Travoprost, a synthetic analog of prostaglandin F2alpha, is a prodrug used to treat elevated intraocular pressure (IOP) and is available as an ophthalmic solution and an intracameral implant. The active component, travoprost free acid, is a selective FP prostanoid receptor agonist. Travoprost is indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. When studied as add-on therapy in patients being treated with timolol 0.5% twice daily, ophthalmic travoprost produced additional IOP reductions of 6 to 7 mmHg from mean baseline IOP pressures of 24 to 26 mmHg. In subgroup analyses of pre-marketing trials, the mean IOP reduction in black patients was up to 1.8 mmHg greater than in non-black patients; it is unknown whether this difference is due to race or to the presence of heavily pigmented tissues. In a study comparing the intracameral implant compared to topical timolol, the implant demonstrated non-inferiority during the first 3 months, but did not demonstrate non-inferiority over the next 9 months. As with other ophthalmic prostaglandin analogs (e.g., latanoprost, bimatoprost), travoprost use has been associated with changes to pigmented tissues, including increased pigmentation and growth of eyelashes, and increased pigmentation of the iris and periorbital tissue. Changes in pigmentation may be permanent. The ophthalmic solution is approved in adults and pediatric patients 16 years and older. The intracameral implant is approved in adults.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Ophthalmic Administration
Ophthalmic solution
-For ophthalmic use only.
-Instruct patient on proper instillation of the eye solution (see Patient Information).
-Wash hands before and after use.
-Contact lenses should be removed prior to ocular application and may be reinserted 15 minutes following drug administration. Travatan contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses.
-Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch and gently close the eyes for 1 to 2 minutes. Do not blink.
-To avoid contamination, do not touch the tip of the dropper to the eye, fingertips, or other surface.
-The 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.
-Since prostaglandins are biologically active and may be absorbed through the skin, women who are pregnant or attempting to become pregnant should not use travoprost and should use caution to avoid direct exposure to travoprost. In case of accidental contact, cleanse the exposed area thoroughly with soap and water.
Intracameral insert
-The insert is for single-use only and should not be readministered to an eye that received a prior travoprost intracameral insert.
-Do not use if pouch has been damaged or opened.
-The insert is administered intracamerally through a small, clear corneal incision and is anchored into the sclera at the iridocorneal angle.
-Preparation of the eye:
--Anesthetize the eye using general, retrobulbar, peribulbar, or topical anesthesia.
-Perform the procedure under magnification that allows clear visualization of the anterior chamber angle and angle structures, including trabecular meshwork.
-Do not dilate the pupil.
-An intracameral miotic can be injected to deepen the angle prior to insertion.
-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. Inspect the angle to ensure a good view of all angle structures is available.
-Inspect the tip of the inserted under magnification to ensure that the implant is present.
-Create a clear corneal incision of approximately 2.4 mm at the temporal limbus location.
-Add a cohesive viscoelastic to the anterior chamber as needed to form the anterior chamber and improve visualization of the angle. Do not overinflate.
-Insertion of the implant:
--Remove the safety clip. Place finger on the release button to ensure in remains in the forward position and does not prematurely release the implant.
-Enter the anterior chamber by sliding the inserter tip with implant "side to side" in the incision.
-Advance to the pupillary margin and ensure there is sufficient cohesive viscoelastic on the cornea before replacing the gonioprism into the cornea.
-Avoid contact with the lens or cornea.
-Advance to the anterior chamber angle and approach the trabecular meshwork.
-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.
-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.
-Ensuring the implant has released from the inserter grasper, slowly remove the inserter straight back. Avoid pulling the implant out of position.
-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.
-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 1/2 clock hour to either side. Do not re-implant at the same location.
-Withdraw the inserter from the eye.
-Location of the implant in the trabecular meshwork:
--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) and securely attached with the anchor thoroughly embedded in the sclera.
-It is normal for an edge of the implant to make contact with the iris. 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.
-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.
-Inflate the anterior chamber with saline solution as needed to achieve physiologic pressure.
