Each ml of solution contains 40 micrograms of travoprost.
Excipients/Inactive Ingredients: Each ml of solution contains polyquaternium-1 (POLYQUAD) 10 microgram (as a preservative), propylene glycol (E1520) 7.5 mg, polyoxyethylene hydrogenated castor oil 40 (HCO-40) 2 mg (see Precautions), Sodium chloride, Boric acid, Sodium hydroxide and/or hydrochloric acid (to adjust pH), Mannitol (E421), Purified water.
Pharmacology: Pharmacotherapeutic group: Ophthalmologicals-antiglaucoma preparations and miotics-prostaglandin analogues. ATC code: S01E E04.
Pharmacodynamics: Mechanism of action: Travoprost, a prostaglandin F2α analogue, is a highly selective full agonist which has a high affinity for the prostaglandin FP receptor, and reduces the intraocular pressure by increasing the outflow of aqueous humour via trabecular meshwork and uveoscleral pathways. Reduction of the intraocular pressure in man starts about 2 hours after administration and maximum effect is reached after 12 hours. Significant lowering of intraocular pressure can be maintained for periods exceeding 24 hours with a single dose.
In a clinical trial, patients with open-angle glaucoma or ocular hypertension who were treated with TRAVATAN eye drops (polyquaternium-1-preserved) dosed once-daily in the evening demonstrated 8 to 9 mmHg reductions (approximately 33%) in intraocular pressure from 24 to 26 mmHg baseline.
Data on adjunctive administration of TRAVATAN eye drops with timolol 0.5% and limited data with brimonidine 0.2% were collected during clinical trials that showed an additive effect of TRAVATAN eye drops with these glaucoma medications. No clinical data available on adjunctive use with other ocular hypotensive medications.
Secondary pharmacology: Travoprost significantly increased optic nerve head blood flow in rabbits following 7 days of topical ocular administration (1.4 micrograms, once-daily).
TRAVATAN eye drops preserved with polyquaternium-1 induced minimal ocular surface toxicity, compared to eye drops preserved with benzalkonium chloride, on cultured human corneal cells and following topical ocular administration in rabbits.
Pharmacokinetics: Absorption: Travoprost is an ester prodrug. It is absorbed through the cornea where the isopropyl ester is hydrolysed to the active free acid. Studies in rabbits have shown peak concentrations of 20 ng/g of the free acid in aqueous humour one to two hours after topical dosing of TRAVATAN eye drops. Aqueous humour concentrations declined with a half-life of approximately 1.5 hours.
Distribution: Following topical ocular administration of TRAVATAN eye drops to healthy volunteers, low systemic exposure to active free acid was demonstrated. Peak active free acid plasma concentration of 25 pg/ml or less were observed between 10 and 30 minutes post-dose. Thereafter, plasma levels declined rapidly to below the 10 pg/ml assay quantitation limit before 1 hour post-administration.
Due to low plasma concentration and rapid elimination following topical dosing, the elimination half-life of active free acid in man could not be determined.
Biotransformation: Metabolism is the major route of elimination of both travoprost and the active free acid. The systemic metabolic pathways parallel those of endogenous prostaglandin F2α which are characterised by reduction of the 13-14 double bond, oxidation of the 15-hydroxyl and β-oxidative cleavages of the upper side chain.
Elimination: Travoprost free acid and its metabolites are mainly excreted by the kidneys. TRAVATAN eye drops have been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment (creatinine clearance as low as 14 ml/min). No dosage adjustment is necessary in these patients.
Toxicology: Preclinical safety data: In ocular toxicity studies in monkeys, administration of travoprost at a dose of 0.45 microgram, twice a day, was shown to induce increased palpebral fissure. Topical ocular administration of travoprost to monkeys at concentrations of up to 0.012% to the right eye, twice daily for one year resulted in no systemic toxicity.
Reproduction toxicity studies have been undertaken in rat, mice and rabbit by systemic route. Findings are related to FP receptor agonist activity in uterus with early embryolethality, post-implantation loss, foetotoxicity. In pregnant rat, systemic administration of travoprost at doses more than 200 times the clinical dose during the period of organogenesis resulted in an increased incidence of malformations. Low levels of radioactivity were measured in amniotic fluid and foetal tissues of pregnant rats administered 3H-travoprost. Reproduction and development studies have demonstrated a potent effect on foetal loss with a high rate observed in rats and mice (180 pg/ml and 30 pg/ml plasma, respectively) at exposures 1.2 to 6 times the clinical exposure (up to 25 pg/ml).
Decrease of intraocular pressure (IOP) in patients with ocular hypertension or open-angle glaucoma (see Pharmacology: Pharmacodynamics under Actions).
Use in adults, including the elderly population: The dose is one drop of TRAVATAN eye drops in the conjunctival sac of the affected eye(s) once daily. Optimal effect is obtained if the dose is administered in the evening.
Nasolacrimal occlusion or gently closing the eyelid after administration is recommended. This may reduce the systemic absorption of medicinal products administered via the ocular route and result in a decrease in systemic adverse reactions.
If more than one topical ophthalmic medicinal product is being used, the medicinal products must be administered at least 5 minutes apart (see Interactions).
If a dose is missed, treatment should be continued with the next dose as planned. The dose should not exceed one drop in the affected eye(s) daily.
When substituting another ophthalmic antiglaucoma agent with TRAVATAN eye drops, the other agent should be discontinued and TRAVATAN eye drops should be started the following day.
