Consumer medicine information

Vizo-PF Bimatoprost Eye Drops

Bimatoprost

BRAND INFORMATION

Brand name

Vizo-PF Bimatoprost

Active ingredient

Bimatoprost

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Vizo-PF Bimatoprost Eye Drops.

What is in this leaflet

This leaflet answers some common questions about Vizo-PF Bimatoprost eye drops. 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 Vizo-PF Bimatoprost eye drops against the benefits they expect it will 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 Vizo-PF Bimatoprost eye drops are used for

Vizo-PF Bimatoprost 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.

Vizo-PF Bimatoprost eye drops lower the pressure in the eye by helping the flow of fluid out of the eye chamber.

Vizo-PF Bimatoprost eye drops can be used alone or together with other eye drops/medicines to lower raised pressure within your eyes.

Although Vizo-PF Bimatoprost eye drops help control your condition, they will not cure it. Vizo-PF Bimatoprost eye drops are only available with a doctor’s prescription from pharmacies. Your doctor may have prescribed Vizo-PF Bimatoprost eye drops for another reason. Ask your doctor if you have any questions about why Vizo-PF Bimatoprost eye drops have been prescribed for you.

For more information about glaucoma, contact Glaucoma Australia Inc (telephone 1800 500 880 or Glaucoma New Zealand (on 09 373 8779).

Before you use Vizo-PF Bimatoprost eye drops

When you must not use it

Do not use Vizo-PF Bimatoprost eye drops if:

  • you have an allergy to bimatoprost or any of the ingredients listed at the end of this leaflet.
  • the product does not look quite right such as discoloured.
  • the packaging shows signs of tampering.
  • the 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 Vizo-PF Bimatoprost eye drops are safe and useful for children and adolescents under 18 years and therefore its use is not recommended.

These drops are for topical use only.

Before you start to use it

Tell your doctor if:

  1. You have had an allergy to any medicines or any other substances, such as foods, preservatives or dyes.
  2. You have breathing problems.
  3. You have liver or kidney problems.
  4. You have low blood pressure or low heart rate.
  5. You have a disease causing swelling of the back of the eye.
  6. You have an inflammatory eye condition.
  7. You are pregnant or intend to become pregnant. Like most medicines, Vizo-PF Bimatoprost eye drops should not be used during pregnancy, unless clearly necessary.
  8. You are breast-feeding or intend to breast-feed.

Before you start using Vizo-PF Bimatoprost eye drops your doctor should tell you that some changes to your eyes may occur which may be permanent.

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 noticeable. None of these changes affect vision. If you have any concerns, ask your doctor or pharmacist.

Hair may grow where Vizo-PF Bimatoprost contacts the skin. It is important to use as directed.

Taking other medicines

Tell your doctor 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 Vizo-PF Bimatoprost will interact with other medicines, however you should always ask your optical practitioner, doctor or pharmacist if you have any concerns about using Vizo-PF Bimatoprost eye drops 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 Vizo-PF Bimatoprost.

How to use Vizo-PF Bimatoprost eye drops

How much to use

Your doctor will tell you how many drops you need to use each day. Use Vizo-PF Bimatoprost eye drops only as prescribed by your doctor.

The usual dose of Vizo-PF Bimatoprost eye drops is one drop in the affected eye(s) once daily, given in the evening.

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

Use Vizo-PF Bimatoprost 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.

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.

  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.

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 contaminating the eye drops.

How long to use it

Vizo-PF Bimatoprost eye drops help control your condition, but do not cure it. Therefore, Vizo-PF Bimatoprost eye drops must be used every day. Continue using Vizo-PF Bimatoprost eye drops for as long as your doctor prescribes.

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 use too much (overdose)

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

If you think that you or anyone else may have swallowed any or all of the contents of a bottle of Vizo-PF Bimatoprost eye drops, immediately telephone your doctor or Poisons Information Centre (Australia: telephone 13 11 26; New Zealand: telephone 0800 POISON or 0800 764 766) for advice, or go to casualty at your nearest hospital. Do this even if there are no signs of discomfort or poisoning.

While you are using Vizo-PF Bimatoprost eye drops

Things you must do

Have your eye pressure checked when your eye specialist says, to make sure Vizo-PF Bimatoprost eye drops are working.

If you develop an eye infection, receive an eye injury, or have eye surgery tell your doctor.

