Instructions for use Akimba eye drops solution 1 mg/ml bottle 5 ml No. 1
Composition
active ingredient: olopatadine;
1 ml of solution contains olopatadine 1 mg (as hydrochloride);
Excipients: benzalkonium chloride, sodium hydrogen phosphate dihydrate, sodium chloride, hydrochloric acid 3.6% solution, sodium hydroxide 4% solution, water for injections.
Dosage form
Eye drops, solution.
Main physicochemical properties: transparent colorless solution without visible particles, pH 6.5–7.5, osmolality 260–340 mOsmol/kg.
Pharmacotherapeutic group
Means for use in ophthalmology. Anti-edematous and anti-allergic agents.
ATX code S01G X09.
Pharmacological properties
Pharmacodynamics. Olopatadine is a potent, selective antiallergic/antihistamine with several distinct mechanisms of action. It antagonizes the release of histamine (the main mediator of allergic reactions in humans) and prevents histamine-induced cytokine production by human conjunctival epithelial cells. In vitro studies have shown that the drug acts on human conjunctival mast cells to inhibit the release of inflammatory mediators. Topical ophthalmic administration of olopatadine in patients with preserved nasolacrimal patency has been shown to reduce the nasal signs and symptoms that often accompany seasonal allergic conjunctivitis. The drug does not cause clinically significant changes in pupil diameter.
Preclinical data revealed no special hazard for humans based on conventional studies of safety, pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, and toxicity to reproduction.
Animal studies have shown developmental delays in pups of lactating dams exposed to systemic doses of olopatadine exceeding the maximum recommended human ophthalmic dose. Olopatadine was excreted in the milk of female rats following oral administration.
Pharmacokinetics: Olopatadine is absorbed systemically, like other topical drugs. However, with topical application of olopatadine, systemic absorption is minimal, and plasma concentrations range from below the level of quantification (< 0.5 ng/mL) to 1.3 ng/mL. These concentrations are 50-200 times lower than those achieved with oral administration of the drug at well-tolerated doses.
Oral pharmacokinetic studies have shown that the plasma half-life of olopatadine is approximately 8-12 hours. The drug is excreted primarily by the kidneys. Approximately 60-70% of the dose was recovered in the urine as the active substance. Two metabolites, monodesmethyl and N-oxide, were detected in the urine at low concentrations.
Since olopatadine is excreted in the urine, mainly as unchanged active substance, the pharmacokinetics of olopatadine are altered in renal impairment: peak plasma concentrations in patients with severe renal insufficiency (mean creatinine clearance 13 ml/min) are 2-3 times higher than in healthy adult volunteers. In patients undergoing hemodialysis after oral administration of 10 mg, plasma concentrations of olopatadine were significantly lower on the day of hemodialysis than on the day when it was not performed, suggesting that olopatadine was eliminated during hemodialysis.
In comparative pharmacokinetic studies of oral administration of a 10 mg dose in young subjects (mean age 21 years) and elderly subjects (mean age 74 years), no significant differences were found between plasma concentrations, protein binding, and urinary excretion of unchanged drug and metabolites.
Studies of oral olopatadine have been conducted in patients with severe renal impairment. The results suggest that somewhat higher plasma concentrations of olopatadine can be expected in this patient population. Since plasma concentrations after topical ophthalmic administration of olopatadine are 50-200 times lower than those after oral administration of the drug at well-tolerated doses, no dosage adjustment is necessary for the elderly or patients with renal impairment. Hepatic metabolism is not a major route of elimination. Therefore, no dosage adjustment is necessary for patients with hepatic impairment.
Indication
For the treatment of seasonal allergic conjunctivitis.
Contraindication
Hypersensitivity to olopatadine or to any of the excipients of the medicinal product.
Interaction with other medicinal products and other types of interactions
No studies have been conducted on the interaction of the drug with other drugs.
In vitro studies have shown that olopatadine does not inhibit the 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.
Application features
Olopatadine is a topically applied antiallergic/antihistamine that is absorbed systemically. If any signs of serious reactions or hypersensitivity occur, the drug should be discontinued.
Olopatadine 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 lesions who use the drug frequently or for a long time should be carefully monitored.
Contact lenses. Benzalkonium chloride is known to discolour contact lenses. Contact with soft contact lenses should be avoided. Patients should be advised to remove contact lenses before using the medicinal product and to wait at least 15 minutes after instillation before reinserting contact lenses.
Use during pregnancy or breastfeeding
Pregnancy: There are no or limited amount of ophthalmic data from the use of olopatadine in pregnant women. Animal studies have shown reproductive toxicity after systemic administration (see section 5.1). Olopatadine is not recommended for use in pregnant women and women of childbearing potential not using contraception.
Breastfeeding. Animal studies have shown that olopatadine is excreted in breast milk after oral administration (see section 5.1 for details). A risk to the newborn/infants cannot be excluded. Olopatadine should not be used by women during breast-feeding.
Reproductive function: Studies of the effects of olopatadine on human reproductive function following topical ophthalmic administration have not been conducted.
Ability to influence the speed of reactions when driving vehicles or other mechanisms. Olopatadine has no or negligible influence on the ability to drive vehicles and other mechanisms. As with the use of any eye drops, temporary blurred vision or other visual disturbances may affect the ability to drive vehicles or operate other mechanisms. If blurred vision occurs during instillation, the patient should wait until the vision clears before driving vehicles or operating other mechanisms.
