Trifluridine (Trifluorothymidine)
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
After ocular instillation, the most common adverse effect of trifluridine is mild, transient stinging. Punctate keratopathy, resulting in blurred vision and intense conjunctival hyperemia, has been reported in association with trifluridine treatment in patients with dendritic keratitis (La-Lau et al., 1981). That study also showed two cases hyperemic conjunctivitis after trifluridine administration (2% ointment) for herpetic keratitis (La-Lau et al., 1982). Corneal toxicity of trifluridine has been reported (Turner and Beckingsale, 2013). Increased intraocular pressure and hypersensitivity with itch, redness, and swelling have been observed infrequently (US Pharmacopeia Drug Information, 2005). Cross-hypersensitivity between trifluridine and idoxuridine or vidarabine is rare (Carmine et al., 1982). Intraocular trifluridine given by intravitreal injection (200 μg/0.1 ml) to rabbits resulted in no evidence of toxicity (Pang et al., 1986). Trifluridine has been found to be cytotoxic and mutagenic when assessed in a mammalian cell mutagenesis assay (Marquardt et al., 1985). Adenocarcinomas, hemangiosarcomas, and ovarian and prostate tumors developed with increased frequency in rats administered trifluridine in doses of 1.5–15 mg/kg/day (US Pharmacopeia Drug Information, 2005).
Trifluridine
Anton C. de Groot in Monographs in Contact Allergy, 2021
Trifluridine is a fluorinated pyrimidine nucleoside with antiviral activity against Herpes simplex virus type 1 and 2 and vacciniavirus and with potential antineoplastic activity. In anticancer therapy, trifluridine is incorporated into DNA and inhibits thymidylate synthase, resulting in inhibition of DNA synthesis, inhibition of protein synthesis, and apoptosis. Trifluridine in ophthalmic solutions is indicated for the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to Herpes simplex virus types 1 and 2. Oral trifluridine, in combination with tipiracil, is indicated for the treatment of metastatic colorectal cancer (1).
Acute and Recurrent Genital Herpes Simplex Virus Infection
Marie Studahl, Paola Cinque, Tomas Bergström in Herpes Simplex Viruses, 2017
In the event of further deterioration, or where an aciclovir-resistant virus is demonstrated, the following treatment options are recommended. Topical trifluridine every 8 hours until complete healing can be used for accessible lesions.IV foscarnet 50 mg/kg twice daily until complete healing is used for inaccessible or systemic lesions.
The discovery of novel antivirals for the treatment of mpox: is drug repurposing the answer?
Published in Expert Opinion on Drug Discovery, 2023
Ahmed A. Ezat, Jameel M. Abduljalil, Ahmed M. Elghareib, Ahmed Samir, Abdo A. Elfiky
For more than a half-century, a group of deoxyuridines analogs has been known for their antiviral potential against DNA viruses. 5-substituted 2´-deoxyuridine analogs are the most important among these analogs. Three 5-substituted 2́-deoxyuridine derivatives (idoxuridine, trifluridine, and brivudine) have been approved as antiviral drugs that inhibit viral DNA biosynthesis [43]. These drugs required a phosphorylation reaction before exerting their inhibitory effect. Both idoxuridine and trifluridine are activated by cellular kinases to the 5́-triphosphate or the 5́-monophosphate forms, respectively, while Brivudine is phosphorylated to mono- or diphosphate forms by viral thymidine kinase. Idoxuridine and trifluridine are approved for keratitis caused by herpes simplex virus as topical medications.
Synthesis and toxicity assessment of Fe3O4 NPs grafted by ∼ NH2-Schiff base as anticancer drug: modeling and proposed molecular mechanism through docking and molecular dynamic simulation
Published in Drug Delivery, 2020
Rahime Eshaghi Malekshah, Bahareh Fahimirad, Mohammadreza Aallaei, Ali Khaleghian
The molecular docking studies along with experimental studies could help to explore a compound as a potential drug candidate. The binding free energy values are dominated by the vdW + Hbond + desolv (kcal/mol) negative energy values, suggesting that the binding events of nanoparticles are a spontaneous process. The DNA-binding affinity of the Fe3O4@SiO2@APTS (–10.85 kcal mol−1) and mitoxantrone (–10.35 kcal mol−1) is stronger than the Fe3O4@SiO2 (–6.46 kcal mol−1), Fe3O4@SiO2@APTS ∼ Schiff base (–7.47 kcal mol−1), Fe3O4@SiO2@APTS ∼ Schiff base-Cu(II) (–7.59 kcal mol−1), and trifluridine (–5.56 kcal mol−1), respectively. The data and figures of compounds are shown in Figure 5 and Table 2. Based on a comparison of among results, all synthesized compounds showed significant affinity to DNA compared to trifluridine (as DNA–drug interaction). Also, compounds and anticancer drugs could bind to the minor groove of DNA.
The safety of trifluridine and tipiracil for the treatment of metastatic colorectal cancer
Published in Expert Opinion on Drug Safety, 2018
Julia Martinez-Perez, M. Carmen Riesco-Martinez, Rocio Garcia-Carbonero
In summary, TAS-102 significantly improves survival of patients with mCRC who are refractory or intolerant to standard chemotherapy. Trifluridine/tipiracil is well tolerated with manageable toxicity across all clinical trials and postmarketing studies. Its favorable safety profile with low cumulative toxicity facilitates patients’ adherence and allows for long-term use. This also makes TAS102 a suitable drug to be combined with other cytotoxic and targeted agents at earlier stages of disease, and offer some potential advantages over classic fluoropyrimidines in this setting.
Related Knowledge Centers
- Antiviral Drug
- Eye
- Herpes Simplex Virus
- Herpesviridae
- Keratitis
- Keratoconjunctivitis
- Aciclovir
- Trifluridine/Tipiracil
- Vaccinia
- Idoxuridine