ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
DuoTrav 40 micrograms/ml + 5 mg/ml eye drops, solution.
2.
Each ml of solution contains 40 micrograms of travoprost and 5 mg of timolol (as timolol maleate).
Excipient(s):
Each ml of solution contains polyquaternium-1 (POLYQUAD) 10 microgram, propylene
glycol 5 mg, polyoxyethylene hydrogenated castor oil 40 1 mg (see section 4.4).
For a full list of excipients, see section 6.1.
3.
Eye drop, solution (eye drop).
Clear, colourless solution.
4.
Decrease of intraocular pressure (IOP) in adult patients with open-angle glaucoma or ocular
hypertension who are insufficiently responsive to topical beta-blockers or prostaglandin analogues (see
section 5.1).
Posology
Use in adults, including the elderly population
The dose is one drop of DuoTrav in the conjunctival sac of the affected eye(s) once daily, in the
morning or evening. It should be administered at the same time each day.
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.
Special Populations
Hepatic and renal impairment
No studies have been conducted with DuoTrav or with timolol 5 mg/ml eye drops in patients with
hepatic or 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 dose adjustment was
necessary in these patients.
Patients with hepatic or renal impairment are unlikely to require dose adjustment with DuoTrav (see
section 5.2).
Paediatric population
The safety and efficacy of DuoTrav in children and adolescents below the age of 18 years have not
been established. No data are available.
Method of administration
For ocular use.
2
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.
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).
When substituting another ophthalmic antiglaucoma medicinal product with DuoTrav, the other
medicinal product should be discontinued and DuoTrav should be started the following day.
Patients must be instructed to remove soft contact lenses prior to application of DuoTrav and wait
15 minutes after instillation of the dose before reinsertion.
4.3
Hypersensitivity to the active substances, or to any of the excipients.
Bronchial asthma, a history of bronchial asthma or severe chronic obstructive pulmonary disease.
Sinus bradycardia, second or third degree atrioventricular block, overt cardiac failure, or cardiogenic
shock.
Severe allergic rhinitis and bronchial hyper reactivity; corneal dystrophies; hypersensitivity to other
beta-blockers.
4.4
Systemic effects
Like other topically applied ophthalmic medicinal products, travoprost and timolol are absorbed
systemically. Due to the beta-adrenergic active substance, timolol, the same types of cardiovascular
and pulmonary adverse reactions as seen with systemic beta adrenergic blocking medicinal products
may occur. Cardiac failure should be adequately controlled before beginning therapy with timolol.
Patients with a history of severe cardiac disease should be watched for signs of cardiac failure and
have their pulse rates checked. Respiratory reactions and cardiac reactions, including death due to
bronchospasm in patients with asthma and, rarely, death in association with cardiac failure, have been
reported following administration of timolol maleate. Beta-adrenergic blocking medicinal products
should be administered with caution in patients subject to spontaneous hypoglycaemia or to diabetic
patients (especially those with labile diabetes) as beta-adrenergic blocking medicinal products may
mask the signs and symptoms of acute hypoglycaemia. They may also mask the signs of
hyperthyroidism and cause worsening of Prinzmetal angina, severe peripheral and central circulatory
disorders and hypotension.
Prostaglandins and prostaglandin analogues are biologically active substances 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.
Anaphylactic reactions
While taking beta adrenergic blocking medicinal products, patients with a history of atopy or a history
of severe anaphylactic reaction to a variety of allergens may be unresponsive to the usual doses of
adrenaline used to treat anaphylactic reactions.
Concomitant therapy
Timolol may interact with other medicinal products (see section 4.5).
3
The effect on intraocular pressure or the known effects of systemic beta-blockade may be potentiated
when DuoTrav is given to patients already receiving an oral beta-blocking medicinal product .
The use of two local beta-adrenergic blocking medicinal products or two local prostaglandins is not
recommended.
Ocular effects
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 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
travoprost has been reported.
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 DuoTrav 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.
Caution is recommended when using DuoTrav 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.
In patients with known predisposing risk factors for iritis/uveitis, DuoTrav can be used with caution.
Excipients
DuoTrav contains propylene glycol which may cause skin irritation.
DuoTrav contains polyoxyethylene hydrogenated castor oil 40 which may cause skin reactions.
Patients must be instructed to remove contact lenses prior to application of DuoTrav and wait 15
minutes after instillation of the dose before reinsertion.
No interaction studies have been performed.
