Allergan Ltd

Section Number

Subject

Change

2

Qualitative and Quantitative Composition

Sentence expanded:

Excipient:

One ml of solution contains 0.05 mg benzalkonium chloride 0.05 mg/ml.

4.2

Posology and method of administration

Words removed:

Use in children and adolescents (under the age of 18):

LUMIGAN  is not recommended for use in children below 18 years, due to a lack of data on safety and efficacy (see sections 5.1 and 5.2).

4.4

Special Warnings and Precautions for Use

Paragraph deleted and  replaced with text below in italics

LUMIGAN contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses.  Contact lenses should be removed prior to instillation and may be reinserted 15 minutes following administration.

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.

Following two warnings added:

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.

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.

Slight rewording of following:

Cystoid macular oedema has been uncommonly reported (≥1/1000 to <1/100) following treatment with bimatoprost 0.3 mg/ml eye drops.  Therefore, LUMIGAN 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).

4.5

Interaction with other medicinal products and other forms of interaction

Wording addition:

No interactions are anticipated in humans, since systemic concentrations of bimatoprost are extremely low (less than 0.2 ng/ml) following ocular dosing with bimatoprost 0.3 mg/ml eye drops, solution. 

4.6

Pregnancy and  lactation

Slight rewording to lactation section, which doesn’t affect overall warning:

Lactation

It is unknown whether bimatoprost is excreted in human breast milk.  Animal studies have shown excretion of bimatoprost in breast milk. A risk to the suckling child cannot be excluded. A risk to the suckling child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to continue/abstain from LUMIGAN therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with LUMIGAN should be made, taking into account the benefit of breast-feeding to the child and the benefit of LUMIGAN therapy to the woman.

4.7

Effects on ability to drive and use machines

As with any ocular treatment, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machinerys.

4.8

Undesirable effects

Wording change before adverse effect list:

The following undesirable effects definitely, probably or possibly related to treatmentadverse reactions were reported during clinical trials with LUMIGAN 0.3 mg/ml eye drops, solutionLUMIGAN.  Most were ocular, mild to moderate, and none was serious:

4.9

Overdose

Typo amendment:

If overdosage occurs, treatment should be symptomatic and supportive. 

5.1

Pharmacodynamic properties

Wording change:

Pharmacotherapeutic group:  other antiglaucoma preparations;

Ophthalmologicals, prostaglandin analogues, ATC code: S01EE03.

Wording change:

The mechanism of action by which bimatoprost reduces intraocular pressure in man humans is by increasing aqueous humour outflow through the trabecular meshwork and enhancing uveoscleral outflow.

Wording change:

Limited experience is available with the use in patients with open-angle glaucoma with pseudoexfoliative and pigmentary glaucoma, and chronic angle-closure glaucoma with patent iridotomy.

5.2

Pharmacokinetic properties

Wording addition:

After ocular administration in adults, the systemic exposure of bimatoprost  is very low with no accumulation over time. 

5.3

Preclinical safety data

Unit change:

Monkeys administered ocular bimatoprost concentrations of ³0.0.03 mg/ml% daily for 1 year had an increase in iris pigmentation and reversible dose-related periocular effects characterised by a prominent upper and/or lower sulcus and widening of the palpebral fissure. 

Wording change:

Bimatoprost did not impair fertility in rats up to doses of 0.6 mg/kg/day (approximately at least 103‑times the intended human exposure).

6.3

Shelf Life

Wording deleted:

Chemical and physical in-use stability has been demonstrated for 28 days at 25°C. 

From a microbiological point of view, the in-use storage times and conditions are the responsibility of the user and would normally not be longer than 28 days at 25°C

Replaced with:

4 weeks after first opening.

10

Date of revision of text

Changed from 2 Septemeber 2009 to 7 January 2010.

Section Number

Subject

Change

4.1

Therapeutic indications

Text amended:

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

4.2

Posology and method

of administration

Text amended:

Use in children and adolescents (under the age of 18):

New text - LUMIGAN  is not recommended for use in children below 18 years, due to a lack of data on safety and efficacy (see sections 5.1 and 5.2) Replaces: LUMIGAN has only been studied in adults and therefore its use is not recommended in children or adolescents.

Use in 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, LUMIGAN had no adverse effect on liver function over 24 months.

4.4

Special warnings and precautions for use

Text amended:

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 LUMIGAN. Some of these changes may be permanent, and may lead to differences in appearance between the eyes when only one eye is treated.  The change in iris pigmentation occurs slowly and may not be noticeable for several months or years.  At 12 months, the incidence was 1.5% and did not increase following 3 years treatment (see section 4.8). Periorbital tissue pigmentation has been reported to be reversible in some patients.

4.6

Pregnancy and lactation

Text amended:

Lactation

It is not known unkown whether bimatoprost is excreted in human breast milk however, this substance is excreted in rat milk after intravenous administration.  It is recommended that LUMIGAN is not used in nursing mothers. Animal studies have shown excretion of bimatoprost in breast milk. A decision on whether to continue/discontinue breast-feeding or to continue/discontinue therapy with LUMIGAN should be made taking into account the benefit of breast-feeding to the child and the benefit of LUMIGAN therapy to the woman.

4.8

Undesirable effects

Text amended:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000) and not known (cannot be estimated from available data) undesirable effects are presented according to System Organ Class in Table 1. Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Text Removed - (≥1/10); (≥1/100 to <1/10); (≥1/1,000 to <1/100); (≥1/10,000 to <1/1,000); (<1/10,000)

Eye disorders:

                      common – cataract

                      not known – enophthalmos

General disorders and administration site conditions:

                        Uncommon – peripheral oedema

5.1

Pharmacodynamic properties

Text amended:

During 12 months’ monotherapy treatment in adults,…..

5.2

Pharmacokinetic properties

Text amended:

…..indicating that a steady drug bimatoprost concentration was reached during the first week of ocular dosing.

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. 

10

Date of revision of text

2 September 2009 replaces 20 February 2007