Drug Interaction Report

ADDITIONAL CONTRACEPTION RECOMMENDED: Coadministration with tipiracil-trifluridine may reduce the efficacy of contraceptive hormones. The mechanism has not been established. Trifluridine is an antineoplastic agent and may cause fetal harm when administered during pregnancy. Data evaluating the interaction are not available.

MANAGEMENT: Because trifluridine may cause fetal harm, it is particularly important that patients not become pregnant during tipiracil-trifluridine treatment. Female patients of childbearing potential using hormonal contraceptives should be advised of the risk of breakthrough bleeding and unintended pregnancy during concomitant tipiracil-trifluridine treatment. The manufacturer recommends use of additional barrier contraceptive methods during and for up to 6 months after tipiracil-trifluridine therapy. No recommendations are available for women using hormone-release intrauterine systems or injectable progestin-only contraceptives. Input from a gynecologist or similar expert on adequate contraception, including emergency contraception, should be sought as needed.

ADJUST DOSING INTERVAL: Administration of trifluridine-tipiracil with a standardized high-fat, high-calorie meal has been shown to decrease trifluridine peak plasma concentration (Cmax) as well as tipiracil Cmax and systemic exposure (AUC) by approximately 40% compared to administration in a fasting state in patients with cancer given a single 35 mg/m2 dose. No change in trifluridine AUC was observed.

MANAGEMENT: Based on the observed correlation between increases in the Cmax of trifluridine and decreases in neutrophil counts, trifluridine-tipiracil should be taken within one hour after completion of the morning and evening meals.