trifluridine/tipiracil

REMS

Metastatic colorectal cancer in patients previously treated with fluoropyrmidine-, oxalplatin- or irinotecan-based chemotherapies, an anti-VEGF based biological and an anti-EGFR agent (if RAS wild-type positive).
Metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with ≥2 lines of chemotherapy including a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, a HER2/neu-targeted therapy.

Action ⬆ ⬇

Trifluridine—following uptake into cells, interferes with DNA synthesis, inhibiting cell proliferation.
tipiracil—increases trifluridine levels by inhibiting thymidine phosphorylase, the enzyme that metabolizes it.

Therapeutic effects:

Decreases spread of metastatic colorectal cancer.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: Trifluridine—>96%.

Metabolism/Excretion: Trifluridine is metabolized by thymidine phosphorylase to an inactive metabolite. Trifluridine—1.5% excreted unchanged in urine; tipiracil—29.3% excreted unchanged in urine.

Half-Life: Trifluridine—2.1 hr; tipiracil—2.4 hr.

Time/Action Profile ⬆ ⬇

(improved survival)

ROUTE	ONSET	PEAK	DURATION
PO	1–2 mo	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Initial ANC <1500/mm³ or platelets <75,000/mm³, resolution of grade 3 or 4 non-hematologic toxicity to grade 0 or 1;
During treatment ANC<500 mm³ or febrile neutropenia, platelets <50,000/mm³ or grade 3 or 4 non-hematologic toxicity;
Moderate to severe hepatic impairment;
OB: Pregnancy (may cause fetal harm);
Lactation: Avoid breast feeding.

Use Cautiously in:

Severe renal impairment (effects of drug are not known);
Moderate renal impairment (↑ risk of toxicity, dose alteration may be required;
Rep: Women of reproductive potential or men with female partners of reproductive potential (use effective contraception);
Geri: risk and severity of myelosuppression in patients 65 yr.

Adv. Reactions/Side Effects ⬆ ⬇

CNS: asthenia

Derm: alopecia

GI: abdominal pain, ↓appetite, diarrhea, nausea, vomiting, stomatitis

Hemat: anemia, neutropenia, THROMBOCYTOPENIA

Misc: fever

Interactions ⬆ ⬇

Drug-drug:

None noted.

Route/Dosage ⬆ ⬇

PO (Adults ): 35 mg/m²/dose (max dose = 80 mg) (based on trifluridine content rounded to the nearest 5 mg) twice daily on days 1–5 and 8–12 of each 28–day cycle; continue until disease progression or unacceptable toxicity.

Availability ⬆ ⬇

Tablets: trifluridine 15 mg/tipiracil 6.14 mg; trifluridine 20 mg/tipiracil 8.19 mg

Assessment ⬆ ⬇

Monitor for signs and symptoms of infection (fever, chills, body aches) periodically during therapy.

Lab Test Considerations:

Obtain a negative pregnancy test before starting therapy.Obtain CBC prior to and on Day 15 of each cycle and as clinically indicated. Do not administer until: absolute neutrophil count (ANC) ≥1500/mm³ or febrile neutropenia resolved, platelet count ≥75,000/mm³, and Grade 3 or 4 non-hematologic adverse reactions are resolved to Grade 0–1. During treatment cycle, withhold trifluridine/tipiracil if: ANC <500/mm³ or febrile neutropenia, platelets <50,000/mm³, or Grade 3 or 4 non-hematologic adverse reactions occur. After recovery, reduce dose by 5 mg/m²/dose from previous dose level if: febrile neutropenia —uncomplicated Grade 4 neutropenia recovered to ≥1500/mm³ or thrombocytopenia —recovered to ≥75,000/mm³ resulting in >1 wk delay in start of next cycle or 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 occur. No more than 3 dose reductions to a minimum dose of 20 mg/m² twice daily are permitted. Do not escalate dose after reductions.

Implementation ⬆ ⬇

PO: Administer twice daily within 1 hr of completion of morning and evening meals on Days 1–5 and Days 8–12 of each 28 day cycle. Swallow tablets whole; do not crush, break, or chew.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. If dose missed or vomited, omit and take next dose at scheduled time; do not double doses. Inform patient that medication comes in two strengths; both strengths may be required for prescribed dose. Advise patient to read Patient Information before starting and with each Rx refill in case of changes.
Advise patient that anyone who handles medication should wear gloves. Wash hands after handling medication.
Advise patient to notify health care professional if signs and symptoms of infection, or persistent nausea, vomiting, or diarrhea occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: Caution patient that medication is teratogenic. Advise females of reproductive potential to use effective contraception during therapy and for 6 mo after last dose, and to notify health care professional if pregnancy is planned or suspected. Advise female patient to avoid breast feeding during and for at least 1 day after last dose of therapy. Advise male patients with female partners of reproductive potential to wear condoms during and for at least 3 mo after last dose of therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