iDose® TR (travoprost intracameral implant) is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT).

{ "type": "p", "children": [], "text": "iDose® TR (travoprost intracameral implant) is indicated for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma (OAG) or ocular hypertension (OHT)." }

iDose TR is a travoprost delivery system consisting of a travoprost releasing implant pre-loaded in a sterile, single-dose inserter. iDose TR is administered intracamerally through a small, clear corneal incision and is anchored into the sclera at the iridocorneal angle. iDose TR should not be readministered to an eye that received a prior iDose TR.

1. The procedure must be carried out under aseptic conditions which include use of sterile gloves and a sterile drape. 2. The eye should be anesthetized using general, retrobulbar, peribulbar, or topical anesthesia per standard operating room procedures. 3. The iDose TR implantation procedure must be performed under magnification that allows clear visualization of the anterior chamber angle and angle structures including trabecular meshwork, with the patient’s head in a stabilized position. The pupil should not be dilated prior to the procedure. 4. An intracameral miotic can be injected to deepen the angle prior to insertion of the iDose TR. 5. It is recommended that the implant surgery be performed from the temporal side, using a temporal clear corneal incision. The implant will be implanted through the angle and the trabecular meshwork into the sclera on the nasal side. 6. Remove the barrier pouch from the carton and examine for damage. Open the barrier pouch, discard the oxygen scavenger packet, and remove the blister tray with Tyvek® lid. Open the Tyvek lid containing the iDose TR pre-loaded inserter and present to the surgeon. The iDose TR implant and single-dose inserter should be handled in the sterile field. Caution: Do not use the iDose TR if the Tyvek lid has been opened or the packaging appears damaged. 7. Prepare for gonioscopy by turning the patient’s head away from the surgeon by approximately 15° to 25° and tilt the scope toward the surgeon by approximately 35°. The total combined angle should be approximately 50° to 60°. 8. Place a small amount of viscoelastic on the cornea. Position the gonioprism on the cornea using light touch gonioscopy. Adjust the microscope to locate and focus on the trabecular meshwork. 9. Inspect the angle with a gonioprism to ensure that a good view of all angle structures is available at the nasal implant location. 10. Hold the single-dose inserter as shown in Figure 1 with your index finger comfortably on the implant release button.

Figure 1

11. Perform a detailed inspection of the tip of the sterile inserter under magnification to ensure that the iDose TR implant is present (Figure 2)

Figure 2

12. Create a clear corneal incision of approximately 2.4 mm at the temporal limbus location using an instrument of the surgeon’s choice. 13. Add a cohesive viscoelastic to the anterior chamber as needed to form the anterior chamber and improve visualization of the angle. Be careful not to overinflate. 14. Insertion of the implant: a. When ready for implantation, remove the safety clip which holds the release button in place by squeezing and rocking the clip backwards (see Figure 2). Place finger on the release button to ensure it remains in the forward position and does not prematurely release the implant. b. To smoothly enter the anterior chamber, slide the inserter tip with implant “side to side” in the incision. c. Advance to the pupillary margin and ensure there is sufficient cohesive viscoelastic on the cornea before replacing the gonioprism onto the cornea. d. Take care to avoid contact with the lens or cornea. e. Advance to the anterior chamber angle and approach the trabecular meshwork (see Figure 3).

Figure 3 f. Press the implant directly through the trabecular meshwork, compressing the tissue until the implant anchor securely penetrates the sclera through the back wall of Schlemm’s canal. The base of the implant reservoir should be firmly in contact with and compressing the trabecular meshwork. g. Once the anchor of the implant is securely embedded in sclera, pause for the tissue to relax. Carefully slide the implant release button backwards to open the inserter tip with grasper and release the implant from the inserter (Figure 4a). Ensuring the implant has released from the inserter grasper, slowly remove the inserter straight back (Figure 4b). Avoid pulling the implant out of position.

Figure 4a

Figure 4b

h. Apply slight pressure to the sides of the implant with the tip of the inserter to ensure the implant is fully anchored into scleral tissue. Note: If for any reason the implant appears loose or disengaged from the scleral tissue after the initial implantation, slide the implant release button back to fully open the graspers. Position the graspers between the ribs on the implant and regrasp the body of the implant between the ribs by pushing the release button forward and re-implant a minimum of ½ clock hour to either side. Do not re-implant at the same location. i. Withdraw the inserter from the eye. 15. Location of iDose TR in Trabecular Meshwork a. Perform a high-magnification examination to confirm that the implant is in proper position (i.e., the proximal end rests in the anterior chamber with an unobstructed membrane) (see Figure 5) and securely attached with the anchor thoroughly embedded in the sclera.

Figure 5

b. It is normal for an edge of the implant to make contact with the iris. Note: In a normal iris (no viscoelastic in the anterior chamber and non-constricted pupil), the iris may obstruct the view of a portion of the cap of the implant. c. Irrigate and aspirate the anterior chamber with balanced salt solution to remove all viscoelastic. Press down on the posterior edge of the incision as needed to facilitate complete removal of viscoelastic. d. Inflate the anterior chamber with saline solution as needed to achieve physiologic pressure.

Intracameral implant containing 75 mcg travoprost, pre-loaded in a single-dose inserter.

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iDose TR (travoprost intracameral implant) is contraindicated in patients with active or suspected ocular or periocular infections.

iDose TR is contraindicated in patients with corneal endothelial cell dystrophy (e.g., Fuch’s Dystrophy, corneal guttatae).

iDose TR is contraindicated in patients with prior corneal transplantation, or endothelial cell transplants (e.g., Descemet’s Stripping Automated Endothelial Keratoplasty [DSAEK]).

iDose TR is contraindicated in patients with hypersensitivity to travoprost or to any other components of the product.

iDose TR should be used with caution in patients with narrow iridocorneal angles (Shaffer grade < 3) or other angle abnormalities (e.g., peripheral anterior synechia, rubeosis iridis) that could impair proper placement of iDose TR at the planned implantation site.

Dislocation of the iDose TR has been observed in clinical trials. Patients should be monitored routinely to confirm the location of the iDose TR at the site of administration. If the iDose TR implant becomes dislocated, it should be surgically removed.

