Trifluridine is a fluorinated pyrimidine nucleoside with in
vitro and in vivo activity against herpes simplex virus, types 1 and 2 and
vacciniavirus. Some strains of adenovirus are also inhibited in vitro.
VIROPTIC is also effective in the treatment of epithelial
keratitis that has not responded clinically to the topical administration of
idoxuridine or when ocular toxicity or hypersensitivity to idoxuridine has occurred.
In a smaller number of patients found to be resistant to topical vidarabine,
VIROPTIC was also effective.
Trifluridine interferes with DNA synthesis in cultured
mammalian cells. However, its antiviral mechanism of action is not completely
In vitro perfusion studies on excised rabbit corneas have
shown that trifluridine penetrates the intact cornea as evidenced by recovery
of parental drug and its major metabolite, 5-carboxy-2'-deoxyuridine, on the
endothelial side of the cornea. Absence of the corneal epithelium enhances the
penetration of trifluridine approximately two-fold.
Intraocular penetration of trifluridine occurs after
topical instillation of VIROPTIC into human eyes. Decreased corneal integrity
or stromal or uveal inflammation may enhance the penetration of trifluridine into
the aqueous humor. Unlike the results of ocular penetration of trifluridine in
vitro, 5-carboxy-2'- deoxyuridine was not found in detectable concentrations
within the aqueous humor of the human eye.
Systemic absorption of trifluridine following therapeutic
dosing with VIROPTIC appears to be negligible. No detectable concentrations of
trifluridine or 5-carboxy-2'-deoxyuridine were found in the sera of adult
healthy normal subjects who had VIROPTIC instilled into their eyes seven times
daily for 14 consecutive days.
During a controlled multicenter clinical trial, 92 of 97
(95%) patients (78 of 81 with dendritic and 14 of 16 with geographic ulcers)
responded to therapy with VIROPTIC as evidenced by complete corneal reepithelialization
within the 14-day therapy period. Fifty-six of 75 (75%) patients (49 of 58 with
dendritic and 7 of 17 with geographic ulcers) responded to idoxuridine therapy.
The mean time to corneal re-epithelialization for dendritic ulcers (6 days) and
geographic ulcers (7 days) was similar for both therapies.
In other clinical studies, VIROPTIC was evaluated in the
treatment of herpes simplex virus keratitis in patients who were unresponsive
or intolerant to the topical administration of idoxuridine or vidarabine. VIROPTIC
was effective in 138 of 150 (92%) patients (109 of 114 with dendritic and 29 of
36 with geographic ulcers) as evidenced by corneal re-epithelialization. The
mean time to corneal reepithelialization was 6 days for patients with dendritic
ulcers and 12 days for patients with geographic ulcers.
The clinical efficacy of VIROPTIC in the treatment of
stromal keratitis and uveitis due to herpes simplex virus or ophthalmic
infections caused by vacciniavirus and adenovirus has not been established by
well-controlled clinical trials. VIROPTIC has not been shown to be effective in
the prophylaxis of herpes simplex virus keratoconjunctivitis and epithelial
keratitis by well-controlled clinical trials. VIROPTIC is not effective against
bacterial, fungal, or chlamydial infections of the cornea or nonviral trophic
Animal Pharmacology And Animal Toxicology
Corneal wound healing studies in rabbits showed that
VIROPTIC did not significantly retard closure of epithelial wounds. However,
mild toxic changes such as intracellular edema of the basal cell layer, mild
thinning of the overlying epithelium and reduced strength of stromal wounds
Whereas instillation of VIROPTIC into rabbit eyes during
a subchronic toxicity study produced some degree of corneal epithelial
thinning, a 12-month chronic toxicity study in rabbits in which VIROPTIC was
instilled into eyes in intermittent, multiple, full-therapy courses showed no
drug-related changes in the cornea.