部份中文卢美根处方资料（仅供参考）
通用名称：贝美前列素滴眼液
商品名称：卢美根
英文名：Bimatoprost Ophthalmic Solution
适应症
主要用于降低对其他降眼压制剂不能耐受或不够敏感的（多次用药无法达到目标眼内压值）的开角型青光眼及高眼压症患者的眼内压。
用法用量
推荐剂量为每日一次，每晚滴一滴于患眼。每日使用本品次数不得超过一次，因为有资料表明频繁使用本品可导致其眼压效果减弱。
首次滴用本品约4小时后眼压开始降低，约于8－12小时之内作用达到最大。
本品可以与其它滴眼剂同时使用以降低眼压。如果同时使用多种治疗药物，则每两种药物的使用应当至少间隔五分钟。
禁忌
本品禁用于对贝美前列素或本品中其它任何成份过敏者。
警告
有报道本品会引起色素组织的变化。包括色素增加，睫毛增生和虹膜及眶周围组织（眼睑）的色素增加。这些变化可能是永久性的。卢美根可逐渐改变眼睛的颜色，通过增加黑色素细胞中的黑素体（色素颗粒）数目使虹膜中的褐色素增加。本品对色素细胞的长期影响以及对黑色素细胞的潜在损伤和/或色素颗粒在眼睛其他部位的沉积情况目前还不清楚。
注意事项
一般情况：有报道患者因使用多剂量包装的滴眼液而致细菌性角膜炎。大多数情况下，包装容器是由于患者同时患有角膜疾病或眼睛上皮表面破裂而被污染的（参加患者须知）。
患者虹膜褐色素沉着的变化是逐渐发生的，可能在数年内也不会有明显变化。通常，褐色素沉着以瞳孔为中心向周边进行扩散，但是整个虹膜或部分的褐色素也会更深。也该经常检查患者眼睛的颜色变化，以便提供更多有关色素沉着的资讯，并且依据临床情况，如果色素沉着继续则应停止用药。停止用药后虹膜的褐色素不会再增加，但已改变的颜色可能是永久性的。虹膜上的痣和斑点不受治疗的影响。患有活动性内眼炎症（如葡萄膜炎）的患者须谨慎用本品。
曾有报道，有患者使用本品后出现了黄斑水肿包括囊样黄斑水肿。无晶体患者、晶状体后囊撕裂的假性无晶体患者或已知有黄斑水肿危险的患者应谨慎用本品。
本品治疗闭角型、炎性及出血性青光眼尚无评价。
配戴有隐形眼镜时不应使用本品。
患者须知：患者应被告知，部分患者使用此药会出现睫毛变长、颜色变深、眼部皮肤颜色加深的现象，此现象可能是永久性的。
只需要治疗单侧眼睛的患者应该被告知出现两眼间睫毛长度，颜色或粗细不同和两眼的眼睑皮肤及虹膜颜色不同的可能。
患者应该被告知勿将药瓶的瓶口直接接触眼睛、眼周组织、手指以及其它物体的表面、以免药液被可致眼睛感染的细菌污染。使用被污染的药液会严重损伤眼睛进而使视力下降。
患者应该被告知在使用过程中，若眼部出现任何状况（如外伤或感染）或进行眼科手术，应立即资讯医生是否可以继续使用此多剂量包装的滴眼液。
患者应该告知在在使用过程中，若眼部出现反应，特别是结膜炎和眼睑反应时应及时咨询医生。
使用本品前应当摘下隐形眼镜，并在滴药15分钟后再配戴。应告诉患者本品中含有苯扎氯铵会被软性隐形眼镜吸收。
如果同时还使用其它药物，每两种药物的使用至少间隔5分钟。
孕妇及哺乳期妇女用药
孕妇：对妊娠期的妇女使用本品还缺少足够有良好对照的研究。因为动物的生殖试验还不能直接遇见人类反应，仅仅当作使用本品的益处远远大于其带给胎儿的危险性时，方可给孕妇使用。
哺乳期妇女：虽然动物试验表明动物的乳汁中分泌有贝美前列腺素，但本品是否会从人类乳汁中分泌还不清楚。由于许多药物都会分泌乳汁中，因此给哺乳期妇女使用本品应当谨慎。
儿童用药
儿童患者使用本品的安全性和有效性尚未确立。
老年患者用药
使用本品的安全性和有效性在老年人和成年人之间没有明显的临床差异。
药物相互作用
本品可以与其它滴眼剂同时使用以降低眼内压。如果同时使用多种治疗药物，则每两种药物的使用应当至少间隔五分钟。
药物过量
没有关于人体使用本品过量的的资料报导。如果过量使用本品，应该根据出现的症状进行相应处理。
贮藏
保持包装完整，储存于2－25C
包装
塑料滴瓶装无菌眼药水，1支/盒
LUMIGAN 0,01% Eye drops
SCHEDULING STATUS:
Schedule 4
PROPRIETARY NAME
(and dosage form):
LUMIGAN 0,01% Eye drops
COMPOSITION
Each mL of sterile solution contains bimatoprost 0,1 mg
Contains benzalkonium chloride 0,02% m/v as a preservative.
