`
` NDA 202514/S-001
`Page 3
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`
`HIGHLIGHTS OF PRESCRIBING INFORMATION
`These highlights do not include all the information needed to use
`
`ZIOPTAN (tafluprost ophthalmic solution) 0.0015% safely and
`
`
`
`effectively. See full prescribing information for ZIOPTAN.
`
`
`
`
`ZIOPTAN™ (tafluprost ophthalmic solution) 0.0015%
`Initial U.S. Approval: 2012
`
`----------------------------INDICATIONS AND USAGE----------------------------
`• ZIOPTAN
`
`
`(tafluprost ophthalmic solution) 0.0015%
`is a
`prostaglandin analog
`intraocular
`indicated
`for reducing elevated
`pressure in patients with open-angle glaucoma or ocular hypertension.
`(1)
`----------------------- DOSAGE AND ADMINISTRATION -----------------------
`
`• One drop in the affected eye(s) once daily in the evening. (2)
`
`--------------------- DOSAGE FORMS AND STRENGTHS ---------------------
`• Ophthalmic solution containing tafluprost 0.015 mg/mL. (3)
`
`-------------------------------CONTRAINDICATIONS-------------------------------
`• None. (4)
`
`
`
`
`
`
`
`
`
`----------------------- WARNINGS AND PRECAUTIONS -----------------------
`• Pigmentation
`Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can
`occur. Iris pigmentation is likely to be permanent. (5.1)
`• Eyelash Changes
`Gradual changes to eyelashes including increased length, thickness
`and number of lashes. Usually reversible. (5.2)
`------------------------------ ADVERSE REACTIONS ------------------------------
`
`• Most common ocular adverse reaction is conjunctival hyperemia
`
`(range 4% – 20%). (6.1)
`To report SUSPECTED ADVERSE REACTIONS, contact Merck
`
`Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-
`
`888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
`
`----------------------- USE IN SPECIFIC POPULATIONS -----------------------
`
`• Use in pediatric patients is not recommended because of potential
`
`
`safety concerns related to increased pigmentation following long-term
`
`chronic use. (8.4)
`
`See 17 for PATIENT COUNSELING INFORMATION and FDA-
`
`approved patient labeling.
`
`Revised: 02/2013
`
`
`
`
`
`FULL PRESCRIBING INFORMATION: CONTENTS*
`
`1
`INDICATIONS AND USAGE
`2 DOSAGE AND ADMINISTRATION
`
`3 DOSAGE FORMS AND STRENGTHS
`4 CONTRAINDICATIONS
`5 WARNINGS AND PRECAUTIONS
`
`5.1 Pigmentation
`5.2 Eyelash Changes
`5.3
`Intraocular Inflammation
`5.4 Macular Edema
`6 ADVERSE REACTIONS
`6.1 Clinical Studies Experience
`6.2 Postmarketing Experience
`8 USE IN SPECIFIC POPULATIONS
`8.1 Pregnancy
`
`8.3 Nursing Mothers
`
`8.4 Pediatric Use
`8.5 Geriatric Use
`
`11 DESCRIPTION
`12 CLINICAL PHARMACOLOGY
`
`12.1 Mechanism of Action
`12.3 Pharmacokinetics
`13 NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`
`14 CLINICAL STUDIES
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`17 PATIENT COUNSELING INFORMATION
`17.1 Nightly Application
`
`17.2 Handling the Single-Use Container
`17.3 Potential for Pigmentation
`17.4 Potential for Eyelash Changes
`17.5 When to Seek Physician Advice
`17.6 Use with Other Ophthalmic Drugs
`17.7 Storage Information
`
`*Sections or subsections omitted from the full prescribing information
`
`are not listed.
`
`
`
`Reference ID: 3264663
`
`
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`NDA 202514/S-001
`Page 4
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`
`FULL PRESCRIBING INFORMATION
`
`
`1
`
`INDICATIONS AND USAGE
`ZIOPTAN™ (tafluprost ophthalmic solution) 0.0015% is indicated for reducing elevated intraocular pressure
`
`in patients with open-angle glaucoma or ocular hypertension.
