HIGHLIGHTS OF PRESCRIBING
`INFORMATION
`
`These highlights do not include all the information
`needed to use PATADAY™ safely and effectively.
`
`See full prescribing information for PATADAY™.
`
`PATADAY™ (olopatadine hydrochloride
`
`ophthalmic solution) 0.2%
`
`Initial U.S. Approval: 1996
`
`
`
`-------------INDICATIONS AND USAGE-----
`PATADAY™ solution is a mast cell stabilizer
`indicated for the treatment of ocular itching
`
`associated with allergic conjunctivitis. (1)
`
`
`---DOSAGE AND ADMINISTRATION-----
`The recommended dose is one drop in each affected
`eye once a day. (2)
`
`---DOSAGE FORMS AND STRENGTHS-----
`
`Ophthalmic solution 0.2%: each ml contains 2.22 mg
`
`of olopatadine hydrochloride. (3)
`
`_____________________________________________________________________
`
`
`----WARNINGS AND PRECAUTIONS-------
`
`For topical ocular use only. Not for injection or oral
`use. (5.1)
`
`----------ADVERSE REACTIONS---------------
`Symptoms similar to cold syndrome and pharyngitis
`
`
`were reported at an incidence of approximately 10%.
`(6)
`
`To report SUSPECTED ADVERSE
`REACTIONS, contact Alcon Laboratories, Inc. at
`
`
`1-800-757-9195 or FDA at 1-800-FDA-1088 or
`
`
`www.fda.gov/medwatch.
`
`See 17 for PATIENT COUNSELING
`INFORMATION and FDA-approved patient
`labeling.
`
`
`Revised: 8/2010
`
`
`
`DESCRIPTION
`
`CLINICAL PHARMACOLOGY
`
`12.1 Mechanism of Action
`12.3 Pharmacokinetics
`NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis,
`
`Impairment of Fertility
`14
`CLINICAL STUDIES
`
`16 HOW SUPPLIED/STORAGE AND
`HANDLING
`
`PATIENT COUNSELING
`INFORMATION
`
`
`
`
`*Sections or subsections omitted from the full
`
`
`prescribing information are not listed.
`_________________________________________________________________________________________
`
`
`
`11
`12
`
`13
`
`17
`
`
`
`FULL PRESCRIBING INFORMATION:
`CONTENTS*
`
`1
`INDICATIONS AND USAGE
`
`
`2
`DOSAGE AND ADMINISTRATION
`
`
`
`3
`DOSAGE FORMS AND STRENGTHS
`
`4
`CONTRAINDICATIONS
`
`5 WARNINGS AND PRECAUTIONS
`
`ADVERSE REACTIONS
`6
`
`USE IN SPECIFIC POPULATIONS
`8
`
`
`Pregnancy
`8.1
`8.3 Nursing Mothers
`8.4
`Pediatric Use
`8.5 Geriatric Use
`
`
`Reference ID: 2873253
`
`NDA 21545/S-013
`Page 4
`
`ARGENTUM PHARM. 1038
`
`000001
`
`

`
`soft contact lenses. Patients who wear soft
`contact lenses and whose eyes are not red,
`should be instructed to wait at least ten
`minutes after instilling PATADAY™
`olopatadine hydrochloride ophthalmic
`solution) 0.2% before they insert their
`
`contact lenses.
`
`6
`
`Symptoms similar to cold syndrome and
`pharyngitis were reported at an incidence of
`approximately 10%.
`
` ADVERSE REACTIONS
`
`
`The following adverse experiences have
`been reported in 5% or less of patients:
`
`
`
`Ocular: blurred vision, burning or stinging,
`conjunctivitis, dry eye, foreign body
`sensation, hyperemia, hypersensitivity,
`keratitis, lid edema, pain and ocular pruritus.
`
`Non-ocular: asthenia, back pain, flu
`syndrome, headache, increased cough,
`infection, nausea, rhinitis, sinusitis and taste
`perversion.
`
`Some of these events were similar to the
`underlying disease being studied.
`
`8
`
`USE IN SPECIFIC POPULATIONS
`
`8.1 Pregnancy
`Teratogenic effects: Pregnancy Category
`C
`Olopatadine was found not to be teratogenic
`in rats and rabbits. However, rats treated at
`600 mg/kg/day, or 150,000 times the
`MROHD and rabbits treated at 400
`mg/kg/day, or approximately 100,000 times
`the MROHD, during organogenesis showed
`a decrease in live fetuses. In addition, rats
`treated with 600 mg/kg/day of olopatadine
`during organogenesis showed a decrease in
`fetal weight. Further, rats treated with 600
`mg/kg/day of olopatadine during late
`
`
`
`
`
`FULL PRESCRIBING INFORMATION
`
`
`1
`
`INDICATIONS AND USAGE
`
`
`
`PATADAY™ solution is indicated for the
`treatment of ocular itching associated with
`allergic conjunctivitis.
`
`
`
`2
`
`DOSAGE AND
`ADMINISTRATION
`
`The recommended dose is one drop in each
`affected eye once a day.
`
`3
`
`DOSAGE FORMS AND
`STRENGTHS
`
`Ophthalmic solution 0.2%: each ml contains
`2.22 mg of olopatadine hydrochloride.
`
`4
`
` CONTRAINDICATIONS
`
`None.
`
`5 WARNINGS AND PRECAUTIONS
`
`5.1 For topical ocular use only. Not for
`injection or oral use.
`
`5.2 Contamination of Tip and Solution
`As with any eye drop, to prevent
`contaminating 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.
`
`5.3 Contact Lens Use
`Patients should be advised not to wear a
`contact lens if their eye is red.
`
`PATADAY™ (olopatadine hydrochloride
`ophthalmic solution) 0.2% should not be
`used to treat contact lens related irritation.
`
`The preservative in PATADAY™ solution,
`benzalkonium chloride, may be absorbed by
`
`
`Reference ID: 2873253
`
`NDA 21545/S-013
`
`000002
`
`