If you become pregnant while using Vizo-PF Bimatoprost eye drops tell your doctor immediately.

Tell your doctor if your condition gets worse or does not get better while using Vizo-PF Bimatoprost eye drops.

If you are about to start any new medicine tell your doctor and pharmacist that you are using Vizo-PF Bimatoprost eye drops.

Things you must not do

Do not give Vizo-PF Bimatoprost eye drops to anyone else, even if they have the same condition as you.

Do not stop using Vizo-PF Bimatoprost eye drops without first talking to your doctor. If you stop using your eye drops, your eye pressure may rise again and damage to your eye may occur.

Things to be careful of

Your vision may blur for a short time after you put in your Vizo-PF Bimatoprost eye drops. If this happens you should wait until you can see well again before you drive or use machinery.

Vizo-PF Bimatoprost eye drops are not expected to cause any problems with your ability to drive a car or operate machinery. However, as a general precaution be careful driving or operating machinery until you know how Vizo-PF Bimatoprost eye drops affect you.

Side effects

Tell your optical practitioner, doctor or pharmacist as soon as possible if you do not feel well while you are using Vizo-PF Bimatoprost eye drops.

Check with your doctor as soon as possible if you have any problems while taking Vizo-PF Bimatoprost eye drops, even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

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

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

  • red, congested eyes
  • itching of eye/s
  • small lesions or erosions on the eye surface
  • feeling of something in the eye
  • dryness of the eye
  • growth of eyelashes
  • pain in the eye
  • irritation of the eye
  • inflamed/red eyelid/s
  • darkening of skin around eye.

Less often the following effects have been seen:

discharge from the eye, eye discomfort, inflamed areas around eye/s, swelling of the conjunctiva, discharge from the eye, eyelash darkening, eyelid itchiness and redness, darkening of the coloured part of the eye, burning of the eye and nearby eyelid, sensitivity to light, tears, changes in/disturbance of vision.

Rarely other eye related problems can occur such as spasm of the eye where there is uncontrolled blinking, eyelid retraction, inflammation of the coloured part of eye, bleeding in eye chamber, deepened eyelid (sockets sunken), redness and inflammation on the eye and surrounding eye area, eyelid swelling, swelling of the back of the eye.

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

After using Vizo-PF Bimatoprost eye drops

Storage

Keep your Vizo-PF Bimatoprost eye drops in a cool place where the temperature stays below 25°C.

Keep the medicine where children cannot reach it.

Disposal

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 Vizo-PF Bimatoprost eye drops look like:

Clear, colourless, sterile solution in a white plastic container

Ingredients

Active ingredient: Bimatoprost 300 micrograms/mL

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

Supplier

AFT Pharmaceuticals Ltd
113 Wicks Road
North Ryde
SYDNEY NSW 2113
Email: [email protected]

Vizo-PF Bimatoprost eye drops can be identified by registration number: AUST R 315400.

Date of preparation:

This leaflet was prepared on 17 January 2020.

Published by MIMS March 2021

BRAND INFORMATION

Brand name

Vizo-PF Bimatoprost

Active ingredient

Bimatoprost

Schedule

S4

 

1 Name of Medicine

Bimatoprost.

2 Qualitative and Quantitative Composition

1 mL of Vizo-PF Bimatoprost contains 300 microgram of Bimatoprost.
For the full list of excipients, see Section 6.1.

3 Pharmaceutical Form

Eye drop solution.
Vizo-PF Bimatoprost is a clear, isotonic, colourless, sterile ophthalmic solution and is practically free from visible particles.
The solution has an osmolality of approximately 290 mOsmol/kg.

4 Clinical Particulars

4.1 Therapeutic Indications

Vizo-PF Bimatoprost 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 Vizo-PF Bimatoprost eye drops in the affected eye(s) once daily, administered in the evening.

Adjunctive therapy.

The recommended dose is one drop of Vizo-PF Bimatoprost 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 Vizo-PF Bimatoprost eye drops.
In order to minimise systemic absorption of Vizo-PF Bimatoprost 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.
For individual patient use only.

4.3 Contraindications

Vizo-PF Bimatoprost 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.