Macular edema, including cystoid macular edema, has been reported during treatment with ophthalmic travoprost, including iDose TR intracameral implant. iDose TR 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.

Prostaglandin analogs, including iDose TR, have been reported to cause intraocular inflammation. iDose TR should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated.

Topical ophthalmic travoprost has been reported to cause increased pigmentation to pigmented tissues. Pigmentation is expected to increase as long as travoprost 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 travoprost, pigmentation of the iris is likely to be permanent. 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 travoprost can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly.

Intraocular surgical procedures and injections have been associated with endophthalmitis. Proper aseptic technique must always be used with administering iDose TR, and patients should be monitored following the administration.

iDose TR is MR Conditional. Patients should be informed that the implant is MR Conditional (as noted on their Patient ID card). If the patient requires magnetic resonance imaging (MRI), they should inform their healthcare provider that they have an iDose TR implanted in their eye.

A patient with the iDose TR may be safely scanned under the following conditions. Failure to follow these conditions may result in injury to the patient.

<div class="scrollingtable"><table class="Noautorules" width="700"> <col align="left" width="30%"/> <col align="left" width="70%"/> <tbody class="Headless"> <tr valign="top"> <td align="left" class="Bold Botrule Italics Lrule Rrule Toprule">Parameter</td><td align="left" class="Bold Botrule Italics Lrule Rrule Toprule">Condition of Use / Information</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">Nominal Values of<br/>Static Magnetic Field (T)</td><td align="left" class="Botrule Lrule Rrule Toprule">3.0 T or less</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">Maximum Spatial Field <br/>Gradient<br/>(T/m and gauss/cm)</td><td align="left" class="Botrule Lrule Rrule Toprule">40-T/m (4,000-gauss/cm)</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">Type of RF Excitation</td><td align="left" class="Botrule Lrule Rrule Toprule">Circularly Polarized (CP) (i.e., Quadrature-Transmission)</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">Transmit RF Coil<br/>Information</td><td align="left" class="Botrule Lrule Rrule Toprule">Any transmit RF coil may be used</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">Operating Mode of MR<br/>System</td><td align="left" class="Botrule Lrule Rrule Toprule">Normal Operating Mode</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">Maximum Whole Body<br/>Averaged SAR</td><td align="left" class="Botrule Lrule Rrule Toprule">2-W/kg (Normal Operating Mode)</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">Maximum Head SAR</td><td align="left" class="Botrule Lrule Rrule Toprule">3.2-W/kg (Normal Operating Mode)</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">Limits on Scan Duration</td><td align="left" class="Botrule Lrule Rrule Toprule">Whole body averaged SAR of 2-W/kg for 60 minutes of continuous<br/>RF exposure (i.e., per pulse sequence or back-to-back<br/>sequences/series without breaks)</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule">MR Image Artifact</td><td align="left" class="Botrule Lrule Rrule Toprule">The presence of this implant produces an imaging artifact. Therefore, carefully select pulse sequence parameters if the implant is located in the area of interest.</td> </tr> </tbody> </table></div>

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The following adverse events rates are derived from three randomized, double-masked clinical trials in which 868 patients with open angle glaucoma (OAG) or ocular hypertension (OHT) received an iDose TR and were followed for one year. The most commonly reported ocular adverse reactions (2% to 6%) were increases in intraocular pressure, iritis, dry eye, visual field defects, eye pain, ocular hyperaemia, and reduced visual acuity. Ocular adverse reactions reported in less than 2% of patients were conjunctival hemorrhage, photophobia, punctate keratitis, blepharitis, eye irritation, corneal abrasion, device dislocation, vitreous detachment, and foreign body sensation in eyes.

Risk Summary

There are no adequate and well-controlled studies of iDose TR (travoprost intracameral implant) administration in pregnant women to inform a drug-associated risk. Subcutaneous administration of travoprost to pregnant mice and rats throughout the period of organogenesis produced embryo-fetal lethality, spontaneous abortion, and premature delivery at potentially clinically relevant doses.

Advise pregnant women of a potential risk to a fetus. iDose TR should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Data

Animal Data

An embryo-fetal development study was conducted in pregnant rats administered travoprost once daily at doses up to 10 mcg/kg by subcutaneous injection from gestation day (GD) 6 to 17, to target the period of organogenesis. At 10 mcg/kg, 116 times the maximum human ocular dose (MHOD) of 1 implant per eye, based on body surface area (BSA), assuming sustained travoprost release from the implant for 6 months or 0.0139 mcg/kg/day, travoprost was teratogenic in rats, evidenced by an increase in the incidence of skeletal malformations as well as external and visceral malformations, including fused sternebrae, domed head and hydrocephaly. Travoprost caused post-implantation loss at 10 mcg/kg. The fetal no observed adverse effect level (NOAEL) was 3 mcg/kg (34.5 times the maximum human ocular dose (MHOD) of 1 implant per eye, based on BSA).

An embryo-fetal development study was conducted in pregnant mice administered travoprost once daily by subcutaneous injection at doses up to 1 mcg/kg from GD 6 to 16, to target the period of organogenesis. Travoprost induced an increase in post-implantation losses and a decrease in fetal viability in mice at subcutaneous doses > 0.3 mcg/kg. The fetal NOAEL was 0.3 mcg/kg (1.7 times the MHOD based on BSA). The maternal NOAEL was 1 mcg/kg (5.8 times the MHOD based on BSA).

Pre/postnatal development studies were conducted in rats administered travoprost once daily by subcutaneous injection from GD 7 (early embryonic period) to postnatal Day 21 (end of lactation period). At doses of greater than or equal to 0.12 mcg/kg/day (1.4 times the MHOD based on BSA), the incidence of post-natal mortality was increased, and neonatal body weight was decreased. Neonatal development was also affected, evidenced by delayed eye opening, pinna detachment and preputial separation, and by decreased motor activity.

Risk Summary

There are no data on the effects of travoprost on the breastfed child or milk production. It is not known if travoprost is present in human milk following ophthalmic administration.

The developmental and health benefits of breastfeeding should be considered, along with the mother’s clinical need for iDose TR and any potential adverse effects on the breast-fed child from iDose TR.

The safety and effectiveness of iDose TR have not been established in pediatric patients.