There is a potential for additive effects results in hypotension and/or marked bradycardia when eye
drops with timolol are administered concomitantly with oral calcium channel blockers, guanethidine or
beta-blocking medicinal products, antiarrhythmics, digitalis glycosides or parasympathomimetics.
4
The hypertensive reaction to sudden withdrawal of clonidine can be potentiated when taking
beta-blockers.
Beta-blockers may increase the hypoglycaemic effect of antidiabetic medicinal products.
Beta-blockers can mask the signs and symptoms of hypoglycaemia (see section 4.4).
Women of childbearing potential/contraception
DuoTrav must not be used in women who may become pregnant 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.
Well controlled epidemiological studies with systemic use of beta-blockers did not indicate
malformative effects, but some pharmacological effects such as bradycardia have been observed in
foetuses or neonates. Data on a limited number of exposed pregnancies indicate no adverse effects of
timolol in eye drops on pregnancy or on the health of the foetus/newborn child but bradycardia and
arrhythmia have been reported in one case in the foetus of a woman treated with timolol eye drops. To
date, no other relevant epidemiological data are available.
DuoTrav should not be used during pregnancy unless clearly necessary.
Breastfeeding
It is unknown whether travoprost from eye drops is excreted in human breast milk. Animal studies
have shown excretion of travoprost and metabolites in breast milk. Timolol is excreted in breast milk.
However, at therapeutic doses of timolol in eye drops the calculated dose of timolol for the infant
would be too low to produce clinical beta-blockade. The use of DuoTrav by breast-feeding women is
not recommended.
Fertility
There are no data on the effects of DuoTrav on human fertility. Animal studies showed no effect of
travoprost or timolol on fertility at doses more than 250 times the maximum recommended human
ocular dose.
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.
In clinical studies involving 938 patients, DuoTrav (benzalkonium chloride-preserved) was
administered once-daily. The most frequently reported treatment-related adverse reaction was ocular
hyperaemia (15.0%). Almost all patients (96%) who experienced ocular hyperaemia did not
discontinue therapy as a result of this reaction.
The following adverse reactions listed in the table below were observed in clinical studies or with
post-marketing experience. They are ranked according to system organ class and classified according
to the following convention: very common (≥1/10), common (≥1/100 to <1/10), uncommon
(≥1/1000 to <1/100), rare (≥1/10,000 to <1/1000), very rare (<1/10,000), or not known (cannot be
estimated from the available data). Within each frequency grouping, adverse reactions are presented in
decreasing order of seriousness.
5
DuoTrav (benzalkonium chloride-preserved)
System Organ Class
Frequency
Adverse Reactions
Psychiatric disorders
Common
nervousness.
Not known
depression.
Nervous system disorders
Common
dizziness, headache.
Not known
cerebrovascular accident, syncope, paraesthesia.
Eye disorders
Very common
ocular discomfort, ocular hyperaemia
Common
punctate keratitis, anterior chamber inflammation,
eye pain, photophobia, eye swelling, conjunctival
haemorrhage, visual acuity reduced, visual
disturbance, vision blurred, dry eye, eye pruritus,
conjunctivitis, lacrimation increased, erythema of
eyelid, blepharitis, asthenopia, growth of eyelashes.
Uncommon
corneal erosion, keratitis, eye allergy, conjunctival
oedema, eyelid oedema.
Rare
iritis.
Not known
macular oedema, eyelid ptosis, corneal disorder.
Cardiac disorders
Common
Uncommon
Not known
heart rate irregular, heart rate decreased.
arrhythmia.
cardiac failure, tachycardia.
Vascular disorders
Common
blood pressure increased, blood pressure decreased.
Respiratory, thoracic and
mediastinal disorders
Common
bronchospasm.
Uncommon
dyspnoea, cough, oropharyngeal pain, throat
irritation, nasal discomfort, postnasal drip.
Not known
asthma.
Hepatobiliary disorders
Uncommon
alanine aminotransferase increased, aspartate
aminotransferase increased.
Skin and subcutaneous tissue
disorders
Common
urticaria, skin hyperpigmentation (periocular).
Uncommon
dermatitis contact.
Rare
alopecia.
Not known
rash.
Musculoskeletal and connective
tissue disorders
Common
pain in extremity.
Renal and urinary disorders
Uncommon
chromaturia.
General disorders and
administration site conditions
Uncommon
thirst.
Not known
chest pain.
