Consumer medicine information

Lumigan Eye Drops

Bimatoprost

BRAND INFORMATION

Brand name

Lumigan

Active ingredient

Bimatoprost

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Lumigan Eye Drops.

SUMMARY CMI

LUMIGAN® EYE DROPS

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

1. Why am I using LUMIGAN® eye drops?

LUMIGAN® eye drops contains the active ingredient bimatoprost. LUMIGAN® eye drops is used to lower raised pressure in the eye and to treat glaucoma.

For more information, see Section 1. Why am I using LUMIGAN® eye drops? in the full CMI.

2. What should I know before I use LUMIGAN® eye drops?

Check the list of ingredients at the end of the CMI. Do not use LUMIGAN® eye drops if you have ever had an allergic reaction to any of them.

Talk to your doctor before you use this medicine if he/she is not aware that you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I use LUMIGAN® eye drops? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with LUMIGAN® eye drops and affect how it works, or LUMIGAN® eye drops may interfere with other medicines and affect how they work.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use LUMIGAN® eye drops?

  • Use one drop in your affected eye(s), according to your doctor's instructions
  • Use the drops each evening.

More instructions can be found in Section 4. How do I use LUMIGAN® eye drops? in the full CMI.

5. What should I know while using LUMIGAN® eye drops?

Things you should do
  • Remind any doctor, dentist, pharmacist, or optometrist you visit that you are using LUMIGAN® eye drops
  • Continue to use LUMIGAN® eye drops every evening unless your doctor tells you to stop
  • Keep all your appointments so your condition can be checked.
Things you should not do
  • Do not touch the dropper tip against your eye, eye lid or any surface
  • Do not stop using LUMIGAN® eye drops without checking with your doctor
  • Do not use LUMIGAN® eye drops while you are wearing contact lenses.
Driving or using machines
  • Wait until your vision clears after using LUMIGAN® eye drops before driving or using machines.
Drinking alcohol
  • There is no information on the effects of using LUMIGAN® eye drops with alcohol.
Looking after your medicine
  • Follow all instructions on the carton and label
  • Store it in a cool dry place, below 25°C, away from moisture, heat, or sunlight.

For more information, see Section 5. What should I know while using LUMIGAN® eye drops? in the full CMI.

6. Are there any side effects?

The most common side effects include red, congested eyes, growth of eyelashes, itching or irritation of the eye. Note that side effects can occur in other parts of the body, including serious allergic reaction (anaphylaxis).

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

LUMIGAN® EYE DROPS (loom-ig-gan)

Active ingredient: bimatoprost (bim-at-oh-prost)

Consumer Medicine Information (CMI)

This leaflet provides important information about using LUMIGAN® eye drops. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using LUMIGAN® eye drops.

Where to find information in this leaflet:

1. Why am I using LUMIGAN® eye drops?
2. What should I know before I use LUMIGAN® eye drops?
3. What if I am taking other medicines?
4. How do I use LUMIGAN® eye drops?
5. What should I know while using LUMIGAN® eye drops?
6. Are there any side effects?
7. Product details

1. Why am I using LUMIGAN® eye drops?

LUMIGAN® eye drops contain the active ingredient bimatoprost.

LUMIGAN® eye drops are used to lower raised pressure in the eye and to treat glaucoma.

Glaucoma is a condition in which the pressure of fluid in the eye may be high. However, some people with glaucoma may have normal eye pressure. Glaucoma is usually caused by a build up of the fluid which flows through the eye. This build up occurs because the fluid drains out of your eye more slowly than it is being pumped in. Since new fluid continues to enter the eye, joining the fluid already there, the pressure continues to rise. This raised pressure may damage the back of the eye resulting in gradual loss of sight. Damage can progress so slowly that the person is not aware of this gradual loss of sight. Sometimes even normal eye pressure is associated with damage to the back of the eye.

There are usually no symptoms of glaucoma. The only way of knowing that you have glaucoma is to have your eye pressure, optic nerve and visual field checked by an eye specialist or optometrist. If glaucoma is not treated it can lead to serious problems, including total blindness. In fact, untreated glaucoma is one of the most common causes of blindness.

LUMIGAN® eye drops lower the pressure in the eye by helping the flow of fluid out of the eye chamber.

