Trifluridine (Monograph)

Brand name: Viroptic
Drug class: Antivirals
CAS number: 70-00-8

Medically reviewed by Drugs.com on Apr 26, 2024. Written by ASHP.

Introduction

Antiviral; fluorinated pyrimidine nucleoside.^{100 104 109}

Uses for Trifluridine

Herpes Simplex Virus Keratitis and Keratoconjunctivitis

Topical treatment of primary keratoconjunctivitis and recurrent epithelial keratitis (dendritic or geographic ulcers) caused by herpes simplex virus types 1 and 2 (HSV-1 and HSV-2).^{100 109 110 111}

Vaccinia Virus Ophthalmic Infections

Topical treatment and prophylaxis of ocular vaccinia infections^{† [off-label]} that occur as a complication of smallpox vaccination in the vaccine recipient or close contact.^{101 103} Inadvertent inoculation (infection) with vaccinia virus at sites other than the vaccination site (e.g., face, eye, eyelid) is a frequently reported adverse effect of smallpox vaccination.¹⁰³

Topical prophylaxis following possible inadvertent inoculation with vaccinia virus in or near the eye^{† [off-label]} (e.g., splash to the eye) involving smallpox vaccine or a laboratory strain of vaccinia virus.^{102 103}

Although safety and efficacy of topical trifluridine not established for treatment or prevention of ocular vaccinia infections,^{100 109} CDC and other experts recommend use of topical ophthalmic antivirals (e.g., trifluridine, vidarabine [no longer commercially available in the US]) for management of such infections.^{101 102 103} Vaccinia immune globulin may also be recommended in some cases.^{101 102 103}

If inadvertent inoculation with vaccinia virus occurs in a smallpox vaccine recipient or close contact of the vaccinee or if inadvertent exposure to vaccinia virus occurs in a laboratory or other setting, consult state/local health departments or the CDC at 800-232-4636 to obtain guidance regarding antiviral treatment or prophylaxis and use of vaccinia immune globulin.^{101 102} Healthcare providers for US military personnel should consult US Department of Defense Vaccine Health Resources at 866-210-6469 or the US Army Medical Research Institute of Infectious Diseases (USAMRIID) at 888-872-7443 or 301-619-2257.^{101 102} Report all complications of smallpox vaccination to state/local health departments and the Vaccine Adverse Event Reporting System (VAERS) at [Web] or 800-822-7967.^{101 102}

Trifluridine Dosage and Administration

Administration

Ophthalmic Administration

Apply 1% ophthalmic solution topically onto the cornea of the eye.^{100 109}

Dosage

Pediatric Patients

Herpes Simplex Virus Keratitis and Keratoconjunctivitis

Ophthalmic

Children ≥6 years of age: Instill 1 drop of 1% ophthalmic solution onto the cornea of the affected eye every 2 hours while awake (maximum 9 drops daily) until reepithelialization occurs.^{100 109} Following reepithelialization, instill 1 drop every 4 hours while awake (minimum 5 drops daily) for an additional 7 days.^{100 109}

If there are no signs of improvement after 7 days or if complete reepithelialization has not occurred after 14 days of therapy, consider other forms of treatment.^{100 109}

Avoid treatment duration >21 days.^{100 109}

Adults

Herpes Simplex Virus Keratitis and Keratoconjunctivitis

Ophthalmic

Instill 1 drop of 1% ophthalmic solution onto the cornea of the affected eye every 2 hours while awake (maximum 9 drops daily) until reepithelialization occurs.^{100 109} Following reepithelialization, instill 1 drop every 4 hours while awake (minimum 5 drops daily) for an additional 7 days.^{100 109}

If there are no signs of improvement after 7 days or if complete reepithelialization has not occurred after 14 days of therapy, consider other forms of treatment.^{100 109}

Avoid treatment duration >21 days.^{100 109}

Vaccinia Virus Ophthalmic Infections† [off-label]

Treatment of Vaccinia Ocular Infections† [off-label]

Ophthalmic

Instill 1 drop of 1% ophthalmic solution in the affected eye every 2 hours while awake (i.e., 9 times daily) for up to 14 days or until all lesions heal.¹⁰¹

Prophylaxis in Patients with Blepharitis or Vaccinia Lesions On or Near the Eyelid† [off-label]

Ophthalmic

Instill 1 drop of 1% ophthalmic solution in the affected eye every 4 hours while awake (i.e., 5 times daily) for up to 14 days or until all periocular and/or lid lesions heal and scabs have fallen off.¹⁰¹

If there is are no signs of improvement or if manifestations worsen after 24–48 hours of therapy, may increase dosage to 1 drop instilled into the affected eye every 2 hours while awake (i.e., 9 times daily).¹⁰¹

Prophylaxis Following Inadvertent Exposure to Vaccinia Virus in Laboratory Setting†

Ophthalmic

Instill 1 drop of 1% ophthalmic solution in the affected eye every 4 hours while awake (i.e., 5 times daily) for up to 5 days.¹⁰²

