Antiherpesvirus Agents: Trifluridine

Trifluridine

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.

Absorption, Metabolism, and Excretion

No detectable trifluridine is found in the blood follow-ing topical instillation of trifluridine into the eyes. Its half-life is approximately 12 minutes.

Clinical Uses

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 vidarabine.

Adverse Effects, Contraindications, and Drug Interactions

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.