Instructions Bimatoprost eye drops solution 0.3 mg/ml bottle 3 ml No. 1
Composition
active ingredient: bimatoprost;
1 ml of solution contains 0.3 mg of bimatoprost;
Excipients: benzalkonium chloride, sodium chloride, sodium hydrogen phosphate heptahydrate, citric acid monohydrate, sodium hydroxide or concentrated hydrochloric acid, water for injections.
Dosage form
Eye drops.
Main physicochemical properties: clear colorless solution, free from visible particles.
Pharmacotherapeutic group
Drugs used in ophthalmology. Antiglaucoma drugs and miotics. Prostaglandin analogues.
ATX code S01E E03.
Pharmacological properties
Pharmacodynamics
The mechanism of action by which bimatoprost reduces intraocular pressure (IOP) in humans is to increase the outflow of aqueous humor through the trabecular meshwork and enhance uveoscleral outflow. IOP reduction begins approximately 4 hours after the first application, and the maximum effect is achieved approximately 8-12 hours later. The duration of the effect is maintained for at least 24 hours.
Bimatoprost is a potent IOP-lowering agent. It belongs to the synthetic prostamides and is structurally related to prostaglandin F2α (PGF2α) and does not affect any of the known types of prostaglandin receptors. Bimatoprost selectively mimics the action of recently discovered biosynthetic substances, the so-called prostamides. However, the structure of the prostamide receptor has not yet been determined.
During 12 months of monotherapy in adult patients with bimatoprost 0.3 mg/ml eye drops compared with timolol, the mean change in IOP from baseline measured in the morning at 8 a.m. ranged from -7.9 to -8.8 mm Hg. At each visit, the mean daily IOP values measured over the 12-month period varied by no more than 1.3 mm Hg during the day and never exceeded 18.0 mm Hg.
Pharmacokinetics
Bimatoprost penetrates well through the human cornea and sclera in vitro. After ophthalmic use in adults, systemic exposure to bimatoprost is very low, and no accumulation is observed over time. After daily instillation of 1 drop of a 0.3 mg/ml bimatoprost solution per day in both eyes for 2 weeks, the maximum concentration (Cmax) in the blood plasma was reached 10 minutes after application and decreased below the detection limit (0.025 ng/ml) within 1.5 hours after instillation. The mean Cmax and AUC0-24h values were similar on the 7th and 14th days of use and were approximately 0.08 ng/ml and 0.09 ng•h/ml, respectively, indicating that the equilibrium concentration of bimatoprost was reached within the first week of topical application.
Bimatoprost is moderately distributed in tissues, and the volume of systemic distribution at steady state was 0.67 l/kg. In the human circulation, bimatoprost is predominantly present in plasma. The binding of bimatoprost to plasma proteins is approximately 88%.
Bimatoprost is the major circulating substance in the blood after it enters the systemic circulation following instillation. Bimatoprost then undergoes oxidation, N-deethylation, and glucuronidation to form various metabolites.
Bimatoprost is excreted primarily by the kidneys: up to 67% of the dose administered intravenously to healthy volunteers was excreted in the urine and 25% in the feces. The elimination half-life determined after intravenous administration was approximately 45 minutes and the total blood clearance was 1.5 l/h/kg.
Pharmacokinetics in elderly patients
After instillation of bimatoprost eye drops at a dosage of 0.3 mg/ml twice daily, the mean AUC0-24h of bimatoprost, which was 0.0634 ng•h/ml in elderly patients (aged 65 years and older), was significantly higher than that observed in young healthy adult volunteers (0.0218 ng•h/ml). However, these data are not clinically relevant, since systemic exposure after ophthalmic administration remains very low in both elderly and young subjects. Accumulation of bimatoprost in the blood over time was not observed, and the safety profile was similar in elderly and young subjects.
Indication
Reduction of elevated intraocular pressure (IOP) in adults with chronic open-angle glaucoma and intraocular hypertension (as monotherapy or as add-on therapy to beta-blockers).
