ANNEX I
SUMMARY OF PRODUCT CHARACTERISTICS
1.
OPATANOL 1 mg/ml eye drops, solution
2.
One ml of solution contains 1 mg olopatadine (as hydrochloride).
Excipients: Benzalkonium chloride 0.1 mg/ml
For a full list of excipients, see section 6.1.
3.
Eye drops, solution (eye drops).
Clear, colourless solution.
4.
Treatment of ocular signs and symptoms of seasonal allergic conjunctivitis.
The dose is one drop of OPATANOL in the conjunctival sac of the affected eye(s) twice daily
(8 hourly). Treatment may be maintained for up to four months, if considered necessary.
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. Keep the bottle tightly closed
when not in use.
In case of concomitant therapy with other topical ocular medicines, an interval of five to ten minutes
should be allowed between successive applications.
Use in elderly
No dosage adjustment in elderly patients is necessary.
Paediatric patients
OPATANOL may be used in paediatric patients (three years of age and older) at the same dose as in
adults.
Use in hepatic and renal impairment
Olopatadine in the form of eye drops (OPATANOL) has not been studied in patients with renal or
hepatic disease. However, no dosage adjustment is expected to be necessary in hepatic or renal
impairment (see section 5.2).
Hypersensitivity to the active substance or to any of the excipients.
2
OPATANOL is an antiallergic/antihistaminic agent and, although administered topically, is absorbed
systemically. If signs of serious reactions or hypersensitivity occur, discontinue the use of this
treatment.
Benzalkonium chloride, which is commonly used as a preservative in ophthalmic products, has been
reported to cause punctate keratopathy and/or toxic ulcerative keratopathy. Since OPATANOL
contains benzalkonium chloride, close monitoring is required with frequent or prolonged use in dry
eye patients, or in conditions where the cornea is compromised.
Contact lenses
Patients should be instructed to wait 10-15 minutes after instillation of OPATANOL before inserting
contact lenses. OPATANOL should not be administered while wearing contact lenses.
No interaction studies have been performed.
In vitro
studies have shown that olopatadine did not inhibit metabolic reactions which involve
cytochrome P-450 isozymes 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. These results indicate that
olopatadine is unlikely to result in metabolic interactions with other concomitantly administered active
substances.
Pregnancy
For olopatadine, no clinical data on exposed pregnancies are available.
Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy,
embryonal/foetal development, parturition or postnatal development (see section 5.3).
Caution should be exercised when prescribing to pregnant women.
Breast-feeding mothers
OPATANOL is not recommended for breast-feeding mothers.
Olopatadine has been detected in the milk of nursing rats following oral administration. Studies in
animals have shown reduced growth of nursing pups of dams receiving systemic doses of olopatadine
well in excess of the maximum level recommended for human ocular use. It is not known whether
topical administration to humans could result in sufficient systemic absorption to produce detectable
quantities in human breast milk.
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.
3
In clinical studies involving 1680 patients, OPATANOL was administered one to four times daily in
both eyes for up to four months as monotherapy or adjunctive therapy to loratadine 10 mg.
Approximately 4.5% of patients can be expected to experience undesirable effects associated with the
use of OPATANOL; however, only 1.6% of patients discontinued from the clinical studies due to
these undesirable effects. No serious ophthalmic or systemic undesirable effects related to
OPATANOL were reported in clinical studies. The most frequent treatment-related undesirable effect
was eye pain, reported at an overall incidence of 0.7%.
The following undesirable effects were assessed to be treatment-related and 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). Within each frequency
grouping, undesirable effects are presented in decreasing order of seriousness.