Method of administration and doses
For ophthalmic use only.
1 drop of the drug should be instilled into the conjunctival sac of the affected eye(s) twice a day (at 8-hour intervals). If necessary, treatment may last up to 4 months.
Use in elderly patients. There is no need for dosage adjustment for this category of patients.
Use in children and adolescents. Olopatadine can be used in pediatric practice in children from 3 years of age at the same dosage as in adults. The safety and efficacy of olopatadine in children under 3 years of age have not been studied. Data are not available for this age group.
Use in hepatic and renal impairment. Olopatadine eye drops have not been studied in patients with hepatic or renal impairment. However, no dosage adjustment is necessary in patients with hepatic or renal impairment (see Pharmacokinetics).
To prevent contamination of the dropper tip and contents of the bottle, care should be taken not to touch the eyelids, surrounding areas, or other surfaces with the dropper tip. The dropper tip should be tightly closed after each use.
If more than one ophthalmic agent is used topically, the interval between their applications should be at least 5 minutes. Eye ointments should be applied last.
Children: Olopatadine can be used in children aged 3 years and older at the same dosage as adults.
Overdose
There are no data on overdose in humans after accidental or intentional ingestion. Olopatadine has shown low acute toxicity in animals. Accidental ingestion of the entire vial of the drug will result in a maximum systemic exposure of 5 mg of olopatadine. This exposure may occur at a final dose of 0.5 mg/ml in a child weighing 10 kg with 100% absorption.
In dogs, QT prolongation was observed only at doses significantly in excess of the maximum human dose, indicating that QT prolongation is unlikely to occur in clinical practice. In a study of 102 healthy male, female, and elderly volunteers administered 5 mg orally twice daily for 2.5 days, there was a slight increase in QT interval compared to placebo. In this study, peak plasma concentrations of olopatadine (35 to 127 ng/mg) were at least 70-fold greater than those observed with topical olopatadine for its effects on cardiac repolarization.
In case of overdose, appropriate examination and treatment of the patient is necessary.
Side effects
In clinical trials involving 1680 patients, olopatadine was administered 1 to 4 times daily to both eyes for four months as monotherapy or as adjunctive therapy to loratadine 10 mg. Adverse reactions related to olopatadine were observed in approximately 4.5% of patients; however, only 1.6% of these patients were withdrawn from clinical trials due to these adverse reactions. No serious ophthalmic or systemic adverse reactions related to the drug were reported during clinical trials. The most common adverse reaction with olopatadine was eye pain, with an incidence of 0.7%.
The following adverse reactions have been reported during clinical trials and post-marketing experience. Adverse reactions are classified according to frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000), very rare (< 1/10,000), not known (frequency cannot be estimated from the available data). Within each grouping, adverse reactions are presented in order of decreasing seriousness.
| Organ systems | Frequency | Adverse reactions |
| Infections and infestations | Infrequently | Rhinitis |
| Immune system | Frequency unknown | Increased sensitivity, facial swelling |
| Nervous system | Often | Headache, dysgeusia |
| Infrequently | Dizziness, hypoesthesia | |
| Frequency unknown | Drowsiness | |
| Organs of vision | Often | Eye pain, eye irritation, dry eye, abnormal eye sensitivity |
| Infrequently | Corneal erosion, corneal epithelial damage, corneal epithelial disorder, punctate keratitis, keratitis, corneal discoloration, eye discharge, photophobia, blurred vision, visual acuity reduced, blepharospasm, eye discomfort, eye pruritus, conjunctival follicles, conjunctival disorder, foreign body sensation in eye, lacrimation increased, eyelid erythema, eyelid edema, eyelid disorder, eye hyperemia | |
| Frequency unknown | Corneal edema, eye edema, eye swelling, conjunctivitis, mydriasis, visual impairment, eyelid margin scaling | |
| Respiratory system, chest organs and mediastinum | Often | Dry nose |
| Frequency unknown | Dyspnea, sinusitis | |
| Gastrointestinal tract | Frequency unknown | Nausea, vomiting |
| Skin and subcutaneous tissue | Infrequently | Contact dermatitis, burning sensation on the skin, dry skin |
| Frequency unknown | Dermatitis, erythema | |
| General condition and injection site condition | Often | Increased fatigue |
| Frequency unknown | Asthenia, malaise | |
In patients with significant corneal damage, cases of corneal calcification have been very rarely observed with the use of eye drops containing phosphates.
Reporting of adverse reactions
Reporting adverse reactions after registration of a medicinal product is of great importance. This allows monitoring of the benefit/risk ratio when using this medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report cases of suspected adverse reactions and lack of efficacy of a medicinal product to the State Expert Center of the Ministry of Health of Ukraine at the link: https://aisf.dec.gov.ua.
Expiration date
3 years.
After opening the bottle, store for no more than 28 days at a temperature not exceeding 25 °C.
Storage conditions
Store at a temperature not exceeding 25 °C in a tightly closed bottle. Keep out of the reach of children.
Packaging
5 ml in a dropper bottle, 1 dropper bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
BALKANPHARMA-RAZGRAD JSC.
Location of the manufacturer and address of its place of business. Aprilsko Vastanie Blvd. 68, Razgrad 7200, Bulgaria.
Applicant
Delta Medical Promotions AG.
Location of the applicant: Ottenbachgasse 26, Zurich CH-8001, Switzerland.
