`
`
` CENTER FOR DRUG EVALUATION AND
`RESEARCH
`
`
`APPLICATION NUMBER:
`
`202514Orig1s000
`LABELING
`
`
`
`

`

`
`
`
`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
`indicated
`for reducing elevated
`intraocular
`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)
`
`6073101
`
`------------------------WARNINGS AND PRECAUTIONS------------------------
`• Pigmentation
`Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can
`occur. Iris pigmentation is l kely 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: XX/2012
`
`
`
`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.
`
`
`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
`
`Reference ID: 3086096
`
`

`

`ZIOPTAN™ (tafluprost ophthalmic solution) 0.0015%
`
`6073101
`
`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).]
`
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`ZIOPTAN™ (tafluprost ophthalmic solution) 0.0015%
`
`6073101
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`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.
`
`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.
`
` 6
`
`ADVERSE REACTIONS
`
`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.
`
`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.
`tafluprost
`in rats and rabbits,
`In embryo-fetal development studies
`Teratogenic effects:
`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 µg/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 µg/kg/day
`corresponding to maternal plasma levels of tafluprost acid during organogenesis that were approximately
`
`Reference ID: 3086096
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`ZIOPTAN™ (tafluprost ophthalmic solution) 0.0015%
`
`6073101
`
`5 times higher than the clinical exposure based on Cmax. At the no-effect dose in rabbits (0.01 µg/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 intravenous dose of 0.3 µg/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.
`
`
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`Reference ID: 3086096
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`ZIOPTAN™ (tafluprost ophthalmic solution) 0.0015%
`
`6073101
`
`
`ZIOPTAN does not contain a preservative.
`
`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 µg/kg/day in rats and for 18 months at doses up to 100 µg/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 µg/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.
`
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`Reference ID: 3086096
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`ZIOPTAN™ (tafluprost ophthalmic solution) 0.0015%
`
`6073101
`
`NDC 0006-3931-30; Unit-of-Use Carton of 30.
`NDC 0006-3931-54; Unit-of-Use Carton of 90.
`
`Storage:
`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
`Patients should be advised 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
`Patients should be advised 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
`Patients should be advised about the potential for increased brown pigmentation of the iris, which
`may be permanent. Patients should also be informed about the possibility of eyelid skin darkening, which
`may be reversible after discontinuation of ZIOPTAN.
`
`17.4 Potential for Eyelash Changes
`Patients should also be informed 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
`Patients should be advised 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
`Patients should be instructed 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.
`
`Rx Only
`
`
`
`Reference ID: 3086096
`
`6
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`

`

`ZIOPTAN™ (tafluprost ophthalmic solution) 0.0015%
`
`6073101
`
`
`
`
`Manufactured by:
`Laboratoire Unither
`ZI de la Guerie
`F-50211 COUTANCES Cedex
`France
`
`US Patent No.: 5,886,035
`
`Copyright © 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
`All rights reserved.
`
`Revised: XX/2012
`
`6073101
`
`Reference ID: 3086096
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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.
`
`What are the possible side effects of ZIOPTAN?
`ZIOPTAN may cause serious side effects including:
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`

`•
`
`• 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.
`
`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:
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`

`• 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.
`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.
`• Throw away all unused ZIOPTAN single-use containers in the opened foil pouch after 28 days.
`• Keep the ZIOPTAN single-use containers in their original foil pouch.
`• After opening the foil pouch, refrigeration is not required.
`
`Keep ZIOPTAN and all medicines out of the reach of children.
`
`General information about the safe and effective use of ZIOPTAN.
`Do not use ZIOPTAN for a condition for which it was not prescribed. Do not give ZIOPTAN to other
`people, even if they have the same symptoms that you have. It may harm them.
`This Patient Information leaflet summarizes the most important information about ZIOPTAN. If you would
`like more information, talk with your doctor. You can ask your pharmacist or doctor for information about
`ZIOPTAN that is written for health professionals.
`
`What are the ingredients in ZIOPTAN?
`Active ingredients: tafluprost
`Inactive ingredients: glycerol, sodium dihydrogen phosphate dihydrate, disodium edetate, and
`polysorbate 80, hydrochloric acid and/or sodium hydroxide, and water
`
`Instructions for Use
`
`Read these Instructions for Use before using your ZIOPTAN and each time you get a refill. There may be
`new information. This leaflet does not take the place of talking with your doctor about your medical
`condition or your treatment.
`
`Important:
`• ZIOPTAN is for the eye only. Do not swallow ZIOPTAN.
`• ZIOPTAN single-use containers are packaged in a foil pouch.
`• Do not use the ZIOPTAN single-use containers if the foil pouch is opened.
`• Write down the date you open the foil pouch in the space provided on the pouch.
`Every time you use ZIOPTAN:
`
`
`Step 1. Wash your hands.
`
`Step 2. Take the strip of single-use containers
`from the foil pouch.
`
`Step 3. Pull off one single-use container from the
`strip.
`
`
`
`
`
`
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`

