PATADAY® solution is indicated for:
• the treatment of ocular itching associated with seasonal allergic conjunctivitis.

Special population
• Pediatric population:
The effectiveness of PATADAY has not been established in pediatric patients <18 years of age.
No overall difference in safety has been observed between pediatric and adult patients.

• Geriatric population
No overall differences in safety and effectiveness have been observed between elderly and other adult patients.

For topical ocular use only. Not for injection or oral use.
Dosing Considerations
No special dosage considerations are necessary for PATADAY.
Recommended Dose and Dosage Adjustment
The recommended dose is one drop in each affected eye once a day.
No dosage adjustment is required in hepatic or renal impairment.
Missed Dose
If a dose is missed, a single drop should be taken as soon as possible before reverting to regular routine. Do not use a double dose to make up for the one missed.
Contamination
As with any eye drop, to prevent contamination of the dropper tip and solution, care should be taken not to touch the eyelids or surrounding areas with the dropper tip of the bottle. Keep bottle tightly closed when not in use.
Patients should be advised not to wear contact lenses if their eye(s) are red.
PATADAY should not be used to treat contact lens related irritation.
Pediatrics
Pediatrics (<18 years): Effectiveness in pediatric patients has not been established. No overall difference in safety has been observed between pediatric and adult patients.
Geriatrics
No overall differences in safety and effectiveness have been observed between elderly and other adult patients.

The preservative in PATADAY, benzalkonium chloride, may cause eye irritation and is known to discolour soft contact lenses. Contact with soft contact lenses should be avoided. Patients must be instructed to remove contact lenses prior to application of PATADAY, and wait at least 15 minutes before they insert their contact lenses.
If using other eye drops, patients should wait at least five minutes between putting in PATADAY and the other drops. Eye ointments should be applied last.

No clinical interaction studies have been conducted with PATADAY. In vitro studies have shown that olopatadine does not inhibit metabolic reactions which involve cytochrome P-450 isoenzymes 1A2, 2C8, 2C9, 2C19, 2D6, 2E1 and 3A4. Olopatadine is moderately bound to plasma proteins (approximately 55%). These results indicate that olopatadine is unlikely to result in interactions with other concomitantly administered medications. Due to the low systemic exposure following topical ocular dosing, it is unlikely that PATADAY would interfere with immediate hypersensitivity skin testing.
Interactions with other drugs, food, herbal products or laboratory tests have not been established.

• Fertility
Studies have not been performed to evaluate the effect of topical ocular administration of olopatadine on human fertility.
• Pregnant Women
There are no adequate and well controlled studies in pregnant women. Studies in animals with olopatadine have shown reproductive toxicity following systemic administration considered sufficiently in excess of the maximum human exposure. Olopatadine was found not to be teratogenic in rats and rabbits at oral doses >90,000 and >60,000 times the maximum recommended ocular human use level, respectively. Because animal studies are not always predictive of human responses, PATADAY should be used in pregnant women only if the potential benefit to the mother justifies the potential risk to the embryo or fetus.
• Breast-feeding
Olopatadine has been identified in the milk of nursing rats following oral administration. It is not known whether topical ocular administration could result in sufficient systemic absorption to produce detectable quantities in human breast milk. Nevertheless, caution should be exercised
when PATADAY is administered to a nursing mother.

Olopatadine is a non-sedating anti-histamine. Temporary blurred vision or other visual disturbances, after the use of PATADAY, may affect the ability to drive or use machines. If blurred vision occurs after instillation, patients must wait until vision clears before driving or using machinery.

