Akimba

INSTRUCTIONS for medical use of the medicinal product AKIMBA (AKIMBA)

Composition:

Active substance: 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.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: clear, colorless solution free from visible particles, pH 6.5–7.5, osmolarity 260–340 mOsmol/kg.

Pharmacotherapeutic group. Agents for ophthalmological use. Anti-edematous 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 the drug acts on mast cells of the human conjunctiva, inhibiting the release of inflammatory mediators. It has been observed that topical ophthalmic use of olopatadine 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.

Preclinical data obtained from standard safety, pharmacology, repeated-dose toxicity, genotoxicity, carcinogenic potential, and reproductive toxicity studies revealed no hazard to humans.

Animal studies revealed delayed development in nursing puppies from females administered systemic doses of olopatadine exceeding the maximum recommended dose for ophthalmic use in humans. Olopatadine was excreted into the milk of female rats following oral administration.

Pharmacokinetics. Olopatadine is systemically absorbed, as are other topically applied drugs. However, systemic absorption following topical application is minimal, with plasma concentrations ranging 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 after oral administration of well-tolerated doses of the drug.

Pharmacokinetic studies following oral administration showed that the elimination half-life of olopatadine in plasma is approximately 8–12 hours. The drug is primarily eliminated via the kidneys. Approximately 60–70% of the administered dose was recovered in urine as unchanged active substance. Two metabolites, monodesmethyl and N-oxide, were detected in urine at low concentrations.

Since olopatadine is excreted in urine mainly as unchanged active substance, its pharmacokinetics are altered in renal impairment: peak plasma concentrations in patients with severe renal insufficiency (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 a 10 mg dose, plasma olopatadine 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) revealed no significant differences in plasma concentrations, protein binding, urinary excretion of unchanged drug, or metabolites.

Pharmacokinetic studies of olopatadine following oral administration in patients with severe renal insufficiency have been conducted. Results indicate that slightly higher plasma concentrations 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 elimination pathway for the drug; therefore, dosage adjustment is not required in patients with hepatic impairment.

Clinical characteristics

Indications. For the treatment of seasonal allergic conjunctivitis.

Contraindications. Hypersensitivity to olopatadine or to any excipient of the medicinal product.

Interaction with other medicinal products and other forms of interaction. No studies on drug interactions with other medicinal products have been conducted.

In vitro studies have shown that olopatadine does not inhibit metabolic reactions of the cytochrome P450 isoforms 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

Olopatadine is an antiallergic/antihistamine agent administered topically but systemically absorbed. The drug should be discontinued if any signs of serious reactions or hypersensitivity occur.

Olopatadine contains benzalkonium chloride, which may cause ocular 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 medication frequently or for prolonged periods should be closely 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 instilling the medication 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 quantity. Animal studies have shown reproductive toxicity following systemic administration (see section "Pharmacological properties"). Olopatadine is not recommended for use in pregnant women or in women of childbearing potential who do not use contraceptive measures.

Breastfeeding. Animal studies have shown that olopatadine passes into breast milk following oral administration (see "Pharmacological properties" for details). A risk to newborns/infants cannot be excluded. Olopatadine should not be used in women who are breastfeeding.

Fertility. There have been no studies on the effect of olopatadine on human fertility following topical ophthalmic administration.

Ability to affect reaction speed when driving or operating machinery. Olopatadine 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.

Method of Administration and Dosage

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 interval of 8 hours). If necessary, treatment may continue for up to 4 months.

Use in elderly patients. No dosage adjustment is required for this patient group.

Use in children and adolescents. Olopatadine may be used in pediatric practice for children aged 3 years and older at the same dosage as in adults. Safety and efficacy of olopatadine in children under 3 years of age have not been established. Data for this age group are lacking.

Use in patients with hepatic or renal impairment. Studies on the use of olopatadine eye drops in patients with hepatic or renal impairment have not been conducted. However, no dosage adjustment is necessary in case of hepatic or renal impairment (see section "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 bottle should be tightly closed after each use.

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

Children. Olopatadine can be used in children aged 3 years and older at the same dosage as in adults.

Overdose. There are no data on overdose of the medicinal product in humans following accidental or intentional ingestion. Olapadine 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 correspond to a dose of 0.5 mg/kg in a child weighing 10 kg assuming 100% absorption.

Prolongation of the QT interval in dogs was observed only at doses significantly exceeding the maximum human dose, indicating a low likelihood of QT prolongation during clinical use. In a study involving 102 healthy volunteers, including young men and women as well as elderly individuals, who received 5 mg of the drug 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 (ranging from 35 to 127 ng/mL) were at least 70 times higher than those achieved with topical administration of olopatadine regarding effects on cardiac repolarization.

In case of overdose, appropriate monitoring and treatment of the patient should be initiated.

Adverse Reactions

In clinical studies involving 1680 patients, olopatadine was administered one 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 reactions related to olopatadine use were observed in approximately 4.5% of patients; however, only 1.6% of patients discontinued participation in clinical studies due to these adverse reactions. During clinical studies, there were no reports of serious ophthalmological or systemic adverse effects associated with the use of the medicinal product. The most common adverse reaction with olopatadine use was ocular pain, occurring at a frequency of 0.7%.

The adverse reactions listed below were reported during clinical studies and in the post-marketing period. Adverse reactions 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), frequency not known (cannot be estimated from available data). Within each frequency grouping, adverse reactions are listed in order of decreasing severity.

In patients with significant corneal involvement, very rare cases of corneal calcification have been observed during treatment with ophthalmic solutions containing phosphates.

Reporting of adverse reactions

Reporting of adverse reactions after drug registration is of great importance. It enables continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical professionals, as well as patients or their legal representatives, should report suspected adverse reactions and lack of efficacy to the State Expert Center of the Ministry of Health of Ukraine via the following link: https://aisf.dec.gov.ua.

Shelf life. 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 container. Keep out of reach of children.

Packaging. 5 ml in a dropper bottle, 1 dropper bottle per cardboard box.

Prescription status. Prescription only.

Manufacturer. BALKANFARMA-RAZGRAD AD.

Manufacturer's address and place of business. 68 Aprilsko Vastanie Blvd., Razgrad 7200, Bulgaria.

Marketing Authorization Holder. Delta Medical Promotions AG.

Address of the Marketing Authorization Holder. Ottenbachstrasse 26, Zurich CH-8001, Switzerland.