`
`
`
`
`2
`
`DOSAGE AND ADMINISTRATION
`
`
`The recommended dose is one drop of ZIOPTAN in the conjunctival sac of the affected eye(s) once daily in
`
`the evening.
`
`The dose should not exceed once daily since it has been shown that more frequent administration of
`
`prostaglandin analogs may lessen the intraocular pressure lowering effect.
`
`
`Reduction of the intraocular pressure starts approximately 2 to 4 hours after the first administration with the
`
`
`maximum effect reached after 12 hours.
`
`ZIOPTAN may be used concomitantly with other topical ophthalmic drug products to lower intraocular
`
`pressure. If more than one topical ophthalmic product is being used, each one should be administered at least 5
`
`
`
`
`minutes apart.
`
`The solution from one individual unit is to be used immediately after opening for administration to one or
`
`both eyes. Since sterility cannot be maintained after the individual unit is opened, the remaining contents should be
`
`discarded immediately after administration.
`
`3
`
`
`4
`
`DOSAGE FORMS AND STRENGTHS
`
`Ophthalmic solution containing tafluprost 0.015 mg/mL.
`
`CONTRAINDICATIONS
`
`None.
`
`5 WARNINGS AND PRECAUTIONS
`5.1 Pigmentation
`
`Tafluprost ophthalmic solution has been reported to cause changes to pigmented tissues. The most frequently
`
`
`
`reported changes have been increased pigmentation of the iris, periorbital tissue (eyelid) and eyelashes.
`
`
`Pigmentation is expected to increase as long as tafluprost is administered. The pigmentation change is due to
`
`increased melanin content in the melanocytes rather than to an increase in the number of melanocytes. After
`
`discontinuation of tafluprost, pigmentation of the iris is likely to be permanent, while pigmentation of the periorbital
`
`
`tissue and eyelash changes have been reported to be reversible in some patients. Patients who receive treatment
`
`should be informed of the possibility of increased pigmentation. The long term effects of increased pigmentation are
`
`
`
`not known.
`
`Iris color change may not be noticeable for several months to years. Typically, the brown pigmentation
`around the pupil spreads concentrically towards the periphery of the iris and the entire iris or parts of the iris become
`
`
`more brownish. Neither nevi nor freckles of the iris appear to be affected by treatment. While treatment with
`
`ZIOPTAN can be continued in patients who develop noticeably increased iris pigmentation, these patients should be
`
`examined regularly. [See Patient Counseling Information (17.3).]
`
`
`5.2 Eyelash Changes
`
`ZIOPTAN may gradually change eyelashes and vellus hair in the treated eye. These changes include
`
`
`increased length, color, thickness, shape and number of lashes. Eyelash changes are usually reversible upon
`
`
`discontinuation of treatment.
`
`
`
`Reference ID: 3264663
`
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`NDA 202514/S-001
`Page 5
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`
`5.3
`
`Intraocular Inflammation
`
`
`
`ZIOPTAN should be used with caution in patients with active intraocular inflammation (e.g., iritis/uveitis)
`because the inflammation may be exacerbated.
`
`
`
`5.4 Macular Edema
`
`Macular edema, including cystoid macular edema, has been reported during treatment with prostaglandin F2α
`analogs. ZIOPTAN should be used with caution in aphakic patients, in pseudophakic patients with a torn posterior
`lens capsule, or in patients with known risk factors for macular edema.
`
`
`ADVERSE REACTIONS
`6
`
`6.1 Clinical Studies Experience
`
`Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in
`
`
`
`the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not
`
`reflect the rates observed in practice.
`
`
`Preservative-containing or preservative-free tafluprost 0.0015% was evaluated in 905 patients in five
`
`
`controlled clinical studies of up to 24-months duration. The most common adverse reaction observed in patients
`
`treated with tafluprost was conjunctival hyperemia which was reported in a range of 4% – 20% of patients.
`
`
`
`Approximately 1% of patients discontinued therapy due to ocular adverse reactions.
