Consumer medicine information

Travatan

Travoprost

BRAND INFORMATION

Brand name

Travatan Eye Drops

Active ingredient

Travoprost

Schedule

What is in this leaflet

Read this leaflet carefully before you start to use Travatan Eye Drops.

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

The information in this leaflet was last updated on the date listed on the final page. More recent information on the medicine may be available.

You should ensure that you speak to your pharmacist or doctor to obtain the most up to date information on the medicine.

You can also download the most up to date leaflet in Australia from www.novartis.com.au or www.medsafe.govt.nz in New Zealand. The updates may contain important information about the medicine and its use of which you should be aware.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Travatan against the expected benefits it will have for you.

The information in this leaflet applies to Travatan Eye Drops only. This information does not apply to similar products, even if they contain the same ingredients.

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

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

What TRAVATAN is used for

Travatan Eye Drops contain the active ingredient travoprost, which belongs to a class of medicines known as "prostaglandins".

Travatan Eye Drops are used, either alone or in combination with other eye drops/medicines, to lower raised pressure in the eye and to treat glaucoma.

Glaucoma is usually caused by a build-up of the fluid which flows through the eye, leading to an increase in the pressure within the eye; some people with glaucoma may, however, have normal pressure within the eye.

Travatan Eye Drops lower the pressure within the eye by increasing the outflow of fluid from the eye.

Although Travatan Eye Drops help to control your glaucoma, it does not cure it.

Before prescribing Travatan Eye Drops for you, your doctor will have examined your eye(s) and decided that Travatan Eye Drops is the right medicine.

Your doctor may have prescribed Travatan Eye Drops for another reason. Ask your doctor if you have any questions about why Travatan Eye Drops have been prescribed for you.

Travatan Eye Drops are not addictive.

For more information about glaucoma contact Glaucoma Australia on 1800 500 880 or Glaucoma New Zealand on 09 373 8779.

Use in children

This medicine is not recommended in children.

The safety and effectiveness of Travatan Eye Drops has not been established in children.

Before you use TRAVATAN

When you must not use it

Do not use Travatan Eye Drops if you have an allergy to:

travoprost or any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

shortness of breath
wheezing or difficulty breathing
swelling of the face, lips, tongue or other parts of the body
rash, itching or hives on the skin.

Do not use Travatan Eye Drops if you are pregnant or intend to become pregnant.

Do not use this medicine if:

the foil overwrap pouch appears damaged in any way (it is possible that the foil overwrap pouch may have been removed by your pharmacist)
the bottle/packaging shows signs of tampering
the expiry date on the bottle/carton has passed. If you use this medicine after the expiry date has passed, it may not work as well.

If it has expired or is damaged, return it to your pharmacist for disposal.

Do not use Travatan Eye Drops while you are wearing contact lenses. You can put your contact lenses into your eyes 15 minutes after you have used Travatan Eye Drops.

If you are not sure whether you should start using Travatan Eye Drops talk to your doctor.

Before you start to use it

Tell your doctor if you have any allergies to any other medicines, preservatives or dyes.

Tell your doctor if you are breastfeeding or intend to breastfeed. Your doctor will discuss the possible risks and benefits of using Travatan Eye Drops when breastfeeding.

Tell your doctor if you suffer from dry eyes, inflammation of the eye or any diseases of the cornea.

If you have not told your doctor about any of the above, tell him/ her before you use Travatan Eye Drops.

Using other medicines

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

Some medicines and Travatan Eye Drops may interfere with each other.

Tell your doctor if you are currently taking or using any other medicines to treat glaucoma or if you are using any other type of eye drops. These medicines may be affected by Travatan Eye Drops or may affect how well it works. You may need different amounts of your medicine, or you may need to use other different medicines.

Your doctor or pharmacist will be able to tell you what to do when using Travatan Eye Drops with other medicines.

How to use TRAVATAN

Carefully follow all directions given to you by your doctor and pharmacist. They may differ from the information contained in this leaflet.

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

If you do not understand the instructions on the carton, ask your doctor or pharmacist for help.

How much to use

The usual dose of Travatan Eye Drops is one drop in the affected eye(s) once each day. The dosing instructions will be printed on the label your pharmacist puts on the bottle or carton.

How to use it

It is important to use Travatan Eye Drops exactly as your doctor or pharmacist has told you. If you use it less often than you should, it may not work as well and the eye problem may not improve. Using it more often than you should may not improve the eye problem any faster and may cause increased side effects.

