Bimican® eco

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT BIMIKAN®ECO (BIMICAN®ECO)

Composition:

Active substance: bimatoprost;

1 ml of solution contains 0.3 mg of bimatoprost;

Excipients: disodium phosphate dodecahydrate; citric acid monohydrate; sodium chloride; hydrochloric acid, 10% solution; water for injections.

Pharmaceutical form. Eye drops, solution.

Main physicochemical properties: colorless transparent solution.

Pharmacotherapeutic group. Agents used in ophthalmology. Anti-glaucoma preparations and miotics. Prostaglandin analogues.

ATC code S01E E03.

Pharmacological properties.

Pharmacodynamics.

The mechanism of action by which bimatoprost reduces intraocular pressure in humans is through increasing the outflow of aqueous humor via the trabecular meshwork and enhancing uveoscleral outflow from the eye. Reduction in intraocular pressure begins approximately 4 hours after the first administration. Maximum effect is achieved within approximately 8–12 hours. The duration of effect lasts at least 24 hours.

Bimatoprost is a potent intraocular pressure-lowering agent belonging to the synthetic prostamide class. Chemically, it is structurally related to prostaglandin F2α (PGF2α), but does not act on any of the known prostaglandin receptors. Bimatoprost selectively mimics the action of recently discovered biologically synthesized compounds called prostamides. However, the prostamide receptor has not yet been structurally identified.

Pharmacokinetics.

In in vitro studies, bimatoprost readily penetrated the human iris and sclera. Following ocular instillation in adults, systemic exposure to bimatoprost is very low. No systemic accumulation has been observed. After administration of one drop of bimatoprost solution to both eyes once daily for 2 weeks, maximum plasma concentration (Cmax) of bimatoprost was reached within 10 minutes after dosing and declined to the lower limit of quantification (0.025 ng/mL) within 1.5 hours after administration. Mean Cmax and area under the concentration-time curve (AUC0–24 h) values of bimatoprost were similar on day 7 and day 14, amounting to 0.08 ng/mL and 0.09 ng*h/mL, respectively, indicating that steady-state plasma concentration of bimatoprost is achieved within the first week of topical administration.

Bimatoprost is moderately distributed into tissues, and the volume of distribution at steady state is 0.67 L/kg. Bimatoprost is primarily distributed to plasma. Plasma protein binding of bimatoprost is approximately 88%.

Bimatoprost is the principal circulating compound in blood after entering systemic circulation following ocular instillation. It is subsequently metabolized via oxidation, N-deethylation, and glucuronidation, forming various metabolites.

Bimatoprost is primarily eliminated by the kidneys. Approximately 67% of the intravenously administered dose was excreted in urine and 25% via the gastrointestinal tract in healthy volunteers. The elimination half-life (T1/2) of bimatoprost, determined after intravenous administration, was approximately 45 minutes, and total systemic clearance was 1.5 L/h/kg.

Parameters in elderly patients.

After instillation of 0.3 mg/mL bimatoprost ophthalmic solution twice daily, the mean area under the concentration-time curve (AUC0–24 h) in elderly patients (aged 65 years and older) was 0.0634 ng*h/mL for bimatoprost, which is significantly higher than in young healthy adult volunteers (0.0218 ng*h/mL). However, these findings are not considered clinically significant, as systemic exposure remained very low in both elderly and younger individuals following ocular instillation. No cumulative increase in plasma bimatoprost concentrations was observed over time, and the safety profile of the drug was nearly identical in elderly and younger patients.

Clinical characteristics.

Indications.

Reduction of elevated intraocular pressure (IOP) in adult patients with chronic open-angle glaucoma and ocular hypertension (as monotherapy or adjunctive therapy to beta-adrenergic blockers).

Contraindications.

Hypersensitivity to the active substance or to any of the excipients contained in the medicinal product.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been conducted.

No interaction is expected in humans due to the extremely low systemic concentration of bimatoprost (less than 0.2 ng/mL) in the body after administration of bimatoprost solution at a dose of 0.3 mg/mL as ophthalmic drops.

Preclinical studies have shown that bimatoprost is biotransformed in the body via multiple enzymes and metabolic pathways and does not affect hepatic enzymes involved in drug metabolism.

During clinical trials, bimatoprost solution as ophthalmic drops was administered concomitantly with several different topical ophthalmic beta-blockers without evidence of interaction.

Concomitant use of bimatoprost with other glaucoma medications, apart from topical beta-blockers, has not been studied in adjunctive glaucoma therapy.

Concomitant use of bimatoprost with other prostaglandin analogs may lead to reduced intraocular pressure-lowering effect in patients with glaucoma or elevated intraocular pressure (see section "Special precautions").

Special precautions for use.

Ophthalmology

Prior to initiating treatment, patients should be informed about periorbital changes associated with prostaglandin analogues, including increased pigmentation of the eyelid skin and iris pigmentation, as these effects have been observed with the use of bimatoprost. Some of these changes may be permanent and may lead to visual field defects and differences in eye color if the drug has been instilled in only one eye (see section "Adverse reactions").

