English

ThisiscontentfromElsevier'sDrugInformation

TRANSFORM HOW YOU USE DRUG INFORMATION

Learn more about Elsevier's Drug Information today! Get the drug data and decision support you need, including TRUE Daily Updates™ including every day including weekends and holidays.

Dec.13.2022

Trifluridine

Indications/Dosage

Labeled

  • herpes simplex virus epithelial keratitis
  • keratoconjunctivitis

Off-Label

  • herpes genitalis
  • herpes simplex virus infection
  • viral conjunctivitis
  • viral keratitis
† Off-label indication

For the treatment of herpes simplex virus epithelial keratitis, including primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus type 1 and type 2

Ophthalmic dosage

Adults

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.[32394]

Children and Adolescents 6 to 17 years

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.[32394]

For the treatment of viral conjunctivitis† or viral keratitis† associated with vaccinia virus† or monkeypox virus (mpox)†

for the treatment of viral conjunctivitis or viral keratitis associated with vaccinia virus†

Ophthalmic dosage

Adults

1 drop in the affected eye(s) every 2 to 4 hours (Max: 9 drops/day) for 7 to 14 days.[32396] [68041] [68042] [68043]

Children and Adolescents

1 drop in the affected eye(s) every 2 to 4 hours (Max: 9 drops/day) for 7 to 14 days.[32396] [68041] [68042] [68043]

for the treatment of viral conjunctivitis or viral keratitis associated with monkeypox virus (mpox)†

Ophthalmic dosage

Adults

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.[68039] [68040]

Children and Adolescents

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.[68039] [68040]

For the treatment of acyclovir-resistant mucocutaneous herpes simplex virus infection†, including herpes genitalis†, in persons living with HIV

Topical dosage

Adults

Apply 1% topical trifluridine 3-times daily for at least 21 to 28 days as an alternative.[34362]

Adolescents

Apply 1% topical trifluridine 3-times daily for at least 21 to 28 days as an alternative.[34362]

Therapeutic Drug Monitoring

Maximum Dosage Limits

  • Adults

    9 drops/day to affected eye(s).

  • Elderly

    9 drops/day to affected eye(s).

  • Adolescents

    9 drops/day to affected eye(s).

  • Children

    > = 6 years: 9 drops/day to affected eye(s).

    < 6 years: Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

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

Patients with Renal Impairment Dosing

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

† Off-label indication
Revision Date: 12/13/2022, 12:32:48 PM

References

32394 - Viroptic (trifluridine) ophthalmic solution package insert. New York, NY: Pfizer Inc.; 2014 Jun.32396 - Pepose JS, Margolis TP, LaRussa P, et al. Ocular complications of smallpox vaccination. Am J Ophthalmol 2003;136:343-52.34362 - Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV: recommendations from the National Institutes of Health, the Centers for Disease Control and Prevention, the HIV Medicine Association, and the Infectious Diseases Society of America. Accessed January 18, 2023. Available at https://clinicalinfo.hiv.gov/en/guidelines/68039 - Milligan AL, Koay SY, Dunning J. Monkeypox as an emerging infectious disease: the ophthalmic implications. Br J Ophthalmol. 2022 Oct 10:bjo-2022-322268. Epub ahead of print.68040 - Centers for Disease Control and Prevention (CDC). Interim Clinical Considerations for Management of Ocular Monkeypox Virus Infection. Last reviewed Oct 7, 2022. Accessed Oct 13, 2022. Available on the World Wide Web at https://www.cdc.gov/poxvirus/monkeypox/clinicians/ocular-infection.html.68041 - Altmann S, Brandt CR, Murphy CJ, et al. Evaluation of therapeutic interventions for vaccinia virus keratitis. J Infect Dis. 2011 Mar 1;203(5):683-90.68042 - Semba RD. The ocular complications of smallpox and smallpox immunization. Arch Ophthalmol. 2003 May;121:715-9.68043 - Cono J, Casey CG, Bell DM; Centers for Disease Control and Prevention. Smallpox vaccination and adverse reactions. Guidance for clinicians. MMWR Recomm Rep. 2003 Feb 21;52:1-28.

