Bimatoprost Actavis

New Zealand - English - Medsafe (Medicines Safety Authority)

Active ingredient:
Bimatoprost 0.1 mg/mL;  
Available from:
Teva Pharma (New Zealand) Limited
INN (International Name):
Bimatoprost 0.1 mg/mL
Dosage:
0.1 mg/mL
Pharmaceutical form:
Eye drops, solution
Composition:
Active: Bimatoprost 0.1 mg/mL   Excipient: Benzalkonium chloride Citric acid monohydrate Dibasic sodium phosphate heptahydrate Hydrochloric acid Sodium chloride Sodium hydroxide Water for injection
Prescription type:
Prescription
Manufactured by:
Yonsung Fine Chemicals Co. Limited
Therapeutic indications:
Bimatoprost Actavis is indicated as monotherapy for the reduction of elevated intraocular pressure (IOP) in patients with chronic glaucoma or ocular hypertension; or as adjunctive therapy in patients not adequately controlled on other agents.
Product summary:
Package - Contents - Shelf Life: Bottle, plastic, LDPE with LDPE dropper nozzle and HDPE cap - 3 mL - 24 months from date of manufacture stored at or below 25°C 28 days opened stored at or below 25°C
Authorization number:
TT50-9585a
Authorization date:
2014-06-30

Read the complete document

CONSUMER MEDICINE INFORMATION

Bimatoprost Actavis

Bimatoprost Eye Drops, Solution

What is in this leaflet

This leaflet answers some common questions about BIMATOPROST ACTAVIS. 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

BIMATOPROST ACTAVIS 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 BIMATOPROST ACTAVIS is used for

BIMATOPROST ACTAVIS 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.

BIMATOPROST ACTAVIS eye drops lower the pressure in the eye by helping the flow of fluid

out of the eye chamber.

BIMATOPROST ACTAVIS eye drops can be used alone or together with other eye

drops/medicines to lower raised pressure within your eyes. Although BIMATOPROST

ACTAVIS eye drops help control your condition, they will not cure it. BIMATOPROST

ACTAVIS eye drops are only available with a doctor’s prescription from pharmacies. Your

doctor may have prescribed BIMATOPROST ACTAVIS eye drops for another reason. Ask

your doctor if you have any questions about why BIMATOPROST ACTAVIS eye drops have

been prescribed for you.

For more information about glaucoma, contact Glaucoma New Zealand, Department of

Ophthalmology, Private Bag 92019, Auckland, telephone 09 373 8779, email:

info@glaucoma.org.nz

Before you use BIMATOPROST ACTAVIS

When you must not use it

Do not use BIMATOPROST ACTAVIS 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 bottle shows signs of tampering.

the expiry date on the pack has passed. If you use this medicine after the expiry date has

passed, it may not work effectively.

It is not known if BIMATOPROST ACTAVIS 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:

you have had an allergy to any medicines or any other substances, such as foods,

preservatives or dyes

you have breathing problems

you have liver or kidney problems

you have low blood pressure or low heart rate

you have a disease causing swelling of the back of the eye

you have an inflammatory eye condition

you are pregnant or intend to become pregnant.

Like most medicines, BIMATOPROST ACTAVIS eye drops should not be used during

pregnancy, unless clearly necessary.

you are breast-feeding or intend to breast-feed.

Before you start using BIMATOPROST ACTAVIS 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.

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 BIMATOPROST ACTAVIS will interact with other medicines, however

you should always ask your optical practitioner, doctor or pharmacist if you have any

concerns about using BIMATOPROST ACTAVIS eye drops as well as other medications.

How to use BIMATOPROST ACTAVIS

How much to use

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

Use BIMATOPROST ACTAVIS eye drops only as prescribed by your doctor.

The usual dose of BIMATOPROST ACTAVIS 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 BIMATOPROST ACTAVIS 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.

1. Wash your hands well with soap and water.

2. 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.

3. If you wear soft contact lenses, they should be removed before using the eye drops and

wait at least 15 minutes before reinserting.

4. BIMATOPROST ACTAVIS is supplied in a plastic bottle with a plastic screw cap. When

using the bottle for the first time, twist the cap open to break the seal.

5. Tilt your head back and look at the ceiling.

6. Pull the lower eyelid downwards to form a pocket.

7. Hold the bottle upside down above the eye and gently squeeze the bottle to release a drop

into your eye.

8. Close your eye and keep it closed. 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. Do not blink or rub your eye.