Bimatoprost should be used with caution in patients at risk of macular edema (e.g., aphakic patients, pseudophakic patients with damaged posterior lens capsule).

Rare cases of recurrence of corneal infiltration or ocular infection have been reported with the use of bimatoprost 0.3 mg/mL solution in multidose containers. Bimatoprost should be used with caution in patients with a history of viral ocular infections (e.g., herpes simplex) or uveitis/iris inflammation.

The use of bimatoprost has not been studied in patients with inflammatory eye diseases, neovascular, inflammatory, congenital glaucoma, or narrow-angle glaucoma.

Respiratory

The use of bimatoprost in patients with respiratory disorders has not been studied. There are limited data on the use of bimatoprost in patients with a history of asthma or COPD. In post-marketing studies, exacerbations of asthma, dyspnea, and COPD have been reported in such patients. The frequency of these symptoms is unknown. Therefore, bimatoprost should be prescribed with caution to patients with COPD, asthma, or impaired respiratory function.

Cardiovascular

The use of bimatoprost has not been studied in patients with heart block greater than first degree or in patients with uncontrolled congestive heart failure. Bimatoprost should be used with caution in patients predisposed to low heart rate or low arterial blood pressure.

Skin

Hair growth may occur in skin areas that are repeatedly exposed to the drug. Bimatoprost should be used strictly according to the instructions for medical use, and care should be taken to avoid runoff of the solution onto the cheek or other skin areas.

Other information

The use of bimatoprost in patients with moderate to severe renal or hepatic impairment has not been studied. Therefore, caution is required when treating such patients. In patients with a history of moderate hepatic impairment or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or bilirubin levels, the use of bimatoprost ophthalmic solution generally did not result in hepatic adverse reactions over a 24-month period.

Administration of more than one dose of bimatoprost per day leads to reduced efficacy in lowering elevated intraocular pressure in patients with glaucoma or ocular hypertension. Patients using bimatoprost together with other prostaglandin analogues should be under medical supervision and have their intraocular pressure monitored (see section "Interaction with other medicinal products and other forms of interaction").

Cases of bacterial keratitis associated with the use of multidose containers for topical ophthalmic preparations have been reported. These containers were accidentally contaminated by patients, most of whom had concomitant ocular disease. Patients with disruption of the ocular epithelial surface are at higher risk of developing bacterial keratitis.

The tip of the dropper bottle must not come into contact with the eye, surrounding surfaces, fingers, or other skin areas to avoid eye injury and/or microbial contamination of the solution.

If more than one topical ophthalmic medicinal product is used, a five-minute interval should be maintained between each instillation.

The use of bimatoprost in patients wearing contact lenses has not been studied. Contact lenses must be removed prior to administration of the drug and may be reinserted 15 minutes after instillation.

Use during pregnancy or lactation.

There are no adequate data on the use of bimatoprost in pregnant women.

Animal studies have demonstrated reproductive toxicity, with toxic effects on the female at high doses of the drug.

Bimatoprost should not be used during pregnancy except in cases of absolute necessity.

It is unknown whether bimatoprost passes into human breast milk. Animal studies have demonstrated excretion of bimatoprost into breast milk. The decision on whether to continue/stop breastfeeding or to continue/stop bimatoprost therapy should be made taking into account the benefits of breastfeeding for the child and the benefits of therapy for the woman.

There are no data on the effect of bimatoprost on fertility.

Ability to affect reaction speed when driving or operating machinery.

Bimatoprost has a negligible influence on the ability to drive or operate machinery. As with other ophthalmic solutions, if transient blurred vision occurs after instillation, patients should wait until vision clears before driving or operating machinery.

Administration and Dosage

For use in adults: instill 1 drop into the affected eye(s) once daily in the evening.

The dose should not exceed 1 instillation once daily, as more frequent use may reduce the effect of lowering elevated intraocular pressure.

Administration

For topical ophthalmic use only.

Nasolacrimal occlusion or eyelid closure for 2 minutes after instillation reduces systemic absorption. This may decrease systemic adverse reactions and enhance local activity of the drug.

If more than one topical ophthalmic agent is being used, a 5-minute interval should be maintained between each instillation. Ophthalmic ointments should be administered last.

Special patient groups

Patients with hepatic or renal impairment

The use of bimatoprost in patients with renal impairment or moderate to severe hepatic impairment has not been studied; therefore, the drug should be used with caution in such patients. In patients with a history of mild liver disease or with baseline abnormalities in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and/or bilirubin, administration of bimatoprost ophthalmic solution 0.3 mg/mL for 24 months did not cause adverse effects on liver function.

Before using eye drops

• Before first use, practice using the dropper bottle by gently squeezing it to ensure you can administer one drop into the eye without touching the eye.
• Once you are confident you can instill one drop, choose the position you find most comfortable (you may sit, lie on your back, or stand in front of a mirror).