LUMIGAN® eye drops can be used alone or together with other eyedrops/medicines to lower raised pressure within your eyes.

Although LUMIGAN® eye drops help control your condition, they will not cure it.

Your doctor may have prescribed this medication for another reason. Ask your doctor if you have any questions about why LUMIGAN® eye drops have been prescribed for you.

2. What should I know before I use LUMIGAN® eye drops?

Warnings

Do not use LUMIGAN® eye drops if:

  • you are allergic to bimatoprost, or any of the ingredients listed at the end of this leaflet.
  • the seal around the cap is broken, the bottle/packaging shows signs of tampering, or the product does not look quite right.

Check with your doctor if:

  • you have or have had inflammation in the eye, such as uveitis
  • you have had eye surgery
  • your eye does not have a lens
  • your eye has an artificial lens, following cataract surgery
  • the capsule ("bag") that normally holds the eye's lens in place is torn, or ruptured
  • you have had other problems with your eyes, such as inflammation or swelling of the light sensitive part of the eye known as the macula
  • you have a diabetes-related eye condition, such as diabetic retinopathy or blockage of a retinal vein
  • you have or have had low blood pressure or a slow heartbeat
  • you have or have had problems with your lungs or airways
  • you have or have had problems with your liver or kidneys
  • you take any medicines for any other condition.
  • you have had an allergy to any medicines or any other substances, such as foods, preservatives or dyes

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

It is not known if LUMIGAN® eye drops are safe and useful for children and adolescents under 18 years.

Pregnancy and breastfeeding

Make sure your doctor is aware that you are pregnant or plan to become pregnant or are breastfeeding or intend to breastfeed.

Cosmetic effects

Before you start using LUMIGAN® eye drops your doctor should tell you that some changes to your eyes may occur which may be permanent.

During treatment, LUMIGAN® may cause a loss of fat around the eye, which may cause your eyelid crease to deepen, your eye to appear sunken, your upper eyelid to droop, the skin around your eye to tighten and the lower white part of your eye to become more visible. The changes are typically mild, but if pronounced, they can affect your field of vision. The changes may disappear if you stop taking LUMIGAN®.

Eyelashes may also grow longer and thicker, and eyelashes, the skin around the eye and the coloured part of the eye (iris) may become darker. If only one eye is being treated the cosmetic differences between the eyes may be noticeable. None of these changes affect vision. If you have any concerns, ask your doctor or pharmacist.

Hair may grow where LUMIGAN® contacts the skin. It is important to use as directed.

3. What if I am taking other medicines?

Tell your doctor or pharmacist if you are taking any other medicines, including any medicines, vitamins or supplements that you buy without a prescription from your pharmacy, supermarket or health food shop.

Some medicines may interfere with LUMIGAN® eye drops and affect how it works, while LUMIGAN® eye drops may affect how other medicines work.

Medicines that may reduce the effect of LUMIGAN® eye drops and where LUMIGAN® eye drops may reduce their effect include:

  • other eye drops in the same class as LUMIGAN® eye drops, such as latanoprost, tafluprost, and travoprost.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect LUMIGAN® eye drops.

4. How do I use LUMIGAN® eye drops?

Follow all directions given to you by your doctor carefully. The directions may differ from the information contained in this leaflet.

How much to use

  • Your doctor will tell you how many drops you need to use each day. Use LUMIGAN® eye drops only as prescribed by your doctor.
  • The usual dose of LUMIGAN® eye drops is one drop in your affected eye(s), according to your doctor's instructions.

When to use LUMIGAN® eye drops

  • Use the drops each evening.

Use LUMIGAN® eye drops every day, at about the same time each day, unless your doctor tells you otherwise. Using your eye drops at the same time each day will have the best effect on your eye pressure. It will also help you remember when to use the eye drops.

In some instances, LUMIGAN® eye drops need to be used with other eye drops. Your doctor will let you know which drops, how to use them, and how long to use them.

If you are using more than one eye drop product, wait 5 minutes before using the second product. If you are also using an eye ointment, instill the eye ointment last.

If you are being changed from one eye drop to another, follow your doctor's instructions carefully as to when to stop the old drops and when to start the new drops.

How to use LUMIGAN® eye drops

Do not put the eye drops into your eye(s) while you are wearing soft contact lenses. The preservative in LUMIGAN® eye drops (benzalkonium chloride) may be deposited in soft contact lenses. You can put your soft contact lenses back into your eyes 15 minutes after you have used LUMIGAN® eye drops.