9. Repeat for the other eye if necessary.

10. Recap the bottle after every use.

11. Wash your hands again with soap and water to remove any residue.

Store the bottle in a cool place where the temperature stays below 25°C.

Discard any remaining solution 28 days after opening the bottle.

How long to use it

BIMATOPROST ACTAVIS eye drops help control your condition, but do not cure it.

Therefore, BIMATOPROST ACTAVIS eye drops must be used every day.

Continue using BIMATOPROST ACTAVIS 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 BIMATOPROST ACTAVIS eye drops, immediately telephone your doctor or National

Poisons Information Centre (telephone 0800 POISON or 0800 764 766) for advice, or go to

accident and emergency at your nearest hospital. Do this even if there are no signs of

discomfort or poisoning.

While you are using BIMATOPROST ACTAVIS

Things you must do

Have your eye pressure checked when your eye specialist says, to make sure

BIMATOPROST ACTAVIS is working.

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

If you become pregnant while using BIMATOPROST ACTAVIS tell your doctor immediately.

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

BIMATOPROST ACTAVIS.

If you are about to start any new medicine tell your doctor and pharmacist that you are using

BIMATOPROST ACTAVIS.

Things you must not do

Do not give BIMATOPROST ACTAVIS to anyone else, even if they have the same condition

as you.

Do not stop using BIMATOPROST ACTAVIS 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 BIMATOPROST ACTAVIS eye

drops. If this happens you should wait until you can see well again before you drive or use

machinery.

BIMATOPROST ACTAVIS 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 BIMATOPROST ACTAVIS eye drops

affect you.

Adverse Effects

Tell your optical practitioner, doctor or pharmacist as soon as possible if you do not feel well

while you are using BIMATOPROST ACTAVIS.

Check with your doctor as soon as possible if you have any problems while using

BIMATOPROST ACTAVIS, 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 the 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 eyelids, 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,

excessive growth of hair, abnormal hair growth, asthma, exacerbation of asthma, shortness of

breath and high blood pressure.

After using BIMATOPROST ACTAVIS

Storage

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

Do not store it 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.

Do not leave the cap off the bottle for any length of time 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 28 days.

Eye drops contain a preservative which helps prevent germs growing in the solution for the

first 28 days after opening the bottle. After this time there is a greater risk that the drops may

become contaminated and cause an eye infection. A new bottle should be opened.

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 BIMATOPROST ACTAVIS looks like

BIMATOPROST ACTAVIS eye drops are a clear, colourless solution in a plastic dropper

bottle with a plastic screw cap.

Ingredients

BIMATOPROST ACTAVIS contains the active ingredient bimatoprost. Each mL contains

bimatoprost 0.03%w/v equivalent to 300 micrograms per mL.

It also contains sodium chloride, sodium phosphate dibasic heptahydrate, citric acid

monohydrate, water for injection and benzalkonium chloride as a preservative. Small

amounts of sodium hydroxide and/or hydrochloric acid may be added to adjust pH.

Supplier

BIMATOPROST ACTAVIS is distributed in New Zealand by:

Teva Pharma (New Zealand) Limited

PO Box 128 244

Remuera

Auckland 1541

Telephone: 0800 800 097

Date of preparation

4 May 2017

Read the complete document

Version 1.0

NEW ZEALAND DATA SHEET

1.

PRODUCT NAME

BIMATOPROST ACTAVIS, Eye drops, solution, 0.1 mg/mL and 0.3 mg/mL

2.

QUALITATIVE AND QUANTITATIVE COMPOSITION

Each mL contains 0.1 mg or 0.3 mg of bimatoprost.

Excipient with known effect:

benzalkonium chloride

For the full list of excipients, see section 6.1.

3.

PHARMACEUTICAL FORM

Eye drops, solution.

BIMATOPROST ACTAVIS is a clear, colourless ophthalmic solution. Bimatoprost is a white to off-

white powder and is very soluble in ethyl alcohol and methyl alcohol and slightly soluble in water.

4.

CLINICAL PARTICULARS

4.1

Therapeutic indications

BIMATOPROST ACTAVIS

is indicated as monotherapy for the reduction of elevated intraocular

pressure (IOP) in patients with chronic glaucoma or ocular hypertension; or as adjunctive therapy in

patients not adequately controlled on other agents.

4.2

Dose and method of administration

Monotherapy

The recommended dose is one drop of BIMATOPROST ACTAVIS

in the affected eye(s) once daily,

administered in the evening.

Adjunctive Therapy

The recommended dose is one drop of BIMATOPROST ACTAVIS

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 BIMATOPROST ACTAVIS

eye drops.