In 3 clinical trials involved in the development of DuoTrav (polyquaternium-1-preserved),
372 patients/subjects were exposed for up to 12 months. The most frequently reported
treatment-related undesirable effect with DuoTrav (polyquaternium-1-preserved) was hyperaemia of
the eye (11.8%), which included ocular or conjunctival hyperaemia. The majority of patients (91%)
who experienced hyperaemia of the eye did not discontinue therapy as a result of this reaction.
The following adverse reactions listed in the table below were observed in the clinical studies.
6
DuoTrav (polyquaternium-1-preserved)
System Organ Classification Frequency
Adverse Reactions
Immune system disorders
Uncommon
hypersensitivity
Nervous system disorders
Uncommon
Headache
Eye disorders
Common
eye pain, ocular discomfort, dry eye, eye
pruritus, ocular hyperaemia
Uncommon
punctate keratitis, iritis, photophobia, vision
blurred, conjunctivitis,meibomianitis, eyelid
margin crusting, asthenopia, lacrimation
increased, growth of eye lashes
Cardiac disorders
Uncommon
Bradycardia
Vascular disorders
Uncommon
hypotension
Skin and subcutaneous tissue
disorders
Uncommon
skin discolouration, hair growth
abnormal
General disorders and
administration site conditions
Uncommon
fatigue
Investigations
Uncommon
heart rate decreased
Additional adverse reactions that have been seen with one of the active substances and may potentially
occur with DuoTrav:
Travoprost
Eye disorders
uveitis, conjunctival disorder, conjunctival follicles, iris hyperpigmentation.
Skin and subcutaneous tissue disorders
skin exfoliation.
Timolol
Metabolism and nutrition disorders
hypoglycaemia.
Nervous system disorders
cerebral ischaemia, myasthenia gravis.
Eye disorders
diplopia.
Cardiac disorders
cardiac arrest, atrioventricular block, palpitations.
Respiratory, thoracic and mediastinal disorders
respiratory failure, nasal congestion.
Gastrointestinal disorders
diarrhoea, nausea.
General disorders and administration site conditions
asthenia.
A topical overdose with travoprost is not likely to occur or to be associated with toxicity.
The most common symptoms of a systemic timolol overdose are bradycardia, hypotension,
bronchospasm and heart failure.
If overdose with DuoTrav occurs, treatment should be symptomatic and supportive. Timolol does not
dialyse readily.
7
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Ophthalmologicals antiglaucoma preparations and miotics.ATC code:
S01ED51.
Mechanism of action
DuoTrav contains two active substances: travoprost and timolol maleate. These two components lower
intraocular pressure by complementary mechanisms of action and the combined effect results in
additional IOP reduction compared to either compound alone.
Travoprost, a prostaglandin F
2
analogue, is a full agonist which is highly selective and 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 IOP in
man starts within approximately 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.
Timolol is a non-selective adrenergic blocking agent that has no intrinsic sympathomimetic, direct
myocardial depressant or membrane-stabilising activity. Tonography and fluorophotometry studies in
man suggest that its predominant action is related to reduced aqueous humour formation and a slight
increase in outflow facility.
Secondary pharmacology
Travoprost significantly increased optic nerve head blood flow in rabbits following 7 days of topical
ocular administration (1.4 micrograms, once-daily).
Pharmacodynamic effects
Clinical effects
In a twelve-month, controlled clinical study in patients with open-angle glaucoma or ocular
hypertension and baseline mean IOP of 25 to 27 mmHg, the mean IOP-lowering effect of DuoTrav
dosed once-daily in the morning was 8 to 10 mmHg. The non-inferiority of DuoTrav as compared to
latanoprost 50 micrograms/ml + timolol 5 mg/ml in the mean IOP reduction was demonstrated across
all time-points at all visits.
In a three-month, controlled clinical study in patients with open-angle glaucoma or ocular
hypertension and baseline mean IOP of 27 to 30 mmHg, the mean IOP-lowering effect of DuoTrav
dosed once-daily in the morning was 9 to 12 mmHg, and was up to 2 mmHg greater than that of
travoprost 40 micrograms/ml dosed once-daily in the evening and 2 to 3 mmHg greater than that of
timolol 5 mg/ml dosed twice daily. A statistically superior reduction in morning mean IOP
(8AM-24 hours after the last dose of DuoTrav) was observed compared to travoprost at all visits
throughout the study.
