tri-FLOO-ri-deen/ti-PEER-a-sil

Therapeutic Classification: antineoplastics

Pharmacologic Classification:

• 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.

• 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.

• Decreases spread of metastatic colorectal cancer.

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.

(improved survival)

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.

CNS: asthenia.

Derm: alopecia.

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

Hemat: anemia, neutropenia, THROMBOCYTOPENIA.

Misc: fever.

Drug-Drug:

• None noted.

• 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.

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

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

• 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.

• 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.

• 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.

• Decreases spread of metastatic colorectal cancer.

Lonsurf

• Risk for infection (Adverse Reactions).

NDC Code^*

• 64842- Taiho Pharmaceutical Co., Ltd.
  • 64842-1020- LONSURF
    • 64842-1020-1- 20 TABLET, FILM COATED in 1 BOTTLE (64842-1020-1)

• 64842- Taiho Pharmaceutical Co., Ltd.
  • 64842-1020- LONSURF
    • 64842-1020-2- 40 TABLET, FILM COATED in 1 BOTTLE (64842-1020-2)

• 64842- Taiho Pharmaceutical Co., Ltd.
  • 64842-1020- LONSURF
    • 64842-1020-3- 60 TABLET, FILM COATED in 1 BOTTLE (64842-1020-3)

• 64842- Taiho Pharmaceutical Co., Ltd.
  • 64842-1025- LONSURF
    • 64842-1025-1- 20 TABLET, FILM COATED in 1 BOTTLE (64842-1025-1)

• 64842- Taiho Pharmaceutical Co., Ltd.
  • 64842-1025- LONSURF
    • 64842-1025-2- 40 TABLET, FILM COATED in 1 BOTTLE (64842-1025-2)

• 64842- Taiho Pharmaceutical Co., Ltd.
  • 64842-1025- LONSURF
    • 64842-1025-3- 60 TABLET, FILM COATED in 1 BOTTLE (64842-1025-3)