4.1. Therapeutic indications

Decrease of elevated intraocular pressure in adult patients with ocular hypertension or open-angle glaucoma (see section 5.1).

Decrease of elevated intraocular pressure in paediatric patients aged 2 months to < 18 years with ocular hypertension or paediatric glaucoma (see section 5.1).

4.2. Posology and method of administration

Posology

Use in adults, including elderly population

The dose is one drop of Travoprost Mylan 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 section 4.5).

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 medicinal product with travoprost eye drops, the other medicinal product should be discontinued and travoprost eye drops should be started the following day.

Hepatic and renal impairment

Travoprost 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 dosage adjustment is necessary in these patients (see section 5.2).

Paediatric population

Travoprost can be used in paediatric patients from 2 months to < 18 years at the same posology as in adults. However, data in the age group 2 months to < 3 years (9 patients) is limited (see section 5.1).

The safety and efficacy of travoprost in children below the age of 2 months have not been established. No data are available.

Method of administration

For ocular use.

For patients who wear contact lenses, please refer to section 4.4.

After cap is removed, if the tamper evident snap collar is loose, remove before using the medicinal product. 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.

1. Immediately before using a bottle for the first time, tear off the overwrap sachet and take out the bottle. Write the date of opening on the carton or bottle label in the space provided

2. Wash your hands

3. Twist off the cap

4. After cap is removed, if tamper evident snap collar is loose, remove before using the product

5. Hold the bottle, pointing down, between your thumb and fingers

6. Tilt your head or your child's head gently back. Pull down your eyelid with a clean finger, until there is a 'pocket' between the eyelid and your eye. The drop will go in here.

7. Bring the bottle tip close to the eye. Use a mirror if it helps.

8. Do not touch your eye or eyelid, surrounding areas or other surfaces with the dropper. It could infect the drops.

9. Gently squeeze the bottle to release one drop of Travoprost Mylan at a time

10. After using Travoprost Mylan, keep the eyelid closed, apply gentle pressure by pressing a finger into the corner of your eye, by the nose for at least 1 minute. This helps to stop Travoprost Mylan getting into the rest of the body

11. If you use drops in both eyes, repeat the steps for your other eye

12. Close the bottle cap firmly immediately after use

13. Only use one bottle at a time.

If a drop misses your eye, try again.

If you or your child are using other eye preparations such as eye drop or eye ointment, wait for at least 5 minutes between putting in Travoprost Mylan and the other eye preparations.

4.3. Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Eye colour change

Travoprost 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 irises, 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 be become more brownish. After discontinuation of therapy, no further increase in brown iris pigment has been observed.

Periorbital and eye lid changes

In controlled clinical trials, periorbital and/or eyelid skin darkening in association with the use of travoprost has been reported in 0.4% of patients. Periorbital and lid changes including deepening of the eyelid sulcus have also been observed with prostaglandin analogues.

Travoprost 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.

Travoprost 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 travoprost 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. Travoprost should therefore be used with caution in patients with active intraocular inflammation.

Aphakic patients

Macular oedema has been reported during treatment with prostaglandin F2α analogues. Caution is recommended when using travoprost 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.

Iritis/uveitis

In patients with known predisposing risk factors for iritis/uveitis, travoprost should be used with caution.

Contact with the skin

Skin contact with travoprost must be avoided as transdermal absorption of travoprost has been demonstrated in rabbits.

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.

Contact lenses

Patients must be instructed to remove contact lenses prior to application of travoprost and wait 15 minutes after instillation of the dose before reinsertion.

Paediatric population

Efficacy and safety data in the age group 2 months to < 3 years (9 patients) is limited (see section 5.1). No data are available for children below the age of 2 months.

In children < 3 years old that mainly suffer from PCG (primary congenital glaucoma), surgery (e.g. trabeculotomy/goniotomy) remains the first line treatment.

No long-term safety data are available in the paediatric population.

Excipients

Travoprost Mylan contains benzalkonium chloride which has been reported to cause eye irritation, symptoms of dry eyes and may affect the tear film and corneal surface. It should be used with caution in dry eye patients and in patients where the cornea may be compromised.

From the limited data available, there is no difference in the adverse event profile in children compared to adults. Generally, however, eyes in children show a stronger reaction for a given stimulus than the adult eye. Irritation may have an effect on treatment adherence in children.

Patients should be monitored in case of prolonged use.

Benzalkonium chloride may be absorbed by soft contact lenses and may change the colour of the contact lenses. Patients should be instructed to remove contact lenses prior to application of Travoprost Mylan and wait 15 minutes after instillation of the dose before reinsertion.

4.5. Interaction with other medicinal products and other forms of interaction

No interaction studies have been performed.

4.6. Fertility, pregnancy and lactation

Women of child-bearing potential/contraception

Travoprost must not be used in women of child bearing age/potential unless adequate contraceptive measures are in place (see section 5.3).