In two three-month, controlled clinical studies in patients with open-angle glaucoma or ocular
hypertension and baseline mean IOP of 23 to 26 mmHg, the mean IOP-lowering effect of DuoTrav
dosed once-daily in the morning was 7 to 9 mmHg. Mean IOP reductions were non-inferior, although
numerically lower, to those achieved by concomitant therapy with travoprost 40 micrograms/ml dosed
once-daily in the evening and timolol 5 mg/ml dosed once-daily in the morning.
In a 6-week, controlled clinical study in patients with open-angle glaucoma or ocular hypertension and
baseline mean IOP of 24 to 26 mmHg, the mean IOP-lowering effect of DuoTrav
(polyquaternium-1-preserved) dosed once-daily in the morning was 8 mmHg and equivalent to that of
DuoTrav (benzalkonium chloride-preserved).
8
Inclusion criteria were common across the studies, with the exception of the IOP entry criteria and
response to previous IOP therapy. The clinical development of DuoTrav included both patients naive
and on therapy. Insufficient responsiveness to monotherapy was not an inclusion criterion.
Existing data suggest that evening dosing might have some advantages in the mean IOP reduction.
Consideration should be given to patient convenience and their likely compliance when
recommending morning vs. evening dosing.
5.2 Pharmacokinetic properties
Absorption
Travoprost and timolol are absorbed through the cornea. Travoprost is a prodrug that undergoes rapid
ester hydrolysis in the cornea to the active free acid. Following once-daily administration of DuoTrav
PQ in healthy subjects (N=22 ) for 5 days, travoprost free acid was not quantifiable in plasma samples
from the majority of subjects (94.4%) and generally was not detectable one hour after dosing. . When
measurable ( 0.01 ng/ml, the assay limit of quantitation), concentrations ranged from
0.01 to 0.03 ng/ml. The mean timolol steady-state C
max
was 1.34 ng/ml and T
max
was approximately
0.69 hours after once-daily administration of DuoTrav.
Distribution
Travoprost free acid can be measured in the aqueous humour during the first few hours in animals and
in human plasma only during the first hour after ocular administration of DuoTrav. Timolol can be
measured in human aqueous humour after ocular administration of timolol and in plasma for up to
12 hours after ocular administration of DuoTrav.
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 F
2
which are characterised by
reduction of the 13-14 double bond, oxidation of the 15-hydroxyl and -oxidative cleavages of the
upper side chain.
Timolol is metabolised by two pathways. One route yields an ethanolamine side chain on the
thiadiazole ring and the other giving an ethanolic side chain on the morpholine nitrogen and a second
similar side chain with a carbonyl group adjacent to the nitrogen. The plasma t
1/2
of timolol is 4 hours
after ocular administration of DuoTrav.
Elimination
Travoprost free acid and its metabolites are mainly excreted by the kidneys. Less than 2% of an ocular
dose of travoprost was recovered in urine as free acid. Timolol and its metabolites are primarily
excreted by the kidneys. Approximately 20% of a timolol dose is excreted in the urine unchanged and
the remainder excreted in urine as metabolites.
5.3 Preclinical safety data
In monkeys, administration of DuoTrav twice–daily was shown to induce increased palpebral fissure
and to increase iris pigmentation similar to that observed with ocular administration of prostanoids.
DuoTrav 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.
Travoprost
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.
9
Reproduction toxicity studies with travoprost 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
3
H-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).
Timolol
Non-clinical data revealed no special hazard for humans with timolol based on conventional studies of
safety pharmacology, repeat dose toxicity, genotoxicity, carcinogenic potential. Reproduction toxicity
studies with timolol showed delayed foetal ossification in rats with no adverse effects on postnatal
development (7000 times the clinical dose) and increased foetal resorptions in rabbits (14000 times the
clinical dose).
6.
6.1 List of excipients
Polyquaternium-1.
Mannitol (E421).
Propylene glycol (E1520).
Polyoxyethylene hydrogenated castor oil 40 (HCO-40).
Boric acid.
Sodium chloride.
Sodium hydroxide and/ or hydrochloric acid (for pH adjustment).
Purified water.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
Discard 4 weeks after first opening.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and contents of container
2.5 ml oval bottle with dispensing plug and screw cap, all polypropylene presented in an overwrap.
Pack sizes of 1, 3 or 6 bottles.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
10
7.
Alcon Laboratories (UK) Ltd.
Boundary Way,
Hemel Hempstead,
Herts HP2 7UD
United Kingdom.
8.
EU/1/06/338/001-3
9.