`
`
`Ocular adverse reactions reported at an incidence of ≥2% in these clinical studies included ocular
`
`stinging/irritation (7%), ocular pruritus including allergic conjunctivitis (5%), cataract (3%), dry eye (3%), ocular
`
`
`pain (3%), eyelash darkening (2%), growth of eyelashes (2%) and vision blurred (2%).
`
`
`
`Nonocular adverse reactions reported at an incidence of 2% – 6% in these clinical studies in patients treated
`
`
`with tafluprost 0.0015% were headache (6%), common cold (4%), cough (3%) and urinary tract infection (2%).
`
`6.2 Postmarketing Experience
`
`The following adverse reactions have been identified during postapproval use of tafluprost. Because
`
`postapproval adverse reactions are reported voluntarily from a population of uncertain size, it is not always possible
`
`
`to reliably estimate their frequency or establish a causal relationship to drug exposure.
`
`Eye disorders: iritis/uveitis
`
`
`In postmarketing use with prostaglandin analogs, periorbital and lid changes including deepening of the
`eyelid sulcus have been observed.
`
`USE IN SPECIFIC POPULATIONS
`8
`
`8.1 Pregnancy
`Pregnancy Category C.
`
`Teratogenic effects: In embryo-fetal development studies in rats and rabbits, tafluprost administered
`intravenously was teratogenic. Tafluprost caused increases in post-implantation losses in rats and rabbits and
`
`
`
`reductions in fetal body weights in rats. Tafluprost also increased the incidence of vertebral skeletal abnormalities in
`
`
`rats and the incidence of skull, brain and spine malformations in rabbits. In rats, there were no adverse effects on
`
`
`embryo-fetal development at a dose of 3 mcg/kg/day corresponding to maternal plasma levels of tafluprost acid that
`were 343 -times the maximum clinical exposure based on Cmax. In rabbits, effects were seen at a tafluprost dose of
`0.03 mcg/kg/day corresponding to maternal plasma levels of tafluprost acid during organogenesis that were
`
`
`approximately 5 times higher than the clinical exposure based on Cmax. At the no-effect dose in rabbits (0.01
`
`
`mcg/kg/day), maternal plasma levels of tafluprost acid were below the lower level of quantification (20 pg/mL).
`
`
`
`
`
`In a pre- and postnatal development study in rats, increased mortality of newborns, decreased body weights
`
`and delayed pinna unfolding were observed in offsprings. The no observed adverse effect level was at a tafluprost
`
`
`
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`Reference ID: 3264663
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`NDA 202514/S-001
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`Page 6
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`intravenous dose of 0.3 mcg/kg/day which is greater than 3 times the maximum recommended clinical dose based
`on body surface area comparison.
`
`
`There are no adequate and well-controlled studies in pregnant woman. Although animal reproduction studies
`
`
`are not always predictive of human response, ZIOPTAN should not be used during pregnancy unless the potential
`benefit justifies the potential risk to the fetus.
`
`
`Women of childbearing age/potential should have adequate contraceptive measures in place.
`
`
`8.3 Nursing Mothers
`A study in lactating rats demonstrated that radio-labeled tafluprost and/or its metabolites were excreted in
`
`
`
`
`milk. It is not known whether this drug or its metabolites are excreted in human milk. Because many drugs are
`excreted in human milk, caution should be exercised when ZIOPTAN is administered to a nursing woman.
`
`
`8.4 Pediatric Use
`Use in pediatric patients is not recommended because of potential safety concerns related to increased
`pigmentation following long-term chronic use.
`
`
`8.5 Geriatric Use
`
`
`No overall clinical differences in safety or effectiveness have been observed between elderly and other adult
`patients.
`
`11
`
`DESCRIPTION
`Tafluprost is a fluorinated analog of prostaglandin F2α. The chemical name for tafluprost is 1-methylethyl
`(5Z)-7-{(1R, 2R, 3R, 5S)-2-[(1E)-3,3-difluoro-4-phenoxy-1-butenyl}-3,5-dihydroxycyclopentyl]-5-heptenoate. The
`
`molecular formula of tafluprost is C25H34F2O5 and its molecular weight is 452.53.