Pregnancy

Travoprost has harmful pharmacological effects on pregnancy and/or the foetus/new-born child. Travoprost should not be used during pregnancy unless clearly necessary.

Breast-feeding

It is unknown whether travoprost from the eye drops is excreted in human breast milk. Animal studies have shown excretion of travoprost and metabolites in breast milk. The use of travoprost by breast-feeding mothers is not recommended.

Fertility

There are no data on the effects of travoprost on human fertility. Animal studies showed no effect of travoprost on fertility at doses more than 250 times the maximum recommended human ocular dose.

4.7. Effects on ability to drive and use machines

Travoprost has no or negligible influence on the ability to drive and use machines, however 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.

4.8. Undesirable effects

Summary of the safety profile

In clinical trials with travoprost, the most common adverse reactions were ocular hyperaemia and iris hyperpigmentation, occurring in approximately 20% and 6% of patients respectively.

Tabulated list of adverse reactions

The following adverse reactions 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 <1/1,000), very rare (<1/10,000), or not known (frequency cannot be estimated from the available data). Within each frequency group, adverse reactions are presented in decreasing order of seriousness. The adverse reactions were obtained from clinical studies and post-marketing data with travoprost.

System Organ Class

Frequency

Adverse Reactions

Immune system disorders

Uncommon

hypersensitivity, seasonal allergy

Psychiatric disorders

Not known

depression, anxiety, insomnia

Nervous system disorders

Uncommon

headache

Rare

dizziness, visual field defect, dysgeusia

Eye disorders

Very common

ocular hyperaemia

Common

iris hyperpigmentation, eye pain, ocular discomfort, dry eye, eye pruritus, eye irritation

Uncommon

corneal erosion, uveitis, iritis, anterior chamber inflammation, keratitis, punctate keratitis, photophobia, eye discharge, blepharitis, erythema of eyelid, periorbital oedema, eyelids pruritus, visual acuity reduced, vision blurred, lacrimation increased, conjunctivitis, ectropion, cataract, eyelid margin crusting, growth of eyelashes

Rare

iridocyclitis, ophthalmic herpes simplex, eye inflammation, photopsia, eczema eyelids, conjunctival oedema, halo vision, conjunctival follicles, hypoaesthesia eye, trichiasis, meibomianitis, anterior chamber pigmentation, mydriasis, asthenopia, eyelash hyperpigmentation, eyelash thickening

Not known

macular oedema, lid sulcus deepened

Ear and labyrinth disorders

Not known

vertigo, tinnitus

Cardiac disorders

Uncommon

palpitations

Rare

heart rate irregular, heart rate decreased

Not known

chest pain, bradycardia, tachycardia, arrhythmia

Vascular disorders

Rare

blood pressure diastolic decreased, blood pressure systolic increased, hypotension, hypertension

Respiratory, thoracic and mediastinal disorders

Uncommon

cough, nasal congestion, throat irritation

Rare

dyspnoea, asthma, respiratory disorder, oropharyngeal pain, dysphonia, rhinitis allergic, nasal dryness

Not known

asthma aggravated, epistaxis

Gastrointestinal disorders

Rare

peptic ulcer reactivated, gastrointestinal disorder, constipation, dry mouth

Not known

diarrhoea, abdominal pain, nausea, vomiting

Skin and subcutaneous tissue disorders

Uncommon

skin hyperpigmentation (periocular), skin discolouration, hair texture abnormal, hypertrichosis

Rare

dermatitis allergic, dermatitis contact, erythema, rash, hair colour changes, madarosis

Not known

pruritus, hair growth abnormal

Musculoskeletal and connective tissue disorders

Rare

musculoskeletal pain, arthralgia

Renal and urinary disorders

Not known

dysuria, urinary incontinence

General disorders and administration site conditions

Rare

asthenia

Investigations

Not known

prostatic specific antigen increased

Paediatric population

In a 3-month phase 3 study and a 7 days pharmacokinetic study, involving 102 paediatric patients exposed to travoprost, the types and characteristics of adverse reactions reported were similar to what has been observed in adult patients. The short-term safety profiles in the different paediatric subsets were also similar (see section 5.1). The most frequent adverse reactions reported in the paediatric population were ocular hyperaemia (16.9%) and growth of eyelashes (6.5%). In a similar 3-month study in adult patients, these events occurred at an incidence of 11.4% and 0.0%, respectively.

Additional adverse drug reactions reported in paediatric patients in the 3-month paediatric study (n=77) compared to a similar trial in adults (n=185) included erythema of eyelid, keratitis, lacrimation increased and photophobia all reported as single events with an incidence of 1.3% versus 0.0% seen in adults.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation 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 via the Yellow Card Scheme at website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

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 travoprost may be flushed from the eye(s) with lukewarm water. Treatment of a suspected oral ingestion is symptomatic and supportive.