Date of first authorisation: 24/04/06
Date of last renewal: 07/10/10
Detailed information on this medicinal product is available on the website of the European Medicines
Agency http://www.ema.europa.eu
11
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDER
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
12
A. MANUFACTURING AUTHORISATION HOLDER RESPONSIBLE FOR BATCH
RELEASE
Name and address of the manufacturer responsible for batch release
S.A. Alcon Couvreur N.V.,
Rijksweg 14,
B-2870,
Puurs,
Belgium
or
Alcon Cusí, S.A.,
Camil Fabra 58,
08320 El Masnou,
Barcelona,
Spain
B. CONDITIONS OF THE MARKETING AUTHORISATION
Medicinal product subject to medical prescription.
CONDITIONS OR RESTRICTIONS WITH REGARD TO THE SAFE AND
EFFECTIVE USE OF THE MEDICINAL PRODUCT
Not applicable.
OTHERCONDITIONS
Pharmacovigilance system
The MAH must ensure that the system of pharmacovigilance, presented in Module 1.8.1. of the
Marketing Authorisation is in place and functioning before and whilst the product is on the market.
Risk Management Plan
The MAH commits to performing the studies and additional pharmacovigilance activities detailed in
the Pharmacovigilance Plan version 4.0 of the Risk Management Plan (RMP) presented in Module
1.8.2. of the Marketing Authorisation Application and any subsequent updates of the RMP agreed by
the CHMP.
As per the CHMP Guideline on Risk Management Systems for medicinal products for human use, the
updated RMP should be submitted at the same time as the following Periodic Safety Update Report
(PSUR).
In addition, an updated RMP should be submitted
When new information is received that may impact on the current Safety Specification,
Pharmacovigilance Plan or risk minimisation activities
Within 60 days of an important (pharmacovigilance or risk minimisation) milestone being
reached.
At the request of the European Medicines Agency.
13
ANNEX III
LABELLING AND PACKAGE LEAFLET
14
A. LABELLING
15
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
CARTON FOR SINGLE BOTTLE 2.5 ml + CARTON FOR 3 x 2.5 ml BOTTLES + CARTON
FOR 6 x 2.5 ml BOTTLES
1.
DuoTrav 40 micrograms/ml + 5 mg/ml eye drops, solution.
travoprost/timolol.
2.
STATEMENT OF ACTIVE SUBSTANCE
Each ml of solution contains 40 micrograms travoprost and 5 mg timolol (as timolol maleate).
3.
LIST OF EXCIPIENTS
Contains:Polyquaternium-1, mannitol (E421), propylene glycol (E1520), polyoxyethylene
hydrogenated castor oil 40 (HCO-40), boric acid, sodium chloride, sodium hydroxide and/or
hydrochloric acid (to adjust pH), purified water.
See leaflet for further details.
4.
Eye drops, solution.
1 x 2.5 ml.
3 x 2.5 ml.
6 x 2.5 ml.
5.
METHOD AND ROUTE OF ADMINISTRATION
Read the package leaflet before use.
Ocular use.
6.
SPECIAL WARNING THAT THE MEDICINAL PRODUCT MUST BE STORED OUT
OF THE REACH AND SIGHT OF CHILDREN
Keep out of the reach and sight of children.
7.
OTHER SPECIAL WARNING(S), IF NECESSARY
8.
EXPIRY DATE
EXP.
Discard 4 weeks after first opening.
Opened.
16
9.
SPECIAL STORAGE CONDITIONS
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Alcon Laboratories (UK) Ltd.,
Boundary Way,
Hemel Hempstead,
Herts, HP2 7UD
United Kingdom.
12. MARKETING AUTHORISATION NUMBERS
EU/1/06/338/001 1 x 2.5 ml.
EU/1/06/338/002 3 x 2.5 ml.
EU/1/06/338/003 6 x 2.5 ml.
13. BATCH NUMBER
Lot.
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16 INFORMATION IN BRAILLE
duotrav
17
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
BOTTLE LABEL
1.
DuoTrav 40 micrograms/ml + 5 mg/ml eye drops.
travoprost/timolol.
Ocular use.
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
<Open here>
3.
EXPIRY DATE
EXP.
Discard 4 weeks after first opening.
Opened.
4.
BATCH NUMBER
Lot.
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
2.5 ml.
6
OTHER
18
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
OVERWRAP
1.
DuoTrav 40 micrograms/ml + 5 mg/ml eye drops.
travoprost/timolol.
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
EXP.
Discard 4 weeks after first opening.
4.
BATCH NUMBER
Lot.
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
2.5 ml.