Contraindication
Hypersensitivity to the active substance or excipients included in the preparation, including benzalkonium chloride.
Interaction with other medicinal products and other types of interactions
No drug interaction studies have been conducted.
No interactions are expected in humans, as systemic concentrations of bimatoprost 0.3 mg/ml eye drops solution are extremely low (less than 0.2 ng/ml). Bimatoprost is metabolized by a variety of enzymes and pathways; no effects on hepatic drug-metabolizing enzymes were observed in preclinical studies.
The concomitant use of bimatoprost and other antiglaucoma agents, other than topical beta-blockers, during combination therapy for glaucoma has not been studied.
Prostaglandin analogues (e.g., Bimatoprost-Pharmaten) have the potential to reduce the IOP-lowering effect when used in patients with glaucoma or ocular hypertension in conjunction with other prostaglandin analogues.
Application features
Before starting treatment, patients should be informed of the possible growth of eyelashes, darkening of the eyelid skin and increased iris pigmentation, as these effects have been observed during treatment with bimatoprost. Some of these changes may be permanent and may result in differences between eyes if only one eye is treated. It is likely that the increased iris pigmentation will be irreversible. The changes in pigmentation are due to an increase in melanin content in melanocytes, not an increase in the number of melanocytes. The long-term effect of increased iris pigmentation is unknown. The changes in iris colour observed with ophthalmic use of bimatoprost may not be noticeable for several months or years. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris, resulting in the iris or part of it becoming more brown in colour. Treatment does not appear to affect either the nevus or the iris spots. After 12 months of treatment with bimatoprost 0.3 mg/ml, the incidence of iris pigmentation was 1.5% and did not increase over the next 3 years of treatment. Periorbital pigmentation changes have been reported to be reversible in some patients.
Since rare cases of cystoid macular edema have been reported following treatment with bimatoprost 0.3 mg/ml eye drops, the drug should be used with caution in patients with known risk factors for macular edema (e.g. aphakia and pseudophakia with posterior capsule tear).
There have been isolated spontaneous reports of reactivation of previous corneal infiltrates or ocular infections with bimatoprost 0.3 mg/ml eye drops. The drug should be used with caution in patients with a previous history of significant ocular viral infections (e.g. herpes simplex) or uveitis/iritis.
Bimatoprost has not been studied in patients with inflammatory eye diseases, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma, or narrow-angle glaucoma.
Hair growth may occur in areas where bimatoprost solution is in constant contact with the skin surface. Therefore, it is important to use the product as directed and avoid contact with the cheek or other areas of the skin.
Bimatoprost eye drops have not been studied in patients with respiratory disorders. While there is limited information on the treatment of patients with a history of asthma or chronic obstructive pulmonary disease (COPD), there have been post-marketing reports of exacerbations of asthma, dyspnea, and COPD, as well as new cases of asthma. The frequency of these symptoms has not been established. The drug should be used with caution in patients with COPD, asthma, or respiratory disorders due to other causes.
Bimatoprost has not been studied in patients with heart block more severe than first degree or uncontrolled congestive heart failure. There have been limited spontaneous reports of bradycardia or hypotension with bimatoprost 0.3 mg/ml eye drops. Therefore, caution should be exercised in patients with a predisposition to low heart rate and low blood pressure.
In studies of patients with glaucoma or ocular hypertension treated with bimatoprost 0.3 mg/ml eye drops, it has been shown that the use of more than 1 dose of bimatoprost per day may reduce the IOP-lowering effect. Patients receiving bimatoprost in combination with other prostaglandin analogues should be monitored for changes in IOP.
Bimatoprost-Pharmaten contains the preservative benzalkonium chloride, which can be absorbed by soft contact lenses. Due to the presence of benzalkonium chloride, eye irritation and discoloration of soft contact lenses may also occur. Contact lenses should be removed before instillation and reinserted no earlier than 15 minutes after application of the drug.
Benzalkonium chloride has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since Bimatoprost-Pharmaten contains benzalkonium chloride, patients with dry eyes or corneal damage should be monitored with frequent or prolonged use.
