Trifluridine / Tipiracil

What it is and how it works

Mechanism of Action LONSURF 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.

Mechanism class: Nucleic Acid Synthesis Inhibitors

Indications

is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of adult patients with: metastatic colorectal cancer as a single agent or in combination with bevacizumab 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. 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. Metastatic Colorectal Cancer LONSURF, as a single agent or in combination with bevacizumab, 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.

Dosage and administration (summary)

Recommended Dosage : 35 mg/m 2 /dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. Recommended Dosage The recommended dosage of LONSURF as a single agent or in combination with bevacizumab is 35 mg/m 2 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. Refer to the Prescribing Information for bevacizumab dosing information. Instruct patients to swallow LONSURF tablets whole.

Contraindications

None. None.

Warnings and precautions

Severe Myelosuppression: Obtain complete blood counts prior to and on Day 15 of each cycle. Withhold and resume at next lower LONSURF dosage as recommended. ( 2.1 , 5.1 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception.

Pregnancy

Pregnancy Risk Summary Based on animal data and its mechanism of action , LONSURF can cause fetal harm. LONSURF caused embryo-fetal lethality and embryo-fetal toxicity in pregnant rats when given during gestation at doses resulting in exposures lower than or similar to human exposures at the recommended clinical dose (see Data ) .

Storage and supply

15 mg/6.14 mg tablets are supplied as white, biconvex, round, film-coated tablet, imprinted with ‘15’ on one side, and ‘102’ and ’15 mg’ on the other side, in gray ink. The tablets are packaged in HDPE bottles with child resistant closures in the following presentations: 20 count: NDC 64842-1025-1 40 count: NDC 64842-1025-2 60 count: NDC 64842-1025…

Source: Trifluridine And Tipiracil (Lonsurf) — US FDA prescribing information, 2025-11-05, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.