6
OTHER
19
B. PACKAGE LEAFLET
20
PACKAGE LEAFLET: INFORMATION FOR THE USER
DuoTrav 40 micrograms/ml + 5 mg/ml eye drops, solution
travoprost/timolol
Read all of this leaflet carefully before you start using this medicine
.
-
Keep this leaflet.
You may need to read it again.
-
If you have any further questions, after reading it, please ask your doctor or your pharmacist.
-
This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even
-
If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet,
please tell your doctor or pharmacist.
In this leaflet
1.
What DuoTrav is and what it is used for
2.
Before you use DuoTrav
3.
How to use DuoTrav
5.
How to Store DuoTrav
6.
Further information
1. WHAT DuoTrav IS AND WHAT IT IS USED FOR
DuoTrav eye drops solution is a combination of two active substances (travoprost and timolol).
Travoprost is a prostaglandin analogue which works by increasing the outflow of liquid of the eye,
which lowers its pressure. Timolol is a beta blocker which works by reducing the production of fluid
within the eye. The two substances work together to reduce pressure within the eye.
DuoTrav eye drops are used to treat high pressure in the eye in adults, including the elderly
.
This
pressure can lead to an illness called glaucoma.
2. BEFORE YOU USE DuoTrav
Do not use DuoTrav eye drops solution
if you are allergic to travoprost, prostaglandins, timolol, beta-blockers or any of the other
ingredients.
if you have respiratory problems
such as asthma, bronchitis or other types of breathing
problems.
if you have severe hay fever.
if you have a slow heart beat, heart failure or disorders of heart rhythm.
If the surface of your eye is cloudy.
Ask your doctor for advice if any of these apply to you.
Take special care with DuoTrav.
DuoTrav may cause breathlessness or wheezing. If you are concerned about changes in your
breathing pattern when using DuoTrav, tell your doctor as soon as possible.
If you get any severe allergic reaction (skin rash, redness and itching of the eye) while using
DuoTrav
,
whatever the cause, adrenaline treatment may not be as effective. So when receiving
any other treatment please tell the doctor that you are using DuoTrav.
21
if their symptoms are the same as yours.
4.
Possible side effects
If you have angina, circulation problems or low blood pressure. DuoTrav may make any of
these worse. If you are concerned about any changes in these symptoms, tell your doctor as soon
as possible.
If you have diabetes. DuoTrav
can mask the symptoms of low blood sugar (hypoglycaemia)
such as shakiness and dizziness. Close monitoring of your blood sugar while using DuoTrav is
advised. If you have any concerns regarding your blood sugar while dosing with DuoTrav see
your doctor.DuoTrav may hide the symptom
s
of thyroid problems (hyperthyroidism). If you
have a thyroid problem talk to your doctor before you use DuoTrav.
If you have had cataract surgery talk to your doctor before you use DuoTrav.
If you have current or previous history of an eye inflammation talk to your doctor before you
use DuoTrav.
DuoTrav may change the colour of your iris (the coloured part of your eye). This change may be
permanent.
DuoTrav may increase the length, thickness, colour and/or number of your eyelashes and may
cause unusual hair growth on your eyelids.
Travoprost may be absorbed through the skin and therefore should not be used by women who
are pregnant or are attempting to become pregnant. If any of the medicine comes into contact
with the skin then it should be washed off straight away.
Children
DuoTrav is not to be used by children and adolescents under 18 years of age.
Using other medicines
DuoTrav can affect or be affected by other medicines you are using, including other eye drops for the
treatment of glaucoma. Tell your doctor if you are using or intend to use medicines to lower blood
pressure, heart medicine or medicines to treat diabetes. Please tell your doctor or pharmacist if you are
taking or have recently taken any other medicines, including medicines obtained without a
prescription.
Pregnancy and breast-feeding
Do not use DuoTrav if you are pregnant unless your doctor considers it necessary.
If you could get
pregnant you must use adequate contraception whilst you use the medicine.
Do not use DuoTrav if you are breast-feeding.DuoTrav may get into your milk
.
Ask your doctor for advice before taking any medicine.
Driving and using machines
You may find that your vision is blurred for a time just after you use DuoTrav. Do not drive or use
machines until this has worn off.
Important information about some of the ingredients of DuoTrav.
DuoTrav contains hydrogenated castor oil and propylene glycol which may cause skin reactions
and irritation.
22
3. HOW TO USE DuoTrav.
Always use DuoTrav eye drops solution exactly as your doctor has told you.You should check with
your doctor or pharmacist if you are not sure.