The tip of the dropper bottle should not come into contact with the eye, surrounding surfaces, fingers, or other surfaces to avoid microbial contamination of the solution.
Ability to influence reaction speed when driving vehicles or other mechanisms
Bimatoprost-Pharmaten has a minor influence on the ability to drive and use machines. As with other eye drops, if blurred vision occurs during instillation of the drug, the patient should wait until vision clears before driving or operating other machines.
Use during pregnancy or breastfeeding
There are no adequate data from the use of bimatoprost in pregnant women. Animal studies have shown reproductive toxicity at high maternally toxic doses.
Bimatoprost-Pharmaten should not be used during pregnancy unless clearly necessary.
It is not known whether bimatoprost is excreted in human milk. Animal studies have shown that bimatoprost is excreted in human milk. A decision should be made whether to discontinue breast-feeding or to discontinue Bimatoprost-Pharmaten therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
There are no data on the effect of bimatoprost on human fertility.
Method of administration and doses
It is recommended to instill 1 drop into the affected eye(s) once daily, in the evening. The dose should not exceed one application per day, as more frequent use of the drug may reduce the effect of lowering elevated IOP.
When using multiple topical ophthalmic medications, they should be instilled at 5-minute intervals.
Certain patient groups
Patients with impaired hepatic or renal function
Bimatoprost treatment has not been studied in patients with renal impairment or moderate to severe hepatic impairment and should be used with caution in such patients. In patients with a history of mild liver disease or with abnormal baseline alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin, bimatoprost eye drops 0.3 mg/ml administered for 24 months did not have any adverse effects on hepatic function.
Children
The safety and efficacy of the drug for the treatment of children under 18 years of age have not been studied, therefore it is not recommended for use in this category of patients.
Overdose
No cases of overdose have been reported. When used topically as eye drops, overdose is unlikely.
In case of overdose, symptomatic and supportive treatment should be provided.
Adverse reactions
The following adverse reactions have been reported in clinical trials and post-marketing experience, the majority of which were ophthalmic, mild to moderate in severity, and non-serious.
From the nervous system: headache, dizziness.
On the part of the organ of vision: conjunctival hyperemia, eye itching, eyelash growth, punctate superficial keratitis, corneal erosion, eye burning, eye irritation, allergic conjunctivitis, blepharitis, visual impairment, asthenopia, conjunctival edema, foreign body sensation in the eye, dry eyes, eye pain, photophobia, lacrimation, eye discharge, vision disorders/blurred vision, iris hyperpigmentation, eyelash darkening, eyelid erythema, eyelid itching, retinal hemorrhage, uveitis, cystoid macular edema, iritis, blepharospasm, eyelid retraction, periorbital erythema, eyelid edema, periorbital and eyelid changes, including deepening of the palpebral sulcus, ocular discomfort.
Vascular disorders: arterial hypertension.
Respiratory system: asthma, asthma exacerbation, COPD exacerbation and dyspnea.
hyperpigmentation of the skin around the eyes, hirsutism, skin discoloration (around the eyes).
General disorders and administration site conditions: asthenia.
Investigations: Abnormal liver function tests.
Immune system disorders: Hypersensitivity reactions, including signs and symptoms of ocular allergy and allergic dermatitis.
Adverse reactions reported for eye drops containing phosphates
In rare cases, corneal calcification has been reported in some patients with significant corneal damage associated with the use of eye drops containing phosphates.
Expiration date
30 months.
Do not use after the expiry date stated on the packaging. Use no more than 4 weeks after first opening the bottle.
Storage conditions
There are no special storage conditions for the drug.
Keep out of reach of children.
Packaging
3 ml of eye drop solution in dropper bottles, closed with tamper-evident caps. 1 dropper bottle in a cardboard box.
Vacation category
According to the recipe.
Producer
Pharmaten S.A.
Location of the manufacturer and its business address
Dervenakion 6, Pallini Attiki 15351, Greece.
