Consumer medicine information

Bimprozt Eye Drops

Bimatoprost

BRAND INFORMATION

Brand name

Bimprozt

Active ingredient

Bimatoprost

Schedule

S4

 

Consumer medicine information (CMI) leaflet

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

What is in this leaflet

This leaflet answers some common questions about Bimprozt. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Bimprozt against the benefits it is expected to have for you.

If you have any concerns about using this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Bimprozt is used for

Bimprozt is 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.

Bimprozt lowers the pressure in the eye by helping the flow of fluid out of the eye chamber.

Bimprozt can be used alone or together with other medicines to lower raised pressure within your eyes.

Although Bimprozt helps control your glaucoma it does not cure it. So you must keep using it until your doctor tells you to stop.

Your doctor may have prescribed Bimprozt for another reason.

Ask your doctor if you have any questions about why Bimprozt has been prescribed for you.

Bimprozt is only available with a doctor’s prescription from pharmacies.

Bimprozt is not addictive.

Before you use Bimprozt

When you must not use it

Do not use Bimprozt if you have an allergy to bimatoprost or any of the ingredients listed at the end of this leaflet.

Symptoms of an allergic reaction may include:

  • asthma, wheezing or shortness of breath
  • swelling of the face, lips or tongue which may cause difficulty in swallowing or breathing
  • hives, itching or skin rash
  • fainting.

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

Do not use Bimprozt if the:

  • seal around the cap is broken
  • bottle/packaging shows signs of tampering
  • product does not look quite right
  • expiry date on the bottle has passed. If you use this medicine after the expiry date has passed, it may not work effectively.

It is not known if Bimprozt is safe or effective for children and adolescents under 18 years of age.

These drops are for application to the eye(s) only.

If you are not sure whether you should start using Bimprozt, talk to your doctor.

Before you start to take it

Tell your doctor if you have:

  • an allergy to any other medicines or any other substances, such as foods, preservatives or dyes
  • any breathing problems
  • liver or kidney problems
  • low blood pressure or heart rate
  • a disease causing swelling of the back of the eye
  • an inflammatory eye condition.

Tell your doctor if you are pregnant or intend to become pregnant Like most medicines, Bimprozt should not be used during pregnancy, unless clearly necessary.

Tell your doctor if you are breast-feeding or intend to breast-feed. It is not known if bimatoprost passes into human milk. Your doctor will discuss the risks involved with using Bimprozt when breastfeeding.

If you have not told your doctor about any of the above, tell him or her before you use Bimprozt.

Before you start using Bimprozt, your doctor should tell you that some changes to your eyes may occur which may be permanent.

During treatment, Bimprozt 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 using Bimprozt.

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

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

Taking other medicines

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

It is not expected that Bimprozt will interact with other medicines, however you should always ask your optical practitioner, doctor or pharmacist if you have any concerns about using Bimprozt as well as other medications.

There is a potential for the eye pressure effect to be reduced if using other glaucoma eye drops of the same type as Bimprozt.

How to use Bimprozt

How much to use

Your doctor will tell you how many drops you need to use each day.

Use Bimprozt only as prescribed by your doctor.

The usual dose for adults is one drop in the affected eye(s) once daily, administered in the evening.

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

Use Bimprozt every day, at about the same times 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.

If you are using more than one eye drop product, wait 5 minutes before using the second product.

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 it

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

If you are wearing soft contact lenses, remove them before putting the drops in your eye(s).

To open a new bottle of Bimprozt, 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.

Instructions:

  1. Wash your hands well with soap and water.
  2. Twist off the protective overcap from the bottle.
  3. Place the cap upside down on a flat surface. Do not touch the inside of the cap. This will help keep the inside of the cap clean and keep germs out of the eye drops.
  4. Hold the bottle upside down in one hand between your thumb and index finger.
  5. Using your other hand, gently pull down the lower eyelid of your affected eye to form a pouch.
  6. Tilt your head back and look up.
  7. Put the tip of the bottle close to your lower eyelid. Do not let it touch your eye.
  8. Squeeze the bottle gently so that only one drop goes into the pouch formed between your eye and eyelid, then release the lower eyelid.
  9. Close your eye and keep it closed. Do not blink or rub your eye.
  10. While your eye is still 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.
  11. Repeat steps 4 to 10 with the other eye if instructed to do so by your doctor.
  12. Replace the cap on the bottle, sealing it tightly. Do not overtighten the cap as you may damage the bottle and cap.
  13. Wash your hands again with soap and water to remove any residue.

Wait at least 15 minutes before replacing your contact lenses.

Be careful not to touch the dropper tip against your eye, eyelid or anything else to avoid contaminating the eye drops. Contaminated eye drops may give you an eye infection.