`
`
`
`
`Chemical Name: 11-[(Z)-3­
`(Dimethylamino) propylidene]-6-11­
`dihydrodibenz[b,e] oxepin-2-acetic acid,
`hydrochloride
`
`Each mL of PATADAY™ solution
`contains: Active: 2.22 mg olopatadine
`hydrochloride equivalent to 2 mg
`olopatadine. Inactives: povidone; dibasic
`sodium phosphate; sodium chloride;
`edentate disodium; benzalkonium chloride
`0.01% (preservative); hydrochloric
`acid/sodium hydroxide (adjust pH); and
`purified water.
`
`
`
`It has a pH of approximately 7 and an
`osmolality of approximately 300 mOsm/kg.
`
`12 CLINICAL PHARMACOLOGY
`
`12.1 Mechanism of Action
`Olopatadine is a mast cell stabilizer and a
`histamine H1 antagonist. Decreased
`chemotaxis and inhibition of eosinophil
`activation has also been demonstrated.
`
`12.3 Pharmacokinetics
`Systemic bioavailability data upon topical
`ocular administration of PATADAY™
`solution are not available. Following topical
`ocular administration of olopatadine 0.15%
`ophthalmic solution in man, olopatadine was
`shown to have a low systemic exposure.
`Two studies in normal volunteers (totaling
`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
`
`
`
`
`
`gestation through the lactation period
`showed a decrease in neonatal survival and
`body weight. There are, however, no
`adequate and well- controlled studies in
`pregnant women. Because animal studies are
`not always predictive of human responses,
`this drug should be used in pregnant women
`only if the potential benefit to the mother
`justifies the potential risk to the embryo or
`fetus.
`
`8.3 Nursing Mothers
`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 the human breast milk.
`Nevertheless, caution should be exercised
`when PATADAY™ olopatadine
`hydrochloride ophthalmic solution) 0.2% is
`administered to a nursing mother.
`
`8.4 Pediatric Use
`Safety and effectiveness in pediatric patients
`below the age of 2 years have not been
`established.
`
`
`8.5 Geriatric Use
`No overall differences in safety and
`effectiveness have been observed between
`elderly and younger patients.
`
`11 DESCRIPTION
`
`PATADAY™ (olopatadine hydrochloride
`ophthalmic solution) 0.2% is a sterile
`ophthalmic solution containing olopatadine
`for topical administration to the eyes.
`Olopatadine hydrochloride is a white,
`crystalline, water-soluble powder with a
`molecular weight of 373.88 and a molecular
`formula of C21H23NO3 • HCl.
`
`The chemical structure is presented below:
`
`
`Reference ID: 2873253
`
`NDA 21545/S-013
`Page 6
`
`000003
`
`

`
`
`
`
`
`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. The elimination half-life in plasma
`following oral dosing was 8 to 12 hours, and
`elimination was predominantly through
`renal excretion. Approximately 60 - 70% of
`the dose was recovered in the urine as parent
`drug. Two metabolites, the mono-desmethyl
`and the N-oxide, were detected at low
`concentrations in the urine.
`
`
`
`13 NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis,
`Impairment of Fertility
`
`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). 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 times the
`MROHD level.
`
`14 CLINICAL STUDIES
`
`
`
`Results from clinical studies of up to 12
`weeks duration demonstrate that
`PATADAY™ solution when dosed once a
`day is effective in the treatment of ocular
`itching associated with allergic
`conjunctivitis.
`
`
`
`Reference ID: 2873253
`
`16 HOW SUPPLIED/STORAGE AND
`HANDLING
`
`
`PATADAY™ (olopatadine hydrochloride
`ophthalmic solution) 0.2% is supplied in a
`white, oval, low density polyethylene
`DROP-TAINER® dispenser with a natural
`low density polyethylene dispensing plug
`and a white polypropylene cap. Tamper
`evidence is provided with a shrink band
`around the closure and neck area of the
`package.
`
`2.5 mL fill in 4 mL bottle (NDC 0065-0272­
`25)
`
`Storage
`Store at 2°C to 25°C (36°F to 77°F)
`
`17 PATIENT COUNSELING
`INFORMATION
`
`17.1 Topical Ophthalmic Use Only
`For topical ophthalmic administration only.
`
`17.2 Sterility of Dropper Tip
`Patients should be advised to not touch
`dropper tip to any surface, as this may
`contaminate the contents.
`
`17.3 Concomitant Use of Contact Lenses
`Patients should be advised not to wear a
`contact lens if their eyes are red. Patients
`should be advised that PATADAY™
`solution should not be use to treat contact
`lens-related irritation. Patients should also
`be advised to remove contact lenses prior to
`instillation of PATADAY™ solution. The
`preservative in PATADAY™ solution
`benzalkonium chloride may be absorbed by
`soft contact lenses. Lenses may be
`reinserted following administration of
`PATADAY™ solution.
`
`U.S. Patents Nos. 5,116,863; 5,641,805;
`6,995,186; 7,402,609
`
`NDA 21545/S-013
`Page 7
`
`000004