Composition:
Each 1ml of sterile ophthalmic solution contains 0.3mg Bimatoprost.
Excipients:
Benzalkonium chloride , Sodium chloride , Disodium Hydrogen Phosphate Dihydrate, Citric acid momohydrate , Sodium Hydroxide , purified water .
Mechanism of action:
The mechanism of action by which bimatoprost reduces intraocular pressure in humans is by increasing aqueous humour outflow through the trabecular meshwork and enhancing uveoscleral outflow. Reduction of the intraocular pressure starts approximately 4 hours after the first administration and maximum effect is reached within approximately 8 to 12 hours. The duration of effect is maintained for at least 24 hours. Bimatoprost is a potent ocular hypotensive agent. It is a synthetic prostamide, structurally related to prostaglandin F2α (PGF2α) that does not act through any known prostaglandin receptors. Bimatoprost selectively mimics the effects of newly discovered biosynthesized substances called prostamides. The prostamide receptor, however, has not yet been structurally identified.
Pharmacokenitic Properities:
Absorption: Bimatoprost penetrates the human cornea and sclera well in vitro. After ocular administration in adults, the systemic exposure of bimatoprost is very low with no accumulation over time. After once daily ocular administration of one drop of bimatoprost 0.3mg/mL to both eyes for two weeks, blood concentrations peaked within 10 minutes after dosing and declined to below the lower limit of detection (0.025ng/ml) within 1.5 hours after dosing. The steady bimatoprost concentration was reached during the first week of ocular dosing.
Distribution: Bimatoprost is moderately distributed into body tissues and the systemic volume of distribution in humans at steady-state was 0.67 l/kg. In human blood, bimatoprost resides mainly in the plasma. The plasma protein binding of bimatoprost is approximately 88%.
Elimination: Bimatoprost is eliminated primarily by renal excretion, up to 67% of an intravenous dose administered to healthy adult volunteers was excreted in the urine, 25% of the dose was excreted via the faeces. The elimination half-life, determined after intravenous administration, was approximately 45 minutes; the total blood clearance was 1.5 l/hr/kg.
Indications:
Reduction of elevated intraocular pressure in chronic open-angle glaucoma and ocular hypertension in adults (as monotherapy or as adjunctive therapy to beta-blockers).
Contraindications:
Hypersensitivity to the active substance or to any of the excipients.
Special Warnings and Precautions:
Ocular:
- Before treatment is initiated, patients should be informed of the possibility of eyelash growth, darkening of the eyelid skin and increased iris pigmentation since these have been observed during treatment with bimatoprost.
- Some of these changes may be permanent, and may lead to differences in appearance between the eyes when only one eye is treated. Increased iris pigmentation is likely to be permanent.
- The pigmentation change is due to increased melanin content in the melanocytes rather than to an increase in the number of melanocytes.
- The long term effects of increased iris pigmentation are not known.
- Iris colour changes seen with ophthalmic administration of bimatoprost may not be noticeable for several months to years. Periorbital tissue pigmentation has been reported to be reversible in some patients.
- Cystoid macular oedema has been uncommonly reported (≥1/1,000 to <1/100) following treatment with bimatoprost 0.3mg/mL eye drops.
Therefore, bimatoprost should be used with caution in patients with known risk factors for macular oedema.
- There have been rare spontaneous reports of reactivation of previous corneal infiltrates or ocular infections with bimatoprost 0.3mg/mL eye drops, solution. Bimatoprost should be used with caution in patients with a prior history of significant ocular viral infections (e.g. herpes simplex) or uveitis/iritis.
There is a potential for hair growth to occur in areas where bimatoprost solution comes repeatedly in contact with the skin surface. Thus, it is important to apply bimatoprost as instructed and avoid it running onto the cheek or other skin areas.
Bimatoprost has not been studied in patients with compromised respiratory function. While there is limited information available on patients with a history of asthma or COPD, there have been reports of exacerbation of asthma, dyspnoea and COPD, as well as reports of asthma, in post marketing experience. The frequency of these symptoms is not known. Patients with COPD, asthma or compromised respiratory function due to other conditions should be treated with caution.
Bimatoprost has not been studied in patients with heartblock more severe than first degree or uncontrolled congestive heart failure. There have been a limited number of spontaneous reports of bradycardia or hypotension with bimatoprost 0.3mg/mL eye drops, solution. Bimatoprost should be used with caution in patients predisposed to low heart rate or low blood pressure.
Side effects:
Nervous system disorders: headache.
Eye disorders:conjunctival hyperaemia, punctate keratitis, eye irritation, foreign body sensation, dry eye, eye pain, eye pruritus, growth of eyelashes, eyelid erythema, asthenopia, conjunctival oedema, photophobia, tearing, increased iris pigmentation; blurred vision, corneal erosion, ocular burning, allergic conjunctivitis, blepharitis, worsening of visual acuity, eye discharge, visual disturbance, eyelash darkening, retinal hemorrhage, uveitis, cystoids macular oedema , retraction.
Skin and subcutaneous tissue disorders: eyelid pruritus, skin hyperpigmentation (periocular),hair growth abnormal.
Vascular disorders: hypertension.
Gastrointestinal disorder: nausea.
Investigations: liver function test abnormal.
Interaction with other medicinal products and other forms of interaction:
There is a potential for the IOP-lowering effect of prostaglandin analogues (e.g. bimatoprost) to be reduced in patients with glaucoma or ocular hypertension when used with other prostaglandin analogues.
Pregnancy :
There are no adequate data from the use of bimatoprost in pregnant women. Bimatoprost should not be used during pregnancy unless clearly necessary.
Breast-feeding:
It is unknown whether bimatoprost is excreted in human breast milk. A decision must be made whether to discontinue breast-feeding or to discontinue from bimatoprost therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Dosage and administration:
The recommended dose is one drop in the affected eye(s) once daily, administered in the evening. The dose should not exceed once daily as more frequent administration may lessen the intraocular pressure lowering effect.
Paediatric Population:
The safety and efficacy of bimatoprost in children aged (0) to (18) years has not yet been established.
Patients with hepatic and renal impairment:
Bimatoprost has not been studied in patients with renal or moderate to severe hepatic impairment and should therefore be used with caution in such patients. In patients with a history of mild liver disease or abnormal alanine aminotransferase (ALT), aspartate aminotransferase (AST) and/or bilirubin at baseline, bimatoprost 0.3mg/mL eye drops, solution had no adverse effect on liver function over 24 months.
Method of administration
If more than one topical ophthalmic medicinal product is being used, each one should be administered at least 5 minutes apart.
Overdose:
No information is available on overdose in humans; overdose is unlikely to occur after ocular administration.