Vizo-PF 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 containing preservative eye drops. Vizo-PF Bimatoprost eye drops should be used with caution in patients predisposed to low heart rate or low blood pressure.
Vizo-PF 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. Increased iris pigmentation has also been reported. The change in iris pigmentation occurs slowly and may not be noticeable for several months to years. Neither naevi nor freckles of the iris appear to be affected by treatment. The effect has been seen in up to 2% of patients treated with bimatoprost containing preservative eye drops for up to 6 months. At 12 months, the incidence of iris pigmentation with bimatoprost containing preservative eye drops was 1.5% and did not increase following 3 years treatment. At 3 months, the incidence of iris hyperpigmentation with bimatoprost preservative free eye drops was 0.3%. The long-term effects of increased iris pigmentation are not known.
Some of these changes may be permanent and may lead to differences in appearance between the eyes when only one eye is treated.
Periorbital tissue pigmentation has been reported to be reversible in some patients.
There is the potential for hair growth to occur in areas where Vizo-PF Bimatoprost solution comes repeatedly in contact with the skin surface. Thus, it is important to apply Vizo-PF Bimatoprost eye drops as instructed and to avoid it running onto the cheek or other skin areas.
Vizo-PF Bimatoprost 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 containing preservative eye drops for elevated IOP. Vizo-PF 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).
Vizo-PF Bimatoprost has not been studied in patients with inflammatory ocular conditions, neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma.
In bimatoprost containing preservative 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 Vizo-PF Bimatoprost with other prostaglandin analogs should be monitored for changes to their intraocular pressure.

Use in hepatic impairment.

Vizo-PF Bimatoprost 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.

Vizo-PF Bimatoprost 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 and therefore its use is not recommended.

Information for patients.

Vizo-PF Bimatoprost has not been studied in patients wearing contact lenses.

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 with bimatoprost containing preservative eye drops. 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 containing preservative eye drops was used concomitantly with a number of different ophthalmic beta-blocking agents without evidence of drug interactions.
Concomitant use of Vizo-PF 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)
There are no adequate and well-controlled studies in pregnant women. 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.
Vizo-PF Bimatoprost 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 Vizo-PF Bimatoprost 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 the vision clears before driving or using machinery.

4.8 Adverse Effects (Undesirable Effects)

In a 3-month clinical study, approximately 29% of patients treated with bimatoprost preservative free eye drops experienced adverse reactions. The most frequently reported adverse reactions were conjunctival hyperaemia (mostly trace to mild and of a non-inflammatory nature) occurring in 24% of patients, and eye pruritus occurring in 4% of patients. Approximately 0.7% of patients in the bimatoprost preservative free eye drop group discontinued due to any adverse event in the 3-month study.
A total of 302 and 295 patients were randomised to the bimatoprost preservative free and bimatoprost containing preservative treatment groups, respectively. The following undesirable effects considered related to treatment were reported in ≥ 1% of patients during treatment with bimatoprost preservative free eye drops. Most were ocular, mild and none was serious. (See Table 1.)
The following undesirable effects definitely, probably or possibly related to treatment were reported during clinical trials or reported as post marketing events with bimatoprost containing preservative. Most were ocular, mild to moderate, and none was serious. No new adverse effects were observed in the bimatoprost preservative free clinical study.

Eye disorders.

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

Gastrointestinal disorders.

Unknown: nausea.

General disorders and administration site conditions.

Common: asthenia.

Respiratory, thoracic and mediastinal disorders.

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

Nervous system disorders.

Common: headache.
Uncommon: depression, vertigo.
Unknown: dizziness.

Skin and subcutaneous tissue disorders.

Uncommon: hirsutism.
Unknown: hair growth abnormal.

Vascular disorders.

Unknown: hypertension.

Post marketing experience.

The following adverse reactions have been identified during post marketing use of bimatoprost preservative free. 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.

Eye discharge, ocular discomfort.

Immune system disorders.

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

Respiratory, thoracic and mediastinal disorders.

Asthma, exacerbation of asthma, dyspnea.

Vascular disorders.

Hypertension.

Nervous system disorders.

Dizziness.

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

No information is available on overdosage in humans; overdose is unlikely to occur after ocular administration.
If overdosage occurs, treatment should be symptomatic and supportive. If Vizo-PF Bimatoprost eye drops are accidentally ingested, the following information may be useful; in short-term oral (by gavage) mouse and rat studies, doses up to 100 mg/kg/day did not produce any toxicity. This dose expressed as mg/m2 is at least 8-times higher than the amount of bimatoprost to which a 10 kg child would be exposed if they were to accidently ingest the entire contents of the package (3 mL) of Vizo-PF Bimatoprost eye drops.
For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

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

Mechanism of action.

