Trifluridine (Viroptic) is a fluorinated pyrimidine
nucle-oside that has in vitro activity against HSV-1 and HSV-2, vaccinia, and
to a lesser extent, some adenoviruses. Activation of trifluridine requires its
conversion to the 5 monophosphate form by cellular enzymes. Trifluridine
monophosphate inhibits the conversion of deoxyuri-dine monophosphate (dUMP) to
deoxythymidine monophosphate (dTMP) by thymidylate synthetase. In addition, it
competes with deoxythymidine triphosphate (dTTP) for incorporation by both
viral and cellular DNA polymerases. Trifluridine-resistant mutants have been
found to have alterations in thymidylate syn-thetase specificity.
No detectable trifluridine is
found in the blood follow-ing topical instillation of trifluridine into the
eyes. Its half-life is approximately 12 minutes.
Trifluridine is administered
as a topical ophthalmic solu-tion for the treatment of primary
keratoconjunctivitis and recurrent keratitis due to HSV-1 or HSV-2. It is not
effective in the prophylaxis of these infections; however, it is effective in treating
patients who were unresponsive or intolerant to topical idoxuridine or
The most frequent adverse
reactions to trifluridine ad-ministration are transient burning or stinging and
palpebral edema. Other adverse reactions include su-perficial punctate
keratopathy, epithelial keratopathy, hypersensitivity, stromal edema,
irritation, keratitis sicca, hyperemia, and increased intraocular pressure.
Trifluridine is mutagenic in
vitro and carcinogenic and teratogenic when administered subcutaneously to
animals. Topical trifluridine was not teratogenic in ani-mal studies. Because
it is applied topically in humans, the likelihood of systemic effects is low.