PALLADA-NS

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PALLADA-NS (PALLADA-NS)

Composition:

Active substance: olopatadine;

1 spray dose contains olopatadine hydrochloride 665 mcg;

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

Pharmaceutical form. Nasal spray, solution.

Main physicochemical properties: clear, colourless solution.

Pharmacotherapeutic group.

Decongestants and other preparations for nasal use. Antiallergic agents, excluding corticosteroids. ATC code R01AC08.

Pharmacological Properties

Pharmacodynamics

The active substance of the medicinal product, olopatadine, is a selective H1-histamine receptor antagonist. The drug exerts a pronounced antiallergic effect.

According to a 12-month study in patients with perennial allergic rhinitis who received olopatadine nasal spray at a dose of 2 sprays in each nostril twice daily, no effect of olopatadine on QT interval prolongation was observed.

Pharmacokinetics

The pharmacokinetic properties of olopatadine were studied after intranasal, oral, intravenous, and ophthalmic administration. Olopatadine demonstrated linear pharmacokinetics following all routes of administration over a wide dose range.

Absorption.

After intranasal administration twice daily to healthy volunteers, individual maximum plasma concentrations (t_max) were observed within 30 minutes to 1 hour. The mean (±SD) steady-state maximum plasma concentration (C_max) of olopatadine was 16.0 ± 8.99 ng/mL. Systemic exposure, expressed as the area under the plasma concentration-time curve (AUC_0–12), averaged 66.0 ± 26.8 ng·h/mL. The mean absolute bioavailability of olopatadine following intranasal administration was 57%. The mean accumulation ratio after repeated intranasal administration was approximately 1.3.

Distribution.

Olopatadine binding to plasma proteins, primarily albumin, is moderate and amounts to approximately 55%, independent of concentration within the range of 0.1 to 1000 ng/mL.

Metabolism.

Olopatadine does not undergo extensive metabolism. Based on metabolite profiles in plasma after oral administration of [14C]-olopatadine, at least six minor metabolites circulating in human plasma were identified. Olopatadine accounted for 77% of total peak radioactivity in plasma, while all metabolites combined accounted for <6%. Two metabolites were identified as olopatadine-N-oxide and N-desmethyl-olopatadine. In in vitro studies using cDNA-expressed human cytochrome CYP isoenzymes and flavin-containing monooxygenases (FMO), the formation of N-desmethyl-olopatadine (M1) was primarily catalyzed by CYP3A4, whereas olopatadine-N-oxide (M3) was predominantly catalyzed by FMO1 and FMO3. At concentrations up to 33,900 ng/mL, olopatadine did not inhibit in vitro metabolism of specific substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. The potential of olopatadine and its metabolites to induce CYP enzymes has not been evaluated.

Elimination.

The elimination half-life of olopatadine from plasma is 8–12 hours. It is primarily excreted in urine—85% in unchanged form, with the remainder as metabolites, including olopatadine-N-oxide and N-desmethyl-olopatadine. Approximately 70% of an oral dose of [14C]-olopatadine was recovered in urine and 17% in feces.

Special patient populations.

Patients with hepatic impairment.

Specific pharmacokinetic studies evaluating the effect of olopatadine in hepatic impairment have not been conducted. Since only a small fraction of the olopatadine dose is eliminated via metabolism, based on available data, no dose adjustment is required for patients with hepatic impairment.

Patients with renal impairment.

Mean C_max values for olopatadine after single intranasal administration did not differ significantly between healthy volunteers (18.1 ng/mL) and patients with mild, moderate, or severe renal impairment (15.5–21.6 ng/mL). The mean AUC_0–12 in patients with severe renal impairment (creatinine clearance <30 mL/min/1.73 m²) was twice as high as in healthy volunteers. At steady state, the C_max of olopatadine in patients with severe renal impairment was approximately 10-fold lower than concentrations observed after administration of higher oral doses (20 mg twice daily), which were well tolerated. Based on available data, no dose adjustment is required for patients with renal impairment.

Gender.

Mean systemic exposure (C_max and AUC_0–12) in women with seasonal allergic rhinitis (SAR) after repeated administration of olopatadine was 40% and 27% higher, respectively, than in men with SAR.

Race.

Pharmacokinetic differences in olopatadine based on race have not been studied.

Pediatric population (children aged 6 to 11 years).

The mean C_max (15.4 ± 7.3 ng/mL) of olopatadine in children was approximately 2-fold lower than in adults (78.0 ± 13.9 ng·h/mL). C_max and AUC_0–12 values for olopatadine-N-oxide were similar to those in adults. C_max and AUC_0–12 values for N-desmethyl-olopatadine were approximately 18% and 37% higher, respectively, than corresponding values in adults.

Drug interaction studies.