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

Follow these steps to use Travatan Eye Drops:

Wash your hands thoroughly with soap and water.
Immediately before using a bottle for the first time, tear off the overwrap pouch and take the bottle out (see Diagram 1).

Shake the bottle.
Remove the cap from the bottle.
Hold the bottle upside down in one hand between your thumb and first finger (see Diagram 2).

While tilting your head back, gently pull down the lower eyelid of your eye to form a pouch / pocket.
Place the tip of the bottle close to your eye. Do not let it touch your eye.
Release one drop into the pouch/pocket formed between your eye and eyelid by gently squeezing the sides of the bottle (see Diagram 3).

Close your eye. Do not blink or rub your eye.
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. This will also reduce the unpleasant taste sensation that some people experience when using these drops.
If necessary, repeat the above steps for the other eye.
Your eyelids can only hold less than one drop at a time, so it is normal for a small amount of the eye drop to spill onto your cheek. You should wipe away any spillage with a tissue.
Replace the cap on the bottle, closing it tightly.
Wash your hands again with soap and water to remove any residue.

You may feel a slight burning sensation in the eye shortly after using the eye drops. If this persists, or is very uncomfortable, contact your doctor or pharmacist.

Be careful not to touch the dropper tip against your eye, eyelid or anything else. This will help prevent the drops becoming dirty or contaminated.

If you have trouble knowing whether you have placed your drops correctly, you may want to store them in the fridge. Some people find it easier to feel the drops in the eye if they are cold.

After using Travatan Eye Drops, wait at least 5 minutes before putting any other eye drops in your eye(s).

Wait 15 minutes before replacing your contact lenses.

When to use it

Use Travatan 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(s) each day will have the best effect on your eye pressure. It will also help you remember when to use the eye drops.

Travatan Eye Drops work most effectively if used during the evening, before going to bed.

How long to use it

Your doctor or pharmacist will tell you how long to use Travatan Eye Drops.

Travatan Eye Drops help control your condition but do not cure it. Therefore, Travatan Eye Drops must be used every day. Continue using Travatan Eye Drops for as long as your doctor prescribes.

Do not use Travatan Eye Drops longer than your doctor tells you. If you use Travatan Eye Drops longer than your doctor or pharmacist tells you, the chance of side effects may increase.

If you are unsure about when or how to stop using Travatan Eye Drops, you should talk to your doctor or pharmacist.

If you forget to use it

If you forget to use Travatan Eye Drops, you should put the drops that you missed in the eye(s) as soon as you remember and then go back to using them as recommended by your doctor. If it is almost time for the next dose, skip the dose that you missed and continue using them as recommended.

Do not use double the amount to make up for the dose that you missed. Using multiple doses may cause unwanted side effects.

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

If you have trouble remembering to use the medicine, ask your pharmacist for some hints.

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 Travatan Eye Drops, immediately telephone your doctor, or the Poisons Information Centre in Australia on 13 1126 or the National Poisons Centre in New Zealand on 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 TRAVATAN

Things you must do

Tell all doctors and pharmacists who are treating you that you are using Travatan Eye Drops.

Tell your doctor if, for any reason, you have not used Travatan Eye Drops exactly as prescribed. Otherwise your doctor may think that it was not effective and change the treatment unnecessarily.

You should have your eye pressure checked when your eye specialist says, to make sure that Travatan Eye Drops are working.

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

If you become pregnant while using Travatan Eye Drops, tell your doctor immediately.

If you are about to be started on any new medicine, tell your doctor and pharmacist that you are using Travatan Eye Drops.

Things you must not do

Do not:

let children handle Travatan Eye Drops
stop using Travatan Eye Drops without first asking your doctor
give this medicine to anyone else, even if they appear to have the same condition as you
use Travatan Eye Drops to treat other complaints unless your doctor or pharmacist tells you to.

Things to be careful of

Be careful driving or operating machinery until you know how Travatan Eye Drops affect you and your vision. As with any eye medicines, temporary blurred vision or other visual disturbances may affect the ability to drive or use machinery in some people. If blurred vision occurs when you use your drops, wait until your vision is clear before driving or operating machinery.

Side effects

Tell your doctor as soon as possible if you do not feel well while you are using Travatan Eye Drops.