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

iDose TR (travoprost intracameral implant) is a sterile intracameral implant containing 75 mcg of travoprost. The intracameral implant consists of a titanium implant reservoir with a membrane controlling the sustained release of travoprost. The sterile implant is pre-loaded in a sterile single-dose inserter to facilitate insertion directly through the trabecular meshwork of the anterior chamber angle into the sclera.

{ "type": "p", "children": [], "text": "iDose TR (travoprost intracameral implant) is a sterile intracameral implant containing 75 mcg of travoprost. The intracameral implant consists of a titanium implant reservoir with a membrane controlling the sustained release of travoprost. The sterile implant is pre-loaded in a sterile single-dose inserter to facilitate insertion directly through the trabecular meshwork of the anterior chamber angle into the sclera." }

Travoprost is a prostaglandin analog. Its chemical name is 5-heptenoic acid, 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-buten-1-yl]cyclopentyl]-, 1-methylethyl ester, (5Z)-. Travoprost has a molecular formula of C26H35F3O6 and a molecular weight of 500.55 g/mol.

{ "type": "p", "children": [], "text": "Travoprost is a prostaglandin analog. Its chemical name is 5-heptenoic acid, 7-[(1R,2R,3R,5S)-3,5-dihydroxy-2-[(1E,3R)-3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-buten-1-yl]cyclopentyl]-, 1-methylethyl ester, (5Z)-. Travoprost has a molecular formula of C26H35F3O6 and a molecular weight of 500.55 g/mol." }

The chemical structure of travoprost is:

{ "type": "p", "children": [], "text": "The chemical structure of travoprost is:" }

Travoprost is a clear, colorless to slightly yellow oil that is very soluble in acetonitrile, methanol, octanol, and chloroform. It is practically insoluble in water.

{ "type": "p", "children": [], "text": "Travoprost is a clear, colorless to slightly yellow oil that is very soluble in acetonitrile, methanol, octanol, and chloroform. It is practically insoluble in water." }

Travoprost free acid, a prostaglandin analog is a selective FP prostanoid receptor agonist, which is believed to reduce IOP by increasing uveoscleral outflow. The exact mechanism of action is unknown at this time.

Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea and other intraocular tissues to its biologically active free acid. Systemically, travoprost free acid is metabolized to inactive metabolites via beta-oxidation of the α (carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13, 14 double bond.

Data from a pharmacokinetic study of 105 subjects evaluating two models of the travoprost intracameral implant with different elution rates have shown that the plasma concentrations of travoprost free acid are below 10 pg/mL (the quantitation limit of the assay, LLOQ) in all subjects at day 10, week 12 and month 12 following administration of iDose TR.

Carcinogenesis

Two-year carcinogenicity studies in mice and rats at subcutaneous doses of 10, 30, or 100 mcg/kg/day did not show any evidence of carcinogenic potential. However, at 100 mcg/kg/day, male rats were only treated for 82 weeks, and the maximum tolerated dose (MTD) was not reached in the mouse study. The high dose (100 mcg/kg) represents > 500 times the MHOD based on BSA.

Mutagenesis

Travoprost was not mutagenic in the Ames test, mouse micronucleus test or rat chromosome aberration assay. A slight increase in the mutant frequency was observed in one of two mouse lymphoma assays in the presence of rat S-9 activation enzymes.

Fertility

Travoprost did not affect mating or fertility indices in male or female rats at subcutaneous doses up to 10 mcg/kg/day (116 times the MHOD based on BSA). At 10 mcg/kg/day (116 times the MHOD based on BSA), the mean number of corpora lutea was reduced, and the post-implantation losses were increased. These effects were not observed at 3 mcg/kg/day (34.5 times the MHOD based on BSA).

iDose TR was evaluated in two multicenter, 12-month, randomized, parallel-group, double-masked, controlled clinical trials in patients with OAG or OHT. In both trials (GC-010, NCT03519386, and GC-012, NCT03868124), iDose TR was compared to twice-daily topical administration of timolol maleate ophthalmic solution, 0.5%. In the first 3 months following administration, iDose TR demonstrated an IOP change from baseline of -6.6 to -8.4 mmHg in the study eye of patients with a mean baseline IOP of 24 mmHg (see Figure 6).

{ "type": "p", "children": [], "text": "iDose TR was evaluated in two multicenter, 12-month, randomized, parallel-group, double-masked, controlled clinical trials in patients with OAG or OHT. In both trials (GC-010, NCT03519386, and GC-012, NCT03868124), iDose TR was compared to twice-daily topical administration of timolol maleate ophthalmic solution, 0.5%. In the first 3 months following administration, iDose TR demonstrated an IOP change from baseline of -6.6 to -8.4 mmHg in the study eye of patients with a mean baseline IOP of 24 mmHg (see Figure 6)." }

Figure 6: Change from Baseline in Study Eye IOP (mmHg) and Treatment Difference

{ "type": "p", "children": [], "text": "\nFigure 6: Change from Baseline in Study Eye IOP (mmHg) and Treatment Difference\n" }

Study GC-010

{ "type": "p", "children": [], "text": "\nStudy GC-010\n" }

Study GC-012

{ "type": "p", "children": [], "text": "\nStudy GC-012\n" }

iDose TR demonstrated non-inferiority to timolol ophthalmic solution in IOP reduction during the first 3 months. Subsequently, iDose TR did not demonstrate non-inferiority over the next 9 months.

{ "type": "p", "children": [], "text": "iDose TR demonstrated non-inferiority to timolol ophthalmic solution in IOP reduction during the first 3 months. Subsequently, iDose TR did not demonstrate non-inferiority over the next 9 months." }

iDose TR (travoprost intracameral implant) (NDC 25357-100-01) is provided sterile and pre-loaded in a sterile, single-dose inserter that is packaged in a blister tray sealed with a Tyvek lid. Implants are individually serialized and the serial number is provided on the tray lid.

{ "type": "p", "children": [], "text": "iDose TR (travoprost intracameral implant) (NDC 25357-100-01) is provided sterile and pre-loaded in a sterile, single-dose inserter that is packaged in a blister tray sealed with a Tyvek lid. Implants are individually serialized and the serial number is provided on the tray lid." }

The tray is sealed inside of a transparent plastic pouch along with an oxygen scavenger packet, which is packaged inside a unit carton. Tamper evidence is provided by a seal on both ends of the carton.