Infections and infestations
Uncommon: rhinitis
Nervous system disorders
Common: headache, dysgeusia
Uncommon: dizziness, hypoaesthesia
Eye disorders
Common: eye pain, eye irritation, dry eye, abnormal sensation in eyes
Uncommon: corneal erosion, corneal epithelium defect, corneal epithelium disorder, punctate keratitis,
keratitis, corneal staining, eye discharge, photophobia, vision blurred, visual acuity reduced,
blepharospasm, ocular discomfort, eye pruritus, conjunctival follicles, conjunctival disorder, foreign
body sensation in eyes, lacrimation increased, eyelids pruritus, erythema of eyelid, eyelid oedema,
eyelid disorder, conjunctival hyperaemia, ocular hyperaemia
Respiratory, thoracic, and mediastinal disorders
Common: nasal dryness
Skin and subcutaneous tissue disorders
Uncommon: dermatitis contact, skin burning sensation, dry skin
General disorders and administration site conditions
Common: fatigue
Not known (cannot be estimated from the available data):
Adverse reactions identified from post-marketing experience that have not been reported previously in
clinical trials with OPATANOL include those detailed below. Unlike data from clinical trials, due to
the nature of post-marketing surveillance, the frequency at which these events occur is not known and
cannot be estimated based upon the available data.
Ocular: corneal oedema, conjunctivitis, eye oedema, eye swelling, mydriasis, visual disturbance,
eyelid margin crusting
Systemic: hypersensitivity, dyspnea, somnolence, swelling face, dermatitis, erythema, nausea,
vomiting, sinusitis, asthenia, malaise
No data are available in humans regarding overdose by accidental or deliberate ingestion. Olopatadine
has a low order of acute toxicity in animals. Accidental ingestion of the entire contents of a bottle of
OPATANOL would deliver a maximum systemic exposure of 5 mg olopatadine. This exposure would
result in a final dose of 0.5 mg/kg in a 10 kg infant, assuming 100% absorption.
4
Prolongation of the QTc interval in dogs was observed only at exposures considered sufficiently in
excess of the maximum human exposure indicating little relevance to clinical use. A 5 mg oral dose
was administered twice-daily for 2.5 days to 102 young and elderly male and female healthy
volunteers with no significant prolongation of QTc interval compared to placebo. The range of peak
steady-state olopatadine plasma concentrations (35 to 127 ng/ml) seen in this study represents at least
a 70-fold safety margin for topical olopatadine with respect to effects on cardiac repolarisation.
In the case of overdose, appropriate monitoring and management of the patient should be
implemented.
5.
5.1 Pharmacodynamic properties
Pharmacotherapeutic Group: ophthalmologicals; decongestant and antiallergics; other antiallergics.
ATC code: S01GX 09
Olopatadine is a potent selective antiallergic/antihistaminic agent that exerts its effects through
multiple distinct mechanisms of action. It antagonises histamine (the primary mediator of allergic
response in humans) and prevents histamine induced inflammatory cytokine production by human
conjunctival epithelial cells. Data from
in vitro
studies suggest that it may act on human conjunctival
mast cells to inhibit the release of pro-inflammatory mediators. In patients with patent nasolacrimal
ducts, topical ocular administration of OPATANOL was suggested to reduce the nasal signs and
symptoms that frequently accompany seasonal allergic conjunctivitis. It does not produce a clinically
significant change in pupil diameter.
5.2 Pharmacokinetic properties
Olopatadine is absorbed systemically, as are other topically administered medicinal products.
However, systemic absorption of topically applied olopatadine is minimal with plasma concentrations
ranging from below the assay quantitation limit (<0.5 ng/ml) up to 1.3 ng/ml. These concentrations are
50-to 200-fold lower than those following well tolerated oral doses. From oral pharmacokinetic
studies, the half-life of olopatadine in plasma was approximately eight to 12 hours, and elimination
was predominantly through renal excretion. Approximately 60-70% of the dose was recovered in the
urine as active substance. Two metabolites, the mono-desmethyl and the N-oxide, were detected at low
concentrations in the urine.
