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Trifluridine

Class: Antivirals
CAS Number: 70-00-8
Brands: Viroptic

Medically reviewed by Drugs.com on Apr 26, 2021. Written by ASHP.

Introduction

Antiviral; fluorinated pyrimidine nucleoside.

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).

Vaccinia Virus Ophthalmic Infections

Topical treatment and prophylaxis of ocular vaccinia infections that occur as a complication of smallpox vaccination in the vaccine recipient or close contact. 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.

Topical prophylaxis following possible inadvertent inoculation with vaccinia virus in or near the eye (e.g., splash to the eye) involving smallpox vaccine or a laboratory strain of vaccinia virus.

Although safety and efficacy of topical trifluridine not established for treatment or prevention of ocular vaccinia infections, 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. Vaccinia immune globulin may also be recommended in some cases.

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. 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. 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.

Trifluridine Dosage and Administration

Administration

Ophthalmic Administration

Apply 1% ophthalmic solution topically onto the cornea of the eye.

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. Following reepithelialization, instill 1 drop every 4 hours while awake (minimum 5 drops daily) for an additional 7 days.

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.

Avoid treatment duration >21 days.

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. Following reepithelialization, instill 1 drop every 4 hours while awake (minimum 5 drops daily) for an additional 7 days.

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.

Avoid treatment duration >21 days.

Vaccinia Virus Ophthalmic Infections†
Treatment of Vaccinia Ocular Infections†
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.

Prophylaxis in Patients with Blepharitis or Vaccinia Lesions On or Near the Eyelid†
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.

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).

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.

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

Prescribing Limits

Pediatric Patients

Herpes Simplex Virus Keratitis and Keratoconjunctivitis
Ophthalmic

Maximum 9 drops of 1% ophthalmic solution daily; avoid treatment duration >21 days.

Adults

Herpes Simplex Virus Keratitis and Keratoconjunctivitis
Ophthalmic

Maximum 9 drops of 1% ophthalmic solution daily; avoid treatment duration >21 days.

Vaccinia Virus Ophthalmic Infections†
Ophthalmic

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

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.

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

Cautions for Trifluridine

Contraindications

  • Known hypersensitivity or chemical intolerance to trifluridine.

Warnings/Precautions

Administration Precautions

For topical ophthalmic use only; use under close supervision of an ophthalmologist.

Because of risk of ocular toxicity, do not exceed recommended dosage and frequency of administration. (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.

Mutagenic and Carcinogenic Effects

Mutagenic, DNA damaging, and cell-transforming effects reported in vitro; possible heritable genetic damage.

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.

Specific Populations

Pregnancy

Category C.

Use during pregnancy only if potential benefits to the woman justify possible risks to the fetus.

Lactation

Distribution into milk unlikely following topical application to the eye.

Do not use in nursing women unless possible benefits to the woman outweigh potential risks to the infant.

Pediatric Use

Safety and efficacy not established in children <6 years of age.

Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.

Common Adverse Effects

Mild, transient burning, stinging, or local irritation upon instillation, palpebral edema. Hyperemia also reported, especially if used for >14 days.

Trifluridine Pharmacokinetics

Absorption

Bioavailability

Systemic absorption following topical application of trifluridine 1% ophthalmic solution appears to be negligible.

Distribution

Extent

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

Stability

Storage

Ophthalmic

Solution

2–8°C.

Contains sodium chloride, acetic acid and sodium acetate as buffers and thimerosal 0.001% as a preservative.

Actions and Spectrum

  • Fluorinated pyrimidine nucleoside antiviral.

  • Exact mechanism of antiviral activity of trifluridine not completely known; appears to interfere with viral DNA synthesis and viral replication.

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

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

  • Active in vitro and in vivo against HSV-1 and HSV-2; may be active against some acyclovir-resistant strains. Active in vitro against vaccinia virus; has shown in vivo activity in the treatment of vaccinia keratitis in rabbits. Also has shown antiviral activity in cell culture against some strains of adenovirus.

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

Advice to Patients

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

  • Importance of informing patients of other important precautionary information. (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

Trifluridine

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Ophthalmic

Solution

1%*

Trifluridine Ophthalmic Solution

Viroptic

Monarch

AHFS DI Essentials™. © Copyright 2021, Selected Revisions May 6, 2016. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

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