{ "type": "p", "children": [], "text": "The tray is sealed inside of a transparent plastic pouch along with an oxygen scavenger packet, which is packaged inside a unit carton. Tamper evidence is provided by a seal on both ends of the carton." }

Storage:

{ "type": "p", "children": [], "text": "\nStorage:" }

Store at 2°C to 25°C (36°F to 77°F). Do not freeze.

{ "type": "p", "children": [], "text": "Store at 2°C to 25°C (36°F to 77°F). Do not freeze." }

Intraocular Inflammation or Endophthalmitis Advise patients about the potential risk for complications including, but not limited to, the development of intraocular inflammation or endophthalmitis [see Warnings and Precautions (5.3, 5.4, 5.6)].

{ "type": "p", "children": [], "text": "\nIntraocular Inflammation or Endophthalmitis\nAdvise patients about the potential risk for complications including, but not limited to, the development of intraocular inflammation or endophthalmitis [see Warnings and Precautions (5.3, 5.4, 5.6)]." }

Potential for Pigmentation Advise patients about the potential for increased brown pigmentation of the iris, which may be permanent [see Warnings and Precautions (5.5)].

{ "type": "p", "children": [], "text": "\nPotential for Pigmentation\nAdvise patients about the potential for increased brown pigmentation of the iris, which may be permanent [see Warnings and Precautions (5.5)]." }

MR Conditional Advise patients that the implant is MR Conditional (as noted on their Patient ID card), and that if they require magnetic resonance imaging (MRI), they should inform their healthcare provider that they have iDose TR implanted in their eye [see Warnings and Precautions (5.7)].

{ "type": "p", "children": [], "text": "\nMR Conditional\nAdvise patients that the implant is MR Conditional (as noted on their Patient ID card), and that if they require magnetic resonance imaging (MRI), they should inform their healthcare provider that they have iDose TR implanted in their eye [see Warnings and Precautions (5.7)]." }

When to Seek Physician Advice Advise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist [see Warnings and Precautions (5.2, 5.4, 5.6)].

{ "type": "p", "children": [], "text": "\nWhen to Seek Physician Advice\nAdvise patients that if the eye becomes red, sensitive to light, painful, or develops a change in vision, they should seek immediate care from an ophthalmologist [see Warnings and Precautions (5.2, 5.4, 5.6)]." }

Symbols that are included in the labeling of this product.

{ "type": "p", "children": [], "text": "Symbols that are included in the labeling of this product." }

<div class="scrollingtable"><table class="Noautorules" width="400"> <col align="left" width="40%"/> <col align="left" width="60%"/> <tbody class="Headless"> <tr valign="top"> <td align="center" class="Bold Botrule Italics Lrule Rrule Toprule">Symbol</td><td align="center" class="Bold Botrule Italics Lrule Rrule Toprule">Definition</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol0" src="/dailymed/image.cfm?name=idose-10.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Catalogue/Model Number</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol1" src="/dailymed/image.cfm?name=idose-11.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Serial Number</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol2" src="/dailymed/image.cfm?name=idose-12.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Lot Number</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbo13" src="/dailymed/image.cfm?name=idose-13.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Do not re-use</td> </tr> <tr valign="top"> <td align="left" class="Botrule Lrule Rrule Toprule"><img alt="symbo14" src="/dailymed/image.cfm?name=idose-14.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Use-by date (year-month)</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol5" src="/dailymed/image.cfm?name=idose-15.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Do not resterilize</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol6" src="/dailymed/image.cfm?name=idose-16.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">See package insert for Full<br/>Prescribing Information</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol7" src="/dailymed/image.cfm?name=idose-17.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Temperature limit</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol8" src="/dailymed/image.cfm?name=idose-18.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Sterilized by Gamma Irradiation</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol9" src="/dailymed/image.cfm?name=idose-19.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">For prescription use only</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol10" src="/dailymed/image.cfm?name=idose-20.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">Do not use if package is damaged</td> </tr> <tr valign="top"> <td align="left" class="Bold Botrule Lrule Rrule Toprule"><img alt="symbol11" src="/dailymed/image.cfm?name=idose-21.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c"/></td><td align="left" class="Botrule Lrule Rrule Toprule">MR Conditional</td> </tr> </tbody> </table></div>

{ "type": "table", "children": [], "text": "<div class=\"scrollingtable\"><table class=\"Noautorules\" width=\"400\">\n<col align=\"left\" width=\"40%\"/>\n<col align=\"left\" width=\"60%\"/>\n<tbody class=\"Headless\">\n<tr valign=\"top\">\n<td align=\"center\" class=\"Bold Botrule Italics Lrule Rrule Toprule\">Symbol</td><td align=\"center\" class=\"Bold Botrule Italics Lrule Rrule Toprule\">Definition</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol0\" src=\"/dailymed/image.cfm?name=idose-10.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Catalogue/Model Number</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol1\" src=\"/dailymed/image.cfm?name=idose-11.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Serial Number</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol2\" src=\"/dailymed/image.cfm?name=idose-12.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Lot Number</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbo13\" src=\"/dailymed/image.cfm?name=idose-13.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Do not re-use</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Botrule Lrule Rrule Toprule\"><img alt=\"symbo14\" src=\"/dailymed/image.cfm?name=idose-14.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Use-by date (year-month)</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol5\" src=\"/dailymed/image.cfm?name=idose-15.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Do not resterilize</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol6\" src=\"/dailymed/image.cfm?name=idose-16.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">See package insert for Full<br/>Prescribing Information</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol7\" src=\"/dailymed/image.cfm?name=idose-17.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Temperature limit</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol8\" src=\"/dailymed/image.cfm?name=idose-18.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Sterilized by Gamma Irradiation</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol9\" src=\"/dailymed/image.cfm?name=idose-19.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">For prescription use only</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol10\" src=\"/dailymed/image.cfm?name=idose-20.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">Do not use if package is damaged</td>\n</tr>\n<tr valign=\"top\">\n<td align=\"left\" class=\"Bold Botrule Lrule Rrule Toprule\"><img alt=\"symbol11\" src=\"/dailymed/image.cfm?name=idose-21.jpg&amp;setid=92f6d3e2-8328-47df-972c-23008f4a1c1c\"/></td><td align=\"left\" class=\"Botrule Lrule Rrule Toprule\">MR Conditional</td>\n</tr>\n</tbody>\n</table></div>" }

Manufactured by Glaukos Corp., 229 Avenida Fabricante, San Clemente, CA 92672 © 2023 Glaukos. All rights reserved. All trademarks are the property of their respective owners.