How Supplied

Trifluridine Ophthalmic drops, solution

Trifluridine 1% Ophthalmic Solution (00065-4044) (Alcon Laboratories, Inc) (off market)

Trifluridine Ophthalmic drops, solution

Trifluridine 1% Ophthalmic Solution (59762-0040) (Greenstone Ltd) nullTrifluridine 1% Ophthalmic Solution package photo

Trifluridine Ophthalmic drops, solution

Trifluridine 1% Ophthalmic Solution (61314-0044) (Sandoz Inc. a Novartis Company) nullTrifluridine 1% Ophthalmic Solution package photo

Trifluridine Ophthalmic drops, solution

Trifluridine 1% Ophthalmic Solution (00591-3558) (Teva/Actavis US) (off market)

Trifluridine Ophthalmic drops, solution

Viroptic 1% Ophthalmic Solution (61570-0037) (Monarch Pharmaceuticals Inc a Pfizer Company) nullViroptic 1% Ophthalmic Solution package photo

Trifluridine Ophthalmic drops, solution

Viroptic 1% Ophthalmic Solution (00173-0968) (Teva Pharmaceuticals USA) (off market)

Description/Classification

Description

Description: Trifluridine (also known as trifluorothymidine) is an ophthalmic antiviral preparation indicated for primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus (HSV) types 1 and 2. Trifluridine is the treatment of choice for this indication and therapy is associated with a cure rate greater than 90%. HSV infections resistant to idoxuridine and/or vidarabine are effectively treated with trifluridine without cross-toxicity or allergenicity. Additionally, trifluridine shows in vitro and in vivo activity against vaccinia virus and in vitro inhibition of some strains of adenovirus.[32399] Off-label use of topical ophthalmic trifluridine can be considered for treatment of vaccinia infection of the conjunctiva or cornea associated with smallpox vaccination.[32396] Prophylactic therapy with trifluridine may also be considered to prevent spread to the conjunctiva and cornea if vaccinia lesions are present on the eyelid or near the eye.[31173] Trifluorothymidine was first developed as an antitumor agent and was later found to inhibit HSV in vitro. Compared to other systemic agents, it displayed low selectivity and high toxicity and, thus, was not developed for systemic use.[32427] This drug was approved by the FDA as a topical 1% ophthalmic solution in April 1980.

Classifications

  • Sensory Organs
    • Ophthalmologicals
      • Ophthalmological Antiviral Agents
Revision Date: 09/25/2015, 08:14:42 AM

References

31173 - Centers for Disease Control and Prevention (CDC). Smallpox vaccination and adverse reactions: guidance for clinicians. MMWR 2003;52(RR04):1-28.32396 - Pepose JS, Margolis TP, LaRussa P, et al. Ocular complications of smallpox vaccination. Am J Ophthalmol 2003;136:343-52.32399 - Lennette DA, Eiferman RA. Inhibition of adenovirus replication in vitro by trifluridine. Arch Ophthalmol 1978;96:1662-3. Abstract32427 - Bean B. Antiviral therapy: current concepts and practices. Clin Microbiol Rev 1992;5:146-82.

Administration Information

General Administration Information

For storage information, see the specific product information within the How Supplied section.

Route-Specific Administration

Ophthalmic Administration

  • 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.

Clinical Pharmaceutics Information

From Trissel's 2‚Ñ¢ Clinical Pharmaceutics Database
    Revision Date: 03/24/2022, 02:16:00 PM

    References

    Adverse Reactions

    Mild

    • blepharedema
    • ocular irritation

    Moderate

    • contact dermatitis
    • corneal edema
    • hyperemia
    • keratopathy

    Severe

    • keratitis
    • ocular hypertension

    The most frequent adverse reactions reported in clinical trials of trifluridine were mild, transient ocular irritation (burning and stinging) upon instillation (4.6%) and palpebral edema (blepharedema, 2.8%). Other reported adverse reactions included superficial punctuate or epithelial keratopathy, hypersensitivity reaction, stromal/corneal edema, keratitis sicca, hyperemia, and ocular hypertension.[32394]

    Trifluridine has been reported to cause an allergic contact dermatitis in patients receiving the ophthalmic solution to treat herpetic keratitis. One patient presented with a history of 3 months of eczema of the eyelids after applying trifluridine eye drops.[32397] The second patient experienced a serious dermatitis around the right eye, which spread within a few days to the whole face, trunk, and proximal parts of the extremities following one week of treatment with 1% trifluridine eyedrops.[32398] Patch testing was used to confirm the cause of the allergic reaction; in both cases trifluridine and not the solution components was associated with the adverse response.