These drops are for use in your eyes only.

You may find it easier to put drops in your eye while you are sitting or lying down.

To open a new bottle of LUMIGAN® eye drops first tear off the protective seal from the bottle. The contents are sterile if the seal is intact.

The seal will break and you can pull it off and then throw it away.

  1. Wash your hands well with soap and water.
  2. Remove the lid/cap.
  3. Hold the bottle upside down in one hand between your thumb and forefinger or index finger.
  4. Using your other hand, gently pull down your lower eyelid to form a pouch or pocket.
  5. Tilt your head back and look up.
  6. Put the tip of the bottle close to your lower eyelid. Do not let it touch your eye.
  7. Release one drop into the pouch or pocket formed between your eye and eyelid by gently squeezing the bottle.
  8. Close your eye. Do not blink or rub your eye.
  9. While your eye is closed, place your index finger against the inside corner of your eye and press against your nose for about two minutes. This will help to stop the medicine from draining through the tear duct to the nose and throat, from where it can be absorbed into other parts of your body. Ask your doctor for more specific instructions on this technique.
  10. Replace the lid/cap, sealing it tightly.
  11. Wash your hands again with soap and water to remove any residue.

If a drop misses your eye, try again. Wipe off any excess that runs down the cheek.

Wait 15 minutes before replacing your contact lenses.

Be careful not to touch the dropper tip against your eye, eyelid or anything else to avoid injury and contaminating the eye drops.

If you forget to use LUMIGAN® eye drops

It is important that you use LUMIGAN® eye drops at the same time each evening.

If you forget to use LUMIGAN® eye drops and it is almost time for your next dose, use your drops at the usual time the next evening.

If you miss your dose and remember through the night or in the morning, use the drops as soon as you remember and go back to using them at your usual time.

If you are not sure whether to skip the dose, talk to your doctor or pharmacist.

Do not use double the number of drops to make up for the dose you missed.

If you use too much LUMIGAN® eye drops

Immediately rinse your eyes with warm water.

If LUMIGAN® eye drops is accidentally swallowed

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26 in Australia or
    0800 POISON (0800 764 766) in New Zealand)    , or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there appear to be no signs of discomfort or poisoning.

5. What should I know while using LUMIGAN® eye drops?

Things you should do

  • Continue to use LUMIGAN® eye drops every evening unless your doctor tells you to stop. LUMIGAN® eye drops help to control your condition but does not cure it.
  • Use all the medication prescribed to treat your eye condition.
  • Keep all your doctor's appointments so that your condition can be monitored, and your eye pressure can be checked.
  • Tell your doctor if you think your condition is not improving while using LUMIGAN® eye drops.

Call your doctor straight away if you:

  • develop any problems with your eye(s), such as, trauma, change of vision, infection in the eye or eyelid, or have eye surgery
  • become pregnant while using LUMIGAN® eye drops.

Remind any doctor, dentist, pharmacist, or optometrist you visit that you are using LUMIGAN® eye drops.

Things you should not do

  • Do not touch the dropper tip against your eye, eyelid or anything else, to avoid contaminating the eye drops.
  • Do not stop using LUMIGAN® eye drops without checking with your doctor. Your eye pressure can rise again and may cause damage to your eye.

Driving or using machines

Your vision may be blurred after using LUMIGAN® eye drops. Wait until your vision clears before driving or using machines.

Looking after your medicine

Follow the instructions on the carton and label on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example:

  • do not store it in the bathroom or near a sink, or
  • do not store it in the car or on window sills.

Ensure the lid is closed tightly after each use.

Keep it where young children cannot reach it.

When to discard your medicine

Discard the bottle 28 days after first opening it.