• Adverse Reaction Overview
In clinical trials involving 1137 patients dosed with long-term ophthalmic topical therapy, PATADAY was administered once-daily for 4 to 12 weeks. The most frequently reported treatment-related undesirable effects were headache (0.8%), eye irritation (0.5%), dry eye (0.4%), and eyelid margin crusting (0.4%). No serious adverse drug reactions related to PATADAY were reported in the clinical trials.
• Clinical Trial Adverse Reactions
Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug. Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use.
No treatment-related adverse drug reactions occurred at an incidence ≥ 1%.
• Less Common Clinical Trial Adverse Reactions
The most frequently reported adverse drug reactions (>0.1%) are presented below.
Treatment-Related Adverse Drug Reactions >0.1% – Long-Term Exposure
Eye disorders: eye irritation, dry eye, eyelid margin crusting, and eye pruritus.
Gastrointestinal disorders: dry mouth.
Nervous system disorders: headache, dysgeusia.
Additional treatment-related adverse drug reactions that occurred at an incidence of 0.1% included the following:
Eye disorders: asthenopia, eye swelling, eyelid disorder, eyelids pruritus, ocular hyperaemia, and vision blurred.
Investigations: heart rate increased.
Respiratory, Thoracic, and Mediastinal disorders: nasal dryness
• Post-Market Adverse Reactions
Approximately 5.4 million units of PATADAY have been sold worldwide. The reporting rate of all reaction terms reported between 22 December 2004 and 31 August 2009 was 0.005%, and no single reaction term occurred with a reporting rate greater than 0.0007%. No post-market reports of serious adverse reactions have been received to date. The most frequent events reported being eye irritation, ocular hyperaemia, eye pain and vision blurred. There were no new major findings bearing on the established overall safety profile of PATADAY. Other events include dizziness, eye discharge, punctate keratitis, keratitis, erythema of eyelid, dermatitis contact, fatigue, hypersensitivity, ocular discomfort, lacrimation increased and nausea.
• To report any side effect(s):
Saudi Arabia
The National Pharmacovigilance Centre (NPC):
o SFDA call center: 19999
o E-mail: npc.drug@sfda.gov.sa
o Website: https://ade.sfda.gov.sa
Patient Safety Department Novartis Consulting AG - Saudi Arabia:
o Toll Free Number: 8001240078
o Phone: +966112658100
o Fax: +966112658107
o Email: adverse.events@novartis.com
• Other GCC States:
- Please contact the relevant competent authority.
To report any complaint(s) : complaints.ksa@novartis.com

No data are available in humans regarding overdose by accidental or deliberate ingestion of PATADAY. No reports of overdose were received during the clinical studies of PATADAY.
If a topical overdose of PATADAY occurs, the eye(s) may be flushed with tap water.
For management of suspected drug overdose, consult your regional poison control centre.

• Mechanism of Action
Olopatadine, a structural analog of doxepin, is a non-steroidal, non-sedating, topically effective anti-allergic molecule that exerts its effects through multiple distinct mechanisms of action. Olopatadine is a mast cell stabilizer and a potent, selective histamine H1 antagonist that inhibits the in vivo type 1 immediate hypersensitivity reaction. In vitro studies have demonstrated the ability of olopatadine to stabilize rodent basophils and human conjunctival mast cells and inhibit immunologically-stimulated release of histamine. In addition, Olopatadine inhibits the release of mast cell inflammatory mediators [i.e., histamine, tryptase, prostaglandin D2 and TNFα] as demonstrated in in vitro studies and confirmed in patients. Olopatadine is a selective histamine H1 receptor antagonist in vitro and in vivo as demonstrated by its ability to inhibit histamine binding and histamine-stimulated vascular permeability in the conjunctiva following topical ocular administration. Olopatadine is also an inhibitor of pro-inflammatory cytokine secretion from human conjunctival epithelial cells. Decreased chemotaxis and inhibition of eosinophil activation has also been reported. Olopatadine is devoid of effects on alpha-adrenergic, dopamine, muscarinic type 1 and 2, and serotonin receptors.
Effects on cardiac repolarization (QTc):
Olopatadine had no observed effect on heart rate, cardiac conduction (PR and QRS interval duration), cardiac repolarization (QT duration) or wave form morphology relative to placebo in 2 double-masked, placebo controlled, 2-way crossover studies of 102 subjects given 5-mg oral doses of olopatadine every 12 hours for 2.5 days and 32 subjects given 20-mg oral doses twice-
daily for 13.5 days. No clinically relevant or statistically significant changes in mean QTcF (determined to be the most appropriate heart correction formula for both study populations) at steady-state from baseline were observed in either study. A categorical analysis of QTc (< 30 ms, 30 ms-60 ms, or > 60 ms) showed no statistically significant differences between olopatadine and placebo in both studies. An analysis of the maximal change from baseline in QTcF showed the difference was higher for placebo than for olopatadine. In addition, no evidence of QT interval prolongation was observed, relative to placebo, in 429 perennial allergic rhinitis patients given olopatadine hydrochloride nasal spray, 665 micrograms twice daily for up to 1 year.