`Step 4. Put
`the remaining strip of single-use
`containers back in the foil pouch and fold
`the edge to close the pouch.
`
`
`
`Step 5. Hold
`the single-use container upright.
`Make sure that your ZIOPTAN medicine is
`in
`the bottom part of
`the single-use
`container.
`See Figure A.
`
`
`
`Step 6. Open the single-use container by twisting
`off the tab.
`See Figure B.
`
`
`
`Step 7. Tilt your head backwards. If you are
`unable to tilt your head, lie down.
`
`
`Step 8. Place the tip of the single-use container
`close to your eye. Be careful not to touch
`your eye with the tip of the single-use
`container.
`See Figure C.
`
`
`
`Step 9. Pull your lower eyelid downwards and look
`up.
`
`
`Step 10. Gently squeeze the container and let 1
`drop of ZIOPTAN fall into the space
`between your lower eyelid and your eye. If
`a drop misses your eye, try again.
`See Figure D.
`
`
`
`
`
`Figure A
`
`
`
`Figure B
`
`Figure C
`
`
`
`Figure D
`
`
`
`•
`
`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.
`• Throw away the opened single-use container with any remaining ZIOPTAN right away.
`
`This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug
`Administration.
`
`Rx only
`
`
`
`Manufactured by:
`Laboratoire Unither
`ZI de la Guerie
`F-50211 COUTANCES Cedex
`France
`
`US Patent No.: 5,886,035
`
`Copyright © 2012 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
`All rights reserved.
`
`Revised: XX/2012
`
`6073101
`
`Reference ID: 3086096
`
`5
`
`

`

`
`
`Not For Retail Sale
`
`ZOFTAN“ (taflu prost ophthalmic solution)
`
`
`Professional Sample—
`Not For Retail Sale
`
`
`Professional Sample—
`
`For Topical Application in the Eye
`STORAG E:
`
`Store refrigerated at 2-8°( (36-46°F). Store in original pouch.
`After the poudt 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.
`
`
`
`
`
`
`
`
`
` %SLOO'0(U0!1ni°$3!lul9llllid01501dnuei)
`
`
`
`alt]aq;uiuonenuddv[aidol105
`
`
`
`
`
`ZIOPTANT”
`..NV.I.dOIZ
`
`
`
`
`(tafluprost ophthalmic
`
`
`
`
`
`solution)
`
`0.0015%
`
`USUAl. DOSAGE
`
`
`
`One drop in the affected qe(s) once dailyin the evering.
`The solution from one singeuse container is to be used
`
`
`
`immediately after opening for administration to one
`or both eyes
`
`
`
`ATTENTION:
`
`
`Usethe eye dops immedately after opening the container.
`
`
`Discard the opened container with any remaining contents
`Single-Use Containers
`
`
`immediately after use.
`
`
`
` Manuffor.
`By: laboratoire Unither
`
`
`
`
`Merci Sharp & Dohrne Corp,
`II de la Guerie
`
`.
`asubsidiaryof
`F50211(01HANCES(edex
`
`
`Contains:
`Oninacmoqruc.
`France
`Active: tafluprost 0.001596
`Whitehomesmion.NJ08889.USA
`TaflUPm rm inqmd) Made in Japan
`Formulated 'n che
`
`
`(4.5 mcg per single-use container)
`
`
`Inactive ingredients: glycerol, sodium dihydrogen
`phosphate dihydrate, disodium edetate, polysorbate 80,
`
`
`Water for Injection. Hydrochloric acid and/or
`
`
`sodium hydroxide are added to adjust pH.
`
`
`
`
`Rx only
`10 Single-Use Containers:
`1 pouch x losingle-use containers
`(0.3 mL each)
`
`6062302
`SRN 7650
`
`
`6062802
`
`1SAFL2561US
`
`
`
`For Topical Application in the Eye
`
`REFRIGERATE (2-8°( or 3646°F)
`
`Preservative-Free, Sterile
`
`
`
`..NV.l.dOIZ
`
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`
`
`
`96]amu!unimuddvI93!d°1Jo:l
`
`
`
`66ETU2561/B
`
`

