Bimatoprost-SZ (Drops) Instructions for Use

Marketing Authorization Holder

Severnaya Zvezda NAO (Russia)

Contact Information

SEVERNAYA ZVEZDA NAO (Russia)

ATC Code

S01EE03 (Bimatoprost)

Active Substance

Bimatoprost (Rec.INN registered by WHO)

Dosage Form

Bimatoprost-SZ

Eye drops 0.3 mg/1 ml: dropper bottles 2.5 ml or 5 ml

Dosage Form, Packaging, and Composition

Eye drops as a clear, colorless solution.

Excipients: benzalkonium chloride, sodium chloride, citric acid monohydrate, anhydrous disodium hydrogen phosphate, 1M hydrochloric acid solution, 1M sodium hydroxide solution, water for injections.

2.5 ml – dropper bottles (1) – cardboard boxes.
5 ml – dropper bottles (1) – cardboard boxes.

Clinical-Pharmacological Group

Antiglaucoma drug – synthetic prostaglandin F2α analogue

Pharmacotherapeutic Group

Agents used in ophthalmology. Antiglaucoma preparations and miotics. Prostaglandin analogues

Pharmacological Action

Bimatoprost reduces intraocular pressure in humans by increasing the outflow of aqueous humor through the trabecular meshwork and increasing uveoscleral outflow.

The reduction in IOP begins approximately 4 hours after the first administration, with the maximum effect reached approximately 8-12 hours later. The effect lasts for at least 24 hours.

Bimatoprost is a potent ophthalmic hypotensive agent. It is a synthetic prostamide, structurally related to prostaglandin F2α (PGF2α), which does not act through known prostaglandin receptors. Bimatoprost selectively mimics the effects of newly discovered biosynthesized substances, prostamides. However, the structure of the prostamide receptor has not yet been identified.

Limited information is available on the efficacy of the drug in the treatment of pseudoexfoliative and pigmentary glaucoma, as well as on the experience with bimatoprost in the treatment of angle-closure glaucoma in patients who have previously undergone iridotomy.

According to clinical studies, no significant effect of the drug on heart rate and blood pressure was noted.

Pharmacokinetics

Absorption

Bimatoprost penetrates well into the human cornea and sclera in vitro. After instillation in adults, systemic exposure to bimatoprost is very low, and no accumulation of the drug has been noted.

After administration of one drop of the drug into both eyes once a day for two weeks, the concentration in the blood reached a maximum 10 minutes after dose administration, and within 1.5 hours this indicator was below the level of quantification (0.025 ng/ml).

The mean C_max and AUC_0-24 values were approximately the same on day 7 and day 14 – approximately 0.08 ng/ml and 0.09 ng×h/ml, respectively, indicating that a steady-state concentration of bimatoprost was reached within the first week of instillations.

Distribution

Bimatoprost is moderately distributed in body tissues, and the systemic V_ss is 0.67 L/kg. In human blood, Bimatoprost is found mainly in plasma. The binding of bimatoprost to plasma proteins is 88%.

Metabolism

Bimatoprost reaches the systemic circulation mainly unchanged. Oxidation, N-deethylation, and glucuronidation then occur to form a number of metabolites.

Excretion

Bimatoprost is excreted mainly through the kidneys. Up to 67% of the intravenously administered dose in healthy adult volunteers was excreted from the body in the urine, and 25% of the dose was excreted in the feces. T_1/2 after intravenous administration was approximately 45 minutes, and the total clearance from the blood was 1.5 L/h/kg.

Indications

For adults over 18 years of age to reduce elevated intraocular pressure (IOP) in

• Open-angle glaucoma;
• Ocular hypertension (as monotherapy or in combination with beta-blockers).

ICD codes

Dosage Regimen

Topically. One drop once a day in the evening.

The recommended dose should not be exceeded, as more frequent instillations may reduce the hypotensive effect of the drug.

If a dose is missed, the instillation should be performed as soon as possible at the prescribed dosage.

The duration of treatment is determined by the doctor.

Special patient groups

Elderly patients

Dose adjustment is not required.

Patients with impaired liver function

The use of ophthalmic solutions of bimatoprost by patients with moderate and severe hepatic insufficiency has not been studied, which requires caution when using the drug in these patient groups.

In patients with a history of mild liver dysfunction or elevated ALT, AST and/or bilirubin levels, there is no pathological effect of bimatoprost on the functional state of the liver during 24 months of use.

Children

The drug is contraindicated for children under 18 years of age, since the efficacy and safety of bimatoprost use from 0 to 18 years of age have not been established (see section “Contraindications”).

Method of administration

For topical use as instillations into the conjunctival sac of the affected eye (eyes).

When using bimatoprost as part of combination therapy, an interval of at least 5 minutes must be observed between instillations of bimatoprost and concomitant therapy drugs.

Adverse Reactions

The following adverse reactions have been observed during clinical studies of the ophthalmic solution of bimatoprost and in the post-registration period.

The frequency of occurrence is presented in accordance with the following classification: very common (>1/10), common (>1/100 but <1/10), uncommon (>1/1000 but <1/100), rare (>1/10000 but <1/1000), very rare (<1/10000), frequency unknown (cannot be estimated from the available data).

