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TRAVOPROST TEVA 40 MICROGRAMS/ML EYE DROPS SOLUTION

Active substance(s): TRAVOPROST / TRAVOPROST / TRAVOPROST

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SUMMARY OF PRODUCT CHARACTERISTICS
1

NAME OF THE MEDICINAL PRODUCT
Travoprost Teva 40 micrograms/ml Eye Drops, Solution

2

QUALITATIVE AND QUANTITATIVE COMPOSITION
Each mL of solution contains 40 micrograms of travoprost.
Excipient(s) with known effect:
Each mL of solution contains 10 microgram of polyquaternium-1, 7.5 mg of
propylene glycol, 2 mg of macrogolglycerol hydroxystearate 40 (see section 4.4.)
For the full list of excipients, see section 6.1.

3

PHARMACEUTICAL FORM
Eye drops, solution. (Eye drops)
Clear, colourless solution.
pH 6.3 to 7.3;
osmolality 265 - 320 mOsmol/kg

4

CLINICAL PARTICULARS

4.1

Therapeutic indications
Decrease of elevated intraocular pressure in adult patients with ocular hypertension or
open-angle 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 Teva 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.
Patients with 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.
Paediatric population
The efficacy and safety of travoprost in children below the age of 18 years have not
been established and its use is not recommended in these patients until further data
become 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.

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 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 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 F2a
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
eye drops and wait 15 minutes after instillation of the dose before reinsertion.
Excipients
Travoprost Teva contains propylene glycol which may cause skin irritation.
Travoprost Teva contains macrogolglycerol hydroxystearate 40 which may cause skin
reactions.

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/newborn child. Travoprost should not be used during pregnancy unless clearly necessary.
Breastfeeding

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 negliglible influence on the ability to drive and use machines.
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 eye drops , the most common adverse reactions were
hyperaemia and iris hyperpigmentation, occurring in approximately 20% and 6% of
pateients 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 <1/1000), or 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 eye drops.

System Organ Class
Infections and infestations

Frequency
Rare

Adverse reactions
herpes simplex, keratitis herpetic

Immune system disorders

Uncommon

hypersensitivity, seasonal allergy

Phychiatric disorders
Nervous system disorder

Not known
Uncommon

depression, anxiety
headache, dizziness, visual field
defect

Rare

dysgeusia

Very common

ocular hyperaemia

Common

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

Eye disorders

pruritus, eye irritation
Uncommon

Rare

Not known

Ear and labyrinth disorders
Cardiac disorders

Not known
Uncommon
Rare

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,
ectropioncataract, eyelid margin
crusting, growth of eyelashes,
eyelash discolouration, asthenopia
iridocyclitis, eye inflammation,
photopsia, eczema eyelids,
conjunctival oedema, halo vision,
conjunctival follicles, hypoaesthesia
eye, meibomianitis, anterior chamber
pigmentation, mydriasis, eyelash
thickening
macular oedema, sunken eyes
vertigo, tinnitus
palpitations
heart rate irregular, heart rate
decreased

Not known
chest pain, bradycardia, tachycardia
blood pressure diastolic decreased,
blood pressure systolic increased,
hypotension, hypertension

Vascular disorders

Rare

Respiratory, thoracic and
mediastinal disorder

Uncommon

dyspnoea, asthma, nasal congestion,
throat irritation

Rare

respiratory disorder, oropharyngeal
pain, cough, dysphonia

Not known

asthma aggravated

Rare

peptic ulcer reactivated,
gastrointestinal disorder,
constipation, dry mouth

Gastrointestinal disorders

Not known
diarrhea, abdominal pain, nausea
Skin and subcutaneous
tissue disorders

Uncommon

skin hyperpigmentation (periocular),
skin discolouration, hair texture

Rare

Musculoskeletal and
connective tissue disorders
Renal and urinary
disorders
General disorders and
administrative site
conditions
Investigations

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

Not known

pruritus, hair growth abnormal

Rare

musculoskeletal pain

Not known
Not known

arthralgia
dysuria, urinary incontinence

Rare

asthenia

Not known

prostatic specific antigen increased

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: www.mhra.gov.uk/yellowcard.

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.

5

PHARMACOLOGICAL PROPERTIES

5.1

Pharmacodynamic properties
Pharmacotherapeutic Group: Ophthalmologicals-antiglaucoma preparations and
miotics-prostaglandin analogues
ATC code: S01E E04
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.
Clinical efficacy and safety
In a clinical trial, patients with open-angle glaucoma or ocular hypertension who were
treated with travoprost eye drops (polyquaternium 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
travoprost with timolol 0.5% and limited data with brimonidine 0.2% were collected
during clinical trials that showed an additive effect of travoprost with these glaucoma
medications. No clinical data are 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).
Travoprost 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.

5.2

Pharmacokinetic properties
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 travoprost. Aqueous humour concentrations declined with a half-life
of approximately 1.5 hours.
Distribution
Following topical ocular administration of travoprost to healthy volunteers, low
systemic exposure to active free acid was demonstrated. Peak active free acid plasma
concentrations of 25 pg/ml or less were observed between 10 and 30 minutes postdose. Thereafter, plasma levels declined rapidly to below the 10 pg/ml assay
quantitation limit before 1 hour post-administration. Due to the low plasma
concentrations and rapid elimination following topical dosing, the elimination halflife 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.
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.

5.3

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).

6

PHARMACEUTICAL PARTICULARS

6.1

List of excipients
Boric acid (E284)
Sodium chloride
Mannitol (E421)
Macrogolglycerol hydroxystearate 40
Polyquaternium-1
Propylene glycol (E1520)
Sodium hydroxide (E524) and/or hydrochloric acid (E507) (for pH adjustment)
Purified water

6.2

Incompatibilities
Not applicable.
Specific in vitro interaction studies were performed with travoprost and medicinal
products containing thiomersal. No evidence of precipitation was observed.

6.3

Shelf life
2 years
Discard 4 weeks after first opening.

6.4

Special precautions for storage
This medicinal product does not require any special temperature storage conditions.
Keep the bottle in the outer carton in order to protect from light.

6.5

Nature and contents of container
Transparent LDPE bottles with transparent LDPE dropper insert and light blue,
tamper-proof HDPE screw cap.
Pack sizes:
1 x 2.5 ml, 3 x 2.5 ml, 6 x 2.5 ml
Not all pack sizes may be marketed.

6.6

Special precautions for disposal
No special requirements.

7

MARKETING AUTHORISATION HOLDER
Teva UK Limited,
Brampton Road
Hampden Park
Eastbourne
East Sussex

BN22 9AG
United Kingdom

8

MARKETING AUTHORISATION NUMBER(S)
PL 00289/1861

9

DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
19/02/2015

10

DATE OF REVISION OF THE TEXT
19/02/2015

Expand Transcript

Source: Medicines and Healthcare Products Regulatory Agency

Disclaimer: Every effort has been made to ensure that the information provided here is accurate, up-to-date and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. This information has been compiled for use by healthcare practitioners and consumers in the United States. The absence of a warning for a given drug or combination thereof in no way should be construed to indicate that the drug or combination is safe, effective or appropriate for any given patient. If you have questions about the substances you are taking, check with your doctor, nurse or pharmacist.

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