`
`Its structural formula is:
`
`
`
`
`
`
`
`Tafluprost is a colorless to light yellow viscous liquid that is practically insoluble in water.
`
`
`
`ZIOPTAN (tafluprost ophthalmic solution) 0.0015% is supplied as a sterile solution of tafluprost with a pH
`range of 5.5 – 6.7 and an Osmolality range of 260 – 300 mOsmol/kg.
`
`
`
`
`ZIOPTAN contains Active: tafluprost 0.015 mg/mL; Inactives: glycerol, sodium dihydrogen phosphate
`dihydrate, disodium edetate, polysorbate 80, hydrochloric acid and/or sodium hydroxide (to adjust pH) and Water
`
`
`
`for Injection.
`
`ZIOPTAN does not contain a preservative.
`
`
`Reference ID: 3264663
`
`
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`NDA 202514/S-001
`Page 7
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`
`12
`CLINICAL PHARMACOLOGY
`
`12.1 Mechanism of Action
`
`Tafluprost acid, a prostaglandin analog is a selective FP prostanoid receptor agonist which is believed to
`
`
`reduce intraocular pressure by increasing uveoscleral outflow. The exact mechanism of action is unknown at this
`time.
`
`12.3 Pharmacokinetics
`
`Absorption
`Following instillation, tafluprost is absorbed through the cornea and is hydrolyzed to the biologically active
`
`
`acid metabolite, tafluprost acid. Following instillation of one drop of the 0.0015% solution once daily into each eye
`
`of healthy volunteers, the plasma concentrations of tafluprost acid peaked at a median time of 10 minutes on both
`
`
`
`
`Days 1 and 8. The mean plasma Cmax of tafluprost acid were 26 pg/mL and 27 pg/mL on Day 1, and Day 8,
`
`
`
`respectively. The mean plasma AUC estimates of tafluprost acid were 394 pg*min/mL and 432 pg*min/mL on Day
`1 and 8, respectively.
`
`Metabolism
`
`Tafluprost, an ester prodrug, is hydrolyzed to its biologically active acid metabolite in the eye. The acid
`
`
`
`metabolite is further metabolized via fatty acid β-oxidation and phase II conjugation.
`
`Elimination
`
`Mean plasma tafluprost acid concentrations were below the limit of quantification of the bioanalytical assay
`
`
`(10 pg/mL) at 30 minutes following topical ocular administration of tafluprost 0.0015% ophthalmic solution.
`
`
`13
`NONCLINICAL TOXICOLOGY
`
`13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
`Tafluprost was not carcinogenic when administered subcutaneously daily for 24 months at doses up to
`
`
`30 mcg/kg/day in rats and for 18 months at doses up to 100 mcg/kg/day in mice (over 1600- and 1300- times,
`
`
`
`respectively, the maximum clinical exposure based on plasma AUC).
`
`Tafluprost was not mutagenic or clastogenic in a battery of genetic toxicology studies, including an in vitro
`
`microbial mutagenesis assay, an in vitro chromosomal aberration assay in Chinese hamster lung cells, and an in vivo
`
`
`
`
`mouse micronucleus assay in bone marrow.
`
`
`In rats, no adverse effects on mating performance or fertility were observed with intravenous dosing of
`tafluprost at a dose of 100 mcg/kg/day (over 14000- times the maximum clinical exposure based on plasma Cmax or
`
`
`over 3600- times based on plasma AUC).
`
`
`
`14
`
`CLINICAL STUDIES
`In clinical studies up to 24 months in duration, patients with open-angle glaucoma or ocular hypertension and
`
`
`baseline pressure of 23 – 26 mm Hg who were treated with ZIOPTAN dosed once daily in the evening demonstrated
`
`
`
`reductions in intraocular pressure at 3 and 6 months of 6 – 8 mmHg and 5 – 8 mmHg, respectively.
`
`
`
`16 HOW SUPPLIED/STORAGE AND HANDLING
`
`ZIOPTAN (tafluprost ophthalmic solution) 0.0015% is supplied as a sterile solution in translucent low
`density polyethylene single-use containers packaged in foil pouches (10 single-use containers per pouch). Each
`
`
`single-use container has 0.3 mL solution corresponding to 0.0045 mg tafluprost.