Excipients: Citric acid monohydrate, dibasic sodium phosphate heptahydrate, sodium chloride, hydrochloric acid or sodium hydroxide (to adjust the pH) and purified water.
PHARMACOLOGICAL CLASSIFICATION
A. 15.4 Ophthalmological preparations. Other
PHARMACOLOGICAL ACTION
Pharmacodynamics
Bimatoprost is an ocular hypotensive agent. It is a synthetic prostamide, structurally related to prostamide F2alpha that does not act through any known prostaglandin receptors. Bimatoprost selectively mimics the effects of prostamides. The prostamide receptor, however, has not yet been structurally identified.
Bimatoprost reduces intraocular pressure (IOP) in humans 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 24 hours.
Limited experience is available with the use of bimatoprost in patients with open-angle glaucoma with pseudoexfoliative and pigmentary glaucoma, and chronic angle-closure glaucoma with patent iridotomy and no recommendation can be made.
No clinically relevant effects on heart rate and blood pressure have been observed in clinical trials.
Pharmacokinetics
Bimatoprost penetrates the human cornea and sclera well in vitro. After ocular administration, the systemic exposure of bimatoprost is very low with no accumulation over time.
After once daily ocular administration of one drop of 0,03% bimatoprost to both eyes of 15 healthy subjects for two weeks, blood concentrations peaked within 10 minutes after dosing and declined to below the lower limit of detection (0,025 ng/mL) in most subjects within 1,5 hours after dosing.
Mean Cmax and AUC0-24hrsvalues were similar on days 7 and 14 at approximately 0,08 ng/mL and 0,09 ng•hr/mL respectively, indicating that a steady drug concentration was reached during the first week of ocular dosing. Bimatoprost is moderately distributed into body tissues and the systemic volume of distribution in humans at steady-state was 0,67 L/kg.
As the concentration of the active substance for LUMIGAN 0,01% has been reduced three-fold it is considered that the systemic medicine exposure will not increase compared with 0,03% bimatoprost.
In human blood, bimatoprost resides mainly in the plasma. The plasma protein binding of bimatoprost is approximately 88%.
Bimatoprost is not extensively metabolised in the human eye.Bimatoprost is the major circulating component 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.
Bimatoprost is eliminated primarily by renal excretion, up to 67% of an intravenous dose administered to healthy 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 patients:
Elderly patients: After twice daily dosing with 0,03% bimatoprost, 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.
INDICATIONS
Reduction of elevated intraocular pressure in chronic open-angle glaucoma and ocular hypertension (as monotherapy or as adjunctive therapy to beta-blockers).
CONTRA-INDICATIONS
Hypersensitivity to bimatoprost or to any of the excipients.
WARNINGS
LUMIGAN 0,01% contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of LUMIGAN 0,01%and may be reinserted 15 minutes following administration. LUMIGAN 0,01%should not be administered while wearing contact lenses.
Due to the possibility of corneal permeability and the danger of disruption of the corneal epithelium with prolonged or repeated usage of benzalkonium chloride, regular ophthalmological examinations are required.
Caution should be exercised in the use of benzalkonium chloride over an extended period in patients with extensive ocular surface disease.
INTERACTIONS
Bimatoprost is biotransformed by multiple enzymes and pathways, and no effects on hepatic medicine metabolising enzymes were observed in pre-clinical studies. Therefore, specific interaction studies with other medicinal products have not been performed with LUMIGAN 0,01%.
In clinical studies, bimatoprost eye drops was used concomitantly with a number of different ophthalmic beta-blocking agents without evidence of medicine interactions.
Concomitant use of bimatoprost eye drops and anti-glaucoma agents other than topical beta-blockers has not been eva luated during adjunctive glaucoma therapy.
PREGNANCY AND LACTATION
The safety of LUMIGAN 0,01% during pregnancy and lactation has not been established. LUMIGAN 0,01% should not be used during pregnancy unless clearly necessary. It is recommended that it not be used in breastfeeding mothers as it is not known if LUMIGAN 0,01% is excreted in human milk.
DOSAGE AND DIRECTIONS FOR USE
When used as monotherapy or as adjunctive therapy, the recommended dose is one drop of LUMIGAN0,01% 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.
To prevent contamination of the dropper tip and solution, care should be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle.
If more than one topical ophthalmic medication is being used, the medicines should be administered at least 5 minutes apart.
Use in elderly:
No dosage adjustment in elderly patients is necessary.
Use in children and adolescents (under the age of 18):
LUMIGAN 0,01% has only been studied in adults and therefore its use is not recommended in children or adolescents.
