New Zealand - English - Medsafe (Medicines Safety Authority)
CONSUMER MEDICINE INFORMATION
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
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
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:
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
If you are using more than one eye drop product, wait 5 minutes before using the second
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
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
If you are about to start any new medicine tell your doctor and pharmacist that you are using
Things you must not do
Do not give BIMATOPROST ACTAVIS to anyone else, even if they have the same condition
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
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
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
darkening of skin around eye.
Less often the following effects have been seen:
discharge from the eye
inflamed areas around the eye/s
swelling of the conjunctiva
discharge from the eye
eyelid itchiness and redness
darkening of the coloured part of the eye
burning of the eye and nearby eyelid
sensitivity to light
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
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.
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.
What BIMATOPROST ACTAVIS looks like
BIMATOPROST ACTAVIS eye drops are a clear, colourless solution in a plastic dropper
bottle with a plastic screw cap.
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.
BIMATOPROST ACTAVIS is distributed in New Zealand by:
Teva Pharma (New Zealand) Limited
PO Box 128 244
Telephone: 0800 800 097
Date of preparation
4 May 2017
NEW ZEALAND DATA SHEET
BIMATOPROST ACTAVIS, Eye drops, solution, 0.1 mg/mL and 0.3 mg/mL
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each mL contains 0.1 mg or 0.3 mg of bimatoprost.
Excipient with known effect:
For the full list of excipients, see section 6.1.
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.
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.
Dose and method of administration
The recommended dose is one drop of BIMATOPROST ACTAVIS
in the affected eye(s) once daily,
administered in the evening.
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
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.
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
eye drops contain the preservative benzalkonium chloride, which may
be absorbed by soft contact lenses. Contact lenses should be removed prior to instillation of
and may be reinserted 15 minutes following administration.
should not be administered while wearing contact lenses.
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.
BIMATOPROST ACTAVIS is contraindicated in patients with hypersensitivity to bimatoprost or to
any component of the medication.
Special warnings and precautions for use
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.
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
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
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
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
prostanglandin analogues should be monitored for changes to their intraocular pressure.
inflammations (e.g. uveitis) because the inflammation may be exacerbated.
bimatoprost 0.03% ophthalmic solution for elevated IOP. BIMATOPROST ACTAVIS
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).
has not been studied in patients with inflammatory ocular conditions,
neovascular, inflammatory, angle-closure glaucoma, congenital glaucoma or narrow-angle glaucoma.
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.
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
or in a mouse micronucleus test.
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
should stop breast feeding.
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.
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
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
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
Deepened lid sulcus (enophthalmos), erythema (periorbital), macular oedema
Skin and subcutaneous tissue disorders:
Hair growth abnormal
Nervous system disorders:
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/
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
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
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.
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.
Mean bimatoprost C
values were similar on days 7 and 14 at 0.0721 and 0.0822 ng/mL
respectively. The mean AUC
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
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.
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 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
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
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.
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
bimatoprost once daily/beta-blocker group; p
0.003 in the bimatoprost twice daily/beta-blocker
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 =
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
microscopic changes related to the periocular effects were observed. The mechanism of action for the
observed periocular changes is unknown.
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.
Shelf life: 2 years.
Discard contents 28 days after first opening the bottle.
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.
Nature and contents of container
Plastic dropper bottles with a plastic screw cap. Each bottle has a fill volume of 3 mL.
Special precautions for disposal
Teva Pharma (New Zealand) Limited
PO Box 128244
Telephone: 0800 800 097
DATE OF FIRST APPROVAL
15 October 2015
DATE OF REVISION OF THE TEXT
12 June 2017
SUMMARY TABLE OF CHANGES
Summary of new information
Update to the SPC-style format