Overview
Trifluridine is a fluorinated pyrimidine nucleoside that is structurally related to idoxuridine . It is an active antiviral agent in ophthalmic solutions used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus. It displays effective antiviral activity against Herpes simplex virus type 1 and 2 . The combination product of trifluridine with tipiracil marketed as Lonsurf has been approved in Japan, the United States, and the European Union for the treatment of adult patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy. In the anticancer therapy, trifluridine acts as a thymidine-based nucleoside metabolic inhibitor that gets incorporated into DNA of cancer cells following cell uptake to aberrate DNA function during cell replication .
Indication
用于Ⅰ及Ⅱ型单纯疱疹病毒、胞病毒、牛痘病毒、巨细胞病毒、带状疱疹病毒及耐阿昔洛韦的疱疹病毒的眼部感染。
Associated Conditions
- Metastatic Colorectal Cancer (CRC)
- Metastatic Gastric Cancers
- Metastatic Gastroesophageal Junction Adenocarcinoma
- Primary keratoconjunctivitis caused by herpes simplex virus type 2
- Recurrent epithelial keratitis caused by herpes simplex 2
Research Report
Trifluridine: A Comprehensive Monograph on a Dual-Indication Nucleoside Analogue
Executive Summary
This report provides an exhaustive analysis of trifluridine, a fluorinated pyrimidine nucleoside with a unique dual role in modern medicine. Initially developed as an antineoplastic agent and later approved as a topical antiviral for herpetic keratitis (Viroptic), trifluridine has been successfully repurposed for systemic oncology in combination with tipiracil (Lonsurf). The monograph details its chemical properties, bifurcated pharmacology, distinct pharmacokinetic profiles, extensive clinical applications in both ophthalmology and oncology, and disparate safety considerations. Furthermore, it explores the drug's developmental history, current research landscape, and future therapeutic potential, offering a comprehensive resource for clinicians, pharmacologists, and researchers.
1. Introduction: The Bifurcated History of a Fluorinated Pyrimidine
Trifluridine, a pyrimidine 2'-deoxyribonucleoside analogue of thymidine, has followed a remarkable and bifurcated trajectory in pharmacotherapy.[1] The molecule was first synthesized in 1964 by Heidelberger and colleagues, originally with antineoplastic intent.[3] However, early clinical investigations of intravenous trifluridine for cancer proved disappointing. The drug exhibited an exceptionally short serum half-life of approximately 12 minutes, which resulted in limited and transient therapeutic responses, halting its initial development as a systemic anticancer agent.[3]
Clinical Trials
Title | Posted | Study ID | Phase | Status | Sponsor |
|---|---|---|---|---|---|
2025/06/09 | Phase 2 | Recruiting | |||
2024/01/09 | Phase 3 | Not yet recruiting | |||
2022/07/21 | Phase 2 | Completed | |||
2022/01/20 | Phase 3 | Active, not recruiting | |||
2021/10/19 | Phase 1/2 | Recruiting | |||
2021/04/22 | Phase 2 | Terminated | |||
2020/07/07 | Phase 3 | Recruiting | |||
2019/06/05 | Phase 1 | Completed | |||
2013/06/04 | Phase 1 | Completed | |||
2001/08/31 | Not Applicable | Completed |
FDA Drug Approvals
Approved Product | Manufacturer | NDC Code | Route | Strength | Effective Date |
|---|---|---|---|---|---|
| Sandoz Inc | 61314-044 | OPHTHALMIC | 10 mg in 1 mL | 8/1/2011 | |
| Taiho Pharmaceutical Co., Ltd. | 64842-1025 | ORAL | 15 mg in 1 1 | 8/8/2023 | |
| Taiho Pharmaceutical Co., Ltd. | 64842-1020 | ORAL | 20 mg in 1 1 | 8/8/2023 |
EMA Drug Approvals
Approved Product | Authorization Holder | Status | Issued Date |
|---|---|---|---|
Authorised | 4/25/2016 |
HSA Drug Approvals
Approved Product | Manufacturer | Approval Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| LONSURF FILM-COATED TABLET 20MG/8.19MG | SIN15494P | TABLET, FILM COATED | 20mg | 5/24/2018 | |
