Trifluridine

Usage

• Trifluridine ophthalmic solution is prescribed for the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis caused by herpes simplex virus (HSV) types 1 and 2. It is also recommended by the Centers for Disease Control (CDC) for accidental smallpox virus ophthalmic infections.
• Pharmacological Classification: Ophthalmic antiviral agent, nucleoside analog.
• Mechanism of Action: Trifluridine inhibits viral DNA synthesis by interfering with the enzyme thymidylate synthetase and by being incorporated into viral DNA in place of thymidine, which disrupts further viral replication.

Alternate Names

• Trifluorothymidine (F3TdR, F3T)
• Brand Name: Viroptic

How It Works

• Pharmacodynamics: Trifluridine, a pyrimidine nucleoside analog, primarily affects actively replicating HSV. Its antiviral activity stems from its ability to impede viral DNA synthesis.

• Pharmacokinetics:

  • Absorption: Trifluridine is absorbed through the cornea, with enhanced penetration when there are epithelial defects or stromal/uveal inflammation.
  • Metabolism: Information not found in provided resources.
  • Elimination: Its elimination half-life is approximately 12 minutes. Elimination pathways have not been specified in the provided sources.

• Mode of Action: Trifluridine inhibits thymidylate synthetase, an enzyme essential for DNA synthesis, and gets incorporated into the viral DNA, halting further viral replication.

• Receptor binding, enzyme inhibition, or neurotransmitter modulation: Trifluridine inhibits the enzyme thymidylate synthetase. Information regarding receptor binding or neurotransmitter modulation was not found in provided sources.

• Elimination pathways: Information regarding specific elimination pathways was not found in the provided sources.

Dosage

Standard Dosage

Adults: One drop of 1% trifluridine ophthalmic solution is instilled onto the cornea of the affected eye every 2 hours while awake, up to a maximum of 9 drops per day, until the corneal ulcer heals completely (re-epithelialization). After re-epithelialization, the dosage is reduced to one drop every 4 hours while awake (minimum 5 drops/day) for 7 days. Treatment should not exceed 21 days.

Children: Children 6 years of age and older follow the adult dosage. Safety and efficacy have not been established in children younger than 6 years.

Special Cases:

• Elderly Patients: No dosage adjustments are generally required.
• Patients with Renal Impairment: No specific dosage adjustment guidelines were found in provided resources.
• Patients with Hepatic Dysfunction: No specific dosage adjustment guidelines were found in provided resources.
• Patients with Comorbid Conditions: No explicit guidance provided in sources. Dosage adjustments should be considered on a case-by-case basis.

Clinical Use Cases Dosage guidelines are not provided in the sources for the following settings:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations (e.g., status epilepticus, cardiac arrest)

Dosage Adjustments: Dosage adjustments may be needed if the patient has hypersensitivity reactions, experiences adverse effects, or shows no improvement after 7 days, or incomplete re-epithelialization after 14 days. The maximum treatment duration is 21 days to prevent ocular toxicity. Specific dose modifications based on renal/hepatic dysfunction, metabolic disorders, or genetic polymorphisms are not mentioned in the sources.

Side Effects

Common Side Effects:

• Mild, transient burning or stinging upon instillation
• Eyelid swelling (palpebral edema)

Rare but Serious Side Effects:

• Superficial punctate keratopathy
• Epithelial keratopathy
• Stromal edema
• Keratitis sicca
• Eye redness (hyperemia)
• Increased intraocular pressure
• Hypersensitivity reactions

Long-Term Effects: Not specified in provided sources.

Adverse Drug Reactions (ADR): Hypersensitivity reactions warrant immediate discontinuation. Other ADRs mentioned above require clinical evaluation and may necessitate dosage adjustments or alternative treatment.

Contraindications

• Hypersensitivity to trifluridine or any component of the formulation.

Drug Interactions

No known clinically significant drug interactions with topical trifluridine have been reported in the provided sources.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (FDA classification). It is not known if or how trifluridine ophthalmic could affect pregnancy or harm an unborn baby. Animal studies suggest potential fetal toxicity at higher dosages, but there are no adequate and well-controlled studies in humans.
• Breastfeeding: It is not known whether trifluridine passes into breast milk. Due to the low dosage used ophthalmically, short half-life, and dilution in body fluids, the risk to the infant is considered low. However, caution is advised.

Drug Profile Summary

• Mechanism of Action: Inhibits viral DNA synthesis by interfering with thymidylate synthetase and incorporating into viral DNA.
• Side Effects: Burning/stinging, eyelid swelling, superficial punctate keratopathy, epithelial keratopathy, stromal edema, keratitis sicca, hyperemia, increased IOP, hypersensitivity.
• Contraindications: Hypersensitivity to trifluridine.
• Drug Interactions: No known significant drug interactions.
• Pregnancy & Breastfeeding: Pregnancy Category C; use with caution if benefits outweigh risks. Breastfeeding: Use with caution if benefits outweigh potential risks.
• Dosage: Adults and children ≥6 years: 1 drop every 2 hours while awake until re-epithelialization (max 9 drops/day), then 1 drop every 4 hours (min 5 drops/day) for 7 days. Max treatment duration: 21 days.
• Monitoring Parameters: Monitor for resolution of HSV keratitis, adverse reactions, and intraocular pressure.

Popular Combinations

Information regarding popular combinations is not found in provided resources.

Precautions

• General Precautions: Diagnose herpetic keratitis before initiating treatment. Closely monitor for hypersensitivity.
• Specific Populations: Use with caution during pregnancy and breastfeeding. Safety and efficacy in children under 6 are not established.
• Lifestyle Considerations: Blurred vision may temporarily impair activities requiring clear vision, such as driving or operating machinery.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Trifluridine?

A: Adults and children ≥6 years: 1 drop of 1% solution every 2 hours while awake until corneal re-epithelialization (max 9 drops/day), then 1 drop every 4 hours (min 5 drops/day) for 7 days. Maximum treatment duration is 21 days.

Q2: What is the mechanism of action of Trifluridine?

A: Trifluridine inhibits viral DNA synthesis by interfering with the enzyme thymidylate synthetase and being incorporated into viral DNA.

Q3: What are the common side effects of Trifluridine?

A: Common side effects are usually mild and transient, including burning or stinging upon instillation and eyelid swelling.

Q4: Is Trifluridine safe to use during pregnancy?

A: Trifluridine is Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Use only if potential benefits justify potential risk to the fetus.

Q5: Can I use Trifluridine while breastfeeding?

A: It is not known whether trifluridine passes into breast milk. Use with caution if the benefits outweigh potential risks.

Q6: How long can I use Trifluridine?

A: Treatment should not exceed 21 days due to the risk of ocular toxicity.

Q7: What should I do if I experience side effects while using Trifluridine?

A: Contact your ophthalmologist. Dosage adjustment or discontinuation may be necessary.

Q8: What if my condition doesn’t improve with Trifluridine?

A: If there’s no improvement after 7 days or complete re-epithelialization hasn’t occurred after 14 days, consult with an ophthalmologist to consider alternative treatments.

Q9: Are there any drug interactions with Trifluridine?

A: No clinically significant drug interactions have been reported with topical Trifluridine.