Loncil

Trifluridine and Tipiracil is a combination of two parts: Trifluridine, a thymidine-based nucleoside analog, and tipiracil, an inhibitor of thymidine phosphorylase. They are present at a molar ratio of 1:0.5 (weight ratio, 1:0.471). Tipiracil is there to raise Trifluridine exposure, because it blocks the breakdown of Trifluridine by thymidine phosphorylase.

Once Trifluridine is taken up into cancer cells, it is built into DNA. This interferes with DNA synthesis and stops the cells from multiplying. In mice, Trifluridine/Tipiracil showed anti-tumor activity against human colorectal cancer xenografts, both KRAS wild-type and mutant.

Pregnancy: Trifluridine and Tipiracil can cause harm to the unborn baby, based on animal data and on how the medicine works.

Lactation: There are no data on whether Trifluridine, Tipiracil or its metabolites pass into human milk. There are also no data on their effects on a breastfed child or on milk production.

Pregnancy Testing: Check the pregnancy status of females who could become pregnant before starting Trifluridine and Tipiracil.

Contraception: Trifluridine and Tipiracil can cause harm to the unborn baby when given to a pregnant woman.

Females: Females who could become pregnant should be advised to use effective contraception during treatment with Trifluridine and Tipiracil and for at least 6 months after the final dose.

Males: Because of the potential for genotoxicity, males whose female partners could become pregnant should be advised to use condoms during treatment with Trifluridine and Tipiracil and for at least 3 months after the final dose.

Patients with renal impairment: In a dedicated renal impairment study, all patients received Trifluridine and Tipiracil 35 mg/m2 twice daily, except those with severe renal impairment, who received 20 mg/m2 twice daily. Mild renal impairment (CrCl of 60 to 89 mL/min, as determined by the Cockcroft-Gault formula) had no clinically important effect on the steady-state AUC0-last of trifluridine and tipiracil. In moderate renal impairment (CrCl of 30 to 59 mL/min), the steady-state AUC0-last went up by 56% for trifluridine and 139% for tipiracil, compared with normal renal function (CrCl ≥ 90 mL/min). In severe renal impairment (CrCl of 15 to 29 mL/min), the dose-normalized steady-state AUC0-last went up by 140% for trifluridine and 614% for tipiracil, again compared with normal renal function. The pharmacokinetics of trifluridine and tipiracil have not been studied in patients with end stage renal disease.

Patients with hepatic impairment: The mean exposures of trifluridine and tipiracil showed no clinically important differences between patients with normal hepatic function (total bilirubin and AST ≤ ULN) and patients with mild hepatic impairment (total bilirubin ≤ULN and AST > ULN, or total bilirubin <1 to 1.5 times ULN and any AST) to moderate hepatic impairment (total bilirubin >1.5 to 3 times ULN and any AST). Even so, 5 of 6 patients with moderate hepatic impairment had Grade 3 or 4 increased bilirubin levels. The pharmacokinetics of trifluridine and tipiracil have not been studied in patients with severe hepatic impairment.

Pediatric use: Safety and effectiveness of Trifluridine and Tipiracil in pediatric patients have not been established.

Geriatric use: No overall differences in effectiveness were seen between patients aged 65 or older and younger patients.

Keep Trifluridine + Tipiracil below 30°C, in a cool and dry place. Protect it from light, and keep it out of the reach of children.