NURSING MOTHERS SECTION.

8.3 Nursing Mothers. 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 tafluprost ophthalmic solution is administered to nursing woman.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE/LABEL PRINCIPAL DISPLAY PANEL NDC 0781-6184-87Tafluprost Ophthalmic Solution0.0015%Single-Use ContainersPreservative-Free, SterileFor Topical Application in the EyeREFRIGERATE (2o to 8oC or 36o to 46oF)Rx Only30 Single-Use Containers:6 Pouches 5 Single-Use Containers(0.3 mL each)SANDOZ A Novartis Division. carton.

PEDIATRIC USE SECTION.

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.

ADVERSE REACTIONS SECTION.

6 ADVERSE REACTIONS. oMost common ocular adverse reaction is conjunctival hyperemia (range 4% to 20%). (6.1)To report SUSPECTED ADVERSE REACTIONS, contact Sandoz Inc. at 1-800-525-8747 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. oMost common ocular adverse reaction is conjunctival hyperemia (range 4% to 20%). (6.1). 6.1 Clinical Studies Experience. Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of 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 range of 4% to 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% to 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 post-approval use of tafluprost. Because post-approval adverse reactions are reported voluntarily from population of uncertain size, it is not always possible to reliably estimate their frequency or establish causal relationship to drug exposure.Respiratory disorders: exacerbation of asthma, dyspneaEye disorders: iritis/uveitisIn postmarketing use with prostaglandin analogs, periorbital and lid changes including deepening of the eyelid sulcus have been observed.

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

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 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 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).

CLINICAL PHARMACOLOGY SECTION.

12 CLINICAL PHARMACOLOGY. 12.1 Mechanism of Action. Tafluprost acid, prostaglandin analog is 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. AbsorptionFollowing 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 median time of 10 minutes on both Days 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 pgmin/mL and 432 pgmin/mL on Day and 8, respectively.MetabolismTafluprost, an ester prodrug, is hydrolyzed to its biologically active acid metabolite in the eye. The acid metabolite is further metabolized via fatty acid -oxidation and phase II conjugation.EliminationMean 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.

CLINICAL STUDIES SECTION.

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 to 26 mm Hg who were treated with tafluprost ophthalmic solution dosed once daily in the evening demonstrated reductions in intraocular pressure at and months of to mmHg and to mmHg, respectively.

CONTRAINDICATIONS SECTION.

4 CONTRAINDICATIONS. None.. oNone. (4). oNone. (4).

DESCRIPTION SECTION.

11 DESCRIPTION. Tafluprost is fluorinated analog of prostaglandin F2. 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 colorless to light yellow viscous liquid that is practically insoluble in water.Tafluprost ophthalmic solution 0.0015% is supplied as sterile solution of tafluprost with pH range of 5.5 to 6.7 and an Osmolality range of 260 to 300 mOsmol/kg.Tafluprost ophthalmic solution 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.Tafluprost ophthalmic solution does not contain preservative.. chemical-structure.

DOSAGE & ADMINISTRATION SECTION.

2 DOSAGE AND ADMINISTRATION. The recommended dose is one drop of tafluprost ophthalmic solution 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 to hours after the first administration with the maximum effect reached after 12 hours.Tafluprost ophthalmic solution 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 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.. oOne drop in the affected eye(s) once daily in the evening. (2). oOne drop in the affected eye(s) once daily in the evening. (2).

DOSAGE FORMS & STRENGTHS SECTION.

3 DOSAGE FORMS AND STRENGTHS. Ophthalmic solution containing tafluprost 0.015 mg/mL.. oOphthalmic solution containing tafluprost 0.015 mg/mL. (3). oOphthalmic solution containing tafluprost 0.015 mg/mL. (3).

GERIATRIC USE SECTION.

8.5 Geriatric Use. No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients.

HOW SUPPLIED SECTION.