This medicine helps most people to lower raised blood pressure in the eye or to treat glaucoma, but may have unwanted side effects in some people. All medicines can have side effects. Sometimes they are serious, however most of the time they are not. You may need to seek medical treatment if you get some of the side effects.

Do not be alarmed by the following list of possible side effects. You may not experience any of them. Ask your doctor or pharmacist to answer any questions you may have.

Tell your doctor if you notice any of the following effects in the eye(s) and the eye area, and they worry you:

redness of the eye
inflammation inside the eye
eye pain or swelling
eye strain
eye irritation
eye discharge
sunken eyes
sensitivity to light
blurred, reduced or abnormal vision
dry or itchy eye
discomfort in or around the eye
increased tear production
abnormal or decreased eye sensation
eyelid abnormality, irritation, itching, redness, pain, swelling or crusting
eczema eyelids
discolouration of the eyelashes
increased or decreased growth or number of eyelashes
changes in the colour of the iris.

Travatan Eye Drops may gradually change the colour of the eye (s); this is due to an increase in pigment within the iris (coloured portion of the eye). This change in eye colour is most frequently seen in eyes with mixed colours (e.g. blue-brown, grey-brown), however, it may also occur with single coloured eyes. This change in eye colour may be permanent.

These are the most common side effects of your medicine. They are usually mild and short-lived.

Additional side effects that are noticed more rarely in the eye include:

inflammation or infection of the conjunctiva
inflammation of the back of the eye
corneal disorder
eye allergy
tired eyes
eye herpes simplex
ingrowth or introversion of the eyelashes
cataract.

Occasionally, some people notice unwanted effects in the rest of the body as a result of using Travatan Eye Drops. These effects may include:

discolouration of the skin around the eye(s)
shortness of breath, asthma or worsening of asthma
increased or decreased blood pressure
irregular, increased or decreased heart rate
chest pain
viral infection
generalized weakness
cough, throat pain or irritation, dry or stuffy nose, nasal discomfort, voice changes
increased allergic symptoms
abdominal pain, gastrointestinal discomfort, ulcer, constipation, diarrhoea, vomiting, nausea
skin inflammation, redness, itching, discolouration
increased body hair
hair colour changes
shoulder pain
bad taste
dry mouth
headache, dizziness, ringing in ears
depression, anxiety
increased prostate antigen
body weakness
muscular or joint pain
painful or inability to control passing of urine.

Stop using Travatan Eye Drops and tell your doctor immediately or go to Accident and Emergency at your nearest hospital if any of the following happen:

skin rash
swelling of the face, hands or feet
wheezing, difficulty in breathing
shortness of breath (dyspnoea, heart failure)
severe and sudden onset of pinkish, itchy swellings on the skin, also called hives or nettle rash.

These hypersensitivity reactions can be very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Other side effects not listed above may also occur in some patients. Let your doctor know if you observe any unwanted effects while using Travatan Eye Drops, even if they do not appear in the list above.

After using TRAVATAN

Storage

Travatan Eye Drops are preserved with polyquaternium-1 which helps to prevent germs growing in the eye drops.

Store Travatan Eye Drops in a cool dry place where the temperature stays below 30°C.

It is not necessary to store Travatan Eye Drops in the refrigerator, but it is acceptable if you prefer to instil cold drops.

Do not freeze.

Do not leave Travatan Eye Drops in the car, in the bathroom or in other warm, damp places. Heat and temperature can destroy some medicines.

Do not leave the top off the bottle for any length of time, to avoid contaminating the eye drops.

Keep Travatan Eye Drops, and all other medicine in a safe place.

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.

Disposal

Discard each bottle of Travatan Eye Drops 4 weeks after it has been opened. Write the date when it was opened on the bottle label to remind you when to discard the bottle.

Eye drops contain a preservative which helps prevent germs growing in the solution for the first four weeks after opening the bottle. After this time, there is a greater risk that the drops may become contaminated and cause an eye infection. A new bottle should then be used.

If your doctor tells you to stop using Travatan Eye Drops or it has passed the expiry date, ask your pharmacist what to do with any that is left over.

Product description

What it looks like

Travatan Eye Drops is a colourless to pale yellow liquid that comes in a 2.5 mL bottle.

Ingredients

The active ingredient in Travatan Eye drops is travoprost 40 mcg in 1 mL.

Travatan Eye Drops are preserved with polyquaternium-1.

