DailyMed Label: IYUZEH

DailyMed Label: IYUZEH

2023

DailyMed Prescription

IYUZEH

Latanoprost Ophthalmic Solution 0.005%

Thea Pharma Inc.

NDC: 82584-003

NDC: 82584-003

Latanoprost is a prostaglandin F 2α analogue. Its chemical name is isopropyl-(Z)-7[(1R,2R,3R,5S)3,5dihydroxy-2-[(3R)-3-hydroxy-5-phenylpentyl]cyclopentyl]-5-heptenoate. Its molecular formula is C 26 H 40 O 5 and its chemical structure is: Latanoprost is a colorless to yellow oil that is very soluble in acetonitrile and freely soluble in ethanol, ethyl acetate, and methanol. It is practically insoluble in water and hexanes. IYUZEH (latanoprost ophthalmic solution) 0.005% is supplied as a sterile, isotonic, aqueous solution of latanoprost with a pH of approximately 7 and an osmolality of approximately 280 mOsmol/kg. Each mL of IYUZEH contains 50 mcg of latanoprost. The inactive ingredients are: polyoxyl 40 hydrogenated castor oil, sorbitol, carbomer 974P, polyethylene glycol 4000, disodium edetate, sodium hydroxide (for pH-adjustment) and water for injections. One drop contains approximately 1.5 mcg of latanoprost. IYUZEH does not contain a preservative. chemstructure

IYUZEH ™ (latanoprost ophthalmic solution) 0.005% is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. IYUZEH is a prostaglandin F2α analogue indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. ( 1 )

The recommended dosage is one drop in the affected eye(s) once daily in the evening. If one dose is missed, treatment should continue with the next dose as normal. The dosage of IYUZEH should not exceed once daily; the combined use of two or more prostaglandins, or prostaglandin analogs including IYUZEH is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the IOP lowering effect or cause paradoxical elevations in IOP. Reduction of the IOP starts approximately 3 to 4 hours after administration and the maximum effect is reached after 8 to 12 hours. IYUZEH may be used concomitantly with other topical ophthalmic drug products to lower IOP. In vitro studies have shown that precipitation occurs when eye drops containing thimerosal are mixed with the preserved 0.005% latanoprost reference product. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart. Contact lenses should be removed prior to the administration of IYUZEH and may be reinserted 15 minutes after administration. 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 )

Ophthalmic solution: opalescent, white to slightly yellow solution containing latanoprost 0.005% (50 mcg/mL). Ophthalmic solution containing latanoprost 0.005% (50 mcg/mL). ( 3 )

Known hypersensitivity to latanoprost or any other ingredients in this product. Known hypersensitivity to latanoprost or any other ingredients in this product. ( 4 )

Pigmentation : Pigmentation of the iris, periorbital tissue (eyelid) and eyelashes can occur. Iris pigmentation likely to be permanent. ( 5.1 ) Eyelash Changes : Gradual change to eyelashes including increased length, thickness and number of lashes. Usually, reversible. ( 5.2 ) Topical latanoprost ophthalmic products, including IYUZEH have 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 latanoprost 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 latanoprost, 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 IYUZEH can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly. Latanoprost ophthalmic products, including IYUZEH may gradually change eyelashes and vellus hair in the treated eye; these changes include increased length, thickness, pigmentation, the number of lashes or hairs, and misdirected growth of eyelashes. Eyelash changes are usually reversible upon discontinuation of treatment. IYUZEH should be used with caution in patients with a history of intraocular inflammation (iritis/uveitis) and should generally not be used in patients with active intraocular inflammation because inflammation may be exacerbated. Macular edema, including cystoid macular edema, has been reported during treatment with latanoprost ophthalmic products, including IYUZEH. IYUZEH 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. Reactivation of herpes simplex keratitis has been reported during treatment with latanoprost. IYUZEH should be used with caution in patients with a history of herpetic keratitis. IYUZEH should be avoided in cases of active herpes simplex keratitis because inflammation may be exacerbated. Contact lenses should be removed prior to the administration of IYUZEH and may be reinserted 15 minutes after administration.

The following adverse reactions have been reported with the use of topical latanoprost products and are discussed in greater detail in other sections of the label:

The combined use of two or more prostaglandins, or prostaglandin analogs including IYUZEH is not recommended. It has been shown that administration of these prostaglandin drug products more than once daily may decrease the IOP lowering effect or cause paradoxical elevations in IOP.

