Bimoptic Rompharm (Drops) Instructions for Use

Marketing Authorization Holder

S.C. Rompharm Company S.R.L. (Romania)

ATC Code

S01EE03 (Bimatoprost)

Active Substance

Bimatoprost (Rec.INN registered by WHO)

Dosage Form

Bimoptic Rompharm

Eye drops 300 mcg/1 ml: 2.5 ml or 3 ml bottle with dropper applicator

Dosage Form, Packaging, and Composition

Eye drops in the form of a transparent solution from colorless to light yellow.

Excipients: citric acid monohydrate – 0.14 mg, disodium phosphate heptahydrate – 2.68 mg, sodium chloride – 8.3 mg, benzalkonium chloride – 0.05 mg, 1M sodium hydroxide solution or 1M hydrochloric acid solution – to pH 7.3±0.1, purified water – up to 1 ml.

2.5 ml – polyethylene bottles with a capacity of 5 ml (1) with a dropper applicator – cardboard boxes.
3 ml – polyethylene bottles with a capacity of 5 ml (1) with a dropper applicator – cardboard boxes.

Clinical-Pharmacological Group

Antiglaucoma drug – synthetic prostaglandin F2α analogue

Pharmacotherapeutic Group

Synthetic prostaglandin F2-alpha analogue

Pharmacological Action

Antiglaucoma agent. Bimatoprost is a synthetic prostatamide, structurally related to prostaglandin F2α, which does not act through known prostaglandin receptors. Bimatoprost selectively mimics the effects of recently discovered biosynthesized substances, prostatamides. However, the structure of prostatamide receptors has not yet been identified.

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

The reduction in intraocular pressure begins approximately 4 hours after the first administration, the maximum effect is achieved approximately 8-12 hours later. The effect lasts for at least 24 hours.

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

Pharmacokinetics

Bimatoprost penetrates well into the human cornea and sclera in vitro. After instillation in adults, the systemic exposure of bimatoprost is very low, and no accumulation of the active substance was noted. After administration of one drop of the drug into both eyes once a day for 2 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 detection (0.025 ng/ml). The mean values of C_max and AUC_{0-24 h} were approximately the same on day 7 and day 14 – approximately 0.08 ng/ml and 0.09 ng×h/ml, respectively, indicating that the C_ss of bimatoprost was reached within 1 week of instillation. Bimatoprost is moderately distributed in body tissues, and the V_d at steady state is 0.67 L/kg. In human blood, Bimatoprost is found mainly in plasma. The binding of bimatoprost to plasma proteins is about 88%. Bimatoprost reaches the systemic circulation mainly unchanged. Then oxidation, N-deethylation and glucuronidation occur with the formation of a number of metabolites.

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

Indications

Open-angle glaucoma and ocular hypertension in adults (as monotherapy or in combination with beta-blockers).

ICD codes

Dosage Regimen

Instill one drop into the affected eye(s) once daily in the evening.

Do not exceed the once-daily dosage; more frequent administration may reduce the intraocular pressure-lowering effect.

If using more than one topical ophthalmic medication, administer them at least 5 minutes apart.

To avoid contamination, do not let the dropper tip touch any surface, including the eye or fingers.

If a dose is missed, resume treatment with the next scheduled dose; do not double the dose to catch up.

Remove contact lenses prior to application and wait at least 15 minutes before reinserting them.

The preservative benzalkonium chloride may be absorbed by soft contact lenses and cause eye irritation.

The therapeutic effect begins approximately 4 hours after administration, with the maximum effect achieved after 8-12 hours.

Adverse Reactions

Definition of categories of frequency of adverse reactions: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1000 to <1/100); rare (≥1/10,000 to <1/1000); very rare (<1/10,000), frequency unknown (cannot be estimated from the available data).

Nervous system disorders: common – headache; uncommon – dizziness.

Eye disorders: very common – conjunctival hyperemia, eye itching, eyelash growth; common – superficial punctate keratitis, corneal erosion, eye burning, eye irritation, allergic conjunctivitis, blepharitis, visual acuity reduced, asthenopia, conjunctival edema, foreign body sensation in eyes, dry eye, eye pain, photophobia, lacrimation, eye discharge, visual disturbance, increased iris pigmentation, eyelash darkening; uncommon – retinal hemorrhagic disorders, uveitis, cystoid macular edema, iritis, blepharospasm, eyelid retraction, periorbital erythema; frequency unknown – enophthalmos. In very rare cases, corneal calcification has been reported with the use of phosphate-containing eye drops in patients with concomitant significant corneal damage.

Cardiac and vascular disorders: common – arterial hypertension.

Hepatobiliary system disorders common – abnormal liver function tests.

Skin and subcutaneous tissue disorders: uncommon – hirsutism.

General disorders: uncommon – asthenia.

Contraindications

Hypersensitivity to bimatoprost; age under 18 years.

Use in Pregnancy and Lactation

There are no clinical study data on the use of bimatoprost during pregnancy. The use of bimatoprost during pregnancy is not recommended, except in cases of strict indications.

Preclinical studies in animals have shown reproductive toxicity when bimatoprost was used in high doses toxic to the maternal organism.

It is not known whether Bimatoprost is excreted in human breast milk. Studies in animals have shown that Bimatoprost is excreted in breast milk. The decision to continue/discontinue breastfeeding or to continue/discontinue treatment with bimatoprost should be made taking into account the benefits of breastfeeding for the child and the benefits of therapy for the mother.

Pediatric Use

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

Geriatric Use

The drug is approved for use in elderly patients.

Special Precautions

Caution is required when using bimatoprost preparations to treat 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); in patients with a history of severe eye infections (for example, caused by the 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 noted.

The effect of bimatoprost on patients with second- and third-degree AV block and on patients with uncontrolled congestive heart failure 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 lentigo of the iris. Periorbital tissue pigmentation is reversible in some patients.

Use with caution in patients with risk factors for macular edema (patients with aphakia, pseudophakia and rupture of the posterior lens capsule).

Drug Interactions

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

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

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.