Dosing & Uses
Dosage Forms & Strengths
trifluridine/tipiracil
tablet
- 15mg/6.14mg
- 20mg/8.19mg
Metastatic Colorectal Cancer
Indicated for patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and an anti-EGFR therapy (if RAS wild-type)
Dose is based on trifluridine component rounded to the nearest 5-mg increment
35 mg/m² PO BID on Days 1-5 and Days 8-12 of each 28-day cycle; not to exceed 80 mg/dose
Continue until disease progression or unacceptable toxicity
Metastatic Gastric Cancer or Gastroesophageal Junction Adenocarcinoma
Indicated for patients previously treated with ≥2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy
Dose is based on trifluridine component rounded to the nearest 5-mg increment
35 mg/m² PO BID on Days 1-5 and Days 8-12 of each 28-day cycle; not to exceed 80 mg/dose
Continue until disease progression or unacceptable toxicity
Dosage Modifications
Obtain CBC counts prior to and on Day 15 of each cycle
Do not initiate the cycle until
- ANC ≥1500/mm³ or febrile neutropenia is resolved
- Platelets ≥75,000/mm³
- Grade 3 or 4 nonhematological adverse reactions are resolved to Grade ≤1
Within a treatment cycle, withhold for any of the following
- ANC <500/mm³ or febrile neutropenia
- Platelets <50,000/mm³
- Grade 3 or 4 nonhematological adverse reactions
Resume drug after reducing dose by 5 mg/m²/dose from the previous dose level
- Febrile neutropenia
- Uncomplicated grade 4 neutropenia (which has recovered to ≥1500/mm³) or thrombocytopenia (which has recovered to ≥75,000/mm³) that results >1 week delay in start of next cycle
- Nonhematologic grade 3 or 4 adverse reaction, except for grade 3 nausea and/or vomiting controlled by antiemetic therapy or grade 3 diarrhea responsive to antidiarrheal medication
- A maximum of 3 dose reductions are permitted to a minimum dose 20mg/m² BID
- Do not escalate dose after it has been reduced
Hepatic impairment
- Mild (total bilirubin [TB] ≤ULN and AST >ULN, or TB <1-1.5x ULN and any AST): No dosage adjustment required
- Moderate-to-severe: Not studied
Renal impairment
- Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment required
- End-stage renal disease: Not studied
-
Severe
- CrCl 15-29 mL/min
- Decrease to 20 mg/m2 PO BID on days 1-5 and 8-12 of each 28-day cycle
- If unable to tolerate 15 mg/m2 PO BID on days 1-5 and 8-12 of each 28-day cycle
- Permanently discontinue if unable to tolerate 15 mg/m2 PO BID
Safety and efficacy not established
Adverse Effects
>10% (Metastatic Colorectal Cancer)
Anemia (77%)
Neutropenia (67%)
Asthenia/fatigue (52%)
Nausea (48%)
Thrombocytopenia (42%)
Decreased appetite (39%)
Neutropenia, Grade 3 or 4 (38%)
Diarrhea (32%)
Vomiting (28%)
Infections (27%)
Pyrexia (19%)
Anemia, Grade 3 or 4 (18%)
>10% (Metastatic Gastric Cancer)
Neutropenia (66%)
Anemia (63%)
Neutropenia, Grade 3 or 4 (38%)
Nausea (37%)
Decreased appetite (34%)
Thrombocytopenia (34%)
Vomiting (25%)
Diarrhea (23%)
Infections (23%)
Anemia, Grade 3 or 4 (19%)
1-10% (Metastatic Colorectal Cancer)
Stomatitis (8%)
Asthenia/fatigue, Grade 3 or 4 (7%)
Dysgeusia (7%)
Alopecia (7%)
Infections, Grade 3 or 4 (6%)
Thrombocytopenia, Grade 3 or 4 (5%)
Decreased appetite, Grade 3 or 4 (4%)
Diarrhea, Grade 3 or 4 (3%)
Nausea, Grade 3 or 4 (2%)
Vomiting, Grade 3 or 4 (2%)
Pyrexia, Grade 3 or 4 (1%)
1-10% (Metastatic Gastric Cancer)
Decreased appetite, Grade 3 or 4 (9%)
Thrombocytopenia, Grade 3 or 4 (6%)
Infections, Grade 3 or 4 (5%)
Vomiting, Grade 3 or 4 (4%)
Nausea, Grade 3 or 4 (3%)
Diarrhea, Grade 3 or 4 (3%)
<1%
Interstitial lung disease
Metastatic colorectal cancer
- Stomatitis, Grade 3 or 4
Warnings
Contraindications
None
Cautions
Severe and life-threatening myelosuppression reported, including anemia, neutropenia, thrombocytopenia, and febrile neutropenia; obtain CBC count prior to and on Day 15 of each cycle, or more frequently as indicated
Stomatitis may occur
Associated with a moderate emetic potential; antiemetics to prevent nausea and vomiting recommended; patient should report severe gastrointestinal toxicity to healthcare professional
Grade 3 or 4 bilirubin elevations reported in patients with hepatic impairment
Based on animal studies and its mechanism of action, trifluridine/tipiracil can cause fetal harm when administered to pregnant women (see Pregnancy)
Pregnancy
Pregnancy
Based on animal data and its mechanism of action, drug can cause fetal harm
Embryo-fetal lethality and embryo-fetal toxicity occurred in pregnant rats when given during gestation at doses resulting in exposures lower than or similar to human exposures at the recommended clinical dose
There are no available data use in pregnant women
Verify pregnancy status in females of reproductive potential before initiating treatment
Contraception
- Females of reproductive potential: Use effective contraception during treatment and for ≥6 months after final dose
- Males with female partners of reproductive potential: Use condoms during treatment and for ≥ 3 months after final dose
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
In nursing rats, trifluridine and tipiracil or their metabolites were present in breast milk
Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment and for 1 day following the final dose
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
Trifluridine: Thymidine-based nucleoside analog that incorporates into DNA, interferes with DNA synthesis, and inhibits cell proliferation
Tipiracil: Thymidine phosphorylase inhibitor; inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase
Absorption
Peak plasma time (trifluridine): 2 hr
Food effect
- A standardized high-fat, high-calorie meal decreased trifluridine peak plasma concentration, tipiracil peak plasma concentration and AUC by ~40%, but did not change trifluridine AUC compared to those in a fasting state in patients with cancer following single-dose administration
Distribution
Protein bound: >96% trifluridine (independent of drug concentration and presence of tipiracil); <8% tipiracil
Metabolism
Trifluridine and tipiracil are not metabolized by cytochrome P450 (CYP) enzymes
Trifluridine is mainly eliminated by metabolism via thymidine phosphorylase to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY)
Elimination
Half-life (steady-state): 2.1 hr trifluridine; 2.4 hr tipiracil
Urinary excretion: 1.5% unchanged trifluridine; 19.2% FTY; 29.3% unchanged tipiracil
Administration
Oral Administration
Dose is based on trifluridine component rounded to nearest 5-mg increment
Administer with food; swallow whole
Do not take additional doses to make up for missed or held doses
Cytotoxic drug; follow applicable special handling and disposal procedures
Storage
Store at controlled room temperature 20-25°C (68-77°F); excursions are permitted from 15-30°C (59-86°F)
If stored outside of original bottle, discard after 30 days
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Patient Handout
Formulary
Adding plans allows you to compare formulary status to other drugs in the same class.
To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.
Adding plans allows you to:
- View the formulary and any restrictions for each plan.
- Manage and view all your plans together – even plans in different states.
- Compare formulary status to other drugs in the same class.
- Access your plan list on any device – mobile or desktop.