Risk Summary There are no adequate and well-controlled studies of IYUZEH administration in pregnant women to inform drug-associated risks. In animal reproduction studies, intravenous (IV) administration of latanoprost to pregnant rabbits and rats throughout the period of organogenesis produced malformations, embryofetal lethality and spontaneous abortion at clinically relevant doses (equivalent to 1.3 – 324 times the maximum recommended human ophthalmic dose, on a mg/m 2 basis, assuming 100% absorption) (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. However, the background risk in the U.S. general population of major birth defects is 2 to 4%, and of miscarriage is 15 to 20% of clinically recognized pregnancies. Data Animal Data Embryofetal studies were conducted in pregnant rabbits administered latanoprost daily by IV injection on gestation days 6 through 18, to target the period of organogenesis. A no observed adverse effect level (NOAEL) was not established for rabbit developmental toxicity. Post-implantation loss due to late resorption was shown as doses ≥0.2 mcg/kg/day (equivalent to 1.3 times the maximum recommended human ophthalmic dose [RHOD], on a mg/m 2 basis, assuming 100% absorption). Spina bifida and abortion occurred at 5 mcg/kg/day (equivalent to 32 times the maximum RHOD). Total litter loss due to early resorption was observed at doses ≥50 mcg/kg/day (324 times the maximum RHOD). Transient signs of maternal toxicity were observed after IV dosing (increased breathing, muscle tremors, slight motor incoordination) at 300 mcg/kg/day (1946 times the maximum RHOD). No maternal toxicity was observed at doses up to 50 mcg/kg/day. Embryofetal studies were conducted in pregnant rats administered latanoprost daily by IV injection on gestation days 6 through 15, to target the period of organogenesis. A NOAEL for rat developmental toxicity was not established. Cleft palate was observed at 1 mcg/kg (equivalent to 3.2 times the maximum RHOD, on a mg/m 2 basis, assuming 100% absorption). Brain porencephalic cyst(s) were observed ≥50 mcg/kg (162 times the maximum RHOD). Skeletal anomalies were observed at 250 mcg/kg (811 times the maximum RHOD). No maternal toxicity was detectable at 250 mcg/kg/day. Prenatal and postnatal development was assessed in rats. Pregnant rats were administered latanoprost daily by IV injection from gestation day 15, through delivery, until weaning (lactation Day 21). No adverse effects on rat offspring were observed at doses up to 10 mcg/kg/day (32 times the maximum RHOD, on a mg/m2 basis, assuming 100% absorption). At 100 mcg/kg/day (324 times the maximum RHOD), maternal deaths and pup mortality occurred. Risk Summary 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 IYUZEH is administered to a nursing woman. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for IYUZEH and any potential adverse effects on the breastfed child from IYUZEH. The safety and effectiveness of IYUZEH have not been established in pediatric patients. No overall differences in safety or effectiveness have been observed between elderly and younger adult patients.

IYUZEH (latanoprost ophthalmic solution) is an opalescent, isotonic, white to slightly yellow solution of latanoprost 50 mcg/mL (0.005%) practically free from foreign particles. It is supplied as a sterile solution in translucent low-density polyethylene single-dose container packaged in foil pouches (5 single-dose containers per pouch). NDC 82584-003-30; Unit-of-Use Carton of 30 Storage: Store at 15°C to 25°C (59°F to 77°F). Store in the original pouch. After the pouch is opened, the single-dose containers may be stored in the opened foil pouch for up to 30 days at room temperature 15°C to 25°C (59°F to 77°F). Patient should be advised to write down the date the foil pouch is opened in the space provided on the pouch. Discard any unused containers 30 days after first opening the pouch.