Travatan Eye Drops preserved with polyquaternium-1 also contain:

polyoxylene hydrogenated castor oil
boric acid
mannitol
sodium chloride
propylene glycol
purified water
sodium hydroxide and/or hydrochloric acid (to adjust pH).

Supplier

Travatan Eye Drops is supplied in Australia by:

Novartis Pharmaceuticals Australia Pty Limited
ABN 18 004 244 160
54 Waterloo Road
Macquarie Park NSW 2113
Telephone No. 1800 671 203
www.novartis.com.au

Travatan Eye Drops is supplied in New Zealand by:

Novartis New Zealand Limited
PO Box 99102
Newmarket
Auckland 1149
New Zealand
Free Phone: 0800 354 335.

Australian Registration Number

AUST R: 173354

Date of Preparation

This leaflet was prepared in November 2023.

® Registered Trademark

Internal document code

(tra071123c) based on PI (tra071123i)

Published by MIMS December 2023

BRAND INFORMATION

Brand name

Travatan Eye Drops

Active ingredient

Travoprost

Schedule

1 Name of Medicine

Travoprost.

2 Qualitative and Quantitative Composition

Travatan 0.004% eye drops contain 40 microgram/mL travoprost.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Eye drops, solution.
Travatan Eye Drops is a clear, colourless, sterile and preserved solution.

4 Clinical Particulars

4.1 Therapeutic Indications

Travatan Eye Drops are indicated to decrease elevated intraocular pressure in: ocular hypertension; open angle glaucoma.
Travatan Eye Drops may be used: as first line monotherapy; as adjunctive therapy.

4.2 Dose and Method of Administration

Instil one drop of Travatan Eye Drops in the conjunctival sac of the affected eye(s) each day. Optimal effect is obtained if the dose is administered in the evening.
If more than one topical ophthalmic medicinal product is being used, the medicines must be administered at least 5 minutes apart.
When substituting another ophthalmic antiglaucoma agent with Travatan Eye Drops, discontinue the other agent and start the following day with Travatan Eye Drops.

Instructions for patients.

In accordance with good clinical practice for the administration of eye drops, patients should be instructed to gently occlude the nasolacrimal ducts for two minutes after instillation.
Discard container 4 weeks after opening.

4.3 Contraindications

Travatan Eye Drops are contraindicated in patients with a known hypersensitivity to travoprost or any of the excipients in the product (see Section 6.1 List of Excipients).
Travatan Eye Drops are also contraindicated in pregnant women or women attempting to become pregnant (see Section 4.6 Fertility, Pregnancy and Lactation).

4.4 Special Warnings and Precautions for Use

Not for injection or oral ingestion.
Travatan Eye Drops have not been studied in patients with narrow-angle glaucoma.

Eye colour changes.

Travatan Eye Drops may gradually change the eye colour by increasing the number of melanosomes (pigment granules) in melanocytes. Before treatment is instituted patients must be informed of the possibility of these changes. Unilateral treatment can result in permanent heterochromia. The long-term effects on the melanocytes and any consequences thereof are currently unknown. The change in iris colour occurs slowly and may not be noticeable for months to years. It may be permanent. The change in eye colour has predominantly been seen in patients with mixed coloured irides, i.e. blue-brown, grey-brown, yellow-brown and green-brown; however, it has also been observed in patients with brown eyes. Typically, the brown pigmentation around the pupil spreads concentrically towards the periphery in affected eyes, but the entire iris or parts of it may become more brownish. After discontinuation of therapy, no further increase in brown iris pigment has been observed.

Periorbital and eyelid changes.

Periorbital and/or eyelid skin darkening has been reported in association with the use of Travatan Eye Drops.
Periorbital and lid changes including deepening of the eyelid sulcus have been observed with prostaglandin analogues.
Travatan Eye Drops may gradually change eyelashes in the treated eye(s); these changes include: increased length, thickness, pigmentation, and/or number of lashes.

Aphakic patients.

Macular oedema has been reported during treatment with prostaglandin F_2α analogues. Use travoprost with caution in aphakic patients, pseudophakic patients with torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for macular oedema.

Iritis and uveitis.

There is no experience of Travatan Eye Drops in inflammatory ocular conditions, inflammatory, neovascular, angle-closure or congenital glaucoma and only limited experience in open-angle glaucoma of pseudophakic patients and in pigmentary glaucoma.
Travatan Eye Drops should be used with caution in patients with active intraocular inflammation, as well as patients with predisposing risk factors for uveitis.