In very rare cases, corneal calcification has been observed with the use of phosphate-containing eye drops in patients with concomitant significant corneal damage.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after registration of a medicinal product in order to ensure continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are encouraged to report any suspected adverse drug reactions through the national adverse reaction reporting system of the member states of the Eurasian Economic Union.

Contraindications

• Hypersensitivity to bimatoprost or to any of the excipients included in the drug.

Use in Pregnancy and Lactation

Pregnancy

There are no clinical study data on the use of bimatoprost in pregnant women. Animal studies have revealed reproductive toxicity when administered at high doses toxic to the maternal organism.

Bimatoprost-SZ should not be used during pregnancy, except in cases where there are no alternative treatment methods.

Breastfeeding period

Data on the penetration of bimatoprost into human breast milk are insufficient. Animal studies have shown that Bimatoprost is excreted in breast milk. If it is necessary to use bimatoprost during breastfeeding, a decision should be made to discontinue breastfeeding or discontinue bimatoprost therapy, taking into account the benefit of breastfeeding for the child and the mother’s need for therapy with the drug.

Use in Hepatic Impairment

The use of ophthalmic solutions of bimatoprost by patients with moderate and severe hepatic insufficiency has not been studied, which requires caution when using the drug in these patient groups. In patients with a history of mild liver dysfunction or elevated ALT, AST and/or bilirubin levels, there is no pathological effect of bimatoprost on the functional state of the liver during 24 months of use.

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age.

Geriatric Use

Dose adjustment in elderly patients is not required.

Special Precautions

Caution should be exercised when using the drug in the treatment of patients with known risk factors for macular edema (for example, in patients with aphakia, in patients with pseudophakia and rupture of the posterior lens capsule).

Should be used with caution in patients with a history of severe ocular infections (e.g., caused by herpes simplex virus) or iritis/uveitis.

There is no experience with the use of bimatoprost in patients with concomitant respiratory dysfunction, which requires caution in such patients. In clinical studies in patients with respiratory dysfunction, no significant adverse effects on the respiratory system were observed.

The effect of bimatoprost on patients with heart block more severe than first-degree or on patients with uncontrolled congestive heart failure has not been studied. A limited number of cases of bradycardia or hypotension have been reported with the use of bimatoprost. Bimatoprost should be used with caution in the treatment of patients predisposed to low heart rate or low blood pressure.

The effect of bimatoprost on patients with inflammatory ocular diseases, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma, or narrow-angle glaucoma has not been studied.

Before starting treatment, patients should be informed about the possibility of eyelash growth, darkening of the eyelid skin, and increased iris pigmentation.

Some of these changes may be permanent and may lead to differences in appearance between the eyes when only one eye is treated. Changes in iris pigmentation occur slowly and may not be noticeable for several months or years.

Most often, the change in iris color is permanent. The change in iris color is more associated with an increase in melanin content in melanocytes than with an increase in the number of melanocytes. The long-term effects of increased iris pigmentation are unknown.

Typically, brown pigment spreads from the area around the pupil to the periphery of the iris, causing the entire iris or parts of it to become more brown. The use of bimatoprost does not affect nevi and lentigines of the iris. Periorbital tissue pigmentation is reversible in some patients.

There are reports of the possibility of developing bacterial keratitis associated with the use of multi-dose eye drop bottles. Dropper bottles have been unintentionally contaminated by patients with concomitant ocular diseases. The risk of developing bacterial keratitis was higher in patients with impaired corneal epithelial integrity. Patients should be warned to avoid contact of the dropper bottle tip with the eye surface and other surfaces to avoid eye damage and bacterial contamination of the drug.

Excipients

The drug Bimatoprost-SZ contains the preservative benzalkonium chloride, which can be absorbed by soft contact lenses. Eye irritation and discoloration of soft contact lenses may also occur due to the presence of benzalkonium chloride. Contact lenses must be removed before instillation and put back on 15 minutes after instillation.

Benzalkonium chloride, used in eye drops as a preservative, can cause punctate keratopathy and/or toxic ulcerative keratopathy. Caution should be exercised when using the drug in patients with dry eye syndrome, with corneal damage, and in case of simultaneous use of several types of eye drops containing benzalkonium chloride. Monitoring of the corneal condition is required with long-term use of the drug in this category of patients.

Effect on ability to drive vehicles and machinery

Bimatoprost-SZ has a minor influence on the ability to drive and use machines. As with the use of other eye drops, if temporary blurred vision occurs after instillation, you should wait until visual clarity is restored before driving or operating machinery.

Overdose

No cases of overdose with topical use have been reported. In case of overdose, treatment should be symptomatic and supportive.

Drug Interactions

Specific studies of interaction with other drugs have not been conducted. No interactions in the human body are expected, since systemic concentrations of bimatoprost are extremely low (less than 0.2 ng/ml) after topical ophthalmic application.

In clinical studies, Bimatoprost was used concomitantly with several different topical ophthalmic beta-blockers, but no interactions were observed.

Concomitant use of bimatoprost and other antiglaucoma drugs, except for ophthalmic beta-blockers, has not been studied in studies of the efficacy and safety of combination therapy.

A decrease in the hypotensive effect of bimatoprost was observed when it was used concomitantly with other prostaglandin analogues in the treatment of ocular hypertension or glaucoma.

Storage Conditions

The drug should be stored at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life – 2 years.

Shelf life after opening the dropper bottle – 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.