In order to minimise systemic absorption of BIMATOPROST ACTAVIS

eye drops, patients should

be instructed to apply pressure to the tear duct immediately following administration of the drug.

Paediatric Use

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

Use in Elderly

No dosage adjustment in elderly patients is necessary.

Information for patients

BIMATOPROST ACTAVIS

eye drops contain the preservative benzalkonium chloride, which may

be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of

BIMATOPROST ACTAVIS

and may be reinserted 15 minutes following administration.

BIMATOPROST ACTAVIS

should not be administered while wearing contact lenses.

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The tip of the bottle should not be allowed to contact the eye, surrounding structures, fingers or any

other surface in order to avoid contamination of the solution.

4.3

Contraindications

BIMATOPROST ACTAVIS is contraindicated in patients with hypersensitivity to bimatoprost or to

any component of the medication.

4.4

Special warnings and precautions for use

General

Bimatoprost eye drops have 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 ACTAVIS

should be used

with caution in patients predisposed to low heart rate or low blood pressure.

BIMATOPROST ACTAVIS

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.

BIMATOPROST ACTAVIS

has not been studied in patients with renal or hepatic impairment and

should therefore be used with caution in such patients.

During treatment with bimatoprost eye drops, 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

also

been

reported.

change

iris

pigmentation occurs slowly and may not be noticeable for several months to years. The effect has

been seen in up to 2% of patients treated with bimatoprost eye drops

for up to 6 months. At 12

months, the incidence of iris pigmentation with bimatoprost eye drops

was 1.5% and did not increase

following 3 years of treatment. The long-term effects of increased iris pigmentation are not known.

Before treatment is initiated,patients should be informed of the possibility of eyelash growth,

darkening of the eyelid skin and increased iris pigmentation. 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 bimatoprost

solution comes repeatedly in

contact with the skin surface. Thus, it is important to apply BIMATOPROST ACTAVIS

as instructed

and to avoid it running onto the cheek or other skin areas.

In studies using bimatoprost eye drops 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

IOP-lowering

effect.

Patients

using

BIMATOPROST

ACTAVIS

with

other

prostanglandin analogues should be monitored for changes to their intraocular pressure.

BIMATOPROST

ACTAVIS

should

used

with

caution

patients

with

active

intraocular

inflammations (e.g. uveitis) because the inflammation may be exacerbated.

Macular

oedema,

including

cystoid

macular

oedema,

been

reported

during

treatment

with

bimatoprost 0.03% ophthalmic solution for elevated IOP. BIMATOPROST ACTAVIS

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 ACTAVIS

has not been studied in patients with inflammatory ocular conditions,

neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma.

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4.5

Interaction with other medicines and other forms of interaction

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 ng/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 ACTAVIS.

In clinical studies, bimatoprost eye drops were used concomitantly with a number of different

ophthalmic beta-blocking agents without evidence of drug interactions.

Concomitant use of BIMATOPROST ACTAVIS

and antiglaucoma 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

Carcinogenicity and Mutagenicity

The carcinogenic potential of orally administered (gavage) bimatoprost was evaluated in mice given

0.3, 1.0 or 2.0 mg/kg/day and in rats given 0.1, 0.3 or 1.0 mg/kg/day for 104 weeks.

There was no evidence of tumorigenic potential at any of the administered dosages in either species.

In the rat carcinogenicity study, a dose-related increase in vacuolated corpora lutea was observed. The

ovarian effects in rats is believed to be species specific.

Bimatoprost was not mutagenic or clastogenic in a bacterial mutation assay, in a mouse lymphoma

test

in vitro

or in a mouse micronucleus test.

Fertility

Bimatoprost did not affect fertility in male or female rats at oral doses up to 0.6 mg/kg/day

(approximately 103 times the intended human exposure).

Pregnancy Category B3

In embryo/ foetal development studies in pregnant mice and rats abortion but no developmental

effects were observed at doses that were at least 33 or 97 times higher, respectively, than the intended

human exposure. In peri/postnatal studies in rats, reduced gestation time, foetal death and decreased

pup body weights were observed in dams given

0.3 mg/kg/day (a rodent-specific pharmacological

effect; systemic exposure estimated to be at least 41 times the intended human exposure). This

maternal toxicity likely resulted in decreased mating performance and gestational body weight gain in

the offspring, but neurobehavioural functions were not affected.

There are no adequate and well-controlled studies in pregnant women. BIMATOPROST ACTAVIS

should not be used during pregnancy unless clearly necessary.