Paediatric population: The efficacy and safety of TRAVATAN eye drops in patients below the age of 18 years have not been established and its use is not recommended in these patients until further data become available.
Hepatic and renal impairment: TRAVATAN eye drops has been studied in patients with mild to severe hepatic impairment and in patients with mild to severe renal impairment (creatinine clearance as low as 14 ml/min). No dose adjustment was necessary in these patients.
Method of Administration: For ocular use.
The patient should remove the protective overwrap 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.
No cases of overdose have been reported. A topical overdose is not likely to occur or to be associated with toxicity. A topical overdose of TRAVATAN eye drops may be flushed from the eye(s) with lukewarm water. Treatment of a suspected oral ingestion is symptomatic and supportive.
Hypersensitivity to the active substances or to any of the excipients.
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 a permanent change in eye colour. 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. 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.
In controlled clinical trials, periorbital and/or eyelid skin darkening in association with the use of TRAVATAN eye drops has been reported in 0.4% of patients.
TRAVATAN eye drops may gradually change eyelashes in the treated eye(s); these changes were observed in about half of the patients in clinical trials and include: increased length, thickness, pigmentation, and/or number of lashes. The mechanism of eyelash changes and their long term consequences are currently unknown.
Periorbital and lid changes including deepening of the eyelid sulcus have been observed with prostaglandin analogues.
TRAVATAN eye drops has been shown to cause slight enlargement of the palpebral fissure in studies in the monkey. However, this effect was not observed during the clinical trials and is considered to be species specific.
There is no experience of TRAVATAN eye drops in inflammatory ocular conditions; nor in neovascular, angle-closure, narrow-angle or congenital glaucoma and only limited experience in thyroid eye disease, in open-angle glaucoma of pseudophakic patients and in pigmentary or pseudoexfoliative glaucoma.
Macular oedema has been reported during treatment with prostaglandin F2α analogues. Caution is recommended when using TRAVATAN eye drops in aphakic patients, pseudophakic patients with a torn posterior lens capsule or anterior chamber lenses, or in patients with known risk factors for cystoid macular oedema.
Skin contact with TRAVATAN eye drops must be avoided as transdermal absorption of travoprost has been demonstrated in rabbits.
TRAVATAN eye drops contain propylene glycol which may cause skin irritation.
TRAVATAN eye drops contain polyoxyethylene hydrogenated castor oil 40 which may cause skin reactions.
In patients with active intraocular inflammation, as well as patients known predisposing risk factors for iritis/uveitis, TRAVATAN eye drops should be used with caution.
Prostaglandins and prostaglandin analogues are biologically active materials that 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 the unlikely event of coming in contact with a substantial portion of the contents of the bottle, thoroughly cleanse the exposed area immediately.
Effects on ability to drive and use machines: TRAVATAN eye drops has no or negligible influence on the 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 machines.
Women of childbearing potential/contraception: TRAVATAN eye drops must not be used in women of child bearing age/potential unless adequate contraceptive measures are in place (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Pregnancy: There are no or limited amount of data from the use of TRAVATAN eye drops in pregnant women. Studies in animals with travoprost have shown reproductive toxicity. Travoprost has harmful pharmacological effects on pregnancy and/or foetus/new-born child. TRAVATAN eye drops should not be used during pregnancy unless clearly necessary.
Breastfeeding: It is unknown whether travoprost or its metabolites is excreted in human breast milk. Animal studies have shown excretion of travoprost and metabolites in breast milk. The use of TRAVATAN eye drops by breast-feeding women is not recommended.
Fertility: There are no data on the effects of TRAVATAN eye drops on human fertility. Animal studies showed no effect of travoprost on fertility at doses more than 250 times the maximum recommended human ocular dose.
In 2 clinical trials involved in the development of TRAVATAN eye drops (polyquaternium-1--preserved), 201 patients were exposed for up to 3 months. No serious ophthalmic or systemic undesirable effects related to the product were reported in either of the clinical trials. The most frequently reported treatment-related undesirable effect with TRAVATAN eye drops (polyquaternium-1-preserved) was hyperaemia of the eye (18.9%), which included ocular or conjunctival hyperaemia. One patients (0.5%) discontinued study participation due to hyperaemia of the eye.
The following adverse reactions have been reported during clinical studies with Travoprost 40 µg/ml Eye Drops, Solution 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). Within each frequency- grouping, adverse reactions are presented in order of decreasing seriousness.
Additional adverse reactions identified from post-marketing surveillance include the following. Frequencies cannot be estimated (not known) from the available data. (see table).
Click on icon to see table/diagram/image
No interaction studies have been performed. However, no clinically relevant interactions have been described.
Special precautions for disposal and other handling: No special requirements.
Incompatibilities: None known.
Specific in vitro interaction studies were performed with TRAVATAN eye drops and medicinal products containing thiomersal. No evidence of precipitation was observed.
Do not store above 30°C.
Discard 4 weeks after first opening.
Keep this medicine out of the sight and reach of children.
Shelf life: 1.5 mL: 1 year. 2.5 mL: 2 years.
S01EE04 - travoprost ; Belongs to the class of prostaglandin analogues. Used in the treatment of glaucoma.
Eye drops (clear, colourless soln) 40 mcg/mL x 1.5 mL x 1's, 2.5 mL x 1's.