Getting rid of any unwanted medicine

If your doctor advises that you no longer need to use this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date has passed.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Effects on the eye(s):
  • red, congested eyes
  • itching or irritation of the eye
  • feeling of something in the eye
  • dry eye
  • growth of eyelashes
  • redness in or around eye or eyelid
  • watery eyes
  • inflamed eyelids
  • eye discomfort
  • eye strain
  • burning of the eye and nearby eyelid
  • itchy eye and eyelid
  • inflammation inside the eye
  • swelling of the surface of the eye
  • sensitivity to light
  • darkening of the area around the eye
  • eyelash darkening
  • darkening of the coloured part of the eye (iris)
  • more often, the following effects have been seen: loss of fat in the eye region which can lead to deepening of your eyelid crease, sunken eye, drooping eyelid, tightening of the skin around your eye, and the lower white part of your eye to become more visible.
Effects on the body as a whole:
  • headache
  • feeling weak and tired
  • symptoms of a cold such as runny nose or nasal congestion
  • excessive or abnormal hair growth in areas where the product repeatedly comes into contact with the skin
  • nausea
  • dizziness
  • allergic skin reaction (rash, itching, hives)
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Effects on the eye(s):
  • eye discharge
  • eye pain
  • small spots on the eye surface
  • blurred vision or changes in/disturbance of vision
  • macular edema (build-up of fluid at the back of the eye, which causes vision to become blurry)
  • spasm of the eyelids where there is uncontrolled blinking and squeezing of eyelid
Effects on the body as a whole:
  • high blood pressure
  • asthma or worsening of asthma
  • difficulty breathing
  • depression (low mood, feelings of worthlessness)
Call your doctor straight away, if you notice any of these serious side effects.
Effects on the body as a whole:
  • severe allergic reaction, including swelling of the tongue, lips and throat, difficulty breathing
Go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems in Australia or to nzphvc.otago.ac.nz/reporting in New Zealand. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

This medicine is only available with a doctor's prescription.

What LUMIGAN® eye drops contains

Active ingredient
(main ingredient)
  • bimatoprost
Other ingredients
(inactive ingredients)
  • benzalkonium chloride
  • citric acid monohydrate
  • dibasic sodium phosphate heptahydrate
  • hydrochloric acid
  • purified water
  • sodium chloride
  • sodium hydroxide

Do not use this medicine if you are allergic to any of these ingredients.

What LUMIGAN® eye drops looks like

LUMIGAN® eye drops is a sterile, clear, colourless solution. It is supplied in plastic dropper bottles containing 3 mL, 5 mL or 7.5 mL of solution. (AUST R 80657).

(Not all presentations may be available).

Who distributes LUMIGAN® eye drops?

LUMIGAN® eye drops eye drops are distributed in Australia by:

AbbVie Pty Ltd
241 O'Riordan Street
Mascot NSW 2020
Australia

LUMIGAN® eye drops eye drops are distributed in New Zealand by:

AbbVie Limited
6th Floor, 156-158 Victoria St
Wellington, 6011
New Zealand

This leaflet was prepared in Aug 2023.

© 2023 AbbVie. All rights reserved.

LUMIGAN and its design are trademarks of Allergan, Inc., an AbbVie company.

Published by MIMS October 2023

BRAND INFORMATION

Brand name

Lumigan

Active ingredient

Bimatoprost

Schedule

S4

 

1 Name of Medicine

Bimatoprost.

2 Qualitative and Quantitative Composition

Lumigan eye drops contains bimatoprost 300 microgram/mL.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye drops, solution.
Lumigan eye drops is a clear, isotonic, colourless, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg. It contains a preservative.

4 Clinical Particulars

4.1 Therapeutic Indications

Lumigan eye drops is indicated for the reduction of elevated intraocular pressure, or open angle glaucoma, as first line therapy or monotherapy or as adjunctive therapy to topical beta-blockers.

4.2 Dose and Method of Administration

Monotherapy.

The recommended dose is one drop of Lumigan eye drops in the affected eye(s) once daily, administered in the evening.

Adjunctive therapy.

The recommended dose is one drop of Lumigan eye drops in the affected eye(s) once daily, administered in the evening.
More frequent administration has not been shown to provide increased efficacy.
If more than one topical ophthalmic medication is to be used, the other medication should not be used within 5 minutes of using Lumigan eye drops.
In order to minimise systemic absorption of Lumigan eye drops, patients should be instructed to apply pressure to the tear duct immediately following administration of the drug.
To avoid contamination of the solution, keep container tightly closed. Do not touch dropper tip to any surface. Discard contents 4 weeks after opening the bottle. Contents are sterile if seal is intact.

4.3 Contraindications

Lumigan eye drops are contraindicated in patients with hypersensitivity to bimatoprost or to any component of the medication.