Instructions for use

1. Wash your hands thoroughly before using the medication.
2. Do not use the medication if the packaging or bottle is damaged.
3. Ensure the tamper-evident seal on the cap is intact. Unscrew the cap before first use; you may feel slight resistance when breaking the tamper-evident ring.
4. If the tamper-evident ring is damaged upon first opening, remove and discard it to avoid injury.
5. Tilt your head backward and gently pull down the lower eyelid to create a pouch between the eyeball and eyelid. Avoid contact between the dropper tip and the eye, eyelids, or fingers.
6. Gently squeeze the bottle wall to release one drop into your eye. Note that there may be a delay of several seconds between squeezing and drop release. Do not squeeze too hard. If you are unsure how to administer eye drops, consult your doctor, pharmacist, or nurse.
7. After instillation, press on the nasolacrimal duct for approximately 2 minutes (press your finger against the inner corner of the eye near the nose) and keep your eyes closed during this time. This ensures the drop is absorbed by the eye and likely reduces the amount of drug passing through the tear duct into the nose.
8. Do not touch the dropper tip to the surface of the eye or surrounding tissues.
9. If your doctor has prescribed use in the conjunctival sac of the other eye, repeat steps 5–6.
10. After use and before subsequent applications, shake the bottle once downward without touching the dropper tip to remove residual solution from the tip. This is necessary to ensure proper delivery of subsequent drops. After instillation, screw the cap back onto the bottle.

Children

The efficacy and safety of Bimican**®** Eco in children have not been established; therefore, the drug is not recommended for use in children (under 18 years of age).

Overdose

No cases of overdose with Bimican**®** Eco have been reported. Overdose is unlikely with topical ophthalmic administration.

In case of overdose, supportive and symptomatic therapy should be administered.

Adverse reactions.

From the nervous system

Uncommon – headache.

Not known – dizziness.

From the eye organs

Very common – conjunctival hyperemia, periorbital changes (periorbitopathy) associated with prostaglandin analogs.

Common – punctate (superficial) keratitis, eye irritation (ocular mucosa), foreign body sensation in the eye, dry eye, eye pain, eye itching, increased eyelash growth, eyelid redness.

Uncommon – asthenopia, conjunctival edema, photophobia (light sensitivity), increased lacrimation, iris hyperpigmentation, visual disturbance/blurry vision, eyelid itching, eyelid edema.

Not known – ocular discharge, eye discomfort.

From the vascular system

Not known – arterial hypertension.

From the gastrointestinal tract

Uncommon – nausea.

From the skin and its derivatives

Common – skin hyperpigmentation (periorbital area).

Uncommon – hypertrichosis (pathological hair growth).

Not known – skin color change (periorbital area).

From the respiratory system and mediastinal organs

Not known – asthma, exacerbation of bronchial asthma, exacerbation of chronic obstructive pulmonary disease (COPD), dyspnea.

From the immune system

Not known – hypersensitivity reactions, including signs and symptoms of ocular allergy and allergic dermatitis.

General disorders and administration site conditions

Asthenia, irritation at the site of instillation.

Investigations

Abnormalities in liver function tests.

Description of individual adverse reactions.

Periorbital changes associated with prostaglandin analogs

Prostaglandin analogs, including Bimican® EKO, may cause periorbital lipoatrophy changes, which can lead to eyelid hollowing, ptosis, enophthalmos, eyelid retraction, involution of dermatochalasis, and involution of dermatochalasis. These changes are usually moderate, may occur as early as one month after initiation of Bimican® EKO treatment, and may impair visual field even if not recognized by the patient. Periorbital changes associated with prostaglandin analogs are also associated with hyperpigmentation or depigmentation of the periorbital skin area and hypertrichosis. It has been reported that all these changes are partially or completely reversible after discontinuation or switching to alternative therapy.

Iris hyperpigmentation

Increased pigmentation of the iris is likely to be permanent. Pigmentation changes occur due to increased melanin content in melanocytes, but not due to an increase in their number. The long-term effect of iris hyperpigmentation is unknown. Iris pigmentation changes occur gradually and may not be noticeable for several months or years. Typically, brown pigmentation around the pupil spreads concentrically toward the periphery of the iris, and the entire iris or parts of it become more brown. Iris nevi or freckles are not treatable. After 12 months of treatment with 0.3 mg/mL bimatoprost, the incidence of pigmentation was 1.5% and did not increase during the following 3 years of treatment.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

2 years.

Do not use the medicinal product after the expiry date stated on the packaging. The shelf life after first opening is 90 days.

Storage conditions.

Store in the original packaging. No special storage conditions required.

Keep out of reach and sight of children.

Packaging.

3 mL of the medicinal product in a 5 mL polyethylene dropper bottle with a cap and tamper-evident ring. 1 bottle in a cardboard box.

Prescription status.

Prescription only.

Manufacturer.

Rafarm S.A./

Rafarm S.A./

Manufacturer's address and place of business.

Thesi Pousi Xatzi Agiou Louka, Paiania, 190 02, Greece

Thesi Pousi Xatzi Agiou Louka, Paiania, 190 02, Greece

Marketing authorization holder.

Pharmaceutical Works «POLPHARMA» S.A./

Pharmaceutical Works «POLPHARMA» S.A.

Address of the marketing authorization holder.

19 Pelplinska Str., 83-200 Starogard Gdanski, Poland/

19, Pelplinska Str., 83-200 Starogard Gdanski, Poland.