How long to use it

Continue using Bimprozt every day for as long as your doctor prescribes.

Bimprozt helps control your condition but does not cure it.

If you forget to use it

If it is almost time for your next dose, skip the dose you missed and use your next dose when you are meant to. Otherwise, use the drops as soon as you remember, and then go back to using them as you would normally.

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

Do not use double the amount to make up for the dose that you missed.

If you have trouble remembering to use your eye drops, ask your pharmacist for some hints.

If you use too much (overdose)

If you accidentally put several drops in your eye, immediately rinse your eye with warm water.

If you think that you or anyone else may have swallowed Bimprozt, or used too many drops, immediately telephone your doctor or the Australian Poisons Information Centre (telephone 131 126) for advice, or go to the Accident and Emergency Department at your nearest hospital. Do this even if there are no signs of discomfort or poisoning.

While you are using Bimprozt

Things you must do

Have your eye pressure checked when your eye specialist says, to make sure Bimprozt is working for you.

If you develop an eye infection, receive an eye injury, or have eye surgery tell your doctor. Your doctor may tell you to use a new bottle of Bimprozt because of possible contamination of the old one, or may advise you to stop your treatment with Bimprozt.

If you become pregnant while using Bimprozt tell your doctor immediately.

If you wear soft contact lenses remove them before using Bimprozt. Leave your lenses out for at least 15 minutes after putting in the eye drops.

Tell your doctor if your condition gets worse or does not get better while using Bimprozt.

If you are about to be started on any new medicine tell your doctor and pharmacist that you are using Bimprozt.

Things you must not do

Do not give Bimprozt to anyone else, even if they have the same condition as you.

Do not stop using Bimprozt without first talking to your doctor. If you stop using your eye drops, your eye pressures may rise again and damage to your eye may occur.

Things to be careful of

Be careful driving or operating machinery until you know how Bimprozt affects you. Bimprozt generally does not cause any problems with your ability to drive a car or operate machinery. However, it may cause blurred vision in some people. Make sure you know how you react to Bimprozt and that your vision is clear before driving a car or operating machinery.

Side Effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while using Bimprozt.

Bimprozt helps most people with high eye pressure and glaucoma, but it may have unwanted side effects in a few people. All medicines can have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Ask your optical practitioner, doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following and they worry you:

  • red, congested eyes
  • growth of eyelashes
  • itching or irritation of eye/s

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.

Less often the following effects have been seen:

  • other eye-related effects such as discharge from the eye, eye discomfort, eye itchiness, redness in or around the eye, increased tears and inflamed areas around eye/s, small lesions or erosions on the eye surface, allergic effects on eye and surrounding eyelid, deepened eyelids, pain in the eye, feeling of something in the eye, burning of eye and nearby eyelid, dryness, irritation, sensitivity to light, an increase in colouring or pigment of area around eye, blurred vision, visual changes, eyelash darkening, darkening of the coloured part of the eye, swelling of the back of the eye.

Rarely:

  • Other eye related problems can occur such as spasm of the eye where there is uncontrolled blinking and squeezing of eyelid, swelling of eyelid, inflammation of the coloured part of eye, bleeding in eye chamber, deepened eyelid sulcus (sockets sunken), eyelid retraction.

There can also be effects on the body as a whole such as headache, weakness, and very rarely dizziness, hypersensitivity, depression, infection, nausea, high blood pressure, skin pigmentation, asthma, exacerbation of asthma, shortness of breath and abnormal hair growth.

Tell your doctor if you notice any other effects. Other side effects not listed above may also occur in some patients.

Do not be alarmed by this list of possible side effects. You may not experience any of them.

After using Bimprozt

Storage

Keep your eye drops in a safe place where the temperature stays below 25°C.

Do not store Bimprozt or any other medicine in the bathroom or near a sink. Do not leave it in the car or on window sills. Do not carry the eye drops in pockets of your clothes. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and a-half metres above the ground is a good place to store medicines.

Put the top back on the bottle right away after use to avoid contaminating the eye drops.

Disposal

Write the date on the bottle when you open the eye drops and throw out any remaining solution after four weeks. Open a new bottle every four weeks. Eye drops contain a preservative which helps prevent germs growing in the solution for the first four weeks after opening the bottle. After this time there is a greater risk that the drops may become contaminated and cause an eye infection.

If your doctor tells you to stop using the eye drops or they have passed their expiry date, ask your pharmacist what to do with any remaining solution.

Product description

What it looks like

Bimprozt comes in plastic bottles, each containing 3 mL of clear colourless, sterile eye drop solution.