Since olopatadine is excreted in urine primarily as unchanged active substance, impairment of renal
function alters the pharmacokinetics of olopatadine with peak plasma concentrations 2.3-fold greater
in patients with severe renal impairment (mean creatinine clearance of 13.0 ml/min) compared to
healthy adults. Following a 10 mg oral dose in patients undergoing haemodialysis (with no urinary
output), plasma olopatadine concentrations were significantly lower on the haemodialysis day than on
the non-haemodialysis day suggesting olopatadine can be removed by haemodialysis.
Studies comparing the pharmacokinetics of 10 mg oral doses of olopatadine in young (mean age
21 years) and elderly (mean age 74 years) showed no significant differences in the plasma
concentrations (AUC), protein binding or urinary excretion of unchanged parent drug and metabolites.
A renal impairment study after oral dosing of olopatadine has been performed in patients with severe
renal impairment. The results indicate that a somewhat higher plasma concentration can be expected
with OPATANOL in this population. Since plasma concentrations following topical ocular dosing of
olopatadine are 50-to 200-fold lower than after well-tolerated oral doses, dose adjustment is not
expected to be necessary in the elderly or in the renally impaired population. Liver metabolism is a
minor route of elimination. Dose adjustment is not expected to be necessary with hepatic impairment.
5
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety,
pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential and toxicity to
reproduction.
6.1 List of excipients
Benzalkonium chloride,
sodium chloride,
disodium phosphate dodecahydrate (E339),
hydrochloric acid (E507) and/or sodium hydroxide (E524) (to adjust pH),
purified water.
6.2 Incompatibilities
Not applicable.
6.3 Shelf-life
3 years.
Discard four weeks after first opening.
6.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
6.5 Nature and content of container
5 ml opaque low density polyethylene bottles with polypropylene screw caps (DROP-TAINER).
Cartons containing 1 or 3 bottles. Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
Alcon Laboratories (UK) Ltd.
Pentagon Park
Boundary Way
Hemel Hempstead
Herts., HP2 7UD
United Kingdom
8.
EU/1/02/217/001-002
6
9.
Date of first authorisation: 17
th
May 2002
Date of last renewal:
22
nd
May 2007
7
ANNEX II
A.
MANUFACTURING AUTHORISATION HOLDERS
RESPONSIBLE FOR BATCH RELEASE
B.
CONDITIONS OF THE MARKETING AUTHORISATION
8
A. MANUFACTURING AUTHORISATION HOLDERS RESPONSIBLE FOR BATCH
RELEASE
Names and addresses of the manufacturer(s) 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.
The printed package leaflet of the medicinal product must state the name and address of the
manufacturer responsible for the release of the concerned batch.
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.
9
ANNEX III
LABELLING AND PACKAGE LEAFLET
10
A. LABELLING
11
PARTICULARS TO APPEAR ON THE OUTER PACKAGING
BOX OF 1 BOTTLE + BOX OF 3 BOTTLES
1.
OPATANOL 1 mg/ml eye drops, solution
Olopatadine
2.
STATEMENT OF ACTIVE SUBSTANCE
1 ml of solution contains 1 mg olopatadine (as hydrochloride).
3.
LIST OF EXCIPIENTS
Benzalkonium chloride, sodium chloride, disodium phosphate dodecahydrate, hydrochloric
acid/sodium hydroxide (to adjust pH) and purified water.
4.
Eye drops, solution;
1 x 5 ml
3 x 5 ml
5.
METHOD AND ROUTE OF ADMINISTRATION
Ocular use. Read the package leaflet before 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: xx/xxxx
Discard four weeks after first opening.
Opened:
Opened (1):
Opened (2):
Opened (3):
9.
SPECIAL STORAGE CONDITIONS
12
10. SPECIAL PRECAUTIONS FOR DISPOSAL OF UNUSED MEDICINAL PRODUCTS
OR WASTE MATERIALS DERIVED FROM SUCH MEDICINAL PRODUCTS, IF
APPROPRIATE
Alcon Laboratories (UK) Ltd.
