TRIFLURIDINE (TRIFLUOROTHYMIDINE)

Indications/Pharmacology

Trifluridine (trifluorothymidine; Viroptic®) is a pyrimidine nucleosideanalog. It is structurally related to 2-deoxythymidine, the natural precursor of DNA synthesis. Trifluridineis poorly absorbed by the cornea and is virostatic. Viroptic® interrupts viral replication by substituting in"nonsense" pyrimidine analogues. For this reason, a competent surface immunity is necessary to resolveocular disease, with or without antiviral therapy. A recent in vitro study in which several strains of felineherpes virus were collected from the United States and were used to infect kidney epithelial cells showedthat trifluridine was more effective at lower concentrations compared with several other agents. For thisreason, trifluridine is often the first choice drug employed in the treatment of feline herpes virus oculardisease. Antiviral agents have also been used in the treatment of superficial punctate keratitis in thehorse, thought to be associated with equine herpes virus-2 (EHV-2) infection of the cornea.Suggested Dosages/Precautions/Adverse Effects - Trifluridine must be applied very frequently. Theauthor (DKO) recommends treatment every 2 hours (waking hours) during the first 2 days of therapy toestablish effective corneal drug levels. After this time, treatment 4-6 times daily is indicated. Becausetrifluridine is virostatic and not viricidal, treatment 1 week beyond the resolution of clinical signs isrecommended, to prevent a rebound effect associated with poor surface immunity in combination withresidual active viral agents.
Anecdotally, improvement with antiviral agents is noted in about 50% of cats in which the treatment isemployed. In some cats the ocular disease persists despite treatment with antiviral agents. It is not certainif these are truly cases of feline herpes virus infection or other disease as the confirmation of feline herpesvirus infection is exceedingly difficult in practice, (except in the acute disease with respiratory and ocularinvolvement, because of the logistics of viral isolation tests for doctors in clinical practice (usually onlyavailable at major institutions or referral centers) and because of the high degree of false negatives withherpes virus FA tests and with available polymerase chain reaction (DNA amplification) technology).
Chronic conjunctivitis in the cat seems to be the most resistant to treatment with antiviral agents.Dosage Forms/Preparations/FDA Approval Status - Veterinary-Approved Products: None

Human-Approved Products:

Trifluridine Ophthalmic Solution 1% in 7.5 ml btls Viroptic® (B-W); (Rx)
Agents for Keratoconjunctivitis Sicca
Keratoconjunctivitis sicca (KCS) is a common ocular disorder in dogs. Recent research efforts indicatethat KCS in dogs is an immune mediated disease. It is similar to Sjogren's Syndrome in humans exceptwe do not recognize a connective tissue disorder in the dog compared to this disease in people (man-dryeye, dry mouth, and connective tissue disorder like rheumatoid arthritis; dogs just dry eye). Immunemediated lacrimal adenitis can result in complete destruction of tear producing glands in dogs. Glandularfibrosis produces absolute sicca and these cases may be better managed with a parotid duct transpositionsurgery because there may be little remaining gland tissue to treat.