4.4 Special Warnings and Precautions for Use

General.

Lumigan eye drops 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 Lumigan eye drops.
Lumigan eye drops should be used with caution in patients predisposed to low heart rate or low blood pressure.
Lumigan eye drops has not been studied in patients with compromised respiratory function and should therefore be used with caution in such patients. In clinical studies, in those patients with a history of a compromised respiratory function, no significant untoward respiratory effects have been seen.
During treatment with bimatoprost, darkening of the eyelid skin and gradual increased eyelash growth (lengthening, darkening and thickening) with no consequent untoward ocular effects have been observed.
Before treatment is initiated, patients should be informed of the possibility of prostaglandin analogue periorbitopathy (PAP) and increased iris pigmentation. 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 Adverse Effects (Undesirable Effects)).
There is the 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 eye drops as instructed and to avoid it running onto the cheek or other skin areas.
In Lumigan eye drops 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. Patients using Lumigan eye drops with other prostaglandin analogues should be monitored for changes to their intraocular pressure.
Lumigan eye drops should be used with caution in patients with active intraocular inflammations (e.g. uveitis) because the inflammation may be exacerbated.
Macular oedema, including cystoid macular oedema, has been reported during treatment with bimatoprost 0.03% ophthalmic solution for elevated IOP. Lumigan eye drops 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 eye drops has not been studied in patients with inflammatory ocular conditions, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma.

Use in hepatic impairment.

Lumigan eye drops has not been studied in patients with hepatic impairment and should therefore be used with caution in such patients.

Use in renal impairment.

Lumigan eye drops has not been studied in patients with renal impairment and should therefore be used with caution in such patients.

Use in the elderly.

No dosage adjustment in elderly patients is necessary.

Paediatric use.

Safety and effectiveness in patients below 18 years of age have not been established.

Information for patients.

Lumigan eye drops contain the preservative benzalkonium chloride, which may be absorbed by and cause discolouration of soft (hydrophilic) contact lenses. Patients wearing soft contact lenses should be instructed to remove their contact lenses prior to instillation of Lumigan eye drops and wait at least 15 minutes following administration before reinserting the contact lenses. Lumigan eye drops should not be administered while wearing contact lenses.
There have been reports of bacterial keratitis associated with the use of multidose 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.
The tip of the bottle should not be allowed to contact the eye, surrounding structures, fingers or any other surface in order to avoid eye injury and contamination of the solution.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

No interaction studies have been performed.
No drug-drug interactions are anticipated in humans since systemic concentrations of bimatoprost are extremely low (less than 0.2 nanogram/mL) following ocular dosing. No effects on hepatic drug metabolising enzymes were observed in pre-clinical studies. Therefore, specific interaction studies with other medicinal products have not been performed with Lumigan eye drops.
In clinical studies, Lumigan eye drops were used concomitantly with a number of different ophthalmic beta-blocking agents without evidence of drug interactions.
Concomitant use of Lumigan eye drops and anti-glaucoma agents other than topical beta-blockers have not been evaluated during adjunctive glaucoma therapy.
There is a potential for the IOP-lowering effect of prostaglandin analogues to be reduced in patients with glaucoma or ocular hypertension when used with other prostaglandin analogues.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Bimatoprost did not affect fertility in male or female rats at oral doses up to 0.6 mg/kg/day corresponding to 30 - 50 times the expected human exposure (based on blood AUC calculated from total blood concentration).
(Category B3)
Bimatoprost and/or its metabolites crossed the placenta in rats. In embryofoetal developmental studies in pregnant mice and rats, abortion was observed at oral doses of bimatoprost of 0.3 and 0.6 mg/kg/day, respectively, resulting in exposures 15 and 34 times the expected human exposure (based on blood AUC calculated from total blood concentration). Bimatoprost was not teratogenic at up to 0.6 mg/kg/day in mice or rats. At doses of ≥ 0.3 mg/kg/day PO in rats, approximately 20 times the expected human exposure, the gestation length was reduced, embryofoetal losses and peri- and postnatal pup mortality were increased, and pup body weights were reduced.
There are no adequate and well-controlled studies in pregnant women. Lumigan eye drops should not be used during pregnancy unless clearly necessary.
 Bimatoprost was excreted in rat milk following PO administration. Increased pup mortality and depressed pup growth occurred when dams were treated PO with bimatoprost from gestation day 7 to lactation day 20 at ≥ 0.3 mg/kg/day, corresponding to exposures approximately 20 times the expected human exposure (based on blood AUC calculated from total blood concentration).
There are no data on the excretion of bimatoprost into human milk or on the safety of bimatoprost exposure in infants. Because many drugs are excreted in human milk, nursing women who use Lumigan eye drops should stop breast feeding.

