Tipiracil HCl, Trifluridine
Indications
Tipiracil HCl, Trifluridine is used for:
Trifluridine
Trifluridine is used for the treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2 in ophthalmic solutions. Trifluridine, in combination with tipiracil as oral tablets, is indicated 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 [FDA Label].
Trifluridine is used for the treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2 in ophthalmic solutions. Trifluridine, in combination with tipiracil as oral tablets, is indicated 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 [FDA Label].
Adult Dose
Child Dose
Renal Dose
Administration
Contra Indications
Precautions
Pregnancy-Lactation
Interactions
Adverse Effects
Side effects of Tipiracil HCl, Trifluridine :
Mechanism of Action
Trifluridine
The mechanism of action of trifluridine as an antiviral agent has not been fully elucidated, but appears to involve the inhibition of viral replication. Trifluridine gets incorporated into viral DNA during replication, which leads to the formation of defective proteins and an increased mutation rate. Trifluridine also mediates antineoplastic activities via this mechanism; following uptake into cancer cells, trifluridine is rapidly phosphorylated by thymidine kinase to its active monophosphate form [A35272]. Subsequent phosphorylation produces trifluridine triphosphate [A35272], which is readily incorporated into the DNA of tumour cells in place of thymidine bases to perturb DNA function, DNA synthesis, and tumour cell proliferation [FDA Label]. As trifluridine is subject to rapid degradation by TPase and readily metabolised by a first-pass effect following oral administration, tipiracil is added in the antineoplastic combination product as an inhibitor of TPase to increase the bioavailability of trifluridine [F649]. Trifluridine monophosphate also reversibly inhibits thymidylate synthetase (TS), an enzyme that is necessary for DNA synthesis and which levels are shown to be elevated different cancer cell lines [A35289]. Up-regulation of the expression of the TS enzyme may also lead to the resistance to antineoplastic therapies, such as 5-fluorouracil (5-FU) [A35289]. However, this inhibitory effect is not considered to be sufficient enough to fully contribute to the cytotoxicity in cancer cells [A35272].
The mechanism of action of trifluridine as an antiviral agent has not been fully elucidated, but appears to involve the inhibition of viral replication. Trifluridine gets incorporated into viral DNA during replication, which leads to the formation of defective proteins and an increased mutation rate. Trifluridine also mediates antineoplastic activities via this mechanism; following uptake into cancer cells, trifluridine is rapidly phosphorylated by thymidine kinase to its active monophosphate form [A35272]. Subsequent phosphorylation produces trifluridine triphosphate [A35272], which is readily incorporated into the DNA of tumour cells in place of thymidine bases to perturb DNA function, DNA synthesis, and tumour cell proliferation [FDA Label]. As trifluridine is subject to rapid degradation by TPase and readily metabolised by a first-pass effect following oral administration, tipiracil is added in the antineoplastic combination product as an inhibitor of TPase to increase the bioavailability of trifluridine [F649]. Trifluridine monophosphate also reversibly inhibits thymidylate synthetase (TS), an enzyme that is necessary for DNA synthesis and which levels are shown to be elevated different cancer cell lines [A35289]. Up-regulation of the expression of the TS enzyme may also lead to the resistance to antineoplastic therapies, such as 5-fluorouracil (5-FU) [A35289]. However, this inhibitory effect is not considered to be sufficient enough to fully contribute to the cytotoxicity in cancer cells [A35272].