Contact lenses.

If patients continue to wear soft (hydrophilic) contact lenses while under treatment with Travatan Eye Drops they should remove their lens(es) prior to instilling Travatan Eye Drops in the affected eye(s) and should not insert their lens(es) until 15 minutes after instillation of the eye drops.

Instructions for patients.

In accordance with good clinical practice for the administration of eye drops, patients should be instructed to gently occlude the nasolacrimal ducts for two minutes after instillation.

Use in hepatic impairment.

Travatan Eye Drops have been studied in patients with mild to severe hepatic impairment. No dosage alteration is necessary in these patients.

Use in renal impairment.

Travatan Eye Drops have been studied in patients with mild to severe renal impairment (creatinine clearance as low as 14 mL/min). No dosage alteration is necessary in these patients.

Use in the elderly.

No dosage alteration in elderly patients is necessary.

Paediatric use.

The safety and effectiveness of Travatan Eye Drops in paediatric patients have not been established.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

The plasma protein binding of the active free acid form of travoprost is moderate (approximately 80%) and, therefore, drug-drug interactions involving protein binding are unlikely.
In clinical studies, travoprost 0.004% eye drops were used concomitantly with timolol or brimonidine eye drops without evidence of additional adverse interactions. Concomitant therapy with miotics or adrenergic agonists has not been evaluated.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

There are no human data on the effects of Travatan Eye Drops on male or female fertility. Travoprost had no effects on mating behaviour or fertility in male and female rats at SC doses up to 10 microgram/kg (equivalent to 54 times human exposure at the MRCD), although embryofetal resorption was increased at 10 microgram/kg (further information on effects on pregnancy is included under Use in pregnancy).
(Category B3)
Studies in animals with travoprost have shown reproductive toxicity. Travoprost and/or its metabolites crossed the placenta in rats. Travoprost was teratogenic in rats at IV doses of 10 microgram/kg/day, equivalent to 98 times the expected human exposure at the proposed dose; it increased the incidence of hydrocephaly and bone abnormalities (e.g. vertebral malformations). Travoprost was not teratogenic in rats at IV doses of up to 3 microgram/kg/day (29 times the expected human exposure) or in mice at SC doses of up to 0.3 microgram/kg/day (1.2 times the human exposure). When administered during organogenesis (gestation days 6 to 17), travoprost produced increases in postimplantation loss and early delivery in mice at SC doses of 1 microgram/kg/day (4 times the human exposure) and in rats at IV doses of 10 microgram/kg/day. Increased postimplantation loss also occurred in rats at SC doses of 10 microgram/kg/day (54 times the expected human exposure) administered from 2 weeks prior to mating to gestation day 7.
Travoprost Eye Drops, 0.003% administered to rabbits during organogenesis, appeared to increase incidence of foetal loss.
In rats administered travoprost from gestation day 7 to lactation day 21 by SC injection, abortions occurred at 0.72 microgram/kg/day (4 times the expected human exposure), and decreased gestation length and increased stillbirths (also see Use in lactation) occurred at ≥ 0.12 microgram/kg/day (0.65 times the expected clinical exposure).
No adequate and well-controlled studies have been performed in pregnant women. Travoprost may interfere with the maintenance of pregnancy. It should not be used by women during pregnancy or by women attempting to become pregnant.
An animal study showed that travoprost and/or its metabolites were excreted in rat milk. Increased pup mortality and depressed pup growth and development occurred in rats subcutaneously administered travoprost to dams from gestation day 7 to lactation day 21 at ≥ 0.12 microgram/kg/day, corresponding to exposures 0.65 times the expected human exposure. There are no data on the excretion of travoprost into human milk or on the safety of travoprost exposure in infants. Because many drugs are excreted in human milk, nursing women who use Travatan Eye Drops should stop breast-feeding.

4.7 Effects on Ability to Drive and Use Machines

As with other ophthalmic medications, patients should be advised to exercise caution if they experience transient blurred vision following instillation of eye drops; patients should wait until their vision clears before driving or using machinery (see Section 4.8 Adverse Effects (Undesirable Effects)).