The usual dose
Adults and elderly: 1 drop in the affected eye or eyes, once a day-in the morning or in the evening.
Use at the same time each day.
Only use DuoTrav in both eyes if your doctor told you to do so. Use it for as long as your doctor told
you to.
Only use DuoTrav for dropping in your eyes.
1
2
3
4
Immediately before using a bottle for the first time, tear-off the overwrap pouch take it out
(picture 1) and write the date of opening on the label in the space provided.
Get the DuoTrav bottle and a mirror.
Wash your hands.
Twist off the cap.
Hold the bottle, pointing down, between your thumb and fingers.
Tilt your head 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 (picture 2)
.
Bring the bottle tip close to the eye. Use the mirror if it helps.
Do not touch your eye or eyelid, surrounding areas or other surfaces with the dropper. It could
infect the drops.
Gently squeeze the bottle to release one drop of DuoTrav at a time (picture 3)
.
After using DuoTrav, press a finger into the corner of your eye, by the nose (picture 4). This
helps to stop DuoTrav getting into the rest of the body.
If you use drops in both eyes, repeat the steps for your other eye.
Close the bottle cap firmly immediately after use.
Only use one bottle at a time. Do not open the pouch until you need to use the bottle.
Turn the page for more advice.
How much to use
<see side 1
If a drop misses your eye, try again.
If you use more DuoTrav than you should, rinse it all out with warm water. Do not put in any more
drops until it is time for your next regular dose.
If you forget to use DuoTrav, continue with the next dose as planned. Do not use a double dose to
make up. The dose should not exceed one daily drop in the affected eye(s).
If you stop using DuoTrav without speaking to your doctor the pressure in your eye will not be
controlled which could lead to loss of sight.
23
If you are using other eye drops, leave at least 5 minutes between putting in DuoTrav and the other
drops.
If you wear soft contact lenses. Do not use the drops with your lenses in. After using the drops wait
15 minutes before putting your lenses back in.
If you have any other questions about your medicine, ask a doctor or pharmacist.
4.
POSSIBLE SIDE EFFECTS
Like all medicines DuoTrav eye drops solution can cause side effects although not everybody gets
them.
You can usually carry on taking the drops, unless the effects are serious. If you're worried, talk to a
doctor or pharmacist. Do not stop using DuoTrav without speaking to your doctor.
The frequency of possible side effects listed below is defined using the following convention
Very common (affects more than 1 user in 10)
Common (affects 1 to 10 users in 100)
Uncommon (affects 1 to 10 users in 1,000)
Rare (affects 1 to 10 users in 10,000)
Not known (frequency cannot be estimated from the available data)
Very common side effects
Effects in the eye
eye irritation, redness of the eye.
Common side effects
Effects in the eye
inflammation inside the eye, eye pain and swelling, sensitivity to light, conjunctival bleeding, blurred
vision, reduced vision, abnormal vision, dry eye, itchy eye, eye discomfort, eye allergy,
increased tear
production, eyelid irritation, itching, redness, pain and swelling; tired eyes, increased growth or
number of eye lashes, abnormal eye sensation.
General side effects
drug allergy, nervousness, dizziness, headache, irregular or decreased heart rate, increased or
decreased blood pressure, shortness of breath, hives, skin darkening around eyes, pain in hands and
feet.
Uncommon side effects
Effects in the eye
thinning or inflammation of the eye surface, inflammation of the eyelid glands, swollen conjunctiva,
eyelid crusting, increased growth of hair (eyebrow), iris inflammation.
General side effects
cough, throat pain or irritation, drip at back of throat, abnormal liver blood tests, fatigue, skin
inflammation and itching, coloured urine, thirst, discomfort inside of nose.
Rare side effects
General side effects
loss of hair.
24
Not known
Effects in the eye
droopy eyelid.
General side effects
rash, heart failure, chest pain, stroke, fainting, depression, asthma, increased heart rate, numbness or
tingling sensation.
Additional side effects that have been reported previously in people using eye drops containing
travoprost or timolol and that have not been reported with DuoTrav include
Effects in the eye
double vision changes in colour of the iris,
General side effects
heart attack, decreased blood flow to the brain, low blood sugar, loss of strength and energy, diarrhoea,
nausea, peeling skin, stuffy nose, chronic neuromuscular weakness, respiratory failure.
If any of the side effects gets serious or if you notice any side effects not listed in this leaflet, please
tell your doctor or pharmacist.
