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Mechanism of Action
US Drug Names
1 drop in the affected eye(s) every 2 hours while awake up to 9 drops/day until the corneal ulcer has completely re-epithelialized, then 1 drop in the affected eye(s) every 4 hours while awake for a minimum of 5 drops/day for 7 days. Consider other forms of therapy if there are no signs of improvement after 7 days of therapy or complete re-epithelization has not occurred after 14 days of therapy. Avoid continuous administration for periods exceeding 21 days due to the potential for ocular toxicity.
1 drop in the affected eye(s) every 2 to 4 hours (Max: 9 drops/day) for 7 to 14 days.   
1 drop in the affected eye(s) every 2 hours (Max: 9 drops/day) until reepithelialization, then 1 drop in the affected eye(s) every 4 hours (Min: 5 drops/day) for 7 days. Continue treatment until all periocular lesions have healed. Max duration: 21 days. 
Apply 1% topical trifluridine 3-times daily for at least 21 to 28 days as an alternative.
9 drops/day to affected eye(s).
> = 6 years: 9 drops/day to affected eye(s).
< 6 years: Safety and efficacy have not been established.
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
Description: Trifluridine (also known as trifluorothymidine) is an ophthalmic antiviral preparation indicated for primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus (HSV) types 1 and 2. Trifluridine is the treatment of choice for this indication and therapy is associated with a cure rate greater than 90%. HSV infections resistant to idoxuridine and/or vidarabine are effectively treated with trifluridine without cross-toxicity or allergenicity. Additionally, trifluridine shows in vitro and in vivo activity against vaccinia virus and in vitro inhibition of some strains of adenovirus. Off-label use of topical ophthalmic trifluridine can be considered for treatment of vaccinia infection of the conjunctiva or cornea associated with smallpox vaccination. Prophylactic therapy with trifluridine may also be considered to prevent spread to the conjunctiva and cornea if vaccinia lesions are present on the eyelid or near the eye. Trifluorothymidine was first developed as an antitumor agent and was later found to inhibit HSV in vitro. Compared to other systemic agents, it displayed low selectivity and high toxicity and, thus, was not developed for systemic use. This drug was approved by the FDA as a topical 1% ophthalmic solution in April 1980.
For storage information, see the specific product information within the How Supplied section.
The most frequent adverse reactions reported in clinical trials of trifluridine were mild, transient ocular irritation (burning and stinging) upon instillation (4.6%) and palpebral edema (blepharedema, 2.8%). Other reported adverse reactions included superficial punctuate or epithelial keratopathy, hypersensitivity reaction, stromal/corneal edema, keratitis sicca, hyperemia, and ocular hypertension.
Trifluridine has been reported to cause an allergic contact dermatitis in patients receiving the ophthalmic solution to treat herpetic keratitis. One patient presented with a history of 3 months of eczema of the eyelids after applying trifluridine eye drops. The second patient experienced a serious dermatitis around the right eye, which spread within a few days to the whole face, trunk, and proximal parts of the extremities following one week of treatment with 1% trifluridine eyedrops. Patch testing was used to confirm the cause of the allergic reaction; in both cases trifluridine and not the solution components was associated with the adverse response.
Trifluridine ophthalmic solution is contraindicated for patients who develop hypersensitivity reactions or chemical intolerance to trifluridine.
Continuous administration of trifluridine for periods exceeding 21 days should be avoided because of potential ocular toxicity. Punctate lesions in the corneal epithelium are clinical manifestations of trifluridine cytotoxicity. Upon discontinuation, toxic changes to the surface of the eye are generally reversible.
Safe and effective use of trifluridine ophthalmic solution has not been established in neonates, infants and children below six years of age. No overall differences in safety or effectiveness have been observed between young adult and geriatric patients.
Trifluridine is classified as FDA pregnancy risk category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, no teratogenic or fetotoxic effects were observed in rabbits following ophthalmic administration of doses approximately 5 times the estimated human exposure. However, offspring of rats and rabbits receiving subcutaneous doses of 2.5—5 mg/kg/day (11.5—23 times the estimated human exposure) experienced toxicities that included delayed ossification, fetal death, and resorption. While systemic absorption following ophthalmic administration is minimal, do not use or prescribed in pregnant women unless clearly needed.
Trifluridine is not likely to be excreted in the breast milk after ophthalmic administration due to its relatively small dosage, its dilution in body fluids, and its extremely short half-life. According to the manufacturer, it should not be prescribed for nursing mothers unless the potential benefits outweigh the potential risks. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Mechanism of Action: Trifluridine is structurally similar to thymidine and, therefore, inhibits thymidine incorporation into replicating viral DNA. Trifluridine is a fluorinated pyrimidine nucleoside which irreversibly inhibits thymidylate synthase and specific DNA polymerases, necessary for the conversion of dUMP to dTMP in the process of DNA synthesis. In cultured mammalian cells, trifluridine is incorporated in place of thymidine into viral DNA, resulting in faulty DNA and the inability to reproduce or to infect or destroy tissue. To a lesser extent, trifluridine is also incorporated into cellular DNA and is capable of decreasing DNA synthesis in both infected and uninfected cells. Viral resistance to trifluridine is rare.
Trifluridine is applied topically to the eye as a solution. The half-life of trifluridine is approximately 12 minutes. Frequent application is necessary in order to inhibit multiplication of the susceptible virus.
Following ophthalmic application, intraocular penetration is adequate. Decreased corneal integrity or stromal or uveal inflammation may enhance the penetration of trifluridine into the aqueous humor. The major metabolite of trifluridine, 5-carboxy-2'-deoxyuridine, is not found in detectable concentrations within the aqueous humor of the human eye. Trifluridine systemic absorption is negligible following therapeutic dosing. No detectable concentrations of trifluridine or 5-carboxy-2'-deoxyuridine are found in the sera of normal healthy adults upon completion of a 14-day regimen using the product seven times daily.
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