Viroptic

The recommended dosage and frequency of administration should not be exceeded (See DOSAGE AND ADMINISTRATION).

You should not use this medicine if you are allergic to trifluridine.

It is not known whether this medicine will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant.

It is not known whether trifluridine ophthalmic passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Trifluridine ophthalmic is not approved for use by anyone younger than 6 years old.

Antiviral; fluorinated pyrimidine nucleoside.100 104 109

Administration

Ophthalmic Administration

Apply 1% ophthalmic solution topically onto the cornea of the eye.100 109

Dosage

Pediatric Patients

Children ≥6 years of age: Instill 1 drop of 1% ophthalmic solution onto the cornea of the affected eye every 2 hours while awake (maximum 9 drops daily) until reepithelialization occurs.100 109 Following reepithelialization, instill 1 drop every 4 hours while awake (minimum 5 drops daily) for an additional 7 days.100 109

If there are no signs of improvement after 7 days or if complete reepithelialization has not occurred after 14 days of therapy, consider other forms of treatment.100 109

Avoid treatment duration >21 days.100 109

Adults

Instill 1 drop of 1% ophthalmic solution onto the cornea of the affected eye every 2 hours while awake (maximum 9 drops daily) until reepithelialization occurs.100 109 Following reepithelialization, instill 1 drop every 4 hours while awake (minimum 5 drops daily) for an additional 7 days.100 109

If there are no signs of improvement after 7 days or if complete reepithelialization has not occurred after 14 days of therapy, consider other forms of treatment.100 109

Avoid treatment duration >21 days.100 109

Instill 1 drop of 1% ophthalmic solution in the affected eye every 2 hours while awake (i.e., 9 times daily) for up to 14 days or until all lesions heal.101

Instill 1 drop of 1% ophthalmic solution in the affected eye every 4 hours while awake (i.e., 5 times daily) for up to 14 days or until all periocular and/or lid lesions heal and scabs have fallen off.101

If there is are no signs of improvement or if manifestations worsen after 24–48 hours of therapy, may increase dosage to 1 drop instilled into the affected eye every 2 hours while awake (i.e., 9 times daily).101

Instill 1 drop of 1% ophthalmic solution in the affected eye every 4 hours while awake (i.e., 5 times daily) for up to 5 days.102

Discontinue if there is no evidence of vaccinia infection after 5 days.102

Prescribing Limits

Pediatric Patients

Maximum 9 drops of 1% ophthalmic solution daily;100 109 avoid treatment duration >21 days.100 109

Adults

Maximum 9 drops of 1% ophthalmic solution daily;100 109 avoid treatment duration >21 days.100 109

Treatment of vaccinia virus ophthalmic infections†: Maximum 9 drops of 1% ophthalmic solution daily for up to 14 days.101

Prophylaxis in patients with blepharitis or vaccinia lesions on or near eyelid†: Maximum 9 drops of 1% ophthalmic solution daily for up to 14 days.101

Prophylaxis following inadvertent exposure to vaccinia virus in laboratory setting†: Maximum 5 drops of 1% ophthalmic solution daily for up to 5 days.102

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.100 109

• Importance of informing patients of other important precautionary information.100 109 (See Cautions.)

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Change in eyesight, eye pain, or very bad eye irritation.
• Eyelid swelling.

Viroptic is the brand name for trifluridine (also known as trifluorothymidine, F3TdR,F3T), an antiviral drug for topical treatment of epithelial keratitis caused by herpes simplex virus. The chemical name of trifluridine is α,α,α -trifluorothymidine; it has the following structural formula:

Viroptic sterile ophthalmic solution contains 1% trifluridine in an aqueous solution with acetic acid and sodium acetate (buffers), sodium chloride, and thimerosal 0.001% (added as a preservative). The pH range is 5.5 to 6.0 and osmolality is approximately 283 mOsm.

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

Clinical Studies

During a controlled multicenter clinical trial, 92 of 97 (95%) patients (78 of 81 with dendritic and 14 of 16 with geographic ulcers) responded to therapy with Viroptic as evidenced by complete corneal re-epithelialization within the 14-day therapy period. Fifty-six of 75 (75%) patients (49 of 58 with dendritic and 7 of 17 with geographic ulcers) responded to idoxuridine therapy. The mean time to corneal re-epithelialization for dendritic ulcers (6 days) and geographic ulcers (7 days) was similar for both therapies.

In other clinical studies, Viroptic was evaluated in the treatment of herpes simplex virus keratitis in patients who were unresponsive or intolerant to the topical administration of idoxuridine or vidarabine. Viroptic was effective in 138 of 150 (92%) patients (109 of 114 with dendritic and 29 of 36 with geographic ulcers) as evidenced by corneal re-epithelialization. The mean time to corneal re-epithelialization was 6 days for patients with dendritic ulcers and 12 days for patients with geographic ulcers.

The clinical efficacy of Viroptic in the treatment of stromal keratitis and uveitis due to herpes simplex virus or ophthalmic infections caused by vacciniavirus and adenovirus has not been established by well-controlled clinical trials. Viroptic has not been shown to be effective in the prophylaxis of herpes simplex virus keratoconjunctivitis and epithelial keratitis by well-controlled clinical trials. Viroptic is not effective against bacterial, fungal, or chlamydial infections of the cornea or nonviral trophic lesions.

Overdosage by ocular instillation is unlikely because any excess solution should be quickly expelled from the conjunctival sac.

Acute overdosage by accidental oral ingestion of Viroptic has not occurred. However, should such ingestion occur, the 75 mg dosage of trifluridine in a 7.5 mL bottle of Viroptic is not likely to produce adverse effects. Single intravenous doses of 1.5 to 30 mg/kg/day in children and adults with neoplastic disease produce reversible bone marrow depression as the only potentially serious toxic effect and only after three to five courses of therapy. The acute oral LD50 in the mouse and rat was 4379 mg/kg or higher.