4.8 Adverse Effects (Undesirable Effects)

In clinical studies involving over 4600 patients, Travatan Eye Drops preserved with polyquaternium-1 was administered once daily as monotherapy or adjunctive therapy to timolol 0.5%. No serious ophthalmic or systemic undesirable effects related to Travatan Eye Drops were reported in any of the clinical studies. The most frequently reported treatment related undesirable effect with Travatan Eye Drops monotherapy was hyperaemia of the eye (21.8%), which included ocular, conjunctival, or scleral hyperaemia. Hyperaemia was mild in 83.8% of those patients who experienced it. Almost all patients (98%) who experienced hyperaemia did not discontinue therapy as a result of this event. In phase III clinical studies ranging from 6 to 12 months in duration, hyperaemia decreased over time.
The following undesirable effects were assessed to be treatment related with Travatan Eye Drops monotherapy and are classified according to the following convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), or very rare (< 1/10,000) (see Table 1). Within each frequency grouping, undesirable effects are presented in decreasing order of seriousness.

Class effects.

As with other prostaglandin analogues, Travatan Eye Drops may gradually change eyelashes in the treated eye(s); these changes were observed in about half of patients in clinical trials and include: increased length, thickness, pigmentation, and/or number of lashes. However, fewer than 1% reported these as adverse events. The mechanism of eyelash changes and their long-term consequences are currently unknown.

Long-term clinical study.

In a postapproval long-term clinical study of 5 years duration involving 502 patients, travoprost 0.004% eye drops preserved with BAK were administered once daily. No serious ophthalmic or systemic undesirable effects related to travoprost 0.004% eye drops were reported in the clinical study. The most frequently reported treatment related undesirable effect with travoprost 0.004% eye drops was iris hyperpigmentation (29.5%). Consequently, classification of this effect has been updated from common to very common. The upward change in frequency category does not represent a safety concern but rather presents a more accurate representation of the expected frequency of this effect associated with long-term exposure to a prostaglandin analogue.
Hyperaemia of the eye assessed as related to the use of travoprost 0.004% eye drops was reported at an incidence of 10.0% with 2% of patients reporting hyperaemia of the eye discontinuing study participation due to the undesirable effect.
In addition, several new adverse reactions have been identified from this long-term clinical study that have not been reported previously in clinical trials with travoprost 0.004% eye drops as monotherapy. All of these effects have been classified as uncommon (≥ 1/1,000 to < 1/100) and are listed in Table 2.

Postmarketing experience.

The following adverse reactions have been reported during postmarketing clinical studies in 4081 patients with Travatan Eye Drops and are classified according to the subsequent convention: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), rare (≥ 1/10,000 to < 1/1,000) and very rare (< 1/10,000) (see Table 3). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.

Additional adverse reactions identified from postmarketing surveillance include the following (see Table 4). Frequencies cannot be estimated from the available data. Within each system organ class adverse reactions are presented in order of decreasing seriousness.

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

A single dose intravenous study in rats was conducted to elucidate maximal acute hazard. The dose employed was 250,000 times the proposed daily clinical exposure and over 5,000 times the possible exposure from the entire contents of one product container. No treatment related pharmacotoxic signs were present in the animals receiving travoprost.
If overdosage with Travatan Eye Drops occurs, treatment should be symptomatic.
A topical overdose of Travatan Eye Drops may be flushed from the eyes with warm tap water.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Travoprost is an ester prodrug of a prostaglandin F_2α analogue. It is hydrolysed to the free acid, which acts with nanomolar potency as a selective, full agonist of the prostaglandin FP receptor, and reduces the intraocular pressure (IOP) by increasing the outflow of aqueous humour via trabecular meshwork and uveoscleral pathways.
Reduction of the IOP in man starts about 2 hours after administration and maximum effect is reached after 12 hours. Significant lowering of IOP can be maintained for periods exceeding 24 hours with a single dose.
The benzalkonium chloride (BAK) free Travatan Eye Drops showed a similar IOP lowering effect to the original travoprost 0.004% eye drops preserved with BAK in a clinical study in 340 patients with a 12 week treatment period.

Secondary pharmacology.

Travoprost slightly, but significantly, increased optic nerve head blood flow in rabbits following 7 days of topical ocular administration (1.2 microgram, once daily).

Clinical trials.

Clinical studies with the BAK free formulation of Travatan Eye Drops.

Pharmacokinetics.

