Viroptic

Ophthalmological Antiviral Agents

Apply trifluridine topically to the eye. For ophthalmic use only.
Instruct patient on proper instillation of eye solution (see Patient Information).
Wash hands before and after use.
Instruct patient to remove contact lenses prior to use.
Care should be taken to avoid contamination. Do not touch the tip of the tube to the eye, fingertips, or other surface.
Tilt the head back slightly and pull the lower eyelid down with the index finger to form a pouch. Squeeze the prescribed number of drops into the pouch and gently close eyes for 1—2 minutes. Do not blink.
If more than one ophthalmic drug is being used, separate administration by at least 5—10 minutes.

keratitis / Delayed / Incidence not known
ocular hypertension / Delayed / Incidence not known

hyperemia / Delayed / Incidence not known
corneal edema / Early / Incidence not known
keratopathy / Delayed / Incidence not known
contact dermatitis / Delayed / Incidence not known

ocular irritation / Rapid / 4.6-4.6
blepharedema / Early / 2.8-2.8

Viroptic

Rx

Ophthalmic antiviral preparation with activity against herpes simplex virus (HSV) types 1 and 2, vaccinia virus, and some adenovirus strains; used for primary keratoconjunctivitis and recurrent epithelial keratitis due HSV types 1 and 2; used for epithelial keratitis that has not responded to idoxuridine or vidarabine.

1 drop in the affected eye(s) every 2 hours while awake up to 9 drops/day until the corneal ulcer has completely re-epithelialized, then 1 drop in the affected eye(s) every 4 hours while awake for a minimum of 5 drops/day for 7 days. Consider other forms of therapy if there are no signs of improvement after 7 days of therapy or complete re-epithelization has not occurred after 14 days of therapy. Avoid continuous administration for periods exceeding 21 days due to the potential for ocular toxicity.

1 drop in the affected eye(s) every 2 hours while awake up to 9 drops/day until the corneal ulcer has completely re-epithelialized, then 1 drop in the affected eye(s) every 4 hours while awake for a minimum of 5 drops/day for 7 days. Consider other forms of therapy if there are no signs of improvement after 7 days of therapy or complete re-epithelization has not occurred after 14 days of therapy. Avoid continuous administration for periods exceeding 21 days due to the potential for ocular toxicity.

1 drop in the affected eye(s) every 2 to 4 hours (Max: 9 drops/day) for 7 to 14 days.

1 drop in the affected eye(s) every 2 to 4 hours (Max: 9 drops/day) for 7 to 14 days.

1 drop in the affected eye(s) every 2 hours (Max: 9 drops/day) until reepithelialization, then 1 drop in the affected eye(s) every 4 hours (Min: 5 drops/day) for 7 days. Continue treatment until all periocular lesions have healed. Max duration: 21 days. Use in consultation with an ophthalmologist.

1 drop in the affected eye(s) every 2 hours (Max: 9 drops/day) until reepithelialization, then 1 drop in the affected eye(s) every 4 hours (Min: 5 drops/day) for 7 days. Continue treatment until all periocular lesions have healed. Max duration: 21 days. Use in consultation with an ophthalmologist.

1 drop in the affected eye(s) every 2 hours (Max: 9 drops/day) until reepithelialization, then 1 drop in the affected eye(s) every 4 hours (Min: 5 drops/day) for 7 days. Continue treatment until all periocular lesions have healed. Max duration: 21 days.

NOTE: Topical formulations of trifluridine are not commercially available and must be extemporaneously compounded using the ophthalmic solution.

Apply 1% topical trifluridine 3-times daily for at least 21 to 28 days as an alternative.

Apply 1% topical trifluridine 3-times daily for at least 21 to 28 days as an alternative.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Trifluridine products.

Trifluridine/Viroptic Ophthalmic Sol: 1%

9 drops/day to affected eye(s).

9 drops/day to affected eye(s).

9 drops/day to affected eye(s).

> = 6 years: 9 drops/day to affected eye(s).
< 6 years: Safety and efficacy have not been established.

Trifluridine is structurally similar to thymidine and, therefore, inhibits thymidine incorporation into replicating viral DNA. Trifluridine is a fluorinated pyrimidine nucleoside which irreversibly inhibits thymidylate synthase and specific DNA polymerases, necessary for the conversion of dUMP to dTMP in the process of DNA synthesis. In cultured mammalian cells, trifluridine is incorporated in place of thymidine into viral DNA, resulting in faulty DNA and the inability to reproduce or to infect or destroy tissue. To a lesser extent, trifluridine is also incorporated into cellular DNA and is capable of decreasing DNA synthesis in both infected and uninfected cells. Viral resistance to trifluridine is rare.

Trifluridine is applied topically to the eye as a solution. The half-life of trifluridine is approximately 12 minutes. Frequent application is necessary in order to inhibit multiplication of the susceptible virus.

Ophthalmic Route
Following ophthalmic application, intraocular penetration is adequate. Decreased corneal integrity or stromal or uveal inflammation may enhance the penetration of trifluridine into the aqueous humor. The major metabolite of trifluridine, 5-carboxy-2'-deoxyuridine, is not found in detectable concentrations within the aqueous humor of the human eye. Trifluridine systemic absorption is negligible following therapeutic dosing. No detectable concentrations of trifluridine or 5-carboxy-2'-deoxyuridine are found in the sera of normal healthy adults upon completion of a 14-day regimen using the product seven times daily.

Trifluridine is classified as FDA pregnancy risk category C. There are no adequate and well-controlled studies in pregnant women. In animal studies, no teratogenic or fetotoxic effects were observed in rabbits following ophthalmic administration of doses approximately 5 times the estimated human exposure. However, offspring of rats and rabbits receiving subcutaneous doses of 2.5—5 mg/kg/day (11.5—23 times the estimated human exposure) experienced toxicities that included delayed ossification, fetal death, and resorption. While systemic absorption following ophthalmic administration is minimal, do not use or prescribed in pregnant women unless clearly needed.

Trifluridine is not likely to be excreted in the breast milk after ophthalmic administration due to its relatively small dosage, its dilution in body fluids, and its extremely short half-life. According to the manufacturer, it should not be prescribed for nursing mothers unless the potential benefits outweigh the potential risks. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.