16 HOW SUPPLIED/STORAGE AND HANDLING. Tafluprost ophthalmic solution 0.0015% is supplied as sterile solution in translucent low density polyethylene single-use containers packaged in foil pouches (5 single-use containers per pouch). Each single-use container has 0.3 mL solution corresponding to 0.0045 mg tafluprost. NDC 0781-6184-8730 Single-Use Containers (6 Pouches 5 Single-Use Containers)Storage:Store refrigerated at to 8C (36 to 46F). During shipment tafluprost ophthalmic solution may be maintained at temperatures up to 40C (104F) for period not exceeding days. Mail-order prescriptions received after two days of the dispensing date noted on the prescribing label should not be used. 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 30 days at room temperature: 20 to 25C (68 to 77F). Protect from moisture. Write down the date you open the foil pouch in the space provided on the pouch. Discard any unused containers 30 days after first opening the pouch.. NDC 0781-6184-8730 Single-Use Containers (6 Pouches 5 Single-Use Containers).

INDICATIONS & USAGE SECTION.

1 INDICATIONS AND USAGE. Tafluprost ophthalmic solution 0.0015% is indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension.. oTafluprost ophthalmic solution 0.0015% is prostaglandin analog indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. (1). oTafluprost ophthalmic solution 0.0015% is prostaglandin analog indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. (1).

INFORMATION FOR PATIENTS SECTION.

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 tafluprost ophthalmic solution.. 17.2 Handling the Single-Use Container. Advise patients that tafluprost ophthalmic solution is sterile solution that does not contain 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 tafluprost ophthalmic solution.. 17.4 Potential for Eyelash Changes. Inform patients of the possibility of eyelash and vellus hair changes in the treated eye during treatment with tafluprost ophthalmic solution. These changes may result in 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 new ocular condition (e.g., trauma or infection), experience sudden decrease in visual acuity, have ocular surgery, or develop any ocular reactions, particularly conjunctivitis and eyelid reactions, they should immediately seek their physicians advice concerning the continued use of tafluprost ophthalmic solution.. 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 to 8C (36 to 46F). After the pouch is opened, the single-use containers may be stored in the opened foil pouch for up to 30 days at room temperature: 20 to 25C (68 to77F). Protect from moisture.

INSTRUCTIONS FOR USE SECTION.

Instructions for Use Read these Instructions for Use before using your tafluprost ophthalmic solution and each time you get 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:oTafluprost ophthalmic solution is for the eye only. Do not swallow tafluprost ophthalmic solution.oTafluprost ophthalmic solution single-use containers are packaged in foil pouch.oDo not use the tafluprost ophthalmic solution single-use containers if the foil pouch is opened. oWrite down the date you open the foil pouch in the space provided on the pouch.Every time you use tafluprost ophthalmic solution: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.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 tafluprost ophthalmic solution medicine is in the bottom part of the single-use container.See Figure A.Figure AStep 6.Open the single-use container by twisting off the tab.See Figure B.Figure BStep 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.Figure CStep 9.Pull your lower eyelid downwards and look up.Step 10.Gently squeeze the container and let drop of tafluprost ophthalmic solution fall into the space between your lower eyelid and your eye. If drop misses your eye, try again.See Figure D.Figure DoIf your doctor has told you to use tafluprost ophthalmic solution drops in both eyes, repeat Steps to 10 for your other eye.oThere is enough tafluprost ophthalmic solution in one single-use container for both of your eyes.oThrow away the opened single-use container with any remaining tafluprost ophthalmic solution right away.This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.Manufactured by The Ritedose Corporation, Columbia, SC 29203 forSandoz Inc. Princeton, NJ 08540. oTafluprost ophthalmic solution is for the eye only. Do not swallow tafluprost ophthalmic solution.. oTafluprost ophthalmic solution single-use containers are packaged in foil pouch.. oDo not use the tafluprost ophthalmic solution single-use containers if the foil pouch is opened. oWrite down the date you open the foil pouch in the space provided on the pouch.. oIf your doctor has told you to use tafluprost ophthalmic solution drops in both eyes, repeat Steps to 10 for your other eye.. oThere is enough tafluprost ophthalmic solution in one single-use container for both of your eyes.. oThrow away the opened single-use container with any remaining tafluprost ophthalmic solution right away.. fidure-a. figure-b. figure-c. figure-d.

MECHANISM OF ACTION SECTION.

12.1 Mechanism of Action. Tafluprost acid, prostaglandin analog is 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.