Ingredients

Active ingredient:
Bimatoprost 300 microgram/ml

Preservative:
Benzalkonium chloride

Inactive ingredients:

  • dibasic sodium phosphate heptahydrate
  • sodium chloride
  • citric acid monohydrate
  • sodium hydroxide and/or hydrochloric acid may be added to adjust pH
  • water for injections.

Name and Address of the Sponsor

Arrotex Pharmaceuticals Pty Ltd
15 – 17 Chapel Street
Cremorne VIC 3121
www.arrotex.com.au

Date of Preparation

November 2022

AUST R 288809

Published by MIMS January 2023

BRAND INFORMATION

Brand name

Bimprozt

Active ingredient

Bimatoprost

Schedule

S4

 

1 Name of Medicine

Bimatoprost.

2 Qualitative and Quantitative Composition

Each mL of Bimprozt solution contains bimatoprost 300 micrograms as the active ingredient.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye drops, solution.
Bimprozt is a clear, colourless, isotonic, sterile ophthalmic solution with an osmolality of approximately 290 mOsmol/kg.

4 Clinical Particulars

4.1 Therapeutic Indications

Bimprozt 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 Bimprozt in the affected eye(s) once daily, administered in the evening.

Adjunctive therapy.

The recommended dose is one drop of Bimprozt 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 Bimprozt eye drops.
In order to minimise systemic absorption of Bimprozt 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

Bimprozt 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.

Bimatoprost 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 eye drops. Bimatoprost should be used with caution in patients predisposed to low heart rate or low blood pressure.
Bimatoprost 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 bimatoprost solution comes repeatedly in contact with the skin surface. Thus, it is important to apply Bimprozt as instructed and to avoid it running onto the cheek or other skin areas.
In bimatoprost 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 bimatoprost with other prostaglandin analogues should be monitored for changes to their intraocular pressure.
Bimatoprost 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. Bimatoprost 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).
Bimatoprost 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.

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

Use in renal impairment.

Bimatoprost 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.

Effects on laboratory tests.

No data available.

Information for patients.

Bimprozt 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 Bimprozt and wait at least 15 minutes following administration before reinserting the contact lenses. Bimprozt 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.

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 bimatoprost.
In clinical studies, bimatoprost was used concomitantly with a number of different ophthalmic beta-blocking agents without evidence of drug interactions.
Concomitant use of bimatoprost 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 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 embryo/foetal 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. Bimprozt 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 Bimprozt 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. However, adverse effects of this medicine include visual disturbance, blurred vision and worsening of visual acuity which could affect the ability to drive or use machines (see Section 4.8 Adverse Effects (Undesirable Effects)). As with any ocular medication, if transient blurred vision occurs at instillation, the patient should wait until the vision clears before driving or using machinery.

4.8 Adverse Effects (Undesirable Effects)

In clinical studies, over 1,700 patients have been treated with bimatoprost.
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 bimatoprost 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 bimatoprost 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 bimatoprost. 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, blepharal 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 postmarketing use of bimatoprost. Because postmarketing 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, dyspnea.

Description of selected adverse reactions.

Prostaglandin analogue periorbitopathy (PAP).

Prostaglandin analogues including bimatoprost 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 bimatoprost, 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 http://www.tga.gov.au/reporting-problems.

4.9 Overdose

If overdosage 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 Bimprozt 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 7.5 mL bottle of bimatoprost eye drops in a 10 kg child.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (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 bimatoprost 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. In each, both once daily and twice daily bimatoprost was compared to twice daily timolol 0.5%. A total of 1198 patients were enrolled in the two studies with 474 receiving bimatoprost once daily, 483 receiving bimatoprost twice daily and 241 receiving timolol. See Table 1.
Bimatoprost 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 bimatoprost 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 bimatoprost 0.03% 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. The numbers and proportions of the different topical beta-blocking agents used in the studies were representative of clinical practice. See Table 2.
Overall, at month 3 in study 1, the mean decreases from baseline IOP at hours 0, 2 and 8 in patients treated with bimatoprost 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 bimatoprost 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. Bimatoprost 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 AUC0-24hr values were also similar on days 7 and 14 at 0.0742 and 0.096 nanogram.hr/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 tissues 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 AUC0-24hr 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

Preclinical findings.

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

Benzalkonium chloride (0.05 mg/mL, as preservative), dibasic sodium phosphate heptahydrate, citric acid monohydrate, sodium chloride, water for injections, hydrochloric acid and/or sodium hydroxide (for pH adjustment).

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.
Discard contents 4 weeks after opening the bottle.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Bimprozt eye drops are supplied in clear polypropylene (PP) bottles with low density polyethylene (LDPE) droppers and white high density polyethylene (HDPE) screw caps.
Pack size: 1 x 3 mL.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

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

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.

7 Medicine Schedule (Poisons Standard)

S4, prescription only medicine.

Summary Table of Changes