Latanoprost is a prostaglandin F 2α analogue that is believed to reduce the IOP by increasing the outflow of aqueous humor. Studies in animals and man suggest that the main mechanism of action is increased uveoscleral outflow. Elevated IOP represents a major risk factor for glaucomatous field loss. The higher the level of IOP, the greater the likelihood of optic nerve damage and visual field loss. Reduction of the IOP in man starts about 3-4 hours after administration and maximum effect is reached after 8-12 hours. IOP reduction is present for at least 24 hours. Absorption Latanoprost is absorbed through the cornea where the isopropyl ester prodrug is hydrolyzed to the acid form to become biologically active. Distribution The distribution volume in humans is 0.16 ± 0.02 L/kg. The acid of latanoprost can be measured in aqueous humor during the first 4 hours, and in plasma only during the first hour after local administration. Studies in man indicate that the peak concentration in the aqueous humor is reached about two hours after topical administration. Elimination Metabolism Latanoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to the biologically active acid. The active acid of latanoprost reaching the systemic circulation is primarily metabolized by the liver to the 1,2-dinor and 1,2,3,4-tetranor metabolites via fatty acid β-oxidation. Excretion The elimination of the acid of latanoprost from human plasma is rapid (t 1/2 = 17 min) after both IV and topical administration. Systemic clearance is approximately 7 mL/min/kg. Following hepatic β-oxidation, the metabolites are mainly eliminated via the kidneys. Approximately 88% and 98% of the administered dose are recovered in the urine after topical and IV dosing, respectively.

Carcinogenesis Latanoprost was not carcinogenic in either mice or rats when administered by oral gavage at doses of up to 170 mcg/kg/day (approximately 2800 times the recommended maximum human dose) for up to 20 and 24 months, respectively. Mutagenesis Latanoprost was not mutagenic in bacteria, in mouse lymphoma, or in mouse micronucleus tests. Chromosome aberrations were observed in vitro with human lymphocytes. Additional in vitro and in vivo studies on unscheduled DNA synthesis in rats were negative. Impairment of Fertility Latanoprost has not been found to have any effect on male or female fertility in rat studies at IV doses up to 250 mcg/kg/day (811 times the maximum RHOD, on a mg/m 2 basis, assuming 100% absorption).

In randomized, controlled clinical trials of patients with open angle glaucoma or ocular hypertension with mean baseline IOP of 19 - 24 mmHg, IYUZEH lowered IOP by 3 – 8 mmHg versus 4 – 8 mmHg by latanoprost ophthalmic solution preserved with benzalkonium chloride. Latanoprost ophthalmic solution preserved with benzalkonium chloride was approximately 1 mmHg more effective than IYUZEH.

This Patient Information has been approved by the U.S. Food and Drug Administration Revised: 12/2022           PATIENT INFORMATION IYUZEH ™ (eye yoo’ zeh) (latanoprost ophthalmic solution) 0.005% For topical ophthalmic use What is IYUZEH? IYUZEH is a prescription sterile eye drop solution which does not contain a preservative. IYUZEH 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. IYUZEH belongs to a group of medicines called prostaglandin analogs. It is not known if IYUZEH is safe and effective in children. Do not use IYUZEH if you are allergic latanoprost or any of the ingredients in IYUZEH. See the end of this Patient Information leaflet for a complete list of ingredients in IYUZEH. Before you use IYUZEH, 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 IYUZEH will harm your unborn baby. If you become pregnant while using IYUZEH talk to your doctor right away. are breastfeeding or plan to breastfeed. It is not known if IYUZEH passes into your breast milk. Talk to your doctor about the best way to feed your baby if you use IYUZEH. Tell your doctor about all the medicines you take, including prescription and over-the-counter 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 IYUZEH? Read the Instructions for Use at the end of this Patient Information leaflet for additional instructions about the right way to use IYUZEH. Use 1 drop of IYUZEH in your eye (or eyes) each evening. Talk to your doctor or pharmacist if you are not sure how to use IYUZEH. Your IYUZEH may not work as well if you use it more than 1 time each evening. If you miss a dose of IYUZEH, skip the missed dose and take the next dose at your regular time. If you use other medicines in your eye, wait at least 5 minutes between using IYUZEH and your other eye medicines. Contact lenses should be taken out before using IYUZEH and you should wait at least 15 minutes after giving the dose of IYUZEH before putting the contact lenses back into your eyes. Use your IYUZEH right away after opening. Each IYUZEH single-dose container is sterile and is to be used 1 time then thrown away. Do not save any IYUZEH that may be left over after you use your medicine. Using IYUZEH that is not sterile may cause other eye problems. What are the possible side effects of IYUZEH? IYUZEH may cause serious side effects including: changes in the color of your eye (iris). Your iris may become more brown in color while using IYUZEH. This color change may not go away when you stop using IYUZEH. If IYUZEH 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 IYUZEH. increasing the length, thickness, color, or number of your eyelashes. These eyelash changes usually go away when you stop using IYUZEH. hair growth on your eyelids. This hair growth usually goes away when you stop using IYUZEH. The most common side effects of IYUZEH include: redness of and around the eye (conjunctival hyperemia) eye irritation eye itching abnormal sensation in the eye foreign body sensation in the eye blurry vision increase of tears in the eye (increased lacrimation) Tell your doctor right away if you have any new eye problems while using IYUZEH, 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 Additionally, the following side effects have been reported in other latanoprost medicines like IYUZEH, when used in the eye (topical use): dizziness headache peeling skin over much of the body (toxic epidermal necrolysis) worsening of asthma shortness of breath (dyspnea) itching viral infection of the cornea (herpes keratitis) chest pain caused by interruptions in the heart’s blood supply, that can occur at rest (angina, unstable angina) awareness of heart rhythm (palpitations) chest pain Tell your doctor if you have any side effect that bothers you or does not go away. These are not all the possible side effects of IYUZEH. 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 IYUZEH? Before opening the foil pouches: Store the unopened foil pouches between 59°F to 77°F (15°C to 25°C). Do not open the foil pouch containing IYUZEH until you are ready to use the eye drops. After opening the foil pouch: Store the opened foil pouch between 59°F to 77°F (15°C to 25°C), for up to 30 days. Write down the date of first opening the foil pouch in the space provided on the pouch. Throw away all unused IYUZEH single-dose containers in the opened foil pouch after 30 days. Keep the IYUZEH single-dose containers in their original foil pouch. Keep IYUZEH and all medicines out of the reach of children. General information about the safe and effective use of IYUZEH. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use IYUZEH for a condition for which it was not prescribed. Do not give IYUZEH to other people, even if they have the same symptoms that you have. It may harm them. You can ask your pharmacist or doctor for information about IYUZEH that is written for health professionals. What are the ingredients in IYUZEH? Active ingredients: latanoprost Inactive ingredients: polyoxyl 40 hydrogenated castor oil, sorbitol, carbomer 974P, polyethylene glycol 4000, disodium edetate, sodium hydroxide (for pH-adjustment) and water. Manufactured for: Thea Pharma Inc. Lexington, MA. All rights reserved. U.S. Patent N°. 8,637,054. ©2021, Laboratoires Théa. All rights reserved. IYUZEH™ is a trademark of Laboratoires Théa.