Bimatoprost is a 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.
The efficacy of bimatoprost preservative free eye drops was demonstrated in a 12 week (double-masked, randomised, parallel group) clinical study comparing bimatoprost preservative free with bimatoprost containing preservative eye drops once daily (evening) for 12 weeks in patients with glaucoma or ocular hypertension. Of the 596 patients treated, 301 received bimatoprost preservative free eye drops and 295 patients received bimatoprost containing preservative eye drops.
Bimatoprost preservative free eye drops was considered to be non-inferior to bimatoprost containing preservative eye drops at each hour evaluated (hours 0, 2 and 8) during the week 12 visit for worse eye IOP change from baseline: upper limit of the 95% CI for between-treatment difference [bimatoprost preservative free minus bimatoprost containing preservative] did not exceed 1.5 mmHg (as well as not exceeding 1.0 mmHg) in the per protocol (PP) population. The upper limit did not exceed 0.75 mmHg at any week 12 timepoint. Non-inferiority was also demonstrated for the intention to treat (ITT) population. Both treatments studied showed statistically and clinically significant mean decreases from baseline in worse eye IOP at all follow-up timepoints (p < 0.001).
Mean worse eye IOP changes from baseline ranged from -7.49 to -5.93 mmHg for bimatoprost preservative free and 7.77 to 6.06 mmHg for bimatoprost containing preservative across weeks 2 to 12 for the PP population. The treatment differences [bimatoprost preservative free minus bimatoprost containing preservative] in IOP change from baseline ranged from 0.02 to 0.37 mmHg across the study (PP population).
Bimatoprost preservative free was equivalent to bimatoprost containing preservative with respect to average eye IOP at each follow-up timepoint at weeks 2, 6 and 12 (the upper limit of the 95% CI was ≤ 1.5 mmHg and the lower limit was ≥ 1.5 mmHg at the timepoint) for the ITT population. Furthermore, the upper limit of the 95% CI for treatment differences in average eye IOPs was ≤ 1.0 mmHg and the lower limit is ≥ -1.0 mmHg at all follow-up timepoints. In fact, at no timepoint was the lower limit of the 95% CI less than -0.50 mmHg, or the upper limit above 0.69 mmHg. The treatment differences in IOP ranged from -0.07 to 0.25 mmHg across the study in the ITT population.
Bimatoprost preservative free was considered equivalent to bimatoprost containing preservative with respect to change from baseline in average eye IOP at each follow-up timepoint in both ITT and PP populations. Both treatments studied showed statistically and clinically significant mean decreases from baseline in average eye IOP at all follow-up timepoints (p < 0.001). Mean changes from baseline in average eye IOP ranged from 7.36 to 5.67 mmHg for bimatoprost preservative free and from 7.50 to 5.70 mmHg for bimatoprost containing preservative across the study as measured on weeks 2, 6 and 12 (hours 0, 2 and 8) in the ITT population.

5.2 Pharmacokinetic Properties

Absorption.

Bimatoprost penetrates the human cornea and sclera in vitro.
After once daily ocular administration of one drop of 300 microgram/mL bimatoprost containing preservative 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 radiolabelled 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

Ocular administration of bimatoprost in monkeys at concentrations of ≥ 0.03% 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

Sodium chloride, disodium hydrogen phosphate heptahydrate, citric acid monohydrate, sodium hydroxide, hydrochloric acid and water for injections.

6.2 Incompatibilities

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

6.3 Shelf Life

36 months.

6.4 Special Precautions for Storage

Store below 25°C. Discard contents 4 weeks after opening the bottle.

6.5 Nature and Contents of Container

Vizo-PF Bimatoprost is supplied in preservative free multidose eye drop device Novelia. The LDPE bottles are 5 mL capacity and are fitted with an HDPE dose delivery nozzle, silicon spring, plug and valve assembly (Novelia Preservative Free System Multidose (PFMD) eyedropper (Nemera La Verpilliere).
The cap and body contain silver which has been shown to maintain sterility in any product remaining on the surface of device.
The bottle does not include an overfill.
Each bottle contains 3 mL eye drop solution.

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: 415.6.
Empirical formula: C25H37NO4.

CAS number.

155206-00-1.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).