Trifluridine/tipiracil
Combination of | |
---|---|
Trifluridine | Cytotoxin |
Tipiracil | Thymidine phosphorylase inhibitor |
Clinical data | |
Trade names | Lonsurf |
Other names | TAS-102 |
AHFS/Drugs.com | Monograph |
MedlinePlus | a615049 |
Pregnancy category |
|
Routes of administration | By mouth |
ATC code | |
Legal status | |
Legal status | |
Identifiers | |
KEGG |
Trifluridine/tipiracil (FTD–TPI), sold under the brand name Lonsurf, is a fixed-dose
The most common side effects include neutropenia (low levels of neutrophils, a type of white blood cell that fights infection), feeling sick, tiredness and anemia (low red blood cell counts).[4][5][6]
Medical uses
It is used as a third- or fourth-line treatment for metastatic colorectal cancer or gastric cancer, after chemotherapy and biologic therapy.[4][5][6]
Contraindications
The combination caused harm to the fetus of pregnant animals, and it was not tested in pregnant women. Pregnant women should not take it, and women should not become pregnant while taking it.[4]
Adverse effects
The combination severely
Between 1 and 10% of people have skin and mucosa issues, like rashes and itchiness, or mouth sores, as well as skin sloughing, numbness, redness, and swelling of their palms and soles.[5] Dizziness and confusion are common as well.[5]
Interactions
Only
Pharmacology
Mechanism of action
The drug consists of the
Tipiracil prevents the degradation of trifluridine via thymidine phosphorylase (TP) when taken orally and also has antiangiogenic properties.[7][8][9]
History
Since the synthesis of
By the late 1960s, Phase I and Phase II clinical trials of intravenous trifluridine alone initially proved to be disappointing.
Researchers later found out that trifluridine, when taken orally, was broken down into the inactive metabolites 5-trifluoromethyluracil and 5-trifluoromethyl-2,4(1H,3,H)-pyrimidinedione (FTY) during its extensive first pass metabolism in the liver via the enzyme thymidine phosphorylase.[8][11] It was then hypothesized that orally administered FTD concentrations could be increased and maintained if the drug was given with a thymidine phosphorylase inhibitor.[11]
Trifluridine/tipiracil was approved by the US FDA in September 2015,[12] and by the European Medicines Agency in April 2016.[13]
References
- ^ "Prescription medicines: registration of new chemical entities in Australia, 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 9 April 2023.
- ^ "Prescription medicines and biologicals: TGA annual summary 2017". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 31 March 2024.
- ^ "Search Page - Drug and Health Product Register". 23 October 2014.
- ^ a b c d e f g h "UK Label: Lonsurf - Summary of Product Characteristics". Electronic Medicines Compendium. August 2017. Retrieved 10 May 2018.
- ^ a b c d e f g h "Lonsurf- trifluridine and tipiracil tablet, film coated". DailyMed. 14 January 2020. Retrieved 20 October 2020.
- ^ a b c d e "Lonsurf EPAR". European Medicines Agency (EMA). 17 September 2018. Retrieved 20 October 2020.
- ^ S2CID 19183535.
- ^ PMID 23182191.
- PMID 10213500.
- S2CID 12355316.
- ^ S2CID 32214949.
- ^ "FDA approves new oral medication to treat patients with advanced colorectal cancer" (Press release). Silver Spring, MD. U.S. Food and Drug Administration. 2015-09-22. Retrieved 2015-09-23.
- ^ "Lonsurf EPAR – Summary for the Public" (PDF). European Medicines Agency. April 2016.