4.7 Effects on Ability to Drive and Use Machines

Based on the pharmacodynamic profile, bimatoprost is not expected to affect the ability to drive and use machines. As with any ocular medication, if transient blurred vision occurs at instillation, the patient should wait until vision clears before driving or using machinery.

4.8 Adverse Effects (Undesirable Effects)

In clinical studies, over 1,700 patients have been treated with Lumigan eye drops.
In the two pivotal monotherapy trials (715 patients) the most frequently reported treatment-related adverse events were: conjunctival hyperemia in up to 42%, growth of eyelashes in up to 36% and ocular pruritus in up to 14% of patients. The incidence of conjunctival hyperemia at baseline was 25.1% and 17.8% in patients allocated to treatment with Lumigan eye drops once daily and timolol twice daily, respectively. At 6 months, the incidence of patients with a greater than mild increase in conjunctival hyperemia was 6.2% and 0.4% in patients treated with Lumigan eye drops once daily and timolol twice daily, respectively. Less than 7% of patients discontinued due to any adverse event.
The following undesirable effects definitely, probably or possibly related to treatment were reported during clinical trials with Lumigan eye drops. Most were ocular, mild to moderate, and none was serious:

Eye disorders.

Very common (> 10%): conjunctival hyperemia, growth of eyelashes, ocular pruritus.
Common (< 10%): allergic conjunctivitis, asthenopia, blepharitis, blepheral pigmentation, conjunctival oedema, corneal erosion, eye discharge, eyelash darkening, eyelid erythema, eyelid pruritus, eye pain, foreign body sensation, increased iris pigmentation, lacrimation increased, ocular burning, ocular dryness, ocular irritation, photophobia, pigmentation of periocular skin, superficial punctate keratitis, tearing, visual disturbance/blurred vision and worsening of visual acuity.
Uncommon (< 1%): blepharospasm, eyelid oedema, eyelid retraction, iritis, retinal hemorrhage.

Nervous system disorders.

Common (< 10%): headache.
Uncommon (< 1%): depression, vertigo.

Musculoskeletal and connective tissue disorders.

Common (< 10%): asthenia.

Respiratory, thoracic and mediastinal disorders.

Uncommon (< 1%): infection (primarily colds and upper respiratory tract infections).

Skin and subcutaneous tissue disorders.

Common (< 10%): skin hyperpigmentation.
Uncommon (< 1%): hirsutism.

Post-marketing experiences.

In addition to what has been observed in clinical trials, the following adverse reactions have been identified during post-marketing use of Lumigan eye drops. Because post-marketing reporting is voluntary and from a population of uncertain size, it is not possible to reliably estimate the frequency of these reactions:

Eye disorders.

Prostaglandin analogue periorbitopathy; erythema (periorbital), eyelid oedema, macular oedema, ocular discomfort.

Skin and subcutaneous tissue disorders.

Hair growth abnormal, skin discolouration.

Gastrointestinal disorders.

Nausea.

Nervous system disorders.

Dizziness.

Immune system disorders.

Hypersensitivity reaction including signs and symptoms of eye allergy and allergic dermatitis.

Vascular disorders.

Hypertension.

Respiratory, thoracic and mediastinal disorders.

Asthma, exacerbation of asthma, dyspnoea.

Description of selected adverse reactions.

Prostaglandin analogue periorbitopathy (PAP).

Prostaglandin analogues including Lumigan 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, and may cause impaired field of vision even in the absence of patient recognition. PAP is also associated with periocular skin hyperpigmentation or discoloration 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 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 appear to be affected by the treatment. At 12 months, the incidence of iris hyperpigmentation with bimatoprost 0.1 mg/mL eye drops, solution was 0.5%. At 12 months, the incidence with bimatoprost 0.3 mg/mL eye drops, solution was 1.5% and did not increase following 3 years treatment.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.9 Overdose

If overdose occurs, treatment should be symptomatic and supportive.

