Treatment of ocular signs and symptoms of seasonal allergic conjunctivitis.

The dose is one drop of OLOPAT 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
OLOPAT 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 (OLOPAT) 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).

OLOPAT 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 OLOPAT
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 OLOPAT before inserting
contact lenses. OLOPAT 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
OLOPAT 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.

In clinical studies involving 1680 patients, OLOPAT 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 OLOPAT; 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
OLOPAT 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 OLOPAT 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 OLOPAT 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.
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.

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 OLOPAT 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.

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 monodesmethyl
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 OLOPAT 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.

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.

Benzalkonium Chloride.
Disodium Hydrogen phosphate anhydrous.
Sodium chloride.
Polysorbate 80
Hydrochloric Acid 1N
And / Or Sodium Hydroxide 1N q.s. to ad. pH
Water for injection q.s to make

Not applicable.

Do not store above 30OC.

LDPE Opaque bottle

No special requirements.