NDC 82584-003-30 IYUZEH™ (latanoprost ophthalmic solution) 0.005% 30 single-dose containers (0.2 mL each) For Topical Ophthalmic Use - Rx only Sterile Contains no preservatives Théa PRINCIPAL DISPLAY PANEL NDC 82584-003-81 Recommended Dosage: one drop in the affected eye(s) once daily in the evening. Single-dose container. Discard unused portion. See carton for inactive ingredients Storage: Store at 15°C to 25°C (59°F to 77°F) Store in the original pouch. After the pouch is opened, the single-dose containers may be stored in the opened foil pouch for up to 30 days. Discard any unused containers 30 days after first opening the pouch. Write down the date you open the pouch         __ / __ / __ IYUZEH™ (latanoprost ophthalmic solution) 0.005% For Topical Ophthalmic Use 5 single-dose containers (0.2 mL each) Rx Only Sterile – Contains no preservatives Manufactured for Thea Pharma Inc. Lexington, MA Théa PRINCIPAL DISPLAY PANEL NDC 82584-003-02 SAMPLE: NOT FOR RESALE IYUZEH™ (latanoprost ophthalmic solution) 0.005% 30 single-dose containers (0.2 mL each) For Topical Ophthalmic Use - Rx only Sterile Contains no preservatives Théa PRINCIPAL DISPLAY PANEL NDC 82584-003-01 Recommended Dosage: one drop in the affected eye(s) once daily in the evening. Single-dose container. Discard unused portion. See carton for inactive ingredients Storage: Store at 15°C to 25°C (59°F to 77°F) Store in the original pouch. After the pouch is opened, the single-dose containers may be stored in the opened foil pouch for up to 30 days. Discard any unused containers 30 days after first opening the pouch. Write down the date you open the pouch         __ / __ / __ IYUZEH™ (latanoprost ophthalmic solution) 0.005% For Topical Ophthalmic Use 5 single-dose containers (0.2 mL each) Rx Only Sterile – Contains no preservatives SAMPLE: NOT FOR RESALE Manufactured for Thea Pharma Inc. Lexington, MA Théa carton carton carton carton