Systemic bioavailability data upon topical ocular administration of PATADAY are not available.
Absorption:
Following topical ocular administration in man, olopatadine was shown to have low systemic exposure. Two studies in healthy volunteers (totalling 24 subjects) dosed bilaterally with Olopatadine 0.15% ophthalmic solution once every 12 hours for 2 weeks demonstrated plasma concentrations to be generally below the quantitation limit of the assay (<0.5 ng/mL). Samples in which olopatadine was quantifiable were typically found within 2 hours of dosing and ranged from 0.5 to 1.3 ng/mL. These plasma concentrations were greater than 300 fold below those observed with a well-tolerated 20 mg oral multiple-dose regimen. In oral studies, olopatadine was found to be well absorbed.
In multiple oral dose studies, olopatadine plasma concentrations were shown to increase in proportion to the dose increment.
Metabolism:
Approximately 60-70% of the oral dose was recovered in the urine as parent drug. Peak plasma concentrations of the active metabolite, N-desmethyl olopatadine and inactive N-oxide metabolite were low, less than 1% and 3% of parent, respectively. Two metabolites, the mono-desmethyl and the N-oxide, were detected at low concentrations in the urine.
Elimination: The elimination half-life in plasma was 7-14 hours, and elimination was predominantly through renal excretion.
Special Populations and Conditions
• Pediatrics - Effectiveness in paediatric patients has not been established. No overall difference in safety has been observed between paediatric and adult patients.
• Geriatrics - No overall differences in safety and effectiveness have been observed between elderly and other adult patients.
• Sex - In multiple oral dose studies, plasma concentrations of olopatadine are higher in female subjects, however, the differences are small and not clinically meaningful.
• Ethnic Origin - No specific pharmacokinetic study examining the effect of race has been conducted.
• Hepatic Insufficiency - No specific pharmacokinetic study examining the effect of hepatic impairment was conducted. Since metabolism of olopatadine is a minor route of elimination, no adjustment of the dosing regimen of PATADAY is warranted in patients with hepatic impairment
• Renal Insufficiency - The mean plasma Cmax values for olopatadine following single intranasal doses of olopatadine hydrochloride nasal spray 0.6% (665 μg/spray) were not markedly different between healthy subjects (18.1 ng/mL) and patients with mild, moderate and severe renal impairment (range 15.5 to 21.6 ng/mL). Plasma AUC was 2.5-fold higher in patients with severe impairment (creatinine clearance <30 mL/min/1.73m2). Predicted peak steady-state plasma concentrations of olopatadine in patients with renal impairment following administration of olopatadine hydrochloride ophthalmic solution, 0.1% are at least 10-fold lower than those observed following administration of olopatadine nasal spray 0.6%, and approximately 300-fold lower than those observed following the safe and well-tolerated administration of 20 mg oral doses for 13.5 days. These findings indicate that no adjustment of the dosing regimen of PATADAY is warranted in patients with renal impairment.

Olopatadine administered orally was not carcinogenic in mice and rats in doses up to 500 mg/kg/day and 200 mg/kg/day, respectively. Based on a 40 μL drop size and a 50 kg person, these doses were approximately 150,000 and 50,000 times higher than the maximum recommended ocular human dose (MROHD) based on body weight comparison. No mutagenic potential was observed when olopatadine was tested in an in vitro bacterial reverse mutation (Ames) test, an in vitro mammalian chromosome aberration assay or an in vivo mouse micronucleus test. Olopatadine administered to male and female rats at oral doses of approximately 100,000 times MROHD level resulted in a slight decrease in the fertility index and reduced implantation rate; no effects on reproductive function were observed at doses of approximately 15,000(based on mg/kg) times the MROHD level.

Benzalkonium chloride (preservative)
Disodium phosphate
Edetate disodium
Hydrochloric acid and/or
Sodium hydroxide (to adjust pH)
Povidone
Purified water
Sodium chloride.

None

Store below 30°C.
Discard the container at the end of treatment or 4 weeks after first opening whichever comes first. Keep out of the reach and sight of children.

PATADAY® (olopatadine hydrochloride ophthalmic solution) 0.2% is supplied in a plastic
2.5 mL fill in 4 mL bottle

No special requirements