A single pharmacokinetic study was conducted to compare the systemic pharmacokinetics of the active metabolite travoprost free acid (AL-5848) following topical ocular administration of the BAK free (polyquaternium-1 preserved) formulation of Travatan Eye Drops and the initially registered travoprost 0.004% eye drops preserved with BAK.
The systemic pharmacokinetics of AL-5848 were assessed after single and multiple dose topical ocular administration. AL-5848 plasma concentrations were below the limit of quantitation (LOQ = 0.0100 nanogram/mL) in 93.8% of all samples analysed after administration of Travatan Eye Drops, and in 97.5% of all samples analysed after administration of travoprost 0.004% eye drops. With such a large proportion of samples below the limit of detection, pharmacokinetic parameters were not calculated.
Low plasma concentrations of AL-5848 were consistent with the concentrations seen in studies supporting the initial registration of travoprost 0.004% eye drops.

Efficacy studies.

One randomised, double masked, parallel group, multicentre study was conducted to compare the efficacy of BAK free Travatan Eye Drops and travoprost 0.004% eye drops preserved with BAK. Patients (n = 371) with open angle glaucoma or ocular hypertension were treated with Travatan Eye Drops or travoprost 0.004% eye drops once daily in the evening. It was found that both products provide equal IOP control over a 24 hour period.
Statistically significant mean reductions from baseline in IOP were observed for both Travatan Eye Drops and travoprost 0.004% eye drops at all time points (p < 0.001). Mean IOP reductions from baseline ranged from 7.6 to 8.7 mmHg for Travatan Eye Drops and from 7.7 to 9.2 mmHg for travoprost 0.004% eye drops, corresponding to IOP reductions of 31% to 33%, and 30% to 34%, respectively. The IOP reductions seen with travoprost 0.004% eye drops in this study are consistent with its performance in other reported studies.
Travatan Eye Drops and travoprost 0.004% eye drops provide comparable IOP control, defined as IOP < 18 mmHg at any time point. The percentage of patients across study time points with IOP < 18 mmHg ranged from 42% to 64% in the Travatan Eye Drops group and from 44% to 62% in the travoprost 0.004% eye drops group.
This study also demonstrated that Travatan Eye Drops provides IOP reduction beyond 24 hours postdose, as shown previously for travoprost 0.004% eye drops. The IOP lowering efficacy of Travatan Eye Drops was shown to be as good as that of travoprost 0.004% eye drops up to 60 hours postdose.
The safety and efficacy of Travatan Eye Drops is further supported by the clinical studies reported with travoprost 0.004% eye drops.
Clinical studies with travoprost 0.004% eye drops preserved with BAK. Three randomised, double masked, active controlled, parallel, multicentre studies were conducted to demonstrate the efficacy of travoprost 0.004% eye drops as monotherapy. Table 5 provides summary information from each of these studies. These studies were designed as "noninferiority" studies, powered to detect a difference of ± 1.5 mmHg in intraocular pressure between treatments.

These studies conclusively demonstrate that monotherapy with travoprost 0.004% eye drops produce clinically relevant and statistically significant reductions in intraocular pressure; these reductions in pressure are maintained over a 12 month dosing period.
Travoprost 0.004% eye drops was noninferior to latanoprost eye drops 0.005% at all visits during the 12 month study. In addition, an earlier onset of intraocular pressure reduction and better intraocular pressure control throughout the day were observed in patients receiving travoprost 0.004% eye drops, compared to latanoprost eye drops 0.005%. However, these were not predefined study endpoints and have only been observed in this single study.
Travoprost 0.004% eye drops were statistically superior to timolol eye drops 0.5% at each IOP measurement time of day, when results were pooled across study visits in the intent to treat analysis for each of the 12 month, 9 month, and 6 month studies but was on most occasions within the predetermined 1.5 mmHg difference in intraocular pressure. Also, travoprost 0.004% eye drops were statistically superior to timolol eye drops 0.5% at all visits in the intent to treat analysis of the 12 month study, at 11 of 15 visits in the intent to treat analysis of the 9 month study, and at 11 of 13 visits in the intent to treat analysis of the 6 month study.
Travoprost 0.004% eye drops have also been studied as adjunctive therapy to timolol and brimonidine. A randomised, double masked, parallel, placebo controlled, multicentre study, involving 427 patients, was conducted in order to demonstrate the additional intraocular lowering effect of travoprost 0.004% eye drops when added to existing timolol eye drops 0.5% bd. Whilst on timolol alone, the patients had a mean IOP of 24-36 mmHg at 8 am and an IOP of 21-36 mmHg at 10 am and 4 pm on 2 days to be assessed as eligible for enrolment. Table 6 provides summary information from this study.

