ZIOPTAN

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-dihydroxycyclopen t y l]-5-heptenoate. The molecular formula of tafluprost is C 25 H 34 F 2 O 5 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 to 6.7 and an Osmolality range of 260 to 300 mOsmo/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. Chemical Structure

ZIOPTAN ® (tafluprost ophthalmic solution) 0.0015% is indicated for reducing elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. 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 )

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. One drop in the affected eye(s) once daily in the evening. ( 2 )

None. None. ( 4 )

Most common ocular adverse reaction is conjunctival hyperemia (range 4% to 20%). ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Thea Pharma Inc. at 1-833-838-4028 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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% 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 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. Respiratory disorders: exacerbation of asthma, dyspnea Eye disorders: iritis/uveitis In postmarketing use with prostaglandin analogs, periorbital and lid changes including deepening of the eyelid sulcus have been observed.

Storage: Store refrigerated at 2° to 8°C (36° to 46°F). During shipment ZIOPTAN ® may be maintained at temperatures up to 40°C (104°F) for a period not exceeding 2 days. Mail-order prescriptions received after two days of the dispensing date noted in 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 25°C (68° to 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 30 days after first opening the pouch.