NDC 0378-9651 Travoprost Ophthalmic Solution, 0.004%

Travoprost Ophthalmic Solution, 0.004%

NDC Product Code 0378-9651

NDC CODE: 0378-9651

Proprietary Name: Travoprost Ophthalmic Solution, 0.004% What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Non-Proprietary Name: Travoprost Ophthalmic Solution, 0.004% What is the Non-Proprietary Name?
The non-proprietary name is sometimes called the generic name. The generic name usually includes the active ingredient(s) of the product.

NDC Code Structure

NDC 0378-9651-32

Package Description: 1 BOTTLE in 1 CARTON > 2.5 mL in 1 BOTTLE

NDC 0378-9651-50

Package Description: 1 BOTTLE in 1 CARTON > 5 mL in 1 BOTTLE

NDC Product Information

Travoprost Ophthalmic Solution, 0.004% with NDC 0378-9651 is a a human prescription drug product labeled by Mylan Pharmaceuticals Inc.. The generic name of Travoprost Ophthalmic Solution, 0.004% is travoprost ophthalmic solution, 0.004%. The product's dosage form is solution/ drops and is administered via ophthalmic form.

Labeler Name: Mylan Pharmaceuticals Inc.

Dosage Form: Solution/ Drops - A solution which is usually administered in a drop-wise fashion.

Product Type: Human Prescription Drug What kind of product is this?
Indicates the type of product, such as Human Prescription Drug or Human Over the Counter Drug. This data element matches the “Document Type” field of the Structured Product Listing.

Travoprost Ophthalmic Solution, 0.004% Active Ingredient(s)

What is the Active Ingredient(s) List?
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.

  • TRAVOPROST .04 mg/mL

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • SORBITOL (UNII: 506T60A25R)
  • WATER (UNII: 059QF0KO0R)

Administration Route(s)

What are the Administration Route(s)?
The translation of the route code submitted by the firm, indicating route of administration.

  • Ophthalmic - Administration to the external eye.

Pharmacological Class(es)

What is a Pharmacological Class?
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.

  • Prostaglandin Analog - [EPC] (Established Pharmacologic Class)
  • Prostaglandins - [CS]

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Mylan Pharmaceuticals Inc.
Labeler Code: 0378
FDA Application Number: ANDA205050 What is the FDA Application Number?
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.

Marketing Category: ANDA - A product marketed under an approved Abbreviated New Drug Application. What is the Marketing Category?
Product types are broken down into several potential Marketing Categories, such as NDA/ANDA/BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Start Marketing Date: 12-18-2019 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2021 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: N - NO What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Travoprost Ophthalmic Solution, 0.004% Product Label Images

Travoprost Ophthalmic Solution, 0.004% Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

1 Indications And Usage

Travoprost Ophthalmic Solution, USP (Ionic Buffered Solution) 0.004% is indicated for the reduction of elevated intraocular pressure in patients with open angle glaucoma or ocular hypertension.

2 Dosage And Administration

The recommended dosage is one drop in the affected eye(s) once daily in the evening. Travoprost ophthalmic solution (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 intraocular pressure lowering effect. Reduction of the intraocular pressure starts approximately 2 hours after the first administration with maximum effect reached after 12 hours. Travoprost ophthalmic solution (Ionic Buffered Solution) may be used concomitantly with other topical ophthalmic drug products to lower intraocular pressure. If more than one topical ophthalmic drug is being used, the drugs should be administered at least five (5) minutes apart.

3 Dosage Forms And Strengths

Ophthalmic solution containing travoprost 0.04 mg/mL.

4 Contraindications


5.1 Pigmentation

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% can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly (see PATIENT COUNSELING INFORMATION, 17.1).

5.2 Eyelash Changes

Travoprost 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.

5.3 Intraocular Inflammation

Travoprost should be used with caution in patients with active intraocular inflammation (e.g., uveitis) because the inflammation may be exacerbated.

5.4 Macular Edema

Macular edema, including cystoid macular edema, has been reported during treatment with travoprost ophthalmic solution. Travoprost 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.

5.5 Angle-Closure, Inflammatory Or Neovascular Glaucoma

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

5.6 Bacterial Keratitis

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, 17.3).

5.7 Use With Contact Lenses

Contact lenses should be removed prior to instillation of travoprost and may be reinserted 15 minutes following its administration.

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. The most common adverse reaction observed in controlled clinical studies with travoprost ophthalmic solution 0.004% 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 studies 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 studies with travoprost ophthalmic 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. Nonocular 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. In post-marketing use with prostaglandin analogs, periorbital and lid changes including deepening of the eyelid sulcus have been observed.