Discontinue if there is no evidence of vaccinia infection after 5 days.¹⁰²

Prescribing Limits

Pediatric Patients

Herpes Simplex Virus Keratitis and Keratoconjunctivitis

Ophthalmic

Maximum 9 drops of 1% ophthalmic solution daily;^{100 109} avoid treatment duration >21 days.^{100 109}

Adults

Herpes Simplex Virus Keratitis and Keratoconjunctivitis

Ophthalmic

Maximum 9 drops of 1% ophthalmic solution daily;^{100 109} avoid treatment duration >21 days.^{100 109}

Vaccinia Virus Ophthalmic Infections†

Ophthalmic

Treatment of vaccinia virus ophthalmic infections^†: Maximum 9 drops of 1% ophthalmic solution daily for up to 14 days.¹⁰¹

Prophylaxis in patients with blepharitis or vaccinia lesions on or near eyelid^†: Maximum 9 drops of 1% ophthalmic solution daily for up to 14 days.¹⁰¹

Prophylaxis following inadvertent exposure to vaccinia virus in laboratory setting^†: Maximum 5 drops of 1% ophthalmic solution daily for up to 5 days.¹⁰²

Cautions for Trifluridine

Contraindications

• Known hypersensitivity or chemical intolerance to trifluridine.^{100 109}

Warnings/Precautions

Administration Precautions

For topical ophthalmic use only;^{100 109} use under close supervision of an ophthalmologist.¹⁰⁵

Because of risk of ocular toxicity, do not exceed recommended dosage and frequency of administration.^{100 109} (See Prescribing Limits under Dosage and Administration.)

If used for topical prophylaxis to prevent extension of vaccinia infection to the conjunctiva or cornea^† in patients with vaccinia lesions on or near the eyelid (see Uses: Vaccinia Virus Ophthalmic Infections), balance potential benefits of the drug against the minimal potential risk of drug toxicity and of introducing the virus into the eye by frequent manipulation.¹⁰¹

Mutagenic and Carcinogenic Effects

Mutagenic, DNA damaging, and cell-transforming effects reported in vitro; possible heritable genetic damage.^{100 109}

Malignancies (e.g., adenocarcinomas of the GI tract and mammary glands, hemangiosarcomas of the spleen and liver, carcinosarcomas of the prostate gland, granulosathecal cell tumors of the ovary) reported in rats.^{100 109}

Specific Populations

Pregnancy

Category C.^{100 109}

Use during pregnancy only if potential benefits to the woman justify possible risks to the fetus.^{100 109}

Lactation

Distribution into milk unlikely following topical application to the eye.^{100 109}

Do not use in nursing women unless possible benefits to the woman outweigh potential risks to the infant.^{100 109}

Pediatric Use

Safety and efficacy not established in children <6 years of age.^{100 109}

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.^{100 109}

Common Adverse Effects

Mild, transient burning, stinging, or local irritation upon instillation, palpebral edema.^{100 109} Hyperemia also reported,^{100 101 109} especially if used for >14 days.¹⁰¹

Trifluridine Pharmacokinetics

Absorption

Bioavailability

Systemic absorption following topical application of trifluridine 1% ophthalmic solution appears to be negligible.^{100 109}

Distribution

Extent

Following topical application of trifluridine 1% solution to the eye, the drug penetrates the cornea and can be detected in aqueous humor.^{100 109} Intraocular penetration is increased in patients with epithelial defect in the cornea or with stromal or uveal inflammation.^{100 109}

Stability

Storage

Ophthalmic

Solution

2–8°C.^{100 109}

Contains sodium chloride, acetic acid and sodium acetate as buffers and thimerosal 0.001% as a preservative.^{100 109}

Actions and Spectrum

• Fluorinated pyrimidine nucleoside antiviral.^{100 104 109}

• Exact mechanism of antiviral activity of trifluridine not completely known;^{100 104 109} appears to interfere with viral DNA synthesis and viral replication.^{100 104 109}

• Irreversibly inhibits thymidylate synthetase,¹⁰⁴ an enzyme required for DNA synthesis;^b competitively inhibits DNA polymerases.¹⁰⁴

• Incorporates into viral and, to a lesser extent, cellular DNA and inhibits DNA synthesis at relatively low concentrations.¹⁰⁴ Also exhibits mutagenic, teratogenic, and antineoplastic activities.¹⁰⁴

• Active in vitro and in vivo against HSV-1 and HSV-2;^{100 104 108 109} may be active against some acyclovir-resistant strains.^{104 110} Active in vitro against vaccinia virus;^{100 104 109} has shown in vivo activity in the treatment of vaccinia keratitis in rabbits.^{107 112} Also has shown antiviral activity in cell culture against some strains of adenovirus.^{100 104 106 109}

• Although clinical importance unknown, trifluridine-resistant HSV have been produced in vitro.¹⁰⁴

Advice to Patients

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{100 109}

• Importance of informing patients of other important precautionary information.^{100 109} (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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