{ "type": "p", "children": [], "text": "\nManufactured by Glaukos Corp., 229 Avenida Fabricante, San Clemente, CA 92672 \n\n\n© 2023 Glaukos. All rights reserved.\n\t\t\t\t\t\t\tAll trademarks are the property of their respective owners." }

Patented. U.S. Patent No. 10,206,813 and U.S. Patent No. 11,426,306.

{ "type": "p", "children": [], "text": "Patented. U.S. Patent No. 10,206,813 and U.S. Patent No. 11,426,306." }

P-000992 Rev 1

{ "type": "p", "children": [], "text": "P-000992 Rev 1" }

Travoprost ophthalmic solution 0.004% (ionic buffered solution) is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension.

{ "type": "p", "children": [], "text": "Travoprost ophthalmic solution 0.004% (ionic buffered solution) is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension." }

The recommended dosage is one drop in the affected eye(s) once daily in the evening. Travoprost ophthalmic solution 0.004% (ionic buffered solution) should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the IOP lowering effect.

{ "type": "p", "children": [], "text": "The recommended dosage is one drop in the affected eye(s) once daily in the evening. Travoprost ophthalmic solution 0.004% (ionic buffered solution) should not be administered more than once daily since it has been shown that more frequent administration of prostaglandin analogs may decrease the IOP lowering effect." }

Reduction of the IOP starts approximately 2 hours after the first administration with maximum effect reached after 12 hours.

{ "type": "p", "children": [], "text": "Reduction of the IOP starts approximately 2 hours after the first administration with maximum effect reached after 12 hours." }

Travoprost ophthalmic solution 0.004% (ionic buffered solution) may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart.

{ "type": "p", "children": [], "text": "Travoprost ophthalmic solution 0.004% (ionic buffered solution) may be used concomitantly with other topical ophthalmic drug products to lower IOP. If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes apart." }

Ophthalmic solution containing travoprost USP, 0.04 mg/mL.

{ "type": "p", "children": [], "text": "Ophthalmic solution containing travoprost USP, 0.04 mg/mL." }

None.

{ "type": "p", "children": [], "text": "None." }

Travoprost 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 travoprost 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 travoprost, 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 travoprost ophthalmic solution 0.004% (ionic buffered solution) can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly [see Patient Counseling Information (17)].

Travoprost ophthalmic solution 0.004% (ionic buffered solution) may gradually change eyelashes and vellus hair in the treated eye. These changes include increased length, thickness, and number of lashes. Eyelash changes are usually reversible upon discontinuation of treatment [see Patient Counseling Information (17)].

Travoprost ophthalmic solution 0.004% (ionic buffered solution) should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated.

Macular edema, including cystoid macular edema, has been reported during treatment with travoprost ophthalmic solution. Travoprost ophthalmic solution 0.004% (ionic buffered solution) 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.

Travoprost ophthalmic solution 0.004% (ionic buffered solution)

has not been evaluated for the treatment of angle-closure, inflammatory or neovascular glaucoma.

There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. These containers had been inadvertently contaminated by patients who, in most cases, had a concurrent corneal disease or a disruption of the ocular epithelial surface [see Patient Counseling Information (17)] .

Contact lenses should be removed prior to instillation of travoprost ophthalmic solution 0.004% (ionic buffered solution) and may be reinserted 15 minutes following its administration.

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most common adverse reaction observed in controlled clinical trials with travoprost ophthalmic solution 0.004% and travoprost ophthalmic solution 0.004% (ionic buffered solution) was ocular hyperemia, which was reported in 30% to 50% of patients. Up to 3% of patients discontinued therapy due to conjunctival hyperemia. Ocular adverse reactions reported at an incidence of 5% to 10% in these clinical trials included decreased visual acuity, eye discomfort, foreign body sensation, pain, and pruritus.

Ocular adverse reactions reported at an incidence of 1% to 4% in clinical trials with travoprost ophthalmic solution 0.004% or travoprost ophthalmic solution 0.004% (ionic buffered solution) included abnormal vision, blepharitis, blurred vision, cataract, conjunctivitis, corneal staining, dry eye, iris discoloration, keratitis, lid margin crusting, ocular inflammation, photophobia, subconjunctival hemorrhage, and tearing.

Non-ocular adverse reactions reported at an incidence of 1% to 5% in these clinical studies were allergy, angina pectoris, anxiety, arthritis, back pain, bradycardia, bronchitis, chest pain, cold/flu syndrome, depression, dyspepsia, gastrointestinal disorder, headache, hypercholesterolemia, hypertension, hypotension, infection, pain, prostate disorder, sinusitis, urinary incontinence, and urinary tract infections.

Additional adverse reactions have been identified during post approval use of travoprost ophthalmic solution 0.004% or travoprost ophthalmic solution 0.004% (ionic buffered solution) in clinical practice. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. The reactions, which have been chosen for inclusion due to either their seriousness, frequency of reporting, possible causal connection to travoprost ophthalmic solution 0.004% or travoprost ophthalmic solution 0.004% (ionic buffered solution), or a combination of these factors, include: arrhythmia, vomiting, epistaxis, tachycardia, and insomnia.

In postmarketing use with prostaglandin analogs, periorbital and lid changes including deepening of the eyelid sulcus have been observed.

Risk Summary

There are no adequate and well-controlled studies in pregnant women to inform a drug-associated risk.

In animal reproduction studies, subcutaneous (SC) administration of travoprost to pregnant mice and rats throughout the period of organogenesis produced embryo-fetal lethality, spontaneous abortion, and premature delivery at potentially clinically relevant doses.

Advise pregnant women of a potential risk to a fetus. Because animal reproductive studies are not always predictive of human response, travoprost ophthalmic solution 0.004% (ionic buffered solution) should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

The background risk of major birth defects and miscarriage for the indicated population is unknown; however, in the U.S. general population, the estimated background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.

