INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
TRAVATAN® Eye Drops

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

TRAVATAN^® Eye Drops
solution (0,004%)

COMPOSITION
TRAVATAN contains 40 micrograms of travoprost per mL in a sterile ophthalmic solution preserved with 0.015% (m/v) benzalkonium chloride. Excipients: polyoxyethylene hydrogenated castor oil 40 (HCO-40), trometamol, disodium edetate, boric acid (E284), mannitol (E421), sodium hydroxide and/or hydrochloric acid (to adjust pH) and purified water.

PHARMACOLOGICAL CLASSIFICATION
A.15.4 Ophthalmic preparations, other.
ATC code: S01EX

PHARMACOLOGICAL ACTION
Pharmacodynamic properties
Travoprost, a prostaglandin F2alpha analogue, is a selective agonist with affinity for the prostaglandin FP-receptor. The exact mechanism of action by which travoprost reduces IOP has not been fully elucidated. As with other topical prostaglandin analogues, travoprost is believed to increase uveoscleral outflow.
Pharmacokinetic properties
Travoprost is an ester prodrug. It is absorbed through the cornea where the isopropyl ester is hydrolysed to the free acid. Metabolism is the major route of elimination of both travoprost and the active free acid. The systemic metabolic pathways parallel those of endogenous prostaglandin- F2alpha, which are characterised by reduction of the 13-14 double bond, oxidation of the 15-hydroxyl and beta-oxidative cleavages of the upper side chain.
Following topical ocular administration of TRAVATAN to healthy volunteers, low systemic exposure to active free acid was demonstrated. Peak active free acid plasma concentrations of 25 micrograms/mL or less were observed within 30 minutes post-dose. Thereafter, plasma levels declined rapidly. 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.

INDICATIONS
TRAVATAN Eye Drops is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension who are intolerant of or insufficiently responsive to another intraocular pressure lowering medication, as monotherapy or as adjunctive therapy.

CONTRA-INDICATIONS

•	Hypersensitivity to TRAVATAN, benzalkonium chloride or any of the excipients.
•	Pregnant women or women attempting to become pregnant as teratogenicity has been demonstrated in experimental animals.
•	Breast-feeding women.
•	Children, as safety and efficacy has not been proven.

Use in children and adolescents
The efficacy and safety of TRAVATAN Eye Drops in patients below the age of 18 have not been established and its use is not recommended in these patients until further data become available.
Women of childbearing potential
TRAVATAN must not be used in women who may become pregnant unless adequate contraceptive measures are in place.
Nursing women
Animal studies indicate that travoprost and its metabolites may pass into breast milk and TRAVATAN must therefore not be used in breast-feeding women.

WARNINGS
TRAVATAN has been reported to cause changes to pigmented tissues. The most frequently reported changes have been increased pigmentation of the iris and periorbital tissue (eyelid) and increased pigmentation and growth of eyelashes. These changes may be permanent.
TRAVATAN may gradually change eye colour, increasing the amount of brown pigmentation in the iris by increasing the number of melanosomes (pigment granules) in melanocytes. The long-term effect on the melanocytes and the consequences of potential injury to the melanocytes and/or deposition of pigment granules to other areas of the eye are currently unknown. The change in iris colour occurs slowly and may not be noticeable for months to years. Patients should be informed of the possibility of iris colour change.
Eyelid skin darkening has been reported in association with the use of TRAVATAN.
TRAVATAN may gradually change eyelashes in the treated eye; these changes include increased length, thickness, pigmentation and/or number of eyelashes.
Patients who are expected to receive treatment in only one eye should be informed about the potential for increased brown pigmentation of the iris, periorbital and/or eyelid tissue and eyelashes in the treated eye and thus heterochromia between the eyes. They should also be advised of the potential for a disparity between the eyes in length, thickness, and/or number of eyelashes.
PRECAUTIONS
General
There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the epithelial surface (see Information for Patients).
Patients may slowly develop increased brown pigmentation of the iris. This change may not be noticeable for months to years (see Warnings). Iris pigmentation changes may be more noticeable 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. The colour change is believed to be due to increased melanin content in the stromal melanocytes of the iris. The exact mechanism of action is unknown at this time. 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. Until more information about increased brown pigmentation is available, patients should be examined regularly and depending on the situation, treatment may be stopped if increased pigmentation ensues.
TRAVATAN should be used with caution in patients with active intraocular inflammation (iritis/uveitis).
Macular oedema, including cystoid macular oedema, has been reported during treatment with prostaglandin F2alpha analogues. These reports have mainly occurred in aphakic patients, pseudophakic patients with a torn posterior lens capsule, or in patients with known risk factors for macular oedema. TRAVATAN should be used with caution in these patients.
TRAVATAN has not been evaluated for the treatment of angle closure, inflammatory or neovascular glaucoma.
TRAVATAN has not been studied in patients with renal or hepatic impairment and should be used with caution in such patients.
TRAVATAN should not be administered while wearing contact lenses.
Patients should be advised that TRAVATAN contains benzalkonium chloride, which may be adsorbed by contact lenses. Contact lenses should be removed prior to the administration of the solution. Lenses may be reinserted 15 minutes following administration of TRAVATAN.
Information for Patients
Patients should be advised concerning all the information contained in the Warning and Precautions sections.
Patients should also be instructed to avoid allowing the tip of the dispensing container to contact the eye or surrounding structures because this could cause the tip to become contaminated by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions.
Patients also should be advised that if they develop an intercurrent ocular condition (e.g. trauma or infection) or have ocular surgery, they should immediately seek their physician’s advice concerning the continued use of the multi-dose container.
Patients should be advised that if they develop any ocular reactions, particularly conjunctivitis and lid reactions, they should immediately seek their physician’s advice.
Instructions for use and handling
The patient should remove the protective over-wrap immediately prior to initial use.
Since prostaglandins are biologically active materials and since they may be absorbed through the skin, women who are pregnant or attempting to become pregnant should exercise appropriate precautions to avoid direct exposure to the contents of the bottle. In case of accidental contact with the contents of the bottle, thoroughly cleanse the exposed area immediately.