This study conclusively demonstrates that travoprost 0.004% eye drops produce clinically relevant and statistically significant intraocular pressure reductions, compared to placebo, when used adjunctively with timolol eye drops 0.5%.
Additional IOP lowering efficacy has also been demonstrated when travoprost eye drops is combined with brimonidine eye drops. A multicentre, randomised, double blind, placebo controlled, parallel group study compared travoprost 0.0015% eye drops combined with brimonidine 0.2% eye drops versus travoprost 0.0015% eye drops versus placebo. A total of 81 patients were enrolled into the study and the treatment phase was of 42 days duration. Combined treatment of travoprost with brimonidine 0.2% eye drops produced a statistically significant greater decrease to mean IOP at the 10 am time point compared to travoprost eye drops alone. There was a significant fall in IOP compared to placebo for all the travoprost groups.
There is limited experience with the use of travoprost 0.004% eye drops in previously untreated patients. In the three pivotal monotherapy studies, the percentage of randomised patients who reported no current glaucoma therapy was 29%. It is not known how many of those patients had received no prior therapy. All patients enrolled in these studies who were on current ocular hypotensive medications underwent a wash out period from 3 days to 3 weeks.

5.2 Pharmacokinetic Properties

Absorption.

Travoprost is absorbed into the eye following topical ocular administration where it is hydrolysed to the active free acid. Following administration of 1.2 microgram ³H-travoprost in rabbits, the highest concentrations of radioactivity are found in the cornea, conjunctiva, aqueous humour and iris ciliary body. Maximum levels were observed 0.5-2 hours after instillation. Radioactivity concentrations in most ocular tissues declined with half-lives of less than 2 hours (> 10 h in cornea and lens). Systemic exposure is low. Maximum plasma concentrations of 0.08 nanogram equivalent/g were observed at 0.5 hours and declined rapidly thereafter.

Distribution.

Following topical ocular administration of Travatan Eye Drops to healthy volunteers, low systemic exposure to active free acid was demonstrated. Due to the low plasma concentrations and rapid elimination following topical dosing, the elimination half-life of active free acid in man could not be determined.

Metabolism.

The metabolic pathways of the acid parallel those of endogenous PGF_2α and are characterised by reduction of the 13-14 double bond, oxidation of the 15-hydroxyl and β-oxidative cleavage of the carboxylic acid chain.

Excretion.

Travatan Eye Drops has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment. No dosage adjustment is necessary in these patients.

5.3 Preclinical Safety Data

Nonclinical data, obtained through in vitro studies with human conjunctiva epithelial cells and in vivo in rats and rabbits, demonstrate that polyquaternium-1 has significantly lower ocular toxicity than benzalkonium chloride.

Genotoxicity.

Travoprost did not cause gene mutation in bacteria or chromosomal aberrations in bone marrow cells of mice and rats. A slight increase in mutation frequency was observed in one of two mouse lymphoma L5178Y assays.

Carcinogenicity.

Long-term studies in mice and rats at SC doses up to 100 microgram/kg/day did not provide any evidence of carcinogenic potential. These doses correspond to exposure levels over 200 times human exposure at the maximum recommended clinical dose (MRCD), based on plasma active drug levels.

6 Pharmaceutical Particulars

6.1 List of Excipients

Ethoxylated hydrogenated castor oil, boric acid, mannitol, sodium chloride, propylene glycol, sodium hydroxide and/or hydrochloric acid (to adjust pH), polyquaternium-1 (preservative) and purified water.

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 30°C.
Discard container 4 weeks after opening.

6.5 Nature and Contents of Container

Travatan Eye Drops 0.004%: Available in LDPE or PP bottle. Pack sizes: 1 x 2.5 mL and 3 x 2.5 mL.
Not all pack sizes or container types may be marketed.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Travoprost is a clear to slightly opalescent, colourless to yellow oil. Travoprost is practically insoluble in water (approximately 44 ppm).

Chemical structure.

Chemical name: (5Z,13E)-(9S,11R,15R)-9,11,15-Trihydroxy-16-(m-trifluoromethylphenoxy)-17,18,19,20-tetranor-5,13-prostadienoic acid, isopropyl ester.
Empirical formula: C₂₆H₃₅F₃O₆.
Molecular weight: 500.56.

CAS number.

157283-68-6.

7 Medicine Schedule (Poisons Standard)

Prescription Only Medicine (Schedule 4).

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