NONCLINICAL TOXICOLOGY SECTION.

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 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 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).

PHARMACOKINETICS SECTION.

12.3 Pharmacokinetics. AbsorptionFollowing 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 median time of 10 minutes on both Days 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 pgmin/mL and 432 pgmin/mL on Day and 8, respectively.MetabolismTafluprost, an ester prodrug, is hydrolyzed to its biologically active acid metabolite in the eye. The acid metabolite is further metabolized via fatty acid -oxidation and phase II conjugation.EliminationMean 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.

PREGNANCY SECTION.

8.1 Pregnancy. Pregnancy Category C. Teratogenic effectsIn 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 dose of 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 tafluprost dose of 0.03 mcg/kg/day corresponding to maternal plasma levels of tafluprost acid during organogenesis that were approximately 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 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 tafluprost intravenous dose of 0.3 mcg/kg/day which is greater than 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, tafluprost ophthalmic solution 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.

SPL PATIENT PACKAGE INSERT SECTION.

PATIENT INFORMATION. Tafluprost Ophthalmic Solution 0.0015%(ta floo prost)Read this Patient Information before you start using tafluprost ophthalmic solution and each time you get 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 Tafluprost Ophthalmic SolutionTafluprost ophthalmic solution is prescription sterile eye drop solution. Tafluprost ophthalmic solution 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. Tafluprost ophthalmic solution belongs to group of medicines called prostaglandin analogs.Tafluprost ophthalmic solution is not for use in children.What should tell my doctor before using tafluprost ophthalmic solutionBefore you use tafluprost ophthalmic solution, tell your doctor if you:ohave or have had eye problems including any surgery on your eye or eyesoare using any other eye medicinesohave any other medical problemsoare pregnant or plan to become pregnant. It is not known if tafluprost ophthalmic solution will harm your unborn baby. You should use an effective method of birth control while you use tafluprost ophthalmic solution. If you become pregnant while using tafluprost ophthalmic solution talk to your doctor right away.oare breastfeeding or plan to breastfeed. It is not known if tafluprost ophthalmic solution passes into your breast milk. Talk to your doctor about the best way to feed your baby if you use tafluprost ophthalmic solution.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 list of them to show your doctor and pharmacist when you get new medicine.How should take tafluprost ophthalmic solutionRead the Instructions for Use at the end of this Patient Information leaflet for additional instructions about the right way to use tafluprost ophthalmic solution.oUse drop of tafluprost ophthalmic solution in your eye (or eyes) each evening. Talk to your doctor or pharmacist if you are not sure how to use tafluprost ophthalmic solution.oYour tafluprost ophthalmic solution may not work as well if you use it more than time each evening.oIf you use other medicines in your eye, wait at least minutes between using tafluprost ophthalmic solution and your other eye medicines.oUse your tafluprost ophthalmic solution right away after opening. Each tafluprost ophthalmic solution single-use container is sterile and is to be used time then thrown away. Do not save any tafluprost ophthalmic solution that may be left over after you use your medicine. Using tafluprost ophthalmic solution that is not sterile may cause other eye problems.What are the possible side effects of tafluprost ophthalmic solutionTafluprost ophthalmic solution may cause serious side effects including:ochanges in the color of your eye (iris). Your iris may become more brown in color while using tafluprost ophthalmic solution. This color change may not go away when you stop using tafluprost ophthalmic solution. If tafluprost ophthalmic solution is used in eye only, the color of that eye may always be different color from the color of your other eye.odarkening of the color of the skin around your eye (eyelid). These skin changes usually go away when you stop using tafluprost ophthalmic solution.oincreasing the length, thickness, color, or number of your eyelashes. These eyelash changes usually go away when you stop using tafluprost ophthalmic solution.ohair growth on your eyelids. This hair growth usually goes away when you stop using tafluprost ophthalmic solution.The most common side effects of tafluprost ophthalmic solution include:oredness, stinging or itching of your eyeocataract formationodry eyeoeye painoblurred visionoheadacheocommon coldocoughourinary tract infectionTell your doctor if you have any new eye problems while using tafluprost ophthalmic solution including:oan eye injuryoan eye infectionoa sudden loss of visionoeye surgeryoswelling and redness of and around your eye (conjunctivitis)oproblems with your eyelidsAdditionally, the following side effects have been reported in general use:oworsening of asthmaoshortness of breathTell your doctor if you have any other side effects that bother you. These are not all the possible side effects of tafluprost ophthalmic solution. 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 store tafluprost ophthalmic solutionImportant information for Mail-Order Patients: Do not use if prescription is not received within two days of dispensing date.Keep the foil pouches and tafluprost ophthalmic solution single-use containers dry.Before opening the foil pouches:oStore the unopened foil pouches in refrigerator between 36F to 46F (2C to 8C).oDo not open the pouch containing tafluprost ophthalmic solution until you are ready to use the eye drops.After opening the foil pouch:oStore the opened foil pouch at room temperature, between 68F to 77F (20C to 25C), for up to 30 days.oThrow away all unused tafluprost ophthalmic solution single-use containers in the opened foil pouch after 30 days.oKeep the tafluprost ophthalmic solution single-use containers in their original foil pouch.oAfter opening the foil pouch, refrigeration is not required.Keep tafluprost ophthalmic solution and all medicines out of the reach of children.General information about the safe and effective use of tafluprost ophthalmic solution.Do not use tafluprost ophthalmic solution for condition for which it was not prescribed. Do not give tafluprost ophthalmic solution 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 tafluprost ophthalmic solution. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about tafluprost ophthalmic solution that is written for health professionals.What are the ingredients in tafluprost ophthalmic solutionActive ingredients: tafluprostInactive ingredients: glycerol, sodium dihydrogen phosphate dihydrate, disodium edetate, polysorbate 80, hydrochloric acid and/or sodium hydroxide, and water for injection.. ohave or have had eye problems including any surgery on your eye or eyes. oare using any other eye medicines. ohave any other medical problems. oare pregnant or plan to become pregnant. It is not known if tafluprost ophthalmic solution will harm your unborn baby. You should use an effective method of birth control while you use tafluprost ophthalmic solution. If you become pregnant while using tafluprost ophthalmic solution talk to your doctor right away.. oare breastfeeding or plan to breastfeed. It is not known if tafluprost ophthalmic solution passes into your breast milk. Talk to your doctor about the best way to feed your baby if you use tafluprost ophthalmic solution.. oUse drop of tafluprost ophthalmic solution in your eye (or eyes) each evening. Talk to your doctor or pharmacist if you are not sure how to use tafluprost ophthalmic solution.. oYour tafluprost ophthalmic solution may not work as well if you use it more than time each evening.. oIf you use other medicines in your eye, wait at least minutes between using tafluprost ophthalmic solution and your other eye medicines.. oUse your tafluprost ophthalmic solution right away after opening. Each tafluprost ophthalmic solution single-use container is sterile and is to be used time then thrown away. Do not save any tafluprost ophthalmic solution that may be left over after you use your medicine. Using tafluprost ophthalmic solution that is not sterile may cause other eye problems.. ochanges in the color of your eye (iris). Your iris may become more brown in color while using tafluprost ophthalmic solution. This color change may not go away when you stop using tafluprost ophthalmic solution. If tafluprost ophthalmic solution is used in eye only, the color of that eye may always be different color from the color of your other eye.. odarkening of the color of the skin around your eye (eyelid). These skin changes usually go away when you stop using tafluprost ophthalmic solution.. oincreasing the length, thickness, color, or number of your eyelashes. These eyelash changes usually go away when you stop using tafluprost ophthalmic solution.. ohair growth on your eyelids. This hair growth usually goes away when you stop using tafluprost ophthalmic solution.. oredness, stinging or itching of your eye. ocataract formation. odry eye. oeye pain. oblurred vision. oheadache. ocommon cold. ocough. ourinary tract infection. oan eye injury. oan eye infection. oa sudden loss of vision. oeye surgery. oswelling and redness of and around your eye (conjunctivitis). oproblems with your eyelids. oworsening of asthma. oshortness of breath. oStore the unopened foil pouches in refrigerator between 36F to 46F (2C to 8C).. oDo not open the pouch containing tafluprost ophthalmic solution until you are ready to use the eye drops.. oStore the opened foil pouch at room temperature, between 68F to 77F (20C to 25C), for up to 30 days.. oThrow away all unused tafluprost ophthalmic solution single-use containers in the opened foil pouch after 30 days.. oKeep the tafluprost ophthalmic solution single-use containers in their original foil pouch.. oAfter opening the foil pouch, refrigeration is not required.. Instructions for Use Read these Instructions for Use before using your tafluprost ophthalmic solution and each time you get 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:oTafluprost ophthalmic solution is for the eye only. Do not swallow tafluprost ophthalmic solution.oTafluprost ophthalmic solution single-use containers are packaged in foil pouch.oDo not use the tafluprost ophthalmic solution single-use containers if the foil pouch is opened. oWrite down the date you open the foil pouch in the space provided on the pouch.Every time you use tafluprost ophthalmic solution: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.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 tafluprost ophthalmic solution medicine is in the bottom part of the single-use container.See Figure A.Figure AStep 6.Open the single-use container by twisting off the tab.See Figure B.Figure BStep 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.Figure CStep 9.Pull your lower eyelid downwards and look up.Step 10.Gently squeeze the container and let drop of tafluprost ophthalmic solution fall into the space between your lower eyelid and your eye. If drop misses your eye, try again.See Figure D.Figure DoIf your doctor has told you to use tafluprost ophthalmic solution drops in both eyes, repeat Steps to 10 for your other eye.oThere is enough tafluprost ophthalmic solution in one single-use container for both of your eyes.oThrow away the opened single-use container with any remaining tafluprost ophthalmic solution right away.This Patient Information and Instructions for Use have been approved by the U.S. Food and Drug Administration.Manufactured by The Ritedose Corporation, Columbia, SC 29203 forSandoz Inc. Princeton, NJ 08540. oTafluprost ophthalmic solution is for the eye only. Do not swallow tafluprost ophthalmic solution.. oTafluprost ophthalmic solution single-use containers are packaged in foil pouch.. oDo not use the tafluprost ophthalmic solution single-use containers if the foil pouch is opened. oWrite down the date you open the foil pouch in the space provided on the pouch.. oIf your doctor has told you to use tafluprost ophthalmic solution drops in both eyes, repeat Steps to 10 for your other eye.. oThere is enough tafluprost ophthalmic solution in one single-use container for both of your eyes.. oThrow away the opened single-use container with any remaining tafluprost ophthalmic solution right away.. fidure-a. figure-b. figure-c. figure-d.