Use in Lactation

Bimatoprost was excreted in rat milk following oral administration. Increased pup mortality and

depressed pup growth occurred when dams were treated orally with bimatoprost from gestation day 7

to lactation day 20 at

0.3 mg/kg/day, corresponding to exposures approximately 41 times the

expected human exposure.

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

BIMATOPROST ACTAVIS

should stop breast feeding.

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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

Undesirable effects

In clinical studies, over 1,700 patients have been treated with bimatoprost eye drops.

In the two pivotal monotherapy trials (715 patients), the most frequently reported treatment related

adverse events were: conjunctival hyperaemia in up to 42%, growth of eyelashes in up to 36% and

ocular pruritus in up to 14% of patients. The incidence of conjunctival hyperaemia at baseline was

25.1% and 17.8% in patients allocated to treatment with bimatoprost eye drops

once daily and timolol

twice daily, respectively. At 6 months, the incidence of patients with a greater than mild increase in

conjunctival hyperaemia was 6.2% and 0.4% in patients treated with bimatoprost 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 bimatoprost eye drops. Most were ocular, mild to moderate, and none was

serious:

Eye Disorders:

Very common (>10%): conjunctival hyperaemia, 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 haemorrhage.

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:

Eye disorders:

Deepened lid sulcus (enophthalmos), erythema (periorbital), macular oedema

Skin and subcutaneous tissue disorders:

Hair growth abnormal

Gastrointestinal disorders:

Nausea

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Nervous system disorders:

Dizziness

Vascular disorders:

Hypertension

Respiratory, thoracic and mediastinal disorders:

Asthma, exacerbation of asthma, dyspnea

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows

continued monitoring of the benefit/risk balance of the medicine. Healthcare professionals are asked

to report any suspected adverse reactions https://nzphvc.otago.ac.nz/reporting/

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:

BIMATOPROST

ACTAVIS

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 (7.5mL) of BIMATOPROST ACTAVIS

a 10 kg child.

For advice on management of overdose please contact the National Poisons Centre on 0800 POISON

(0800 764766).

5.

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties

Pharmacotherapeutic group: Prostaglandin analogues, ATC code: S01EE03

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 humor 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.

5.2

Pharmacokinetic properties

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 ng/mL) within 1.5 hours after dosing.

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Mean bimatoprost C

values were similar on days 7 and 14 at 0.0721 and 0.0822 ng/mL

respectively. The mean AUC

0-24hr

values were also similar on days 7 and 14 at 0.0742 and

0.096ng.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.

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.

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.

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 AUC

0-24hr

value of 0.0634 ng.hr/mL for bimatoprost in the elderly

(subjects 65 years or older) was statistically significantly higher than that of 0.0218 ng.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.

Clinical Studies

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 comparative 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.

Pooled efficacy data from the two clinical studies demonstrates that in the intent-to-treat population

bimatoprost 0.03% ophthalmic solution, administered both once and twice daily as a monotherapy

agent is superior to timolol 0.5% twice daily over a six month period at hours 0, 2 and 8 (p

0.05). At

the primary endpoint (hour 0 at month 6) mean decrease from baseline IOP in patients treated with

bimatoprost once daily was –8.28 mmHg and was superior to that in patients treated with timolol (-

6.44 mmHg, p < 0.001). At the primary endpoint (hour 0 at month 6) the mean decrease from baseline

IOP in patients treated with bimatoprost once daily was -8.28 mmHg and was superior to that in

patients treated with bimatoprost twice daily (-7.15 mmHg, p < 0.001). Therefore, twice daily dosing

did not show any increased efficacy compared to once daily dosing. Mean IOP changes from baseline

Version 1.0

for bimatoprost once daily range from 7.01 mmHg to 8.75 mmHg from hours 0 to 8 over the six

month period of evaluation. The similar range for timolol was 4.38 mmHg to 6.44 mmHg.

Overall, bimatoprost once daily produced a reduction in IOP of 33%. Timolol twice daily produced a

reduction of 23%.

In addition to mean change from baseline, a frequency analysis of the IOP recorded at hour 0 at each

visit was performed. Consistently 50% 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

approximately 30% in the timolol group. In addition, those whose IOP was recorded as over 22

mmHg were consistently less than 10% in the bimatoprost group compared to approximately 20% in

the timolol group. These results provide positive clinical interpretation to the statistical superiority of

the once daily regimen over timolol seen at all visits at hours 0, 2 and 8.

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.