Ophthalmic overdose.

No case of overdose has been reported, and is unlikely to occur after ocular administration.

Systemic overdose resulting from accidental ingestion.

If Lumigan eye drops is accidentally ingested, the following information may be useful: in two week oral rat and mouse studies, doses up to 250 mg/kg/day did not produce any toxicity. This dose expressed as mg/kg is 1,100 times higher than the accidental dose of one bottle (7.5 mL) of Lumigan eye drops in a 10 kg child.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

Pharmacotherapeutic group: anti-glaucoma preparation; prostaglandin analogues; ATC code: S01EE03.

5.1 Pharmacodynamic Properties

Mechanism of action.

Bimatoprost is a novel synthetic prostamide analogue with potent ocular hypotensive activity. It selectively mimics the effects of a newly discovered naturally occurring substance, prostamide. Prostamide is biosynthesised from anandamide by a pathway involving COX-2 but not COX-1, suggesting a new pathway that leads to the synthesis of endogenous lipid amides that lower intraocular pressure (IOP). Bimatoprost and prostamides differ from prostaglandins (PGs) in that prostamides are biosynthesized from a different precursor, anandamide; bimatoprost does not stimulate any previously described prostanoid receptor, it is not mitogenic, it does not contract the human uterus, and it is electrochemically neutral.
Bimatoprost reduces intraocular pressure in man 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.
Clinical studies have shown mean intraocular pressure decreases of up to 9 mmHg.

Clinical trials.

Elevated IOP presents a major risk factor in the pathogenesis of glaucomatous visual field loss. The higher the level of intraocular pressure, the greater the likelihood of optic nerve damage and glaucomatous visual field loss. Bimatoprost has the action of lowering intraocular pressure with no clinically relevant effects on heart rate and blood pressure observed in clinical trials.

Monotherapy.

The efficacy of Lumigan eye drops was demonstrated in two multi-centre studies compared with timolol 0.5% after 6 months treatment in subjects with chronic glaucoma or ocular hypertension (see Table 1). In each, both once daily and twice daily bimatoprost was compared to twice daily timolol 0.5%. A total of 1,198 patients were enrolled in the two studies with 474 receiving bimatoprost once daily, 483 receiving bimatoprost twice daily and 241 receiving timolol.
Lumigan eye drops, administered once daily as monotherapy, have consistently shown clinically and statistically superior IOP reduction vs timolol 0.5% twice daily over a six month period. Mean IOP changes from baseline for Lumigan eye drops once daily ranged from 6.88 to 7.88 mmHg in study 1 and 7.14 to 8.69 mmHg in study 2. These were superior to the decreases seen in the timolol group (4.17 to 6.27 mmHg and 4.96 to 6.63 mmHg respectively). Twice daily dosing did not show any increased efficacy compared to once daily dosing.
In addition to mean change from baseline, a frequency analysis of the IOP recorded at hour 0 at each visit was performed. In the two studies 46% and 52.5% of patients achieved an IOP of 17 mmHg or less (a commonly agreed 'target IOP') with bimatoprost once daily over the time period studied, compared to 25.4% and 29% in the timolol group. These results corroborate the statistical and clinical superiority of the once daily regimen over timolol seen at all visits.

Adjunctive therapy.

The ability of Lumigan eye drops to lower IOP when used as adjunctive therapy to topical beta-blocker monotherapy has been evaluated in two large scale multi-centre, randomised 3 month studies, involving 722 patients of which 489 received bimatoprost (see Table 2). The numbers and proportions of the different topical beta-blocking agents used in the studies were representative of clinical practice.
Overall, at month 3 in study 1, the mean decreases from baseline IOP at hours 0, 2 and 8 in patients treated with Lumigan eye drops once daily/beta-blocker ranged from 6.03 to 7.95 mmHg. These were non-inferior to the decreases seen in the latanoprost/beta-blocker group (5.89 to 7.35 mmHg) at all time points.
Overall at month 3 in study 2, the mean decreases from baseline IOP at hours 0, 2 and 8 in patients treated with Lumigan eye drops once daily/beta-blocker ranged from 6.39 to 7.38 mmHg. These were superior to the decreases seen in the vehicle/beta-blocker group (2.62 to 3.59 mmHg) at all time points. Lumigan eye drops once daily/beta-blocker showed superiority to vehicle/beta-blocker at all time points at all visits.

