Fludin

• Approved Indications:
• Treatment of herpetic keratitis (herpes simplex virus infections of the cornea).
• Used for ocular infections caused by herpes simplex virus types 1 and 2.
• In oncology, trifluridine in combination with tipiracil is indicated for metastatic colorectal cancer refractory to standard therapies (as oral tablets in combination form).
• Off-label Uses:
• Treatment of other ocular viral infections caused by herpes viruses, including keratoconjunctivitis.
• Occasionally used in topical antiviral therapy in research settings.

• For Ocular Herpetic Keratitis (Trifluridine Ophthalmic Drops):
• Instill one drop into the affected eye every 2 hours while awake (up to 9 drops daily).
• Continue treatment for 7–10 days or until healing is evident.
• Reduce frequency gradually once improvement occurs.
• For Oncology (Trifluridine/Tipiracil oral combination):
• Administered orally at a dose based on body surface area, typically 35 mg/m² twice daily on days 1–5 and 8–12 of each 28-day cycle.
• Dosage adjustment based on tolerability, renal and hepatic function, and blood counts.
• Pediatrics & Elderly:
• Safety and efficacy in pediatric patients not well established for ocular use.
• Use in elderly follows adult dosing, with careful monitoring.
• Special Populations:
• Dose adjustments may be necessary in severe renal or hepatic impairment (oncology use).
• Ocular formulation requires caution to avoid contamination.
• Administration Route:
• Ocular: Topical ophthalmic solution.
• Oncology: Oral tablets (in combination with tipiracil).

Trifluridine is a nucleoside analog antiviral agent that is phosphorylated intracellularly to its active triphosphate form. This active metabolite competitively inhibits viral thymidylate synthase, disrupting DNA synthesis in herpes simplex virus–infected cells. It also incorporates into viral DNA, causing faulty DNA strands and inhibiting viral replication. In oncology, trifluridine acts as an antimetabolite, integrating into DNA and interfering with tumor cell proliferation.

• Absorption: Poor systemic absorption after topical ocular administration; oral bioavailability is low due to rapid metabolism.
• Distribution: Limited systemic distribution after ocular use; systemic use leads to widespread tissue distribution.
• Metabolism: Rapidly metabolized by thymidine phosphorylase enzyme; tipiracil co-administered in oral therapy inhibits this metabolism to increase trifluridine’s bioavailability.
• Elimination: Metabolites are primarily excreted via urine and feces.
• Half-life: Short plasma half-life (~12 minutes) for trifluridine alone; extended with tipiracil.
• Onset of Action: Rapid antiviral effects seen in ocular infections; antitumor effects develop over weeks in systemic use.

• Pregnancy:
• FDA pregnancy category C (ocular use).
• Use only if potential benefits justify potential risks. Systemic use in cancer patients carries risks; animal studies show fetal toxicity.
• Lactation:
• Unknown if excreted in human milk; caution advised. Avoid breastfeeding during systemic use.

• Primary Class: Antiviral agent (ophthalmic) / Antineoplastic antimetabolite (systemic).
• Subclass: Nucleoside analog.

• Known hypersensitivity to trifluridine or any formulation components.
• Ocular use: Avoid use if active eye inflammation unrelated to HSV is present.
• Systemic use: Contraindicated in patients with severe bone marrow suppression.

• Ocular use may cause local irritation, punctate keratitis, or allergic reactions; monitor for worsening symptoms.
• Avoid contact lenses during treatment.
• Systemic use carries risk of myelosuppression, anemia, neutropenia, and thrombocytopenia; monitor blood counts regularly.
• Caution in patients with hepatic or renal impairment.
• Risk of severe gastrointestinal toxicity during systemic use; monitor closely.
• Not recommended during pregnancy or lactation unless benefits outweigh risks.

• Ocular (topical):
• Eye irritation, burning, stinging, redness.
• Conjunctival hyperemia.
• Punctate keratitis or corneal edema (rare).
• Systemic (oral combination):
• Hematologic: Neutropenia, anemia, thrombocytopenia.
• Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain.
• Fatigue, weakness.
• Rare allergic reactions.

• Systemic trifluridine metabolism inhibited by tipiracil to enhance bioavailability.
• Concomitant use with other myelosuppressive agents may increase hematologic toxicity.
• Avoid other topical ocular medications during treatment unless prescribed.
• No significant CYP450-mediated interactions reported.

• Approval of trifluridine/tipiracil oral combination has expanded therapeutic options for refractory metastatic colorectal cancer.
• Updated ophthalmology guidelines reaffirm trifluridine ophthalmic solution as an effective first-line antiviral for herpetic keratitis.
• Emphasis on monitoring hematologic toxicity during systemic use and adherence to recommended dosing schedules.

• Store ophthalmic solution at 2°C to 25°C (36°F to 77°F); protect from freezing and light.
• Keep bottle tightly closed to avoid contamination.
• Oral tablets stored at room temperature (20°C to 25°C), away from moisture and heat.
• Do not freeze ophthalmic solution; discard if contamination suspected.