For the bimatoprost once daily/ beta-blocker regimen hour 0, mean decreases from baseline were

consistent over the three month period studied. The values ranged from 6.97 to 7.74 mmHg.

In the first study, bimatoprost 0.03% once or twice daily as an adjunct to beta-blocker therapy was

compared with latanoprost 0.005% ophthalmic solution once daily, as an adjunct to betablocker

therapy. At month 3, the mean decreases in IOP from baseline at hours 0, 2 and 8 in patients treated

with bimatoprost once daily/beta-blocker in the intent to treat population 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. At the primary endpoint (hour 0 at month 3) mean decrease from

baseline IOP in patients treated with bimatoprost once daily/beta-blocker was –7.95 mmHg and was

non-inferior to that in patients treated with latanoprost/beta-blocker (-7.35 mmHg). At the primary

endpoint (hour 0 at month 3) mean decrease from baseline IOP in patients treated with bimatoprost

twice daily/betablocker was –7.26 mmHg and was non-inferior to that in patients treated with

latanoprost/beta-blocker (-7.35 mmHg). Mean changes from baseline hour 0 IOP across all follow-up

visits ranged from –7.23 to –7.95 mmHg with bimatoprost once daily/beta-blocker, and from –6.91 to

–7.53 mmHg with latanoprost/beta-blocker. The decrease in IOP from baseline hour 0 was

statistically significant within each treatment group at each follow-up visit (p < 0.001).

In the second study, bimatoprost 0.03% once or twice daily as an adjunct to beta-blocker therapy was

compared with vehicle twice daily, as an adjunct to beta-blocker therapy. At month 3, the mean

decreases in IOP from baseline at hours, 0, 2 and 8 in patients treated with bimatoprost once

daily/beta-blocker in the intent to treat population 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 (p< 0.001). At the primary endpoint (hour 0 at month 3) mean decrease from baseline IOP in

patients treated with bimatoprost once daily/beta-blocker was –7.38 mmHg and was superior to that in

patients treated with vehicle/beta-blocker (-3.59 mmHg, p < 0.001). At the primary endpoint (hour 0

at month 3) mean decrease from baseline IOP in patients treated with bimatoprost twice daily/beta-

blocker was –6.34 mmHg and was superior to that in patients treated with vehicle/beta-blocker (-3.59

mmHg, p < 0.001). Mean decreases from baseline hour 0 IOP across all follow-up visits ranged from

6.53 to 7.38 mmHg with bimatoprost once daily/beta-blocker, and from 2.04 to 3.59 mmHg with

vehicle/beta-blocker. Mean decreases from baseline IOP at hours 0, 2 and 8 were superior to those

seen in the vehicle/beta-blocker group at each time point at each follow-up visit (p < 0.001 in the

Version 1.0

bimatoprost once daily/beta-blocker group; p

0.003 in the bimatoprost twice daily/beta-blocker

group).

In a pooled analysis of both studies, at the primary endpoint (hour 0 at month 3) the mean decrease

from baseline IOP in patients treated with bimatoprost once daily/beta-blocker was –7.74 mmHg and

was superior to that in patients treated with bimatoprost twice daily/betablocker (-6.89 mmHg, p =

0.017).

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

humans

after

ocular

administration.

functional

microscopic changes related to the periocular effects were observed. The mechanism of action for the

observed periocular changes is unknown.

6.

PHARMACEUTICAL PARTICULARS

6.1

List of excipients

Benzalkonium chloride, sodium chloride, sodium phosphate dibasic heptahydrate, citric acid

monohydrate, water for injection. Sodium hydroxide and hydrochloric acid added to adjust pH.

6.2

Incompatibilities

Not applicable.

6.3

Shelf life

Shelf life: 2 years.

Discard contents 28 days after first opening the bottle.

6.4

Special precautions for storage

Store below 25

To avoid contamination of the solution, keep container tightly closed. Do not touch dropper tip to any

surface. Contents are sterile if seal is intact.

6.5

Nature and contents of container

Plastic dropper bottles with a plastic screw cap. Each bottle has a fill volume of 3 mL.

6.6

Special precautions for disposal

None.

7.

MEDICINE SCHEDULE

Prescription Medicine

8.

SPONSOR

Teva Pharma (New Zealand) Limited

PO Box 128244

Remuera

Auckland 1541

Telephone: 0800 800 097

Version 1.0

9.

DATE OF FIRST APPROVAL

15 October 2015

10.

DATE OF REVISION OF THE TEXT

12 June 2017

SUMMARY TABLE OF CHANGES

Section changed

Summary of new information

Update to the SPC-style format

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