Pentagon Park
Boundary Way
Hemel Hempstead
Herts., HP2 7UD
United Kingdom
12. MARKETING AUTHORISATION NUMBERS
EU/1/02/217/001 1 x 5 ml
EU/1/02/217/002 3 x 5 ml
13. BATCH NUMBER
Lot: xxxxx
14. GENERAL CLASSIFICATION FOR SUPPLY
Medicinal product subject to medical prescription.
15. INSTRUCTIONS ON USE
16. INFORMATION IN BRAILLE
Opatanol
13
MINIMUM PARTICULARS TO APPEAR ON SMALL IMMEDIATE PACKAGING UNITS
BOTTLE LABEL
1.
OPATANOL 1 mg/ml eye drops.
Olopatadine. Ocular use.
2.
METHOD OF ADMINISTRATION
Read the package leaflet before use.
3.
EXPIRY DATE
Exp: xx/xxxx
Discard four weeks after first opening.
Opened:
4.
BATCH NUMBER
Lot:
5.
CONTENTS BY WEIGHT, BY VOLUME OR BY UNIT
5 ml
6
OTHER
14
B. PACKAGE LEAFLET
15
PACKAGE LEAFLET: INFORMATION FOR THE USER
OPATANOL 1 mg/ml eye drops, solution.
Olopatadine.
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 , ask your doctor
or pharmacist.
This medicine has been prescribed for you. Do not pass it on to others. It may harm them even if their
symptoms are the same as yours.
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.
1.
WHAT OPATANOL DOES
OPATANOL is used for the treatment of signs and symptoms of seasonal allergic conjunctivitis.
Allergic conjunctivitis.
Some materials (allergens) like pollens, house dust or animal fur may cause
allergic reactions resulting in itching, redness as well as swelling of the surface of your eye.
OPATANOL is a medicine
for treatment of allergic conditions of the eye. It works by reducing the
intensity of the allergic reaction.
2.
BEFORE YOU USE OPATANOL
Do not use OPATANOL
•
If you are allergic
(hypersensitive) to olopatadine or any of the other ingredients of
OPATANOL.
Ask your doctor for advice.
Take special care with OPATANOL...
•
Do not use OPATANOL in children under the age of 3 years.
Using other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines,
including medicines obtained without a prescription.
If you are using other eye drops
at the same time as OPATANOL, follow the advice at the end of
section 3.
Pregnant women
If you are pregnant, or might get pregnant,
talk to your doctor before you use OPATANOL.
Breast feeding women
If you are breast feeding. Do not use OPATANOL,
it 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 OPATANOL. Do not drive or
use machines until this has worn off.
16
Important information about some of the ingredients of OPATANOL
If you wear soft contact lenses.
Do not use the drops while your contact lenses are in your eyes. Wait
10-15 minutes after using the eye drops before putting your lenses back into your eyes. A preservative
in OPATANOL (benzalkonium chloride) can affect soft lenses.
3.
HOW TO USE OPATANOL
Always use OPATANOL exactly as your doctor has told you. Check with your doctor or pharmacist
if you are not sure.
The usual dose is…
one
drop in the eye or eyes, twice a day
– morning and evening.
Use this much unless your doctor tells you to do differently. Only use OPATANOL in both eyes if
your doctor told you to. Use it for as long as your doctor told you to.
Only
use OPATANOL as an eye drop.
TURN THE PAGE FOR MORE ADVICE
Now turn over>
17
3.
HOW TO USE OPATANOL (
continued)
1
2
How much to use
< see side 1
•
Get the OPATANOL bottle and a mirror.
•
Wash your hands.
•
Take the bottle and twist off the cap.
•
Hold the bottle, pointing down, between your thumb and middle finger.
•
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 1).
•
Bring the bottle tip close to the eye. Use the mirror if it helps.