`

`8/099201399
`
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`
`ZIOPTAN"
`(tafluprost
`ophthalmic solution)
`0.001596
`
`ForTopical Application in the Eye
`STORAGE:
`
`Store refrigerated at 2-8°C (36-46°F). Store in original pouch.
`After the pouch is opened, the single-use containers maybe
`stored in the opened foil pouch for up to 28 days at
`room temperature: 20-25°C (68 - 77°F).
`Protectfrom moisture.
`
`USUAL DOSAGE:
`
`One drop in the affected eye(s) once daily in the evening.
`The solution from one single-use container is to be used
`immediately after opening for administration to one
`or both eyes.
`ATTENTION:
`
`Use the eye drops immediately after opening the
`container. Discard the opened container with any
`remaining contents inmediately after use.
`
`Manuf. foc
`MetdtSharpSrDohmeCorp,
`a subsidiary of
`0 "macaw.
`Wlitehoirse Station, m 08889, USA
`
`By'. laboratoire Unither
`thklaGuerie
`F6021] COUTANCES Cedex
`Frame
`lafluprost (active inged.) Made it Japan
`Formulated i1 France
`
`thVldOIZ
`
`
`
`%Sl00'0(uonnlosDiwieumdorsmdnum)
`
`M]aminuouziuddvmade1105
`
`Imidouor
`
`NDC 0006-3931-30
`
`MNVLdOIZ
`
`
`
`%Sl00'0(uonnlosJiwreumdomdnum)
`
`
`
`allall:m.uouenuddv
`
`ZIOPTANT”
`(tafluprost ophthalmic
`solution)
`0.0015%
`
`For Topical Application in the Eye
`
`REFRIGERATE (2-8°C or 36-46°F)
`
`Single-Use Containers
`
`Preservative-Free, Sterile
`
`Contains:
`
`Active: tafluprost 0.001596
`(4.5 mcg per single‘use container)
`Inactive ingredients: glycerol, sodium dihydrogen
`phosphate dihydrate, disodium edetate, polysorbate 80,
`Water for Injection. Hydrodiloric acid and/or
`sodium hydroxide are added to adjust pH.
`
`Rx only
`30 Single-Use Containers:
`3 poudres x 10 single-use containers
`(0.3 mL each)
`
`66ETU2560lB
`
`

`

`HIZQQanEQQ
`
`
`
`
`
`ZIOPTANT”
`(tafluprost ophthalmic
`solution)
`0.0015%
`
`For Topical Application in the Eye
`STORAGE:
`
`Store refrigerated at 2-8°C (3646”F). Store in original pouch.
`After the pouch is opened, the single—use containers may be
`stored in the opened foil poudi for up to 28 days at
`room temperature: 20-25°C (68 - 77°F).
`Protect from moisture.
`
`USUAL DOSAGE:
`
`
`
`
`
`
`
`
`
`One drop in the affected eye(s) once daily in the evening.
`The solution from one singleuse container is to be used
`
`
`immediately after opening for administration to one
`or both eyes.
`
`ATTENTION:
`
`Use the eye drops immediately after opening the
`container. Discard the opened container with any
`remaining contents immedately after use.
`
`NDC0006-393l-S4
`
`%Sl00'0
`
`For Topical Application in the Eye
`
`
`
`9A3auru!uoumuddv|2er01103
`
`
`(uonmos)iur|eu1qdo1sordnue1)w.NVJ.dOIZ
`
`
`
`
`
`
`
` ZIOPTANT”
`
`(tafluprost ophthalmic
`
`solution)
`0.0015%
`
`
`
`
`
`
`
`
`Manuf. fon
`By. [immune Unither
`
`
`REFRIGERATE (2-8°C or 36-46°F)
`MerckSlnrpSiDolmeCorp,
`ZldelaGuerie
`
`a subsidiary of
`F-SOZ‘II COUTANCES Cedex
`
`
`,
`,
`.
`Frame
`9 Mincxacomc.
`
`
`Single-Use Containers
`
`Tafliprost (actwe Ingred.) Made In Jqsan
`Whitehouse Station, M08889, USA
`Formulated h France
`
`
`Preservative-Free, Sterile
`
`
` Contains:
`
`Active: tafluprost 0.0015%
`
`(4.5 mcg per single-use container)
`
`Inactive ingredients: glycerol, sodium dihydrogen
`phosphate dihydrate, disodium edetate, polysorbate 80,
`
`Water for Injection. Hydrochloric acid and/or
`
`sodium hydroxide are added to adjust pH.
`
`
`
`Rx only
`90 Single-Use Containers:
`
`9 pouches x10 single-use containers
`(0.3 ml eadi)
`
`6011003
`
`
`w.NV.I.dOIZ
`
`
`
`%Sl00'0
`
`
`
`aliaouru!uoumuddv|e)id01101
`
`(uormlosmuleumdo1sordnu21)
`
`
`
`
`
`
`
`6011003
`1SAFL256ZUS
`
`66ETU2562/B
`
`

`

`
`

`

`T
`
`Professional Sample—
`Not For Retail Sale
`
`NDCooos-3931-36
`
`ZIOPTANT"
`(tafluprost ophthalmic
`solution)
`ForTopical Application in the Eye
`
`0.0015%
`
`USUAL DOSAGE: One drop in the affected eye(s) once daily
`"It the evening. 'lhesolution from ones'ngleuse container is
`to be used 'I'nmediately after opening for
`athninistration to oneor both eyes.
`
`Single-Use Containers
`Preservative-Free, Sterile
`Contains: Active: tafluprost0.0015%
`(45 mcg per single-use container)
`Inactive ingredients: glycerol, sodium ditydrogen phosphate
`dihydrate, disodium edetate, polysorbate 80, Water for Injection.
`Hydrochloric acid and/or sodium hydroxide are added to adjust pH.
`SIOMGE : Store refrigerated at 2-81 (36-46°F). Store in original pouch.
`Afterthe poudt is opened, the singleuse containers may bestored in
`the openedde pouch for up to 28 days at room temperature:
`20-25°C (68—77“F). Protect from moisture.
`Write down the datethe poudtisopened here:
`
`SAFLBGIUS
`
`
`
`AHENIION: Use the eye drops immediatel