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 |