•
Don’t touch your eye or eyelid, surrounding areas or other surfaces with the dropper.
It
could infect the drops left in the bottle.
•
Gently press on the base
of the bottle to release one drop of OPATANOL at a time.
•
Don’t squeeze the bottle,
it is designed so that just a gentle press on the bottom is needed
(picture 2).
•
If you use drops in both eyes, repeat the steps for your other eye.
•
Put the bottle cap back on firmly immediately after use.
•
Use up one bottle before opening the next bottle.
If a drop misses your eye
, try again.
If you use more OPATANOL than you should
rinse it all out with warm water. Don’t put in any
more drops until it’s time for your next regular dose.
If you forget to use OPATANOL,
use a single drop as soon as you remember, and then go back to
your regular routine.
Do not
use a double dose to make up for the one missed.
If you are using other eye drops,
wait at least five to ten minutes between putting in OPATANOL
and the other drops.
If you have any further questions on the use of this product, ask your doctor or pharmacist
4.
POSSIBLE SIDE EFFECTS
Like all medicines, OPATANOL can cause side effects, although not everybody gets them.
Common side effects
These may affect up to 10 in every 100 people
Effects in the eye
: eye pain or swelling, eye irritation, dry eye, abnormal eye sensation
Effects in the body
: headache, fatigue, dry nose, bad taste
Uncommon side effects
These may affect up to 1 in every 100 people
18
Effects in the eye
: blurred, reduced, or abnormal vision, corneal disorder, inflammation or infection of
the conjunctiva, eye discharge, eye allergy, sensitivity to light, increased tear production, itchy eye,
redness of the eye, eyelid abnormality, itching, redness, swelling, or crusting of the eyelid.
Effects in the body
: abnormal or decreased sensation, dizziness, runny nose, dry skin, skin
inflammation, redness, and itching.
Additional side effects that have been reported include:
Effects in the eye:
change in pupil size
Effects in the body
: shortness of breath, increased allergic symptoms, facial swelling, drowsiness,
generalized weakness, nausea, vomiting, sinus infection
You can usually carry on taking the drops
, unless the effects are serious.
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 OPATANOL
Keep out of the reach and sight of children.
Do not use OPATANOL after the expiry date which is stated on the bottle and the boxafter ‘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 four weeks after you first opened it,
to prevent infections, and use
a new bottle. Write down the date you opened it in the space on each bottle label and box
Medicines should not be disposed of via waste water or household waste. Ask your pharmacist how to
dispose of medicines no longer required. This will help protect the environment.
6
FURTHER INFORMATION
What OPATANOL CONTAINS
The active substance is olopatadine
1 mg/ml (as hydrochloride).
The other ingredients are: benzalkonium chloride, sodium chloride, disodium phosphate
dodecahydrate (E339), and purified water. Tiny amounts of hydrochloric acid (E507) and/or sodium
hydroxide (E524) are sometimes added to keep acidity levels (pH levels) normal.
What OPATANOL looks like and the contents of the pack
OPATANOL
is a clear liquid (a solution) supplied in a pack containing either one 5 ml plastic bottle
or three 5 ml bottles with screw caps. Not all pack sizes may be marketed.
19
The marketing authorisation holder Manufacturer
Manufacturer
Alcon Laboratories (UK) Ltd
S.A. Alcon –Couvreur N.V. Alcon Cusí. S.A.
Camil Fabra 58
Boundary Way
B-2870 Puurs
08320 El Masnou
Hemel Hempstead
Belgium
Spain
Herts HP2 7UD
United Kingdom
20
Pentagon Park
Rijksweg 14
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
21
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
Latvija
Alcon Pharmaceuticals Ltd
+ 371 7 321 121
This leaflet was last approved on XXXXX
Detailed information on this medicine is available on the European Medicines Agency website:
http://www.ema.europa.eu
22
Source: European Medicines Agency
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