Metastatic Colorectal Cancer: This combination tablet is indicated for the treatment of adult patients with metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Metastatic Gastric Cancer: This combination tablet is indicated for the treatment of adult patients with metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

Trifluridine and Tipiracil consists of a thymidine-based nucleoside analog, Trifluridine, and the thymidine phosphorylase inhibitor, Tipiracil, at a molar ratio 1:0.5 (weight ratio, 1:0.471). Inclusion of Tipiracil increases Trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase. Following uptake into cancer cells, Trifluridine is incorporated into DNA, interferes with DNA synthesis and inhibits cell proliferation. Trifluridine/Tipiracil demonstrated anti-tumor activity against KRAS wild-type and mutant human colorectal cancer xenografts in mice.

The recommended dosage of Trifluridine and Tipiracil is 35 mg/m2 up to a maximum of 80 mg per dose (based on the Trifluridine component) orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until disease progression or unacceptable toxicity. Round dose to the nearest 5 mg increment. Instruct patients to swallow the tablet whole. Instruct patients not to retake doses of Trifluridine and Tipiracil that are vomited or missed and to continue with the next scheduled dose. Trifluridine and Tipiracil is a cytotoxic drug. Follow applicable special handling and disposal procedures.

In vitro studies indicated that Trifluridine, Tipiracil, and FTY did not inhibit CYP enzymes and had no inductive effect on CYP1A2, CYP2B6, or CYP3A4/5. In vitro studies also showed that Trifluridine was neither an inhibitor nor a substrate for human uptake and efflux transporters.

The most common adverse reactions or laboratory abnormalities (≥10%) include anemia, neutropenia, fatigue/asthenia, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, and pyrexia.

Pregnancy: Based on animal data and mechanism of action, Trifluridine and Tipiracil can cause fetal harm.

Lactation: There are no data on the presence of Trifluridine, Tipiracil or its metabolites in human milk or its effects on the breastfed infant or milk production.

Pregnancy Testing: Verify pregnancy status in females of reproductive potential before initiating treatment.

Contraception: Trifluridine and Tipiracil can cause fetal harm when given during pregnancy.

Females: Advise effective contraception during treatment and for at least 6 months after the final dose.

Males: Advise condom use during treatment and for at least 3 months after the final dose due to potential genotoxicity.

Severe Myelosuppression: In clinical studies (RECOURSE and TAGS), Trifluridine and Tipiracil caused severe and life-threatening myelosuppression including anemia (18%), neutropenia (38%), thrombocytopenia (5%), and febrile neutropenia (3%). Some patients experienced fatal infections or septic shock. Regular blood count monitoring is required before and during treatment. Dose adjustment or interruption may be needed in severe cases.

Embryo-Fetal Toxicity: The drug can cause fetal harm based on animal studies. It may lead to embryo-fetal death and toxicity. Pregnant women should be informed of risks and effective contraception should be used during and after treatment.

Renal Impairment: Mild renal impairment has no significant effect. Moderate and severe renal impairment increases drug exposure significantly. Pharmacokinetics in end-stage renal disease are not established.

Hepatic Impairment: Mild to moderate hepatic impairment shows no major differences, but moderate cases may have increased bilirubin. Severe hepatic impairment is not studied.

Pediatric Use: Safety and effectiveness are not established.

Geriatric Use: No major difference in effectiveness between elderly and younger patients.

Store below 30°C, in a cool and dry place. Keep away from light. Keep out of the reach of children.