5.2 Pharmacokinetic Properties

Absorption.

Bimatoprost penetrates the human cornea and sclera in vitro.
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 nanogram/mL) within 1.5 hours after dosing. Mean bimatoprost Cmax values were similar on days 7 and 14 at 0.0721 and 0.0822 nanogram/mL respectively. The mean AUC0-24 hr values were also similar on days 7 and 14 at 0.0742 and 0.096 nanogram.hour/mL respectively, indicating that a steady systemic exposure to bimatoprost was reached during the first week of ocular dosing. The systemic exposure of bimatoprost is very low with no accumulation over time.

Distribution.

Bimatoprost is moderately distributed into body tissue with a steady state systemic volume of distribution in humans of 0.67 L/kg. In human blood, bimatoprost resides mainly in the plasma. The plasma protein binding of bimatoprost is approximately 90%.
Data from in vitro studies showed that the overall extent of melanin binding was not dependent on concentration and the binding was reversible.

Metabolism.

Bimatoprost is the major circulating species in the blood once it reaches the systemic circulation following ocular dosing in humans. Bimatoprost then undergoes oxidation, N-deethylation and glucuronidation to form a diverse variety of metabolites.

Excretion.

Bimatoprost is eliminated primarily by renal excretion. Up to 67% of an intravenous dose of radiolabeled bimatoprost 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 of unchanged bimatoprost was 1.5 L/hr/kg.
After twice daily dosing, the mean AUC0-24 hr value of 0.0634 nanogram.hr/mL for bimatoprost in the elderly (subjects 65 years or older) was statistically significantly higher than that of 0.0218 nanogram.hr/mL in young healthy adults, suggesting the existence of an age effect. However, this finding is not clinically relevant as systemic exposure for 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.

5.3 Preclinical Safety Data

Ocular administration of bimatoprost in monkeys at concentrations of 0.03% or 0.1% once or twice daily for 1 year caused 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. No associated increase in melanocyte number was observed with the pigmentation. It appears that the mechanism of increased iris pigmentation is due to increased stimulation of melanin production in melanocytes and not to an increase in melanocyte number.
Periocular effects were also observed in an intravenous toxicity study at systemic exposures at least 235-fold higher than that observed in humans after ocular administration. No functional or microscopic changes related to the periocular effects were observed. The mechanism of action for the observed periocular changes is unknown.

Genotoxicity.

Bimatoprost was not mutagenic or clastogenic in a bacterial mutation assay, in a mouse lymphoma test in vitro or in a mouse micronucleus test.

Carcinogenicity.

Long-term studies in mice and rats revealed no evidence of carcinogenicity following oral (by gavage) administration of bimatoprost at doses up to 2 and 1 mg/kg/day, respectively. These doses resulted in systemic bimatoprost levels 85 - 95 times the maximum anticipated human exposure (based on blood AUC). In the rat carcinogenicity study, a dose related increase in vacuolated corpora lutea was observed. The clinical relevance of this ovarian effect is unclear.

6 Pharmaceutical Particulars

6.1 List of Excipients

Preservative.

Benzalkonium chloride 0.05 mg/mL.

Inactives.

Dibasic sodium phosphate heptahydrate; citric acid monohydrate; sodium chloride; and purified water. Hydrochloric acid and/or sodium hydroxide may be added to adjust pH.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Lumigan bimatoprost 300 microgram/mL eye drops sterile solution is supplied in plastic dropper bottles with a plastic screw cap. Each bottle has a fill volume of 3 mL, 5 mL or 7.5 mL.
AUST R 80657.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Chemical name.

(Z)-7-[(1R,2R,3R,5S)-3,5- dihydroxy-2-[(1E,3S)-3- hydroxy-5-phenyl-1-pentenyl] cyclopentyl]-N-ethyl-5-heptenamide.

Molecular weight.

415.58.

Empirical formula.

C25H37NO4.

CAS number.

155206-00-1.

Description.

Bimatoprost is a white to off-white powder and is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water.

7 Medicine Schedule (Poisons Standard)

S4: Prescription Only Medicine.

Summary Table of Changes