5. HOW TO STORE DuoTrav
Keep out
of the reach and sight of children.
Do not use DuoTrav eye drops solution after the expiry date which is stated on the bottle and outer
carton after “EXP”. The expiry date refers to the last day of the month.
This medicine does not require any special storage conditions.
You must throw away the bottle 4 weeks after you first opened it to prevent infections and use a new
bottle. Write down the date you open it in the space on each bottle label and box.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to
dispose of medicines no longer required. These measures will help protect the environment.
6.
FURTHER INFORMATION
What DuoTrav contains
The active substances are Travoprost and timolol. Each ml of solution contains 40 micrograms of
travoprost and 5 mg of timolol (as timolol maleate).
The other ingredients are Polyquaternium-1, mannitol (E421), propylene glycol (E1520),
polyoxyethylene hydrogenated castor oil 40, boric acid, sodium chloride, sodium hydroxide or
hydrochloric acid (to adjust pH), purified water.
Tiny amounts of sodium hydroxide or hydrochloric acid are added to keep acidity levels (pH levels)
normal.
What DuoTrav looks like and the contents of the pack
DuoTrav is a liquid (a clear, colourless solution) supplied in a 2.5 ml plastic bottle with a screw cap
Each bottle is placed in a pouch.
Packs of 1, 3 or 6 bottles.
25
Not all pack sizes may be marketed.
Marketing Authorisation Holder
Manufacturer
Manufacturer
Alcon Laboratories (UK) Ltd.
S.A. Alcon-Couvreur N.V.
Alcon Cusí, S.A.,
Boundary Way,
Rijksweg 14,
Camil Fabra 58,
Hemel Hempstead,
B-2870 Puurs,
08320 El Masnou,
Herts HP2 7UD
Belgium.
Spain.
United Kingdom.
26
For any information about this medicine, please contact the local representative of the Marketing
Authorisation Holder.
België/Belgique/Belgien
Luxembourg/Luxemburg
SA Alcon-Couvreur NV
+ 32 (0)3 890 27 11 (België/Belgique/Belgien)
Lietuva
Alcon Pharmaceuticals Ltd. atstovybė
+ 370 5 2 314 756
България
Алкон България ЕООД
+ 359 2 950 15 65
Magyarország
Alcon Hungária Gyógyszerkereskedelmi Kft.
+ 36-1-463-9080
Česká republika
Alcon Pharmaceuticals (Czech Republic) s.r.o
.
+ 420 225 377 333
Nederland
Alcon Nederland BV
+ 31 (0) 183 654321
Danmark
Alcon Danmark A/S
+ 45 3636 3434
Norge
Alcon Norge AS
+47 23 25 25 50
Deutschland
Alcon Pharma GmbH
+ 49 (0)761 1304-0
Österreich
Alcon Ophthalmika GmbH
+ 43 (0)1 596 69 70
Ελλάδα
Κύπρος
Άλκον Λαμποράτορις Ελλάς ΑΕΒΕ
+ 30 210 68 78 300
(Ελλάδα)
Polska
Alcon Polska Sp. z o.o.
+ 48 22 820 3450
Eesti
Alcon Eesti
+ 372 6 313 214
Portugal
Alcon Portugal – Produtos e Equipamentos
Oftalmológicos, Lda.
+ 351 214 400 300
España
Alcon Cusí, S.A.
+ 34 93 497 7000
România
S.C. Alcon Romania S.R.L.
: + 40 21 203 93 24
France
Laboratoires Alcon
+ 33 (0)1 47 10 47 10
Slovenija
Alcon d.o.o.
+ 386 1 422 5280
Ireland
Malta
United Kingdom
Alcon Laboratories (UK) Ltd.
+ 44 (0) 1442 34 1234 (United Kingdom)
Slovenská republika
Alcon Pharmaceuticals Ltd – oz
+ 421 2 5441 0378
Ísland
Alcon Danmark A/S
+ 45 3636 3434
Suomi/Finland
Alcon Finland Oy
+358 207 871 600
Italia
Alcon Italia S.p.A.
+ 39 02 81803.1
Sverige
Alcon Sverige AB
+ 46 (0)8 634 40 00
E-post: receptionen@alconlabs.com
27
Latvija
Alcon Pharmaceuticals Ltd
+ 371 7 321 121
This leaflet was last approved in.
Detailed information on this medicine is available on the website of the European Medicines Agency
http://www.ema.europa.eu
28
Source: European Medicines Agency
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