    Revision Date: 03/27/2011, 04:37:54 AM

    References

    32394 - Viroptic (trifluridine) ophthalmic solution package insert. New York, NY: Pfizer Inc.; 2014 Jun.32397 - Millan-Parrilla F, de la Cuadra J. Allergic contact dermatitis from trifluoridine in eyedrops. Contact Dermatitis 1990;22:289.32398 - Cirkel PK, van Ketel WG. Allergic contact dermatitis to trifluorothymidine eyedrops. Contact Dermatitis 1981;7:49-50.

    Contraindications/Precautions

    Absolute contraindications are italicized.

    • breast-feeding
    • children
    • geriatric
    • infants
    • neonates
    • pregnancy

    Trifluridine ophthalmic solution is contraindicated for patients who develop hypersensitivity reactions or chemical intolerance to trifluridine.[32394]

     

    Continuous administration of trifluridine for periods exceeding 21 days should be avoided because of potential ocular toxicity.[32394] Punctate lesions in the corneal epithelium are clinical manifestations of trifluridine cytotoxicity. Upon discontinuation, toxic changes to the surface of the eye are generally reversible.[32396]

    Safe and effective use of trifluridine ophthalmic solution has not been established in neonates, infants and children below six years of age. No overall differences in safety or effectiveness have been observed between young adult and geriatric patients.[32394]

    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.[32394]

    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.[32394]

    Revision Date: 01/05/2012, 09:20:36 AM

    References

    32394 - Viroptic (trifluridine) ophthalmic solution package insert. New York, NY: Pfizer Inc.; 2014 Jun.32396 - Pepose JS, Margolis TP, LaRussa P, et al. Ocular complications of smallpox vaccination. Am J Ophthalmol 2003;136:343-52.

    Mechanism of Action

    Mechanism of Action: 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.[32426] 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.[32394] To a lesser extent, trifluridine is also incorporated into cellular DNA and is capable of decreasing DNA synthesis in both infected and uninfected cells.[32427] Viral resistance to trifluridine is rare.

    Revision Date: 02/07/2009, 03:33:40 AM

    References

    32394 - Viroptic (trifluridine) ophthalmic solution package insert. New York, NY: Pfizer Inc.; 2014 Jun.32426 - De Clercq E. Antiviral drugs in current clinical use. J Clin Virol 2004;30:115-33.32427 - Bean B. Antiviral therapy: current concepts and practices. Clin Microbiol Rev 1992;5:146-82.

    Pharmacokinetics

    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.[32394]

    Route-Specific Pharmacokinetics

    Other Route(s)

    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.

    Revision Date: 03/15/2010, 01:11:37 PM

    References

    32394 - Viroptic (trifluridine) ophthalmic solution package insert. New York, NY: Pfizer Inc.; 2014 Jun.

    Pregnancy/Breast-feeding

    pregnancy

    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.[32394]

    breast-feeding

    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.[32394]

    Revision Date: 01/05/2012, 09:20:36 AM

    References

    32394 - Viroptic (trifluridine) ophthalmic solution package insert. New York, NY: Pfizer Inc.; 2014 Jun.32396 - Pepose JS, Margolis TP, LaRussa P, et al. Ocular complications of smallpox vaccination. Am J Ophthalmol 2003;136:343-52.

    Interactions

    There are no drug interactions associated with Trifluridine products.
    Revision Date: 09/13/2016, 09:51:00 AM

    References

    Monitoring Parameters

    • laboratory monitoring not necessary

    US Drug Names

    • Viroptic
    ;