

Pharmacokinetics.

Olopatadine is systemically absorbed, as with other locally applied medicinal agents. However, systemic absorption following topical application 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 with oral administration at well-tolerated doses.

Pharmacokinetic studies following oral administration indicate that the elimination half-life of olopatadine in plasma is approximately 8–12 hours. It is 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 predominantly as unchanged active substance, its pharmacokinetics are altered in renal impairment. Maximum 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 oral administration of 10 mg olopatadine, plasma concentrations were significantly lower on dialysis days compared to non-dialysis days, suggesting that olopatadine is removed during hemodialysis.

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

Studies of olopatadine following oral administration in patients with severe renal impairment have been conducted. Results indicate that somewhat higher plasma concentrations of olopatadine may be expected in this patient population. However, since plasma concentrations following topical ophthalmic administration of olopatadine are 50–200 times lower than those achieved with well-tolerated oral doses, dosage adjustment is not necessary for elderly individuals or patients with renal impairment. Hepatic metabolism is not a major route of olopatadine elimination; therefore, dosage adjustment is not required for 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 olopatadine 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. These results indicate that olopatadine does not cause metabolic interactions with other active substances when used concomitantly.

Special precautions for use.

The medicinal product is an antiallergic/antihistamine agent used locally but which is systemically absorbed. If any signs of serious reactions or increased sensitivity occur, treatment should be discontinued.

The medicinal product contains benzalkonium chloride, which may cause eye irritation. Benzalkonium chloride has also been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Patients with "dry eye syndrome" or corneal damage who use the medicinal product frequently or over a prolonged period should be carefully monitored.

Use in patients wearing 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 medicinal product and to wait at least 15 minutes after instillation before reinserting contact lenses.

Use during pregnancy or breastfeeding.

Pregnancy.

Data on the ophthalmic use of olopatadine in pregnant women are lacking or limited in quantity. Animal studies have shown reproductive toxicity following systemic administration (see section "Pharmacological properties"). The medicinal product is not recommended for use during pregnancy and in women of childbearing potential who are not using contraceptive measures.

Breastfeeding period.

Animal studies have shown that olopatadine passes into breast milk after oral administration (see section "Pharmacological properties"). A risk to newborns/infants cannot be excluded. The medicinal product should not be used during breastfeeding.

Fertility.

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

Ability to influence the speed of reactions when driving vehicles or operating machinery.

Olopatadine has no or negligible influence on the ability to drive vehicles or operate machinery. However, as with the use of any eye drops, transient blurred vision or other visual disturbances may affect the ability to drive vehicles 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

The medicinal product is intended for topical use only.

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

Use in elderly patients

There is no need for dosage adjustment in this patient population.

Use in patients with hepatic or renal impairment

Studies with olopatadine in the form of eye drops in patients with hepatic or renal impairment have not been conducted. However, dosage adjustment is not considered necessary in cases of hepatic or renal impairment (see section "Pharmacological Properties" (Pharmacokinetics)).

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

If more than one ophthalmic agent is used locally, an interval of at least 5 minutes should be maintained between their applications. Ophthalmic ointments should be administered last.

Children

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

The safety and efficacy of olopatadine in children under 3 years of age have not been established. Data for this age group are lacking.

Overdose

There are no reports of olopatadine overdose in humans following accidental or intentional ingestion. Olopatadine has shown a low level of acute toxicity in animal studies. Accidental ingestion of the entire contents of one bottle would result in a maximum systemic exposure of 5 mg of olopatadine. This corresponds to a dose of 0.5 mg/kg in a 10-kg child assuming 100% absorption.

QT interval prolongation in dogs was observed only at doses substantially exceeding the maximum recommended human dose, suggesting a low likelihood of QT prolongation with clinical use. In a study involving 102 healthy volunteers, including young men and women as well as elderly individuals, who received 5 mg of olopatadine orally twice daily for 2.5 days, a slight increase in 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 case of overdose, appropriate patient evaluation and treatment should be initiated.

Adverse reactions.

In clinical studies involving 1680 patients, olopatadine was administered 1 to 4 times daily in both eyes for up to 4 months either as monotherapy or as add-on therapy to loratadine 10 mg. Adverse reactions related to olopatadine use were observed in approximately 4.5% of patients; however, only 1.6% were discontinued from clinical studies due to these adverse reactions. No serious ophthalmological or systemic adverse reactions related to olopatadine use were reported during clinical studies. The most common adverse reaction with olopatadine use was ocular pain, occurring at a frequency of 0.7%.

The adverse reactions listed below were observed during clinical studies and in the post-marketing period, and are classified according to MedDRA system organ classes and frequency: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), and not known (frequency cannot be estimated from available data). Within each group, adverse reactions are listed in order of decreasing severity.

Infections and infestations:

Uncommon – rhinitis.

Immune system disorders:

Not known – hypersensitivity, facial swelling.

Nervous system disorders:

Common – headache, dysgeusia; uncommon – dizziness, hypoesthesia; not known – somnolence.

Eye disorders:

Common – eye pain, eye irritation, dry eye, abnormal eye sensation; uncommon – corneal erosion, corneal epithelial damage, corneal epithelial disorder, punctate keratitis, keratitis, corneal discoloration, eye discharge, photophobia, blurred vision, decreased visual acuity, blepharospasm, eye discomfort, eye pruritus, conjunctival follicles, conjunctival disorder, foreign body sensation in the eye, increased lacrimation, eyelid erythema, eyelid edema, eyelid disorder, ocular hyperemia; not known – corneal edema, eye swelling, eye swelling, conjunctivitis, mydriasis, visual disturbance, scaling along eyelid margins.

Respiratory, thoracic and mediastinal disorders:

Common – nasal dryness; not known – dyspnea, sinusitis.

Gastrointestinal disorders:

Not known – nausea, vomiting.

Skin and subcutaneous tissue disorders:

Uncommon – contact dermatitis, burning sensation of the skin, dry skin; not known – dermatitis, erythema.

General disorders and administration site conditions:

Common – increased fatigue; not known – asthenia, malaise.

In patients with significant corneal damage, very rare cases of corneal calcification have been reported with ophthalmic solutions containing phosphates.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine authorization is important. It allows continuous monitoring of the benefit-risk balance of the medicine. Healthcare professionals are encouraged to report any suspected adverse reactions through the national reporting system.

Shelf life.

3 years.

After first opening of the bottle, the product may be used for up to 28 days.

Storage conditions.

Store at temperatures not exceeding 25°C, in a place inaccessible to children.

Packaging.

5 ml solution in a dropper bottle; 1 dropper bottle in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

UORLД MEDICIN ILAC SAN. VE TIC. A.Ш./
WORLD MEDICINE ILAC SAN. VE TIC. A.S.

Manufacturer's address and location of operations.

15 Temmuz Mahallesi Cami Yolu Caddesi No:50 Gunesli Bagcilar/Istanbul, Turkey.

Marketing Authorization Holder.

WORLD MEDICINE, LLC, Ukraine.