轉移性大腸直腸癌、胃癌 Colorectal cancer, metastatic; Gastric cancer, metastatic
#仿單變更2021

Antineoplastic Agent, Antimetabolite (Pyrimidine Analog)
the active cytotoxic component of trifluridine/tipiracil, is a thymidine-based nucleic acid analogue; the triphosphate form of trifluridine is incorporated into DNA which interferes with DNA synthesis and inhibits cell proliferation.
Thymidine Phosphorylase Inhibitor
Tipiracil is a potent thymidine phosphorylase inhibitor which prevents the rapid degradation of trifluridine, allowing for increased trifluridine exposure.

Distribution:
1. Protein binding: Trifluridine: >96% (primarily to albumin)
2. Tipiracil: <8%
Metabolism:
1. Trifluridine and tipiracil are not metabolized by cytochrome P450 (CYP) enzymes.
2. Trifluridine is mainly eliminated by metabolism via thymidine phosphorylase to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY)
Excretion:
1. Trifluridine: Urine (55% [as inactive metabolite]; <3% [as unchanged drug]); feces (<3% [as unchanged drug]); expired air (<3%)
2. Tipiracil: Urine (27% [as tipiracil and 6-HMU]); feces (50% [as tipiracil and 6-HMU])
Half-life elimination:
1. Trifluridine: 2.1 hours (at steady state)
2. Tipiracil: 2.4 hours (at steady state)
Time to peak, plasma:
~2 hours

There are no contraindications listed in the manufacturer's labeling.

Based on animal studies and on the mechanism of action, use of trifluridine/tipiracil would be expected to cause fetal harm when used during pregnancy.
1. Females of reproductive potential should use effective contraception during therapy.
2. Males who have female partners of reproductive potential should use condoms during therapy and for at least 3 months following the final dose.

Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for one day following the last dose.

Fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, anemia, neutropenia, thrombocytopenia, weakness, fever

Oral: 35 mg/m2 (based on the trifluridine component) twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle (maximum per dose: trifluridine 80 mg); continue until disease progression or unacceptable toxicity (Mayer 2015).
The manufacturer recommends rounding each dose to the nearest 5 mg increment.
Missed dose: Do not take additional doses to make up for missed or held doses.

Note: Renal function may be estimated by the Cockcroft-Gault equation.<20211019>

CrCl ≥30 mL/minute:
1. No initial dosage adjustment is necessary.
2. Monitor closely; patients with moderate impairment (CrCl 30 to 59 mL/minute) may experience greater toxicity and may require dose reduction during treatment.
CrCl <30 mL/minute and ESRD:
1. 20 mg/m² twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle.
2. If unable to tolerate the 20 mg/m² dose: Further reduce the dose to 15 mg/m².
3. If unable to tolerate the 15 mg/m² dose: Permanently discontinue. <20211019>

1. Mild impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin <1 to 1.5 times ULN and any AST): No dosage adjustment necessary.
2. Moderate impairment (total bilirubin >1.5 to 3 times ULN and any AST) or severe impairment (total bilirubin >3 times ULN and any AST): Do not initiate therapy.