POM: Prescription only medicine
This information is intended for use by health professionals
PosologyThe 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 LUMIGAN in children aged 0 to 18 years has not yet been established.
Patients with hepatic and renal impairment:LUMIGAN 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 0.3 mg/ml eye drops, solution had no adverse effect on liver function over 24 months.
Method of administrationIf more than one topical ophthalmic medicinal product is being used, each one should be administered at least 5 minutes apart.
OcularBefore 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 LUMIGAN. 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. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts become more brownish. Neither naevi nor freckles of the iris appears to be affected by the treatment. At 12 months, the incidence of iris pigmentation with bimatoprost 0.3mg/ml was 1.5% (see section 4.8) and did not increase following 3 years treatment. 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 0.3 mg/ml eye drops. Therefore, LUMIGAN should be used with caution in patients with known risk factors for macular oedema (e.g. aphakic patients, pseudophakic patients with a torn posterior lens capsule).There have been rare spontaneous reports of reactivation of previous corneal infiltrates or ocular infections with bimatoprost 0.3 mg/ml eye drops, solution. LUMIGAN should be used with caution in patients with a prior history of significant ocular viral infections (e.g. herpes simplex) or uveitis/iritis.LUMIGAN has not been studied in patients with inflammatory ocular conditions, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma.
SkinThere is a potential for hair growth to occur in areas where LUMIGAN solution comes repeatedly in contact with the skin surface. Thus, it is important to apply LUMIGAN as instructed and avoid it running onto the cheek or other skin areas.
RespiratoryLUMIGAN 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.
CardiovascularLUMIGAN has not been studied in patients with heart block 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 0.3 mg/ml eye drops, solution. LUMIGAN should be used with caution in patients predisposed to low heart rate or low blood pressure.
Other InformationIn studies of bimatoprost 0.3 mg/ml in patients with glaucoma or ocular hypertension, it has been shown that the more frequent exposure of the eye to more than one dose of bimatoprost daily may decrease the IOP-lowering effect (see section 4.5). Patients using LUMIGAN with other prostaglandin analogues should be monitored for changes to their intraocular pressure. Bimatoprost 0.3 mg/ml eye drops, solution contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Eye irritation and discolouration of the soft contact lenses may also occur because of the presence of benzalkonium chloride. Contact lenses should be removed prior to instillation and may be reinserted 15 minutes following administration. Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since LUMIGAN contains benzalkonium chloride, monitoring is required with frequent or prolonged use in dry eye patients or where the cornea is compromised. There have been reports of bacterial keratitis associated with the use of multiple dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent ocular disease. Patients with a disruption of the ocular epithelial surface are at greater risk of developing bacterial keratitis.Patients should be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures, to avoid eye injury and contamination of the solution.
PregnancyThere are no adequate data from the use of bimatoprost in pregnant women. Animal studies have shown reproductive toxicity at high maternotoxic doses (see section 5.3).LUMIGAN should not be used during pregnancy unless clearly necessary.
Breast-feedingIt is unknown whether bimatoprost is excreted in human breast milk. Animal studies have shown excretion of bimatoprost in breast milk. A decision must be made whether to discontinue breast-feeding or to discontinue from LUMIGAN therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
FertilityThere are no data on the effects of bimatoprost on human fertility.
|System Organ class||Frequency||Adverse reaction|
|Nervous system disorders||common||headache|
|Eye disorders||very common||conjunctival hyperaemia, ocular pruritus, growth of eyelashes|
|common||superficial punctate keratitis, corneal erosion, ocular burning, ocular irritation, allergic conjunctivitis, blepharitis, worsening of visual acuity, asthenopia, conjunctival oedema, foreign body sensation, ocular dryness, eye pain, photophobia, tearing, eye discharge, visual disturbance/blurred vision, increased iris pigmentation, eyelash darkening, eyelid erythema, eyelid pruritus|
|uncommon||retinal haemorrhage, uveitis, cystoid macular oedema, iritis, blepharospasm, eyelid retraction, periorbital erythema, eyelid oedema|
|not known||periorbital and lid changes including deepening of the eyelid sulcus|
|Respiratory, thoracic and mediastinal disorders||not known||asthma, asthma exacerbation, COPD exacerbation and dyspnoea|
|Skin and subcutaneous tissue disorders||common||pigmentation of periocular skin|
|General disorders and administration site conditions||uncommon||asthenia|
|Investigations||common||liver function test abnormal|
|Immune systems disorders||not known||Hypersensitivity reaction including signs and symptoms of eye allergy and allergic dermatitis|
Mechanism of actionThe 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 biosynthesised substances called prostamides. The prostamide receptor, however, has not yet been structurally identified.During 12 months' monotherapy treatment with LUMIGAN 0.3 mg/ml in adults, versus timolol, mean change from baseline in morning (08:00) intraocular pressure ranged from -7.9 to -8.8 mm Hg. At any visit, the mean diurnal IOP values measured over the 12-month study period differed by no more than 1.3 mmHg throughout the day and were never greater than 18.0 mmHg.In a 6-month clinical study with LUMIGAN 0.3 mg/ml, versus latanoprost, a statistically superior reduction in morning mean IOP (ranging from -7.6 to -8.2 mmHg for bimatoprost versus 6.0 to -7.2 mmHg for latanoprost) was observed at all visits throughout the study. Conjunctival hyperaemia, growth of eyelashes, and eye pruritus were statistically significantly higher with bimatoprost than with latanoprost, however, the discontinuation rates due to adverse events were low with no statistically significant difference.Compared to treatment with beta-blocker alone, adjunctive therapy with beta-blocker and LUMIGAN 0.3 mg/ml lowered mean morning (08:00) intraocular pressure by -6.5 to -8.1 mmHg.Limited experience is available in patients with open-angle glaucoma with pseudoexfoliative and pigmentary glaucoma, and chronic angle-closure glaucoma with patent iridotomy.No clinically relevant effects on heart rate and blood pressure have been observed in clinical trials.
Paediatric populationThe safety and efficacy of LUMIGAN in children aged 0 to less than 18 years has not been established.
AbsorptionBimatoprost 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 LUMIGAN 0.3 mg/ml to both eyes for two weeks, blood concentrations peaked within 10 minutes after dosing and declined to below the lower limit of detection (0.025 ng/ml) within 1.5 hours after dosing. Mean Cmax and AUC 0-24hrs values were similar on days 7 and 14 at approximately 0.08 ng/ml and 0.09 ng•hr/ml respectively, indicating that a steady bimatoprost concentration was reached during the first week of ocular dosing.
DistributionBimatoprost 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%.
BiotransformationBimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites.
EliminationBimatoprost 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.
Characteristics in elderly patientsAfter twice daily dosing of LUMIGAN 0.3 mg/ml, the mean AUC0-24hr value of 0.0634 ng•hr/ml bimatoprost in the elderly (subjects 65 years or older) were significantly higher than 0.0218 ng•hr/ml in young healthy adults. However, this finding is not clinically relevant as systemic exposure for both elderly and young subjects remained very low from ocular dosing. There was no accumulation of bimatoprost in the blood over time and the safety profile was similar in elderly and young patients.