Indications
Metastatic Colorectal Cancer : This combination tablet is indicated for the treatment of adult patients with metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin-and irinotecanbased chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an ... Read more Metastatic Colorectal Cancer : This combination tablet is indicated for the treatment of adult patients with metastatic colorectal cancer previously treated with fluoropyrimidine, oxaliplatin-and irinotecanbased 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.
Composition
Pharmacology
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.
Dosage & Administration
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.
Contraindications
Side Effects
The most common adverse reactions or laboratory abnormalities (≥10%) are anemia, neutropenia, fatigue/ asthenia, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, and pyrexia.
Pregnancy & Lactation
Pregnancy : Based on animal data and its 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 child or on milk production. Pregnancy Testing : Verify pregnancy status in females of reproductive potential prior to initiating Trifluridine and Tipiracil. Contraception : Trifluridine and Tipiracil can cause fetal harm when administered to a pregnant woman. Females : Advise females of reproductive potential 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, advise males with female partners of reproductive potential to use condoms during treatment with Trifluridine and Tipiracil and for at least 3 months after the final dose.
Precautions & Warnings
Severe Myelosuppression : In the 868 patients who received Trifluridine and Tipiracil in RECOURSE and TAGS, Trifluridine and Tipiracil caused severe and life-threatening myelosuppression (Grade 3-4) consisting of anemia (18%), neutropenia (38%), thrombocytopenia (5%) and febrile neutropenia (3%). Two patients (0.2%) died due to neutropenic infection/sepsis and four other patients (0.5%) died due to septic shock. A total of 12% of Trifluridine and Tipiracil-treated patients received granulocyte-colony stimulating factors. Obtain complete blood counts prior to and on Day 15 of each cycle of Trifluridine and Tipiracil and more frequently as clinically indicated. Withhold Trifluridine and Tipiracil for severe myelosuppression and resume at the next lower dosage. Embryo-Fetal Toxicity : Based on animal studies and its mechanism of action, Trifluridine and Tipiracil can cause fetal harm when administered to a pregnant woman. Trifluridine/tipiracil caused embryo-fetal lethality and embryo-fetal toxicity in pregnant rats when orally administered during gestation at dosage levels resulting in exposures lower than those achieved at the recommended dosage of 35 mg/m2 twice daily. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with Trifluridine and Tipiracil and for at least 6 months after the final dose.
Therapeutic Class
Storage Conditions
Store below 30°C, in a cool and dry place. Keep away from light. Keep out of the reach of children.