Visallergol^® (Drops) Instructions for Use

Marketing Authorization Holder

Sentiss Pharma, Pvt. Ltd. (India)

Contact Information

SENTISS RUS LLC (Russia)

ATC Code

S01GX09 (Olopatadine)

Active Substance

Olopatadine (Rec.INN registered by WHO)

Dosage Form

Visallergol®

Eye drops 0.2%: 2.5 ml bottle with dropper cap

Dosage Form, Packaging, and Composition

Eye drops as a clear, colorless to light yellow solution.

Excipients : benzalkonium chloride, povidone K-29/32, anhydrous sodium phosphate dibasic, sodium chloride, disodium edetate, sodium hydroxide, hydrochloric acid, purified water.

2.5 ml – polyethylene bottles (1) with dropper cap – cardboard packages.

Clinical-Pharmacological Group

An antiallergic drug for topical use in ophthalmology

Pharmacotherapeutic Group

Agents used in ophthalmology; decongestants and antiallergic agents; other antiallergic agents

Pharmacological Action

Olopatadine is a potent selective antiallergic/antihistamine drug, the pharmacological effects of which develop through several different mechanisms of action.

It is a histamine antagonist (the main mediator of allergic reactions in humans) and prevents histamine-induced release of inflammatory cytokines in conjunctival epithelial cells.

Based on in vitro studies, it is assumed to inhibit the release of inflammatory mediators from conjunctival mast cells.

In patients with patent nasolacrimal ducts, topical application of olopatadine as instillations into the conjunctival sac helped reduce the severity of nasal symptoms often accompanying seasonal allergic conjunctivitis.

Olopatadine does not have a clinically significant effect on pupil diameter.

Pharmacokinetics

Absorption

Olopatadine undergoes systemic absorption, like other drugs intended for topical use.

However, plasma concentrations of olopatadine after its topical use in ophthalmology are low and range from below the quantitation limit (< 0.5 ng/ml) to 1.3 ng/ml.

The reported plasma concentrations are 50-200 times lower than those with oral administration of therapeutic doses of olopatadine.

Elimination

According to pharmacokinetic studies of oral forms of olopatadine, T_1/2 is from 8 to 12 hours, and the drug is eliminated primarily by the kidneys.

60-70% of the administered dose is excreted unchanged in the urine, and low concentrations of 2 metabolites – monodesmethyl and N-oxide – are also detected in the urine.

Since Olopatadine is excreted by the kidneys mainly unchanged, impaired renal function leads to a change in the pharmacokinetics of olopatadine, resulting in a significant (2.3-fold) increase in plasma concentration of olopatadine in patients with severe renal failure (CrCl 13 ml/min).

The plasma concentration of olopatadine after its topical use as instillations is 50-200 times lower than with oral administration of therapeutic doses, therefore, no dose adjustment is required in patients with impaired renal function.

Since the hepatic elimination pathway is not the main one for olopatadine, no dose adjustment is required when used by patients with impaired liver function.

After oral administration of 10 mg of olopatadine to patients on hemodialysis, the plasma concentration of olopatadine was significantly lower on the day of hemodialysis compared to days when hemodialysis was not performed.

This indicates that elimination of olopatadine by hemodialysis is possible.

Based on the results of comparative pharmacokinetic studies of the oral dosage form of olopatadine at a concentration of 10 mg in young (mean age 21 years) and elderly patients (mean age 74 years), no significant differences were noted in plasma concentrations of olopatadine, plasma protein binding, and parameters of excretion of the drug unchanged and as metabolites.

Indications

Adults and children aged 2 years and older

• Relief of ocular itching in allergic conjunctivitis.

ICD codes

Dosage Regimen

Adults

The drug Visallergol^® is instilled as 1 drop once a day into the affected eye(s).

The duration of the course of therapy, if necessary, can be up to 4 months.

Special patient groups

Elderly patients

No dose adjustment is required in elderly patients.

Patients with impaired renal/hepatic function

The use of olopatadine in the eye drops dosage form has not been studied in patients with renal or hepatic impairment.

No dose adjustment is required for the stated category of patients.

Children

The use of the drug Visallergol^® is possible in children over 2 years of age in the same doses as in adults.

The efficacy and safety of olopatadine use in children under 2 years of age has not been established.

Method of administration

Topically, as instillations into the conjunctival sac.

Do not touch the tip of the bottle to the eyelids, periorbital skin, or other surfaces to avoid microbial contamination of the drug.

Tightly close the cap after using the drug.

