Travoprost

Solution · Ophthalmic

Prescription (Rx) Prostaglandin Analog 2 recalls

Uses

Travoprost ophthalmic solution 0.004% is indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension. Travoprost ophthalmic solution is a prostaglandin analog indicated for the reduction of elevated intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (1)

Dosage and administration

The recommended dosage is one drop in the affected eye(s) once daily in the evening. Travoprost ophthalmic 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. Travoprost ophthalmic 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. One drop in the affected eye(s) once daily in the evening

Dosage forms and strengths

Ophthalmic solution containing travoprost 0.04 mg/mL. Ophthalmic solution containing travoprost 0.04 mg/mL

Contraindications

None. None

Warnings and precautions

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) 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 can be continued in patients who develop noticeably increased iris pigmentation, these patients should be examined regularly . 5.2 Eyelash Changes Travoprost ophthalmic 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. 5.3 Intraocular Inflammation Travoprost ophthalmic solution 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 ophthalmic 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. 5.5 Angle-closure, Inflammatory or Neovascular Glaucoma Travoprost ophthalmic solution 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. 5.7 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.

Side effects

Most common adverse reaction (30% to 50%) is conjunctival hyperemia (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Somerset Therapeutics, LLC at 1-800-417-9175 or the FDA at 1-800-FDA-1088 or www.fda.gov/ medwatch. 6.1 Clinical Trials Experience 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% 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%, 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. 6.2 Postmarketing Experience Additional adverse reactions have been identified during post approval use of travoprost ophthalmic solution 0.004% 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, 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.

Use in specific populations

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 (8.4) 8.1 Pregnancy 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 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 MRHOD, based on estimated plasma C max ). The NOAEL for maternal toxicity was 0.72 mcg/kg (4 times the MRHOD, based on estimated plasma C max ). 8.2 Lactation 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 and any potential adverse effects on the breast-fed child from travoprost ophthalmic solution. 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.

Description

Travoprost is a synthetic prostaglandin F analog. Its chemical name is [1 R - [1α( Z ),2β(1 E ,3 R *),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 26 H 35 F 3 O 6 and a molecular weight of 500.55 g/mol. The chemical structure of travoprost is: Travoprost is a colorless to slightly yellow viscous oil that is freely soluble in acetonitrile, toluene, ethyl acetate and methanol; practically insoluble in hexane and in water. Travoprost ophthalmic solution, USP 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, USP contains Active: travoprost 0.04 mg/mL; 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. Preserved in the bottle with an ionic buffered system (boric acid, propylene glycol, sorbitol, zinc chloride). Image

How supplied

Travoprost ophthalmic solution, USP is a sterile, isotonic, buffered, preserved, aqueous solution of travoprost (0.04 mg/mL). Travoprost ophthalmic solution, USP is supplied as a 2.5 mL solution in a 5 mL and a 5 mL solution in a 10 mL natural LDPE bottle plugged with a natural LDPE nozzle, capped with turquoise colored HDPE cap and tamper-evident seal. 2.5 mL fill NDC 70069-586-01 5 mL fill NDC 70069-587-01 Storage: Store at 2°C to 25°C (36°F to 77°F). After opening, travoprost ophthalmic solution, USP can be used until the expiration date on the bottle.

Patient information

Potential for Pigmentation 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 [see Warnings and Precautions (5.1)] . Potential for Eyelash Changes Inform the patient about 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 [see Warnings and Precautions (5.2)] . Handling the Container 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)] . When to Seek Physician Advice 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 [see Warnings and Precautions (5.3, 5.4, 5.5)] . 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 [see Warnings and Precautions (5.7)] . Use with Other Ophthalmic Drugs 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.

Label text from the FDA structured product label by Somerset Therapeutics, LLC (revised Oct 10, 2024). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Travoprost in 4 products

Travoprost NDC products (4)

NDC	Strength & form	Labeler	Type
60505-0593	Travoprost .04 mg/mL Solution	Apotex Corp.	ANDA
51407-731	Travoprost .04 mg/mL Solution	Golden State Medical Supply, Inc.	ANDA
70069-586	Travoprost .04 mg/mL Solution/ Drops	Somerset Therapeutics, LLC	ANDA
70069-587	Travoprost .04 mg/mL Solution/ Drops	Somerset Therapeutics, LLC	ANDA

Travoprost recalls

D-0867-2023 Jun 14, 2023 · Class II · Terminated
Lack of Assurance of Sterility: Tamper Evidence Seal is missing on secondary container.
D-0425-2021 Jun 2, 2021 · Class II · Terminated
CGMP Deviations: Intermittent exposure to temperature excursion during storage.

Frequently asked questions

What is Travoprost used for?

What are the side effects of Travoprost?

Who makes Travoprost?

Travoprost is listed by 3 labelers in the FDA NDC directory, including Apotex Corp., Golden State Medical Supply, Inc., Somerset Therapeutics, LLC.

Has Travoprost been recalled?

The FDA enforcement database lists 2 recalls for Travoprost, most recently D-0867-2023 (class ii): Lack of Assurance of Sterility: Tamper Evidence Seal is missing on secondary container.