`
`
`
`NDC 0006-3931-30; Unit-of-Use Carton of 30.
`NDC 0006-3931-54; Unit-of-Use Carton of 90.
`
`
`Storage:
`
`
`
`Reference ID: 3264663
`
`
`
`
`
` NDA 202514/S-001
`Page 8
`
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`Store refrigerated at 2 – 8°C (36 – 46°F). Store in the original pouch. After the pouch is opened, the single-
`
`
`
`
`
`use containers may be stored in the opened foil pouch for up to 28 days at room temperature: 20 – 25°C (68 – 77°F).
`
`Protect from moisture. Write down the date you open the foil pouch in the space provided on the pouch. Discard any
`unused containers 28 days after first opening the pouch.
`
`17
`
`PATIENT COUNSELING INFORMATION
`
`See FDA-Approved Patient Labeling (Patient Information).
`
`
`17.1 Nightly Application
`
`Advise patients to not exceed once daily dosing since more frequent administration may decrease the
`
`
`intraocular pressure lowering effect of ZIOPTAN.
`
`
`
`17.2 Handling the Single-Use Container
`Advise patients that ZIOPTAN is a sterile solution that does not contain a preservative. The solution from one
`
`individual unit is to be used immediately after opening for administration to one or both eyes. Since sterility cannot
`
`
`
`be maintained after the individual unit is opened, the remaining contents should be discarded immediately after
`
`administration.
`
`17.3 Potential for Pigmentation
`
`Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent.
`
`
`
`Also inform patients about the possibility of eyelid skin darkening, which may be reversible after discontinuation of
`
`
`
`ZIOPTAN.
`
`
`17.4 Potential for Eyelash Changes
`
`Inform patients of the possibility of eyelash and vellus hair changes in the treated eye during treatment with
`
`ZIOPTAN. These changes may result in a disparity between eyes in length, thickness, pigmentation, number of
`
`eyelashes or vellus hairs, and/or direction of eyelash growth. Eyelash changes are usually reversible upon
`
`discontinuation of treatment.
`
`17.5 When to Seek Physician Advice
`
`
`Advise patients that if they develop a new ocular condition (e.g., trauma or infection), experience a sudden
`decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid
`reactions, they should immediately seek their physician’s advice concerning the continued use of ZIOPTAN.
`
`
`17.6 Use with Other Ophthalmic Drugs
`
`If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5)
`minutes between applications.
`
`17.7 Storage Information
`Instruct patients on proper storage of cartons, unopened foil pouches, and opened foil pouches [see How
`
`
`Supplied/Storage and Handling (16)]. Recommended storage for cartons and unopened foil pouches is to store
`
`
`
`refrigerated at 2 – 8°C (36 – 46°F). After the pouch is opened, the single-use containers may be stored in the opened
`
`
`
`
`
`
`foil pouch for up to 28 days at room temperature: 20 – 25°C (68 – 77°F). Protect from moisture.
`
`
`
`
`
`
`
`Manufactured by:
`Laboratoire Unither
`
`ZI de la Guerie
`
`F-50211 COUTANCES Cedex
`France
`
`
`Reference ID: 3264663
`
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`NDA 202514/S-001
`Page 9
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`US Patent No.: 5,886,035
`
`Copyright © 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
`
`
`
`
`
`All rights reserved
`
`
`USPI-OS-24521302RXXX
`
`
`Reference ID: 3264663
`
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`NDA 202514/S-001
`Page 10
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`PATIENT INFORMATION
`
`ZIOPTAN™ (zye OP tan)
`
`
`(tafluprost ophthalmic solution) 0.0015%
`
`
`
`Read this Patient Information before you start using ZIOPTAN™ and each time you get a refill. There may be new
`
`
`information. This information does not take the place of talking to your doctor about your medical condition or your
`treatment.
`
`
`What is ZIOPTAN?
`
`
`
`ZIOPTAN is a prescription sterile eye drop solution. ZIOPTAN is used to lower the pressure in the eye (intraocular
`
`
`pressure) in people with open-angle glaucoma or ocular hypertension when their eye pressure is too high. ZIOPTAN
`belongs to a group of medicines called prostaglandin analogs.