| LONSURF FILM-COATED TABLET 15MG/6.14MG | SIN15491P | TABLET, FILM COATED | 15mg | 5/24/2018 |
NMPA Drug Approvals
Approved Product | Company | Approval Number | Drug Type | Dosage Form | Approval Date |
|---|---|---|---|---|---|
| No NMPA approvals found for this drug. | |||||
PPB Drug Approvals
Approved Product | Registration No. | Company | Licence No. | Strength | Registration Date |
|---|---|---|---|---|---|
| No PPB approvals found for this drug. | |||||
TGA Drug Approvals
Approved Product | ARTG ID | Sponsor | Registration Type | Status | Registration Date |
|---|---|---|---|---|---|
| ORCANTAS 15/6.14 trifluridine 15 mg/ tipiracil hydrochloride 7.065 mg (equivalent to tipiracil 6.14 mg) film-coated tablet blister pack | 273237 | Medicine | A | 5/23/2017 | |
| LONSURF 15/6.14 trifluridine 15 mg/ tipiracil hydrochloride 7.065 mg (equivalent to tipiracil 6.14 mg) film-coated tablet blister pack | 273239 | Medicine | A | 5/23/2017 | |
| ORCANTAS 20/8.19 trifluridine 20 mg/ tipiracil hydrochloride 9.420 mg (equivalent to tipiracil 8.19 mg) film-coated tablet blister pack | 273240 | Medicine | A | 5/23/2017 | |
| LONSURF 20/8.19 trifluridine 20 mg/ tipiracil hydrochloride 9.420 mg (equivalent to tipiracil 8.19 mg) film-coated tablet blister pack | 273238 | Medicine | A | 5/23/2017 |
Health Canada Drug Approvals
Approved Product | Company | DIN | Dosage Form | Strength | Market Date |
|---|---|---|---|---|---|
| APO-TRIFLURIDINE OPHTHALMIC SOLUTION | 02248119 | Solution - Ophthalmic | 1 % | N/A | |
| SANDOZ TRIFLURIDINE | 02248529 | Solution - Ophthalmic | 1 % | 1/23/2004 | |
| LONSURF | taiho pharma canada, inc. | 02472104 | Tablet - Oral | 15 MG | 3/22/2018 |
| VIROPTIC | bausch & lomb inc | 00687456 | Solution - Ophthalmic | 1 % | 12/31/1987 |
| LONSURF | taiho pharma canada, inc. | 02472112 | Tablet - Oral | 20 MG | 3/22/2018 |
CIMA AEMPS Drug Approvals
Approved Product | Company | Registration Number | Pharmaceutical Form | Prescription Type | Status |
|---|---|---|---|---|---|
| LONSURF 20 MG/8,19 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 1161096004 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Diagnóstico Hospitalario | Commercialized | |
| LONSURF 15 MG/6,14 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 1161096003 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Diagnóstico Hospitalario | Commercialized | |
| LONSURF 15 MG/6,14 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 1161096001 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Diagnóstico Hospitalario | Commercialized | |
| LONSURF 20 MG/8,19 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 1161096006 | COMPRIMIDO RECUBIERTO CON PELÍCULA | Diagnóstico Hospitalario | Commercialized | |
| LONSURF 15 MG/6,14 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 1161096003IP | COMPRIMIDO RECUBIERTO CON PELÍCULA | Diagnóstico Hospitalario | Not Commercialized | |
| LONSURF 15 MG/6,14 MG COMPRIMIDOS RECUBIERTOS CON PELICULA | 1161096001IP | COMPRIMIDO RECUBIERTO CON PELÍCULA | Diagnóstico Hospitalario | Not Commercialized |
Philippines FDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Philippines FDA approvals found for this drug. | |||||
Saudi SFDA Drug Approvals
Approved Product | Company | License Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Saudi SFDA approvals found for this drug. | |||||
Malaysia NPRA Drug Approvals
Approved Product | Company | Registration Number | Dosage Form | Strength | Approval Date |
|---|---|---|---|---|---|
| No Malaysia NPRA approvals found for this drug. | |||||
UK EMC Drug Information
Medicine Name | MA Holder | MA Number | Pharmaceutical Form | Active Ingredient | Authorization Date |
|---|---|---|---|---|---|
| No UK EMC drug information found for this drug. | |||||
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