Data

Animal Data

An embryo-fetal study was conducted in pregnant rats administered travoprost once daily by SC injection from gestation day (GD) 6 to 18, to target the period of organogenesis. At 10 mcg/kg (60 times the maximum recommended human ocular dose [MRHOD], based on estimated plasma C max), travoprost was teratogenic in rats, evidenced by an increase in the incidence of skeletal malformations as well as external and visceral malformations, including fused sternebrae, domed head and hydrocephaly. Travoprost caused post-implantation loss at 10 mcg/kg. The no observed adverse effect level (NOAEL) for post-implantation loss was 3 mcg/kg (18 times the MRHOD, based on estimated plasma C max). The maternal NOAEL was 10 mcg/kg.

An embryo-fetal study was conducted in pregnant mice administered travoprost once daily by SC injection from GD 6 to 11, to target the period of organogenesis. At 1 mcg/kg (6 times the MRHOD, based on estimated plasma C max), travoprost caused postimplantation loss and decreased fetal weight. The no observed adverse effect level (NOAEL) for malformations was 0.3 mcg/kg (2 times the MRHOD, based on estimated plasma C max). The maternal NOAEL was 1 mcg/kg.

Pre/postnatal studies were conducted in rats administered travoprost once daily by subcutaneous injection from GD 7 (early embryonic period) to postnatal Day 21 (end of lactation period). At doses of greater than or equal to 0.12 mcg/kg/day (0.7 times the MRHOD, based on estimated plasma C max), adverse pregnancy outcomes (embryo-fetal lethality, abortion, and early delivery), low-birth weight and developmental delays were observed. The NOAEL for adverse pregnancy outcomes, low-birth weight and developmental delay was 0.1 mcg/kg (0.6 times the MHROD, based on estimated plasma C max). The NOAEL for maternal toxicity was 0.72 mcg/kg (4 times the MHROD, based on estimated plasma C max).

Risk Summary

There are no data on the effects of travoprost on the breastfed child or milk production. It is not known if travoprost is present in human milk following ophthalmic administration. A study in lactating rats demonstrated that radio-labeled travoprost and/or its metabolites were excreted in milk following subcutaneous administration.

The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for travoprost ophthalmic solution 0.004% (ionic buffered solution) and any potential adverse effects on the breast-fed child from travoprost ophthalmic solution 0.004% (ionic buffered solution).

Use in pediatric patients below the age of 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use.

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

Travoprost ophthalmic solution 0.004% has been studied in patients with hepatic impairment and also in patients with renal impairment. No clinically relevant changes in hematology, blood chemistry, or urinalysis laboratory data were observed in these patients.

Travoprost is a synthetic prostaglandin F analog. Its chemical name is [1R-[1α(Z),2β(1E,3R*),3α,5α]]-7-[3,5-Dihydroxy-2-[3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]cyclopentyl]-5-heptenoic acid, 1-methylethylester. It has a molecular formula of C 26H 35F 3O 6 and a molecular weight of 500.55 g/mol. The chemical structure of travoprost is:

{ "type": "p", "children": [], "text": "Travoprost is a synthetic prostaglandin F analog. Its chemical name is [1R-[1α(Z),2β(1E,3R*),3α,5α]]-7-[3,5-Dihydroxy-2-[3-hydroxy-4-[3-(trifluoromethyl)phenoxy]-1-butenyl]cyclopentyl]-5-heptenoic acid, 1-methylethylester. It has a molecular formula of C\n \n \n 26H\n \n \n 35F\n \n \n 3O\n \n \n 6 and a molecular weight of 500.55 g/mol. The chemical structure of travoprost is:\n \n\n " }

Travoprost, USP is a clear, colorless to slightly yellow oil that is very soluble in acetonitrile, methanol, octanol, and chloroform. It is practically insoluble in water.

{ "type": "p", "children": [], "text": "Travoprost, USP is a clear, colorless to slightly yellow oil that is very soluble in acetonitrile, methanol, octanol, and chloroform. It is practically insoluble in water." }

Travoprost ophthalmic solution USP, 0.004% (ionic buffered solution) is supplied as sterile, buffered aqueous solution of travoprost with a pH of approximately 5.7 and an osmolality of approximately 290 mOsmol/kg.

{ "type": "p", "children": [], "text": "Travoprost ophthalmic solution USP, 0.004% (ionic buffered solution) is supplied as sterile, buffered aqueous solution of travoprost with a pH of approximately 5.7 and an osmolality of approximately 290 mOsmol/kg." }

Each mL of travoprost ophthalmic solution USP, 0.004% (ionic buffered solution) contains

{ "type": "p", "children": [], "text": "Each mL of travoprost ophthalmic solution USP, 0.004% (ionic buffered solution) contains " }

Active: travoprost USP, 0.04 mg/mL;

{ "type": "p", "children": [], "text": "\nActive: travoprost USP, 0.04 mg/mL; \n \n\n " }

Inactives: Polyoxyl 40 hydrogenated castor oil, boric acid, propylene glycol, sorbitol, zinc chloride, sodium hydroxide and/or hydrochloric acid (to adjust pH) and water for injection.

{ "type": "p", "children": [], "text": "\nInactives: Polyoxyl 40 hydrogenated castor oil, boric acid, propylene glycol, sorbitol, zinc chloride, sodium hydroxide and/or hydrochloric acid (to adjust pH) and water for injection.\n \n\n " }

Travoprost free acid, a prostaglandin analog is a selective FP prostanoid receptor agonist which is believed to reduce IOP by increasing uveoscleral outflow. The exact mechanism of action is unknown at this time.

Travoprost is absorbed through the cornea and is hydrolyzed to the active free acid. Data from 4 multiple dose pharmacokinetic studies (totaling 107 subjects) have shown that plasma concentrations of the free acid are below 0.01 ng/mL (the quantitation limit of the assay) in two-thirds of the subjects. In those individuals with quantifiable plasma concentrations (N = 38), the mean plasma C max was 0.018 ± 0.007 ng/mL (ranged 0.01 to 0.052 ng/mL) and was reached within 30 minutes. From these studies, travoprost is estimated to have a plasma half-life of 45 minutes. There was no difference in plasma concentrations between Days 1 and 7, indicating steady-state was reached early and that there was no significant accumulation.