The most common ocular adverse effect associated with travoprost ophthalmic drops in clinical trials was conjunctival hyperemia, which was reported in 30% to 50% of patients and resulted in up to 3% of patients discontinuing therapy. Additional ocular adverse effects occurring in approximately 5% to 10% of patients using the ophthalmic drops include visual impairment manifested as decreased visual acuity, ocular irritation, foreign body sensation, ocular pain, and ocular pruritus. Less frequent ocular adverse effects (1% to 4%) include unspecified visual disturbance, blepharitis, blurred vision, cataracts, conjunctivitis, corneal staining, eyelid margin crusting, iritis, keratitis, ocular inflammation, subconjunctival ocular hemorrhage, lacrimation, photophobia, and xerophthalmia. Aqueous flare and infiltration of cells into the anterior chamber was also reported at a frequency of 1% to 4%. Postmarketing reports of periorbital and lid changes, including deepening of the eyelid sulcus were noted. The most commonly reported adverse events (2% to 6%) following the insertion of the intracameral implant include increased intraocular pressure, iritis, xerophthalmia, visual field defects, ocular pain, ocular hyperaemia, and reduced visual capacity. Other ocular effects reported in fewer than 2% of patients include conjunctival hemorrhage, photophobia, punctate keratitis, blepharitis, ocular irritation, corneal abrasion, vitreous detachment and foreign body sensation.
Nervous system and musculoskeletal adverse effects reported in 1% to 5% of patients receiving travoprost ophthalmic drops in clinical trials included anxiety, arthralgia, back pain, depression, headache, and unspecified pain. Insomnia has been reported with travoprost ophthalmic drops in postmarketing surveillance.
Cardiovascular and related adverse effects that were reported in 1% to 5% of patients receiving travoprost ophthalmic drops in clinical trials include angina, bradycardia, chest pain (unspecified), hypertension, hypotension, and hypercholesterolemia. Arrhythmia exacerbation, including sinus tachycardia, has been reported with travoprost ophthalmic drops in postmarketing surveillance.
Gastrointestinal adverse effects reported in 1% to 5% of patients receiving travoprost ophthalmic drops in clinical trials include dyspepsia and unspecified gastrointestinal disorder. Epistaxis and vomiting have been reported with travoprost ophthalmic drops in postmarketing surveillance.
Unspecified infection, bronchitis, sinusitis, urinary tract infection, and cold/flu syndrome were reported in 1% to 5% of patients receiving travoprost ophthalmic drops in clinical trials.
Urogenital adverse effects reported in 1% to 5% of patients receiving travoprost ophthalmic drops in clinical trials include unspecified prostate disorder and urinary incontinence.
Iridal discoloration manifested as increased pigmentation of the iris was reported in 1% to 4% of patients treated with topical ophthalmic travoprost. These changes may also occur with the use of the intracameral implant. Pigmentation changes are caused by an increase in the amount of melanosomes in melanocytes. The change in iris color occurs slowly and may not be noticeable for several months to years. The increase in brown iris pigment is not expected to progress further upon discontinuation of treatment, but the resultant color change may be permanent. Travoprost may also gradually change the eyelashes (e.g., increased length, thickness, pigmentation, and hypertrichosis of lashes). After discontinuation, 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.
Endophthalmitis has been associated with intraocular surgical procedures and injections; therefore, patients should be monitored after the administration of the travoprost intracameral implant. Additionally, device dislocation (fewer than 2% of patients) has been observed in trials. Routine monitoring to confirm location is necessary. If the implant becomes dislocated, it should be surgically removed.
Travoprost should not be used in patients with closed-angle glaucoma, inflammatory or neovascular glaucoma. The implant should be used with caution in patients with narrow iridocorneal angles (Shaffer grade less than 3) or other angle abnormalities (e.g., peripheral anterior ocular synechia, rubeosis iridis) that could impair proper place at the planned implantation site.
Travoprost should be used with caution in patients with active intraocular inflammation (e.g., iritis, uveitis) as imflammation may be exacerbated. Some patients may also develop photophobia and may be more sensitive to sunlight (UV) exposure.
Travoprost should be used with caution in patients with aphakia, pseudophakic patients with a tearing or rupture of posterior ocular lens capsule, and patients with known risk factors for macular edema. Macular edema, including cystoid macular edema, has been reported during treatment.
Contact lenses should be removed prior to administration of ophthalmic travoprost and may be reinserted after 15 minutes. Travatan ophthalmic solution contains the preservative benzalkonium chloride, which may be absorbed by soft contact lenses. Travatan Z does not contain this preservative; however, contact lense removal is still recommended.
The travoprost intracameral implant is contraindicated for use in patients with active or suspected ocular infection or periocular infection. There have been reports of bacterial keratitis associated with the use of multiple-dose containers of topical ophthalmic products. Inadvertent contamination of the containers may increase the risk of infection if the patient has an ocular infection, or develops ocular trauma including corneal abrasion, or undergoes ocular surgery while using travoprost.
