Trifluridine

INDICATIONS AND USAGE: Trifluridine Ophthalmic Solution is indicated for the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2.

DOSAGE AND ADMINISTRATION: Instill one drop of Trifluridine Ophthalmic Solution onto the cornea of the affected eye every 2 hours while awake for a maximum daily dosage of nine drops until the cornea ulcer has completely re-epithelialized. Following re-epithelialization, treatment for an additional 7 days of one drop every 4 hours while awake for a minimum daily dosage of five drops is recommended. If there are no signs of improvement after 7 days of therapy or complete re-epithelialization has not occurred after 14 days of therapy, other forms of therapy should be considered.

Continuous administration of trifluridine for periods exceeding 21 days should be avoided because of potential ocular toxicity.

WARNINGS: The recommended dosage and frequency of administration should not be exceeded .

CONTRAINDICATIONS: Trifluridine Ophthalmic Solution is contraindicated for patients who develop hypersensitivity reactions or chemical intolerance to trifluridine.

Pregnancy: Teratogenic Effects: Trifluridine was not teratogenic at doses up to 5 mg/kg/day (23 times the estimated human exposure) when given subcutaneously to rats and rabbits. However, fetal toxicity consisting of delayed ossification of portions of the skeleton occurred at dose levels of 2.5 and 5 mg /kg /day in rats and at 2.5 mg/kg/day in rabbits. In addition, both 2.5 and 5 mg/kg/day produced fetal death and resorption in rabbits.

In both rats and rabbits, 1 mg/kg/day (5 times the estimated human exposure) was a no-effect level. There were no teratogenic or fetotoxic effects after topical application of trifluridine (approximately 5 times the estimated human exposure) to the eyes of rabbits on the 6th through the 18th days of pregnancy. In a non-standard test, trifluridine solution has been shown to be teratogenic when injected directly into the yolk sac of chicken eggs.

There are no adequate and well-controlled studies in pregnant women. Trifluridine Ophthalmic Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nursing Mothers: It is unlikely that trifluridine is excreted in human milk after ophthalmic instillation of trifluridine because of the relatively small dosage (5mg/day), its dilution in body fluids and its extremely short half-life (approximately 12 minutes). The drug should not be prescribed for nursing mothers unless the potential benefits outweigh the potential risks.

ADVERSE REACTIONS: The most frequent adverse reactions reported during controlled clinical trials were mild, transient burning or stinging upon instillation (4.6%) and palpebral edema (2.8%). Other adverse reactions in decreasing order of reported frequency were superficial punctate keratopathy, epithelial keratopathy, hypersensitivity reaction, stromal edema, irritation, keratitis sicca, hyperemia, and increased intraocular pressure.