Travoprost, an isopropyl ester prodrug, is hydrolyzed by esterases in the cornea to its biologically active free acid. Systemically, travoprost free acid is metabolized to inactive metabolites via beta-oxidation of the α (carboxylic acid) chain to give the 1,2-dinor and 1,2,3,4-tetranor analogs, via oxidation of the 15-hydroxyl moiety, as well as via reduction of the 13, 14 double bond.

The elimination of travoprost free acid from plasma was rapid and levels were generally below the limit of quantification within one hour after dosing. The terminal elimination half-life of travoprost free acid was estimated from fourteen subjects and ranged from 17 minutes to 86 minutes with the mean half-life of 45 minutes. Less than 2% of the topical ocular dose of travoprost was excreted in the urine within 4 hours as the travoprost free acid.

Two-year carcinogenicity studies in mice and rats at subcutaneous doses of 10, 30, or 100 mcg/kg/day did not show any evidence of carcinogenic potential. However, at 100 mcg/kg/day, male rats were only treated for 82 weeks, and the maximum tolerated dose (MTD) was not reached in the mouse study. The high dose (100 mcg/kg) corresponds to exposure levels 326 times (mouse) and 547 times (rat) the human exposure at the MRHOD of 0.04 mcg/kg, based on estimated plasma C max for active travoprost free acid.

Travoprost was not mutagenic in the Ames test, mouse micronucleus test or rat chromosome aberration assay. A slight increase in the mutant frequency was observed in one of two mouse lymphoma assays in the presence of rat S-9 activation enzymes.

Travoprost did not affect mating or fertility indices in male or female rats at subcutaneous doses up to 3 mcg/kg/day (18 times the MRHOD based on estimated plasma C max). At 10 mcg/kg/day (60 times the MRHOD, based on estimated plasma C max), the mean number of corpora lutea was reduced, and the post-implantation losses were increased.

In clinical studies, patients with open-angle glaucoma or ocular hypertension and baseline pressure of 25 to 27 mmHg, who were treated with travoprost ophthalmic solution 0.004% or travoprost ophthalmic solution 0.004% (ionic buffered solution) dosed once daily in the evening, demonstrated 7 to 8 mmHg reductions in IOP. In sub-group analyses of these studies, mean IOP reduction in black patients was up to 1.8 mmHg greater than in non-black patients. It is not known at this time whether this difference is attributed to race or to heavily pigmented irides.

{ "type": "p", "children": [], "text": "In clinical studies, patients with open-angle glaucoma or ocular hypertension and baseline pressure of 25 to 27 mmHg, who were treated with travoprost ophthalmic solution 0.004% or travoprost ophthalmic solution 0.004% (ionic buffered solution) dosed once daily in the evening, demonstrated 7 to 8 mmHg reductions in IOP. In sub-group analyses of these studies, mean IOP reduction in black patients was up to 1.8 mmHg greater than in non-black patients. It is not known at this time whether this difference is attributed to race or to heavily pigmented irides." }

In a multi-center, randomized, controlled trial, patients with mean baseline IOP of 24 to 26 mmHg on TIMOPTIC** 0.5% twice daily who were treated with travoprost ophthalmic solution 0.004%  dosed daily adjunctively to TIMOPTIC** 0.5% twice daily demonstrated 6 to 7 mmHg reductions in IOP.

{ "type": "p", "children": [], "text": "In a multi-center, randomized, controlled trial, patients with mean baseline IOP of 24 to 26 mmHg on TIMOPTIC** 0.5% twice daily who were treated with travoprost ophthalmic solution 0.004%  dosed daily adjunctively to TIMOPTIC** 0.5% twice daily demonstrated 6 to 7 mmHg reductions in IOP." }

Travoprost Ophthalmic Solution USP, 0.004% (Ionic Buffered Solution) is a sterile, isotonic, buffered, preserved, aqueous solution of travoprost, USP (0.04 mg/mL) supplied in 3 piece open nozzle container.

{ "type": "p", "children": [], "text": "Travoprost Ophthalmic Solution USP, 0.004% (Ionic Buffered Solution) is a sterile, isotonic, buffered, preserved, aqueous solution of travoprost, USP (0.04 mg/mL) supplied in 3 piece open nozzle container." }

Travoprost Ophthalmic Solution USP, 0.004% (Ionic Buffered Solution) is supplied as a 2.5 mL solution in a 5 mL and 5 mL solution in a 5 mL natural polypropylene container with a polypropylene open nozzle and an HDPE Turquoise color cap.

{ "type": "p", "children": [], "text": "Travoprost Ophthalmic Solution USP, 0.004% (Ionic Buffered Solution) is supplied as a 2.5 mL solution in a 5 mL and 5 mL solution in a 5 mL natural polypropylene container with a polypropylene open nozzle and an HDPE Turquoise color cap." }

NDC: 72162-2432-2: 2.5 mL fill in 5 mL

{ "type": "p", "children": [], "text": "NDC: 72162-2432-2: 2.5 mL fill in 5 mL" }

NDC: 72162-2432-4: 5 mL fill in 5 mL

{ "type": "p", "children": [], "text": "NDC: 72162-2432-4: 5 mL fill in 5 mL" }

Storage: Store at 2° to 25°C (36° to 77°F).

{ "type": "p", "children": [], "text": "Storage: Store at 2° to 25°C (36° to 77°F)." }

After opening, travoprost ophthalmic solution USP, 0.004% (ionic buffered solution) can be used until the expiration date on the bottle.

{ "type": "p", "children": [], "text": "After opening, travoprost ophthalmic solution USP, 0.004% (ionic buffered solution) can be used until the expiration date on the bottle." }

Repackaged/Relabeled by:Bryant Ranch Prepack, Inc.Burbank, CA 91504

{ "type": "p", "children": [], "text": "Repackaged/Relabeled by:Bryant Ranch Prepack, Inc.Burbank, CA 91504" }

Potential for Pigmentation

{ "type": "p", "children": [], "text": "\nPotential for Pigmentation\n" }

Advise the patient about the potential for increased brown pigmentation of the iris, which may be permanent. Inform the patient about the possibility of eyelid skin darkening, which may be reversible after discontinuation of travoprost ophthalmic solution 0.004% (ionic buffered solution) [see Warnings and Precautions (5.1)] .