Drug interactions with inhibitors of hepatic enzymes are not expected, as olopatadine is primarily eliminated by the kidneys. Olopatadine does not inhibit in vitro metabolism of specific substrates for CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4. Therefore, drug interactions due to inhibition of the cytochrome P450 system are not anticipated. Due to moderate plasma protein binding of olopatadine (55%), drug interactions resulting from displacement from plasma proteins are also not expected.

Clinical characteristics.

Indications.

Symptomatic treatment of seasonal allergic rhinitis in adults and children aged 6 years and older.

Contraindications.

Hypersensitivity to the active substance and/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.

Interaction with liver enzyme inhibitors is not expected, since olopatadine is predominantly eliminated from the body via the kidneys.

Interactions related to inhibition of cytochrome P450 and plasma protein binding are also not expected.

Special precautions for use.

During the use of the medicinal product, nasal bleeding, nasal mucosa ulceration, and nasal septum perforation may occur.

Before initiating treatment, a nasal cavity examination should be performed to confirm the absence of other nasal disorders apart from allergic rhinitis. During treatment, regular nasal cavity examinations should be carried out to detect any adverse effects on the mucous membrane. If nasal mucosa ulceration occurs, discontinuation of the medicinal product should be considered.

Concomitant use of the medicinal product with alcoholic beverages or other agents that depress the central nervous system should be avoided due to the potential for additional reduction in alertness and impairment of central nervous system function.

The medicinal product contains benzalkonium chloride, which may cause irritation of the nasal mucosa and skin reactions.

Use during pregnancy or breastfeeding.

Pregnancy.

Adequate and well-controlled studies in pregnant women have not been conducted. Animal studies have revealed reproductive toxicity following systemic administration.

The medicinal product should be used during pregnancy only if the benefit to the woman outweighs the potential risk to the fetus.

Breastfeeding period.

Animal studies have shown that olopatadine passes into breast milk after oral administration. It is unknown whether intranasal local application leads to systemic absorption and transfer into breast milk in detectable amounts. During breastfeeding, the medicinal product should be used only if the benefit to the woman outweighs the potential risk to the infant.

Ability to influence reaction rate while driving or operating machinery.

Olopatadine may cause drowsiness; therefore, patients should refrain from driving or operating machinery during treatment with this medicinal product.

Method of Administration and Dosage.

Method of Administration.

The medicinal product is intended for intranasal use.

Before the first use, the dosing device should be primed by releasing 5 sprays or until a fine mist appears. If the medicinal product has not been used for more than 7 days, the device should be re-primed.

Avoid getting the medicinal product into the eyes.

Dosage.

Adults and children aged 12 years and older.

The recommended dose is 2 sprays into each nostril twice daily.

Children aged 6 to 11 years.

The recommended dose is 1 spray into each nostril twice daily.

Children under 6 years of age.

The efficacy and safety of intranasal administration of olopatadine in children under 6 years of age have not been established.

Elderly patients.

The medicinal product should be used with caution, considering the higher frequency of impaired liver, kidney, or heart function, concomitant diseases, and concomitant use of other medicinal products.

Children.

The medicinal product should be administered to children aged 6 years and older.

Overdose.

Symptoms

There have been no reports of overdose with intranasal administration of olopatadine.

Acute overdose following accidental or intentional ingestion of olopatadine in this dosage form is unlikely. Symptoms of overdose with antihistamines may include drowsiness in adults and excitation with restlessness followed by drowsiness in children.

Treatment

In case of overdose, symptomatic and supportive therapy should be administered. There is no specific antidote.

Adverse reactions.

Frequency of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency not known (frequency cannot be estimated from available data).

The most clinically significant adverse reactions are considered to be: epistaxis, nasal ulceration, nasal septum perforation, somnolence.

In adults and children aged 12 years and older, the following adverse reactions were commonly observed:

Infections and infestations: upper respiratory tract infections.

Nervous system disorders: headache.

Respiratory, thoracic and mediastinal disorders: epistaxis, pharyngolaryngeal pain, postnasal drip syndrome, cough.

Gastrointestinal disorders: bitter taste in mouth.

In adults and children aged 6 to 11 years, the following adverse reactions were commonly observed:

Infections and infestations: upper respiratory tract infections.

Nervous system disorders: headache.

Respiratory, thoracic and mediastinal disorders: epistaxis.

Gastrointestinal disorders: bitter taste in mouth.

Skin and subcutaneous tissue disorders: rash.

General disorders and administration site conditions: fever.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after medicine registration is very important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national pharmacovigilance system.

Shelf life.

3 years.

Storage conditions.

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

Packaging.

30 ml (240 doses) in a bottle with a metering device and protective cap; 1 bottle per cardboard box.

Prescription status.

Prescription only.

Manufacturer.

UORLД MEDICINE ILAC SAN. VE TIC. A.S. /
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.

LLC "WORLD MEDICINE", Ukraine /
WORLD MEDICINE, LLC, Ukraine.