If necessary, it can be used in combination with other drugs for topical use in ophthalmology; in this case, the interval between their use should be at least 5 minutes.

Eye ointments should be applied last.

Adverse Reactions

Summary of the safety profile

In clinical studies involving 1680 patients, the dosing regimen ranged from 1 to 4 drops/day, the duration of the course of therapy was up to 4 months, and the use of olopatadine was both as monotherapy and in combination with loratadine at a dose of 10 mg.

The overall incidence of adverse reactions was about 4.5%, while discontinuation from the clinical study due to the development of adverse reactions was noted in only 1.6% of cases.

No serious adverse reactions, either ocular or systemic, were noted during the clinical studies.

The most frequent treatment-related adverse reaction was eye pain, which was noted in 0.7% of patients.

Tabulated summary of adverse reactions

The following adverse reactions have been observed during clinical studies and post-marketing use of the drug and are classified according to the following frequency gradation: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1000 to <1/100), rare (≥1/10000 to <1/1000), very rare (<1/10000), frequency not known (cannot be estimated from the available data).

Within each group, adverse reactions are listed in order of decreasing severity.

In very rare cases, the use of phosphate-containing drops by patients with concomitant significant corneal damage has led to corneal calcification.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after registration of the drug in order to ensure continuous monitoring of the benefit-risk ratio of the drug.

Healthcare professionals are recommended to report any suspected adverse drug reactions through the national adverse reaction reporting systems of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to olopatadine or to any of the excipients included in the drug;
• Pregnancy;
• Breastfeeding period;
• Children under 2 years of age.

Use in Pregnancy and Lactation

Pregnancy

Data on the topical use of olopatadine in ophthalmology in pregnant women are absent or limited.

Animal studies have obtained data on the toxic effect of olopatadine on reproductive function with systemic use.

The use of olopatadine during pregnancy and by women of childbearing potential not using contraception is not recommended.

Breastfeeding period

Excretion of olopatadine into breast milk has been noted with the use of the drug in animals.

The risk to newborns and infants cannot be excluded.

The use of the drug Visallergol^®® during breastfeeding is not recommended.

Fertility

No studies have been conducted on the effect of topical use of olopatadine in ophthalmology on human fertility.

Use in Hepatic Impairment

No dose adjustment is required in patients with hepatic impairment.

Use in Renal Impairment

No dose adjustment is required in patients with renal impairment.

Pediatric Use

The use of the drug is contraindicated in children under 2 years of age.

Geriatric Use

No dose adjustment is required in elderly patients.

Special Precautions

Olopatadine hydrochloride is an antiallergic/antihistamine drug for topical use in ophthalmology and, despite topical application, can be absorbed into the systemic circulation.

If severe hypersensitivity reactions occur, the use of the drug should be discontinued.

The drug Visallergol^® should not be used to relieve conjunctival hyperaemia caused by the use of contact lenses.

Excipients

The drug contains benzalkonium chloride, which can be adsorbed by soft contact lenses and cause eye irritation.

It is necessary to remove contact lenses before instillation and reinsert them no earlier than 15 minutes after instillation of the drug.

According to a number of studies, benzalkonium chloride can provoke the development of punctate keratopathy and/or toxic ulcerative keratopathy.

Careful monitoring of the eye condition of patients is required with frequent or prolonged use of the drug Visallergol^® in cases of concomitant dry eye syndrome, as well as in cases of corneal damage.

Effect on ability to drive vehicles and mechanisms

The drug Visallergol^® does not have a significant effect on the ability to drive vehicles and mechanisms.

In case blurred vision is noted immediately after instillation, it is necessary to refrain from driving vehicles and operating mechanisms until visual clarity is restored.

Overdose

There is no information on the development of toxic phenomena with accidental administration of an excessive amount of the drug into the conjunctival cavity or with accidental ingestion.

Treatment in case of overdose due to accidental ingestion is symptomatic therapy.

Drug Interactions

Studies of the interaction of olopatadine with other drugs have not been conducted.

In vitro studies have demonstrated no inhibition of metabolic reactions mediated by cytochrome P-450 isoenzymes 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4.

Based on the results obtained, the likelihood of olopatadine entering into metabolic reactions when used concomitantly with other drugs is assessed as low.

Storage Conditions

The drug should be stored out of the reach of children at a temperature from 2°C (35.6°F) to 25°C (77°F).

Do not freeze.

Shelf Life

Shelf life – 2 years. Do not use after the expiration date stated on the packaging.

After first opening the bottle, store at a temperature not exceeding 25°C (77°F) for no more than 28 days.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.