{ "type": "p", "children": [], "text": "Advise the patient about the potential for increased brown pigmentation of the iris, which may be permanent. Inform the patient about the possibility of eyelid skin darkening, which may be reversible after discontinuation of travoprost ophthalmic solution 0.004% (ionic buffered solution) \n \n \n [see \n \n \n Warnings and Precautions (5.1)]\n \n \n .\n \n\n " }

Potential for Eyelash Changes

{ "type": "p", "children": [], "text": "\nPotential for Eyelash Changes\n" }

Inform the patient about the possibility of eyelash and vellus hair changes in the treated eye during treatment with travoprost ophthalmic solution 0.004% (ionic buffered solution). 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 [see Warnings and Precautions (5.2)] .

{ "type": "p", "children": [], "text": "Inform the patient about the possibility of eyelash and vellus hair changes in the treated eye during treatment with travoprost ophthalmic solution 0.004% (ionic buffered solution). 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 \n \n \n [see \n \n \n Warnings and Precautions (5.2)]\n \n \n .\n \n\n " }

Handling the Container

{ "type": "p", "children": [], "text": "\nHandling the Container\n" }

Instruct the patient to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions [see Warnings and Precautions (5.6)] .

{ "type": "p", "children": [], "text": "Instruct the patient to avoid allowing the tip of the dispensing container to contact the eye, surrounding structures, fingers, or any other surface in order to avoid contamination of the solution by common bacteria known to cause ocular infections. Serious damage to the eye and subsequent loss of vision may result from using contaminated solutions \n \n \n [see \n \n \n Warnings and Precautions (5.6)]\n \n \n .\n \n\n " }

When to Seek Physician Advice

{ "type": "p", "children": [], "text": "\nWhen to Seek Physician Advice\n" }

Advise the patient that if they develop an intercurrent ocular condition (e.g., trauma or infection), 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 travoprost ophthalmic solution 0.004% (ionic buffered solution) [see Warnings and Precautions ( 5.3, 5.4, 5.5)] .

{ "type": "p", "children": [], "text": "Advise the patient that if they develop an intercurrent ocular condition (e.g., trauma or infection), 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 travoprost ophthalmic solution 0.004% (ionic buffered solution) \n \n \n [see \n \n \n Warnings and Precautions (\n \n \n 5.3, \n \n \n 5.4, \n \n \n 5.5)]\n \n \n .\n \n\n " }

Use with Contact Lenses

{ "type": "p", "children": [], "text": "\nUse with Contact Lenses\n" }

Contact lenses should be removed prior to instillation of travoprost ophthalmic solution 0.004% (ionic buffered solution) and may be reinserted 15 minutes following its administration [see Warnings and Precautions (5.7)] .

{ "type": "p", "children": [], "text": "Contact lenses should be removed prior to instillation of travoprost ophthalmic solution 0.004% (ionic buffered solution) and may be reinserted 15 minutes following its administration \n \n \n [see \n \n \n Warnings and Precautions (5.7)]\n \n \n .\n \n\n " }

Use with Other Ophthalmic Drugs

{ "type": "p", "children": [], "text": "\nUse with Other Ophthalmic Drugs\n" }

If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes between applications.

{ "type": "p", "children": [], "text": "If more than one topical ophthalmic drug is being used, the drugs should be administered at least 5 minutes between applications." }

TIMOPTIC** is a registered trademark of Merck & Co., Inc.

{ "type": "p", "children": [], "text": "TIMOPTIC** is a registered trademark of Merck & Co., Inc." }

DROP-TAINER is a trademark of Alcon

{ "type": "p", "children": [], "text": "DROP-TAINER is a trademark of Alcon" }

Travoprost Ophthalmic Solution USP, 0.004% (Ionic Buffered Solution)

{ "type": "p", "children": [], "text": "\nTravoprost Ophthalmic Solution USP, 0.004% (Ionic Buffered Solution)\n" }

Before you use Travoprost Ophthalmic Solution USP, 0.004% (Ionic Buffered Solution) for the first time:

{ "type": "p", "children": [], "text": "\nBefore you use Travoprost Ophthalmic Solution USP, 0.004% (Ionic Buffered Solution) for the first time:\n" }

1.  Check to make sure that the tamper evident ring between the bottle and the cap is not broken ( See Figure A). If the tamper evident ring is broken or missing, contact your pharmacist.

{ "type": "p", "children": [], "text": "1.  Check to make sure that the tamper evident ring between the bottle and the cap is not broken (\n \n \n See Figure A). If the tamper evident ring is broken or missing, contact your pharmacist.\n \n\n " }

2.  Tear off the tamper evident ring ( See Figure B).

{ "type": "p", "children": [], "text": "2.  Tear off the tamper evident ring (\n \n \n See Figure B).\n \n\n " }

3.  To open the bottle, remove the cap by turning it in the counter clockwise direction ( See Figure C).

{ "type": "p", "children": [], "text": "3.  To open the bottle, remove the cap by turning it in the counter clockwise direction (\n \n \n See Figure C).\n \n\n " }

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

{ "type": "p", "children": [], "text": "This Instructions for Use has been approved by the U.S. Food and Drug Administration." }

Manufactured by: Micro Labs Limited Bangalore-560099. INDIA.

{ "type": "p", "children": [], "text": "Manufactured by:\n \n \n \nMicro Labs Limited\n Bangalore-560099. INDIA.\n \n\n " }

Manufactured for: Micro Labs USA, Inc. Somerset, NJ 08873

{ "type": "p", "children": [], "text": "Manufactured for:\n \n \n \nMicro Labs USA, Inc.\n Somerset, NJ 08873\n \n\n " }

Rev. 01/2022

{ "type": "p", "children": [], "text": "\nRev. 01/2022\n" }

Travoprost 0.004% Ophth Solution #2.5

{ "type": "p", "children": [], "text": "Travoprost 0.004% Ophth Solution #2.5" }

Extended Label

{ "type": "p", "children": [], "text": "Extended Label" }