The use of ophthalmic travoprost in neonates, infants, children, and adolescents younger than 16 years is not recommended because of potential safety concerns related to increased pigmentation following long-term chronic use. The intracameral insert is not intended for pediatric use.
The travoprost intracameral implant is contraindicated in patients with prior corneal transplant or endothelial cell transplants (e.g., Descemet's Stripping Automated Endothelial Keratoplasty [DSAEK]). It is also contraindicated in patients with corneal endothelial dystrophy (e.g., Fuch's Dystrophy, corneal guttata).
Patients with the travoprost intracameral implant can be safely scanned with magnetic resonance imaging (MRI) only under certain MRI system conditions. Should a patient with the implant need to have an examination that involves an MRI, the patient should inform their healthcare provider and scan technician that the implant is in place before the MRI procedure. Refer to the specific information for the implant (an MR Conditional device) prior to scheduling any MRI procedure.
There are no adequate and well-controlled studies regarding the ophthalmic use or intracameral implantation of travoprost during pregnancy to inform a drug-associated risk; however, systemic absorption with the ophthalmic and intracameral implant are low. In animal studies, clinically relevant subcutaneous doses administered to pregnant rats and mice during organogenesis resulted in embryo-fetal lethality, spontaneous abortions, and premature deliveries. Administer travoprost during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus.
It is unknown whether travoprost or its metabolites are excreted into human milk following ophthalmic or intracameral administration; however, the systemic absorption with each route of administration is low. Further, there are no data regarding the effects of travoprost on a breast-fed infant or on milk production. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.
For the reduction of elevated intraocular pressure (IOP) in patients with open angle glaucoma or ocular hypertension:
Ophthalmic dosage:
Adults: Apply 1 drop to each affected eye once daily in the evening. More frequent administration may decrease the IOP-lowering effect.
Adolescents 16 years or more: Apply 1 drop to each affected eye once daily in the evening. More frequent administration may decrease the IOP-lowering effect.
Intracameral implant dosage:
Adults: 75 mcg implant administered by intracameral insertion in the affected eye(s).
Maximum Dosage Limits:
-Adults
1 ophthalmic drop/day per affected eye; 75 mcg intracameral implant per affected eye.
-Geriatric
1 ophthalmic drop/day per affected eye; 75 mcg intracameral implant per affected eye.
-Adolescents
16 to 17 years: 1 ophthalmic drop/day per affected eye; safety and efficacy of the intracameral implant has not been established.
13 to 15 years: Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustment is needed.
Patients with Renal Impairment Dosing
No dosage adjustment is needed.
*non-FDA-approved indication
There are no drug interactions associated with Travoprost products.
Travoprost, is an analog of prostaglandin F2alpha, and a prodrug hydrolyzed to the active drug, travoprost free acid. Travoprost free acid selectively stimulates a subtype of prostaglandin receptors, known as the FP receptor. This is believed to reduce intraocular pressure by increasing uveoscleral outflow. The exact mechanism of action is unknown.
Travoprost is administered topically to the eye or inserted as an implant intracamerally. Travoprost is an isopropyl ester prodrug, hydrolyzed by esterases in the cornea and other intraocular tissues to its biologically active free acid. Travoprost free acid is systemically metabolized to inactive metabolites via beta-oxidation of the alpha (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.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Other Route(s)
Ophthalmic Route
Travoprost is absorbed primarily through the cornea. Peak blood concentrations of travoprost free acid (up to 25 pg/mL) are achieved within 30 minutes and are undetectable (less than 1 pg/mL) within 1 hour. Reduction of IOP begins approximately 2 hours after the first dose with maximum effect occurring after 12 hours.
Intracameral Implant Route
The intracameral implant consists of a titanium implant reservoir with a membrane controlling the sustained release of travoprost. Data from a pharmacokinetic study of 105 subjects evaluating 2 models of the 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) in all subjects at day 10, week 12, and month 12 after administration.
-Special Populations
Hepatic Impairment
No clinically significant changes in hematology, blood chemistry, or urinalysis laboratory data have been observed in patients with hepatic impairment receiving ophthalmic travoprost.
Renal Impairment
No clinically significant changes in hematology, blood chemistry, or urinalysis laboratory data have been observed in patients with renal impairment receiving ophthalmic travoprost.
Geriatric
No overall clinical differences in safety or effectiveness have been observed between elderly and other adult patients receiving travoprost.