Trifluridine clinical pharmacology

Trifluridine
VIROPTIC® FDA Package Insert
Description
Clinical Pharmacology
Indications and Usage
Contraindications
Warnings and Precautions
Adverse Reactions
Overdosage
Clinical Studies
Dosage and Administration
How Supplied
Labels and Packages

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]

Clinical Pharmacology

Trifluridine is a fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vaccinia virus. 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 known.

In vitro perfusion studies on excised rabbit cornea 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.

References

Adapted from the FDA Package Insert.