DOSAGE AND DIRECTIONS FOR USE:
The recommended dose is one drop of TRAVATAN in the conjunctival sac of the affected eye(s) once daily 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, discontinue the other agent and start the following day with TRAVATAN.
Method of administration
The patient should remove the protective over-wrap immediately prior to initial use. To prevent contamination of the dropper tip and solution, care must be taken not to touch the eyelids, surrounding areas or other surfaces with the dropper tip of the bottle.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-Effects
The most frequently reported treatment-related side-effect was ocular hyperaemia, which was reported in 35% to 50% of patients. Approximately 3% of patients discontinued treatment due to conjunctival hyperaemia.
The following undesirable effects assessed as definitely, probably or possibly related to treatment were reported during clinical trials with TRAVATAN. Their incidence was either very common (greater than 10.0%), common (1.0% to 10%), or uncommon (0.2% to less than 1.0%). All other effects were single reports, of which none were serious or related.
Ocular effects
Very common: ocular hyperaemia.
Common: ocular pruritus, ocular discomfort (transient burning or stinging upon instillation), ocular pain, iris discolouration, dry eye, foreign body sensation, photophobia, cells, keratitis and flare, tearing, blurred vision, conjunctivitis, eyelash lengthening, ocular irritation, iritis, lid oedema, sticky sensation, conjunctival follicles, abnormal vision, blepharitis, brow-ache and conjunctival papillae, cataracts, lid margin crusting, subconjunctival haemorrhage.
Systemic effects
Body as a whole:
Common: headache.
Cardiovascular:
Uncommon: hypotension and bradycardia.
Skin and appendages:
Uncommon: periorbital tissue and/or eyelid discolouration.
Interaction with other medicinal products and other forms of interaction
Data on adjunctive administration of TRAVATAN with timolol and with brimonidine eye drops confirmed the additive effect of TRAVATAN with these glaucoma medications. No data are available on adjunctive use with other ocular hypotensive medications. Data on concomitant administration with brimonidine are limited.
Interactions of TRAVATAN with other medications have not been specifically evaluated.
Effects on ability to drive and use machines
As with any eye drop, temporary blurred vision or other visual disturbances may affect the ability to drive or use machines. If blurred vision occurs at instillation, the patient must wait until the vision clears before driving or using machinery.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
If overdosage with TRAVATAN occurs, treatment should be symptomatic.

IDENTIFICATION
Clear, colourless to pale yellow solution.

PRESENTATION
2.5 mL oval bottle with dispensing plug and screw cap, all polypropylene.

STORAGE INSTRUCTIONS
Store below 25°C.
DO NOT USE MORE THAN 30 DAYS AFTER OPENING.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER
36/15.4/0333

NAME AND BUSINESS ADDRESS OF THE APPLICANT
Alcon Laboratories (SA) (Pty) Ltd
261, Surrey Avenue
Randburg, 2194

DATE OF PUBLICATION OF THIS PACKAGE INSERT
27 November 2002

Rev.11/02

New to this site: March 2003
        Source: Pharmaceutical Industry
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