Use in hepatic and renal impairment:
LUMIGAN 0,01% 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 ALT, AST and/or bilirubin at baseline, bimatoprost 0,03% had no adverse effect on liver function over 24 months.
SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects
In clinical studies with LUMIGAN 0,01% the most common adverse event was conjunctival hyperaemia (25%). Approximately 0,5% of patients discontinued therapy due to conjunctival hyperaemia with LUMIGAN 0,01% eye drops. The following side-effects were reported during clinical trials with LUMIGAN 0,01% and were considered to be treatment-related:
Ocular effects:
Eye disorders:
Very common (> 10%): Conjunctival hyperaemia
Common (> 1% to < 10%): Ocular irritation, punctate keratitis, eye pruritus
Uncommon (> 0,1% to < 1%): Asthenopia, conjunctival disorder, conjunctival oedema, erythema of eyelid, eyelid margin crusting, eyelids pruritus, growth of eyelashes, madarosis, vision blurred
Skin and subcutaneous tissue disorders:
Common (> 1% to < 10%): Abnormal hair growth around the eyes (hypertrichosis)
Systemic effects:
Immune system disorders:
Uncommon (> 0,1% to < 1%): Medicine hypersensitivity
Gastro-intestinal disorders:
Uncommon (> 0,1% to < 1%): Nausea
Skin and subcutaneous tissue disorders:
Uncommon (>  0,1% to < 1%): Pruritus
Nervous system disorders:
Uncommon (> 0,1% to < 1%): Headache
Additional adverse events that have been seen with 0,03% bimatoprost and may potentially occur also with LUMIGAN 0,01%:
Eye disorders:
Allergic conjunctivitis, blepharitis, blepharospasm, cataract, corneal erosion, cystoid macular oedema, eye discharge, eyelash darkening, eyelid retraction, eye pain, foreign body sensation, increased iris pigmentation, iritis, ocular burning, ocular dryness, photophobia, pigmentation of peri-ocular skin, retinal haemorrhage, tearing, uveitis, visual disturbance, worsening of visual acuity
Nervous system disorders:
Dizziness
Respiratory, thoracic and mediastinal disorders:
Infection (primarily colds and upper respiratory symptoms)
Investigations:
Liver function test (LFT) abnormal
Vascular disorders:
Hypertension
General disorders and administration site condition:
Asthenia, peripheral oedema
Skin and subcutaneous tissue disorders:
Hirsutism
Special precautions
During treatment with LUMIGAN 0,01% gradual increased eyelash growth (lengthening, darkening and thickening) with no consequent untoward ocular effects has been observed.
Increased iris pigmentation (darkening) has also been reported with 0,03% bimatoprost. The change in iris pigmentation occurs slowly and may not be noticeable for several months. The effect has been seen with up to 2% of patients treated with 0,03% bimatoprost for up to 12 months and the incidence did not increase following 3 years treatment.
Before treatment is initiated, patients should be informed of the possibility of eyelash growth. Some of these changes may be permanent and may lead to differences in appearance between the eyes when only one eye is treated.
LUMIGAN 0,01% has not been studied in patients with compromised respiratory function and should therefore be used with caution in such patients. In clinical studies of 0,03% bimatoprost, in those patients with a history of compromised respiratory function, no significant untoward respiratory effects have been seen.
LUMIGAN 0,01% has not been studied in patients with heart block more severe than first degree or uncontrolled congestive heart failure.
LUMIGAN 0,01% has not been studied in patients with inflammatory ocular conditions, or in the following types of glaucoma: neovascular, inflammatory, angle-closure glaucoma, congenital or narrow-angle glaucoma.
Cystoid macular oedema has been uncommonly reported (= 0,1% to < 1,0%) following treatment with 0,03% bimatoprost and should therefore 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).
KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
No case of overdose has been reported, and is unlikely to occur after ocular administration. If overdosage occurs, treatment should be symptomatic and supportive.
IDENTIFICATION
A clear colourless solution with no foreign particles.
PRESENTATION
2,5 mL filled in 5 mL; 5 mL and 7,5 mL filled in 10 mL white opaque low density polyethylene bottles with a turquoise polystyrene screw cap. Each bottle is packed into an outer carton.
STORAGE INSTRUCTIONS:
Store at or below 25°C. Do not use more than 30 days after opening. Keep bottle tightly closed when not in use. KEEP OUT OF REACH OF CHILDREN
REGISTRATION NUMBER
42/15.4/0835
NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
Allergan Pharmaceuticals (Pty) Ltd
30 New Road (entrance off Bavaria Road)
Randjespark Ext. 11, Midrand, 1682
Johannesburg, Gauteng
SOUTH AFRICA
DATE OF PUBLICATION OF THIS PACKAGE INSERT
20 June 2011