8.1 Pregnancy

Pregnancy Category C:Teratogenic Effects: Travoprost was teratogenic in rats, at an intravenous (IV) dose up to 10 mcg/kg/day (250 times the maximal recommended human ocular dose (MRHOD), evidenced by an increase in the incidence of skeletal malformations as well as external and visceral malformations, such as fused sternebrae, domed head and hydrocephaly. Travoprost was not teratogenic in rats at intravenous doses up to 3 mcg/kg/day (75 times the MRHOD), or in mice at subcutaneous doses up to 1 mcg/kg/day (25 times the MRHOD). Travoprost produced an increase in post-implantation losses and a decrease in fetal viability in rats at intravenous doses >3 mcg/kg/day (75 times the MRHOD) and in mice at subcutaneous doses >0.3 mcg/kg/day (7.5 times the MRHOD). In the offspring of female rats that received travoprost subcutaneously from Day 7 of pregnancy to lactation Day 21 at doses of ≥0.12 mcg/kg/day (3 times the MRHOD), the incidence of postnatal mortality was increased, and neonatal body weight gain was decreased. Neonatal development was also affected, evidenced by delayed eye opening, pinna detachment and preputial separation, and by decreased motor activity. There are no adequate and well controlled studies of travoprost ophthalmic solution 0.004% administration in pregnant women. Because animal reproductive studies are not always predictive of human response, travoprost should be administered during pregnancy only if the potential benefit justifies the potential risk to the fetus.

8.3 Nursing Mothers

A study in lactating rats demonstrated that radiolabeled travoprost 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 travoprost is administered to a nursing woman.

8.4 Pediatric Use

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.

8.5 Geriatric Use

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

8.6 Hepatic And Renal Impairment

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.

11 Description

Travoprost is a synthetic prostaglandin F analogue. 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 C26H35F3O6 and a molecular weight of 500.55. The chemical structure of travoprost is: Travoprost, USP is a pale yellow to yellowish viscous oil that is freely soluble in acetonitrile, toluene, ethyl acetate and methanol. It is practically insoluble in hexane and water. Travoprost ophthalmic solution, USP (Ionic Buffered Solution), 0.004% is supplied as sterile, buffered aqueous solution of travoprost with a pH of approximately 5.7 and an osmolality of approximately 290 mOsmol/kg.Travoprost ophthalmic solution (Ionic Buffered Solution) contains Active: travoprost USP, 0.04 mg/mL; Inactives: boric acid, polyoxyl 40 hydrogenated castor oil, propylene glycol, sodium hydroxide and/or hydrochloric acid (to adjust pH), sorbitol, water for injection and zinc chloride.

12.1Mechanism Of Action

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


Travoprost is absorbed through the cornea and is hydrolyzed to the active free acid. Data from four 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 Cmax 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 14 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.

13.1 Carcinogenesis, Mutagenesis, Impairment Of Fertility

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 over 400 times the human exposure at the maximum recommended human ocular dose (MRHOD) of 0.04 mcg/kg, based on plasma active drug levels. 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 10 mcg/kg/day [250 times the maximum recommended human ocular dose of 0.04 mcg/kg/day on a mcg/kg basis (MRHOD)]. At 10 mcg/kg/day, 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 (75 times the MRHOD).

14 Clinical Studies

In clinical studies, patients with open-angle glaucoma or ocular hypertension and baseline pressure of 25 to 27 mm Hg who were treated with travoprost ophthalmic solution 0.004% dosed once daily in the evening demonstrated 7 to 8 mm Hg reductions in intraocular pressure. In subgroup analyses of these studies, mean IOP reduction in black patients was up to 1.8 mm Hg 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 multicenter, randomized, controlled trial, patients with mean baseline intraocular pressure of 24 to 26 mm Hg on timolol maleate ophthalmic solution 0.5% BID who were treated with travoprost ophthalmic solution 0.004% dosed QD adjunctively to timolol maleate ophthalmic solution 0.5% BID demonstrated 6 to 7 mm Hg reductions in intraocular pressure.

16 How Supplied/Storage And Handling

Travoprost Ophthalmic Solution, USP (Ionic Buffered Solution) 0.004% is a clear colorless, sterile, aqueous solution of travoprost, USP (0.04 mg/mL). Travoprost ophthalmic solution (Ionic Buffered Solution) is supplied as a 2.5 mL or 5 mL solution in a 5 mL natural colored low density polyethylene bottle with a turquoise, high density polyethylene, tamper evident screw cap and a low density polyethylene nozzle. 2.5 mL fillNDC 0378-9651-32carton of one bottle5 mL fillNDC 0378-9651-50carton of one bottleStorage: Store at 2° to 25°C (36° to 77°F).

17.1 Potential For Pigmentation

Patients should be advised about the potential for increased brown pigmentation of the iris, which may be permanent. Patients should also be informed about the possibility of eyelid skin darkening, which may be reversible after discontinuation of travoprost ophthalmic solution 0.004%.

17.2 Potential For Eyelash Changes

Patients should also be informed of the possibility of eyelash and vellus hair changes in the treated eye during treatment with travoprost ophthalmic 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.

17.3 Handling The Container

Patients should be instructed 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.

17.4 When To Seek Physician Advice

Patients should also be advised 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.

17.5 Use With Contact Lenses

Contact lenses should be removed prior to instillation of travoprost ophthalmic solution and may be reinserted 15 minutes following its administration.

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.Manufactured for:Mylan Pharmaceuticals Inc.Morgantown, WV 26505 U.S.A.Manufactured by:Wintac LimitedBangalore, IndiaJULY 2019

Package/Label Display Panel

NDC 0378-9651-32Travoprost Ophthalmic Solution, USP 0.004% (Ionic Buffered Solution)FOR USE IN THE EYES ONLYRx onlyMylan2.5 mL

NDC 0378-9651-50Travoprost Ophthalmic Solution, USP 0.004% (Ionic Buffered Solution)FOR USE IN THE EYES ONLYRx onlyMylan5 mL

* Please review the disclaimer below.