Lumigan 0,01 %/0,1 mg Solution

Reduction of elevated intraocular pressure in chronic open-angle glaucoma and ocular hypertension (as monotherapy or as adjunctive therapy to beta-blockers).

Posology
When used as monotherapy or as adjunctive therapy, the recommended dose is one drop of LUMIGAN 0,01 % 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.

Special populations
Elderly population
No dosage adjustment in elderly patients is necessary.
Patients with 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.
Paediatric population
LUMIGAN 0,01 % has only been studied in adults and therefore its use is not recommended in children or adolescents (under the age of 18).

Method of administration
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 (see section 4.4). If more than one topical ophthalmic medicine is being used, the medicines should be administered at least 5 minutes apart.

Hypersensitivity to bimatoprost or to any of the excipients listed in section 6.1.

Ocular
Before treatment is initiated, patients should be informed of the possibility of prostaglandin analogue periorbitopathy (PAP) and increased iris pigmentation, since these have been observed during treatment with LUMIGAN 0,01 %. Some of these changes may be permanent and may lead to impaired field of vision and differences in appearance between the eyes when only one eye is treated (see section 4.8). Patients should be informed of the possibility of eyelash growth since this has been observed during treatment with prostaglandin analogues, including LUMIGAN 0,01 %. Increased iris pigmentation has occurred when LUMIGAN 0,01 % has been administered. Patients should be advised about the potential for increased brown iris pigmentation which is likely to be permanent (see section 4.8). Macular oedema, including cystoid macular oedema, has been reported following treatment with bimatoprost 0,03 % eye drops, solution for elevated IOP. LUMIGAN 0,01 % should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular oedema (e.g. intraocular surgery, retinal vein occlusions, ocular inflammatory disease and diabetic retinopathy). LUMIGAN 0,01 % should be used with caution in patients with active intraocular inflammation (e.g. uveitis) because the inflammation may be exacerbated.

Skin
Bimatoprost ophthalmic solution has been reported to cause changes to pigmented tissues. When bimatoprost 0,03 % (multi-dose) was instilled directly into the eye (for treatment of elevated IOP), the most frequently reported pigmentary changes have been increased pigmentation of periorbital tissue (eyelid), eyelashes and the iris. There is the potential for hair growth to occur in areas where LUMIGAN 0,01 % solution comes repeatedly in contact with the skin surface. Thus, it is important to apply LUMIGAN 0,01 % as instructed and to avoid it running onto the cheek or other skin areas.

Respiratory
LUMIGAN 0,01 % has not been studied in patients with compromised respiratory function and should therefore be used with caution in such patients. 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.

Cardiovascular
LUMIGAN 0,01 % 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 0,03 % eye drops, solution. LUMIGAN 0,01 % should be used with caution in patients predisposed to low heart rate or low blood pressure.

Other Information
In bimatoprost 0,03 % studies in patients with glaucoma or ocular hypertension, it has been shown that 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 0,01 % with other prostaglandin analogues should be monitored for changes to their intraocular pressure. LUMIGAN 0,01 % 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 (BAK), which is commonly used as a preservative in ophthalmic products, has been reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since LUMIGAN 0,01 % contains benzalkonium chloride, it should be used with caution in dry eye patients, in patients where the cornea may be compromised and in patients taking multiple BAK-containing eye drops. In addition, monitoring is required with prolonged use in such patients. 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. 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.

No interaction studies have been performed. Bimatoprost is biotransformed by multiple enzymes and pathways, and no effects on hepatic medicine metabolising enzymes were observed in pre-clinical studies. In clinical studies, bimatoprost 0,03 % eye drops (multi-dose) was used concomitantly with a number of different ophthalmic beta-blocking agents without evidence of medicine interactions. Concomitant use of LUMIGAN 0,01 % and anti-glaucoma agents other than topical beta-blockers has not been evaluated during adjunctive glaucoma therapy. There is a potential for the IOP-lowering effect of prostaglandin analogues (e.g. LUMIGAN 0,01 %) to be reduced in patients with glaucoma or ocular hypertension when used with other prostaglandin analogues (see section 4.4).

The safety of LUMIGAN 0,01 % during pregnancy and lactation has not been established.
Pregnancy
LUMIGAN 0,01 % should not be used during pregnancy unless clearly necessary.
Breastfeeding
It is not known whether LUMIGAN 0,01 % is excreted in human milk, although in animal studies, bimatoprost has been shown to be excreted in breast milk. It is recommended that it not be used in breastfeeding mothers.

If transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machinery.

Summary of the safety profile
In clinical studies with LUMIGAN 0,01 % the most common adverse event was conjunctival hyperaemia (29 %). Approximately 1,6 % of patients discontinued therapy due to conjunctival hyperaemia with LUMIGAN 0,01 % eye drops.

Tabulated summary of adverse reactions
The following side effects were reported during clinical trials or in the post-marketing period with LUMIGAN 0,01 % and were considered to be treatment related.
The frequency is defined as follows: Very Common (u2265 1/10); Common (u22651/100 to <1/10); Uncommon (u2265 1/1 000 to < 1/100); Rare (u2265 1/10 000 to < 1/1 000); Very Rare (< 1/10 000); Not known (cannot be estimated from available data).

Table 1
System organ class Frequency Adverse reaction
Nervous system disorders Uncommon Headache
Not known Dizziness
Eye disorders Very common Ocular/conjunctival hyperaemia, prostaglandin analogue periorbitopathy
Common Punctate keratitis, eye irritation, eye pruritus, growth of eyelashes, eye pain, erythema of eyelid, eyelid pruritus
Uncommon Asthenopia, blurred vision, conjunctival disorder, conjunctival oedema, iris hyperpigmentation, madarosis
Not known Blepharal pigmentation, macular oedema, dry eye, eye discharge, eye oedema, foreign body sensation in eyes, lacrimation increased, ocular discomfort, photophobia, eyelid oedema
Respiratory, thoracic and mediastinal disorders Not known Asthma, asthma exacerbation, COPD exacerbation, dyspnoea
Gastro-intestinal disorders Uncommon Nausea
Skin and subcutaneous tissue disorders Common Skin hyperpigmentation, abnormal hair growth around the eyes (hypertrichosis)
Uncommon Dry skin, eyelid margin crusting, pruritus
Not known Skin discolouration (periocular)
General disorders and administration site conditions Common Instillation site irritation
Immune system disorders Not known Hypersensitivity reaction including signs and symptoms of eye allergy and allergic dermatitis
Vascular disorders Not known Hypertension

Description of selected adverse reactions
Prostaglandin analogue periorbitopathy (PAP)
Prostaglandin analogues including LUMIGAN 0,01 % can induce periorbital lipodystrophic changes which can lead to deepening of the eyelid sulcus, ptosis, enophthalmos, eyelid retraction, involution of dermatochalasis and inferior scleral show. Changes are typically mild, can occur as early as one month after initiation of treatment with LUMIGAN 0,01 %, and may cause impaired field of vision even in the absence of patient recognition. PAP is also associated with periocular skin hyperpigmentation or discolouration and hypertrichosis. All changes have been noted to be partially or fully reversible upon discontinuation or switch to alternative treatments.
Iris hyperpigmentation
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 LUMIGAN 0,01 % 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 appear to be affected by the treatment. At 12 months, the incidence of iris hyperpigmentation with LUMIGAN 0,01 % eye drops, solution was 0,5 %. At 12 months, the incidence with bimatoprost 0,03 % eye drops, solution was 1,5 % (see section 4.8 Table 2) and did not increase following 3 years treatment.
Adverse reactions reported in phosphate containing eye drops
Cases of corneal calcification have been reported very rarely in association with the use of phosphate containing eye drops in some patients with significantly damaged corneas. Additional adverse events that have been seen with 0,03 % bimatoprost and may potentially occur also with LUMIGAN 0,01 % are presented in Table 2.

Table 2
System organ class Adverse reaction
Eye disorders Corneal erosion, ocular burning, allergic conjunctivitis, blepharitis, worsening of visual acuity, visual disturbance, eyelash darkening, cataract, retinal haemorrhage, uveitis, cystoid macular oedema, iritis, blepharospasm, eyelid retraction, periorbital erythema
Skin and subcutaneous tissue disorders Pigmentation of peri-ocular skin, hirsutism, abnormal hair growth
General disorders and administration site condition Asthenia, peripheral oedema
Investigations Liver function test (LFT) abnormal
Infections and infestations Infection (primarily colds and upper respiratory tract infections)

Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. In case of a side effect, please contact [email protected]

No information is available on overdosage in humans. If overdosage occurs, treatment should be symptomatic and supportive.