`
`
`ZIOPTAN is not for use in children.
`
`What should I tell my doctor before using ZIOPTAN?
`Before you use ZIOPTAN, tell your doctor if you:
`
`• have or have had eye problems including any surgery on your eye or eyes
`
`
`
`
`
`• are using any other eye medicines
`
`
`• have any other medical problems
`
`
`
`
`• are pregnant or plan to become pregnant. It is not known if ZIOPTAN will harm your unborn baby. You
`
`
`
`should use an effective method of birth control while you use ZIOPTAN. If you become pregnant while
`
`
`
`
`
`
`using ZIOPTAN talk to your doctor right away.
`
`
`• are breastfeeding or plan to breastfeed. It is not known if ZIOPTAN passes into your breast milk. Talk to
`
`
`
`your doctor about the best way to feed your baby if you use ZIOPTAN.
`
`
`
`
`Tell your doctor about all the medicines you take, including prescription and non-prescription medicines,
`
`
`
`vitamins, and herbal supplements.
`Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new
`
`medicine.
`
`How should I take ZIOPTAN?
`Read the Instructions for Use at the end of this Patient Information leaflet for additional instructions about the right
`
`
`
`
`way to use ZIOPTAN.
`
`• Use 1 drop of ZIOPTAN in your eye (or eyes) each evening. Talk to your doctor or pharmacist if you are
`
`not sure how to use ZIOPTAN.
`• Your ZIOPTAN may not work as well if you use it more than 1 time each evening.
`
`•
`
`If you use other medicines in your eye, wait at least 5 minutes between using ZIOPTAN and your other eye
`medicines.
`• Use your ZIOPTAN right away after opening. Each ZIOPTAN single-use container is sterile and is to be
`
`
`
`used 1 time then thrown away. Do not save any ZIOPTAN that may be left over after you use your
`
`medicine. Using ZIOPTAN that is not sterile may cause other eye problems.
`
`
`
`Reference ID: 3264663
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`NDA 202514/S-001
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`Page 11
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`What are the possible side effects of ZIOPTAN?
`ZIOPTAN may cause serious side effects including:
`
`• changes in the color of your eye (iris). Your iris may become more brown in color while using
`
`
`
`ZIOPTAN. This color change may not go away when you stop using ZIOPTAN. If ZIOPTAN is used in 1
`
`
`eye only, the color of that eye may always be a different color from the color of your other eye.
`
`• darkening of the color of the skin around your eye (eyelid). These skin changes usually go away when
`
`
`you stop using ZIOPTAN.
`
`•
`
`
`increasing the length, thickness, color, or number of your eyelashes. These eyelash changes usually go
`
`away when you stop using ZIOPTAN.
`
`• hair growth on your eyelids. This hair growth usually goes away when you stop using ZIOPTAN.
`
`
`
`
`
`
`
`
`The most common side effects of ZIOPTAN include:
`•
`
`redness, stinging or itching of your eye
`
`• cataract formation
`
`
`• dry eye
`
`
`• eye pain
`
`
`• blurred vision
`
`
`
`• headache
`
`
`• common cold
`
`
`
`• cough
`
`
`
`• urinary tract infection
`
`
`
`
`Tell your doctor if you have any new eye problems while using ZIOPTAN including:
`
`
`• an eye injury
`
`
`• an eye infection
`
`
`• a sudden loss of vision
`
`
`
`
`• eye surgery
`
`
`•
`
`
`swelling and redness of and around your eye (conjunctivitis)
`
`
`
`• problems with your eyelids
`
`
`
`
`Tell your doctor if you have any other side effects that bother you.
`
`
`
`
`
`
`Reference ID: 3264663
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`NDA 202514/S-001
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`Page 12
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`These are not all the possible side effects of ZIOPTAN. For more information, ask your doctor or pharmacist.
`
`
`
`
`Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
`
`
`
`
`
`
`
`
`How should I store ZIOPTAN?