SPL UNCLASSIFIED SECTION.

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 tafluprost ophthalmic solution can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see Patient Counseling Information (17.3)].

USE IN SPECIFIC POPULATIONS SECTION.

8 USE IN SPECIFIC POPULATIONS. oUse in pediatric patients is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. (8.4). oUse in pediatric patients is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. (8.4). 8.1 Pregnancy. Pregnancy Category C. Teratogenic effectsIn 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 dose of 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 tafluprost dose of 0.03 mcg/kg/day corresponding to maternal plasma levels of tafluprost acid during organogenesis that were approximately 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 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 tafluprost intravenous dose of 0.3 mcg/kg/day which is greater than 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, tafluprost ophthalmic solution 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. 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 tafluprost ophthalmic solution is administered to 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.

WARNINGS AND PRECAUTIONS SECTION.

5 WARNINGS AND PRECAUTIONS. oPigmentationPigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation is likely to be permanent. (5.1)oEyelash ChangesGradual changes to eyelashes including increased length, thickness and number of lashes. Usually reversible. (5.2). oPigmentationPigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation is likely to be permanent. (5.1). oEyelash ChangesGradual changes to eyelashes including increased length, thickness and number of lashes. Usually reversible. (5.2). 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 tafluprost ophthalmic solution 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. Tafluprost ophthalmic solution 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. Tafluprost ophthalmic solution 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 F2 analogs. Tafluprost ophthalmic solution should be used with caution in aphakic patients, in pseudophakic patients with torn posterior lens capsule, or in patients with known risk factors for macular edema.