`
`Keep the foil pouches and ZIOPTAN single-use containers dry.
`
`
`Before opening the foil pouches:
`
`
`• Store the unopened foil pouches in a refrigerator between 36°F to 46°F (2°C to 8°C).
`
`
`
`
`
`• Do not open the pouch containing ZIOPTAN until you are ready to use the eye drops.
`
`
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`After opening the foil pouch:
`• Store the opened foil pouch at room temperature, between 68°F to 77°F (20°C to 25°C), for up to 28 days.
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`• Throw away all unused ZIOPTAN single-use containers in the opened foil pouch after 28 days.
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`• Keep the ZIOPTAN single-use containers in their original foil pouch.
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`• After opening the foil pouch, refrigeration is not required.
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`Keep ZIOPTAN and all medicines out of the reach of children.
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`General information about the safe and effective use of ZIOPTAN.
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`Do not use ZIOPTAN for a condition for which it was not prescribed. Do not give ZIOPTAN to other people, even
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`if they have the same symptoms that you have. It may harm them.
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`This Patient Information leaflet summarizes the most important information about ZIOPTAN. If you would like
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`more information, talk with your doctor. You can ask your pharmacist or doctor for information about ZIOPTAN
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`that is written for health professionals.
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`What are the ingredients in ZIOPTAN?
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`Active ingredients: tafluprost
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`Inactive ingredients: glycerol, sodium dihydrogen phosphate dihydrate, disodium edetate, and polysorbate 80,
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`hydrochloric acid and/or sodium hydroxide, and water
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`Instructions for Use
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`Read these Instructions for Use before using your ZIOPTAN and each time you get a refill. There may be new
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`information. This leaflet does not take the place of talking with your doctor about your medical condition or your
`treatment.
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`Important:
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`• ZIOPTAN is for the eye only. Do not swallow ZIOPTAN.
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`• ZIOPTAN single-use containers are packaged in a foil pouch.
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`Reference ID: 3264663
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` NDA 202514/S-001
`Page 13
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`• Do not use the ZIOPTAN single-use containers if the foil pouch is opened.
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`• Write down the date you open the foil pouch in the space provided on the pouch.
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`Every time you use ZIOPTAN:
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`Step 1. Wash your hands.
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`Step 2. Take the strip of single-use containers from
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`the foil pouch.
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`Step 3. Pull off one single-use container from the
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`strip.
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`Step 4. Put
`strip of
`remaining
`the
`single-use
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`containers back in the foil pouch and fold the
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`edge to close the pouch.
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`Step 5. Hold the single-use container upright. Make
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`sure that your ZIOPTAN medicine is in the
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`bottom part of the single-use container.
`See Figure A.
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`Step 6. Open the single-use container by twisting off
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`the tab.
`See Figure B.
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`Step 7.
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`Step 8.
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`Tilt your head backwards. If you are unable to
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`tilt your head, lie down.
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`Place the tip of the single-use container close
`to your eye. Be careful not to touch your eye
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`with the tip of the single-use container.
`See Figure C.
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`Figure A
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`Figure B
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`Figure C
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`Reference ID: 3264663
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` NDA 202514/S-001
`Page 14
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`Step 9. Pull your lower eyelid downwards and look
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`up.
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`Step 10. Gently squeeze the container and let 1 drop of
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`ZIOPTAN fall into the space between your
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`lower eyelid and your eye. If a drop misses
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`your eye, try again.
`See Figure D.
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`Figure D
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`•
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`If your doctor has told you to use ZIOPTAN drops in both eyes, repeat Steps 7 to 10 for your other eye.
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`• There is enough ZIOPTAN in one single-use container for both of your eyes.
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`• Throw away the opened single-use container with any remaining ZIOPTAN right away.
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`This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug
`Administration.
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`Rx only
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`Manufactured by:
`Laboratoire Unither
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`ZI de la Guerie
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`F-50211 COUTANCES Cedex
`France
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`US Patent No.: 5,886,035
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`Copyright © 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
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`All rights reserved.
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`Revised: 02/2013
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`USPI-OS-24521302RXXX
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`Reference ID: 3264663
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