Tipiracil-trifluridine

Name: Tipiracil-trifluridine

Dosing & Uses

Dosage Forms & Strengths

tipiracil/trifluridine

tablet

  • 6.14mg/15mg
  • 8.19mg/20mg

Colorectal Cancer

Indicated for metastatic colorectal cancer in patients previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR 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

Administer within 1 hr of completion of morning and evening meals

Administer 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 0 or 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 with reduced dose

  • After recovery, resume drug after reducing the dose by 5 mg/m²/dose from the previous dose level, if the following occur
    • 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 <1-1.5 xULN 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; however, patients with moderate impairment (30-59 mL/min) may require dose modification for increased toxicity
  • Severe (CrCl <30 mL/min): Not studied

Gastric Cancer (Orphan)

Orphan designation for treatment of gastric cancer including cancer of the gastroesophageal junction

Sponsor

  • Taiho Oncology, Inc; 101 Carnegie Center, Suite 101; Princeton, New Jersey 08540

Safety and efficacy not established

Pregnancy

Pregnancy

Based on animal studies and its mechanism of action, trifluridine/tipiracil can cause fetal harm when administered to pregnant women

Caused embryo-fetal lethality and embryo-fetal toxicity in pregnant rats when orally administered during gestation at dose levels resulting in exposures lower than those achieved at the recommended dose of 35 mg/m² BID

Advise pregnant women of the potential risk to the fetus

Advise females of reproductive potential to use effective contraception during treatment

Lactation

Unknown if distributed in human breast milk

In nursing rats, trifluridine and tipiracil or their metabolites were present in breast milk

Because of the potential for serious adverse reactions in breastfeeding infants, 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.

Patient Handout

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What Is Tipiracil-trifluridine?

Tipiracil and trifluridine is a combination cancer medicine that interferes with the growth and spread of cancer cells in the body.

Tipiracil and trifluridine is used to treat colorectal cancer that has spread to other parts of the body (metastatic).

Tipiracil and trifluridine is usually given after other cancer medicines have been tried without success.

Tipiracil and trifluridine may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not use this medicine if you are allergic to tipiracil or trifluridine.

To make sure tipiracil and trifluridine is safe for you, tell your doctor if you have:

  • kidney disease; or
  • if you are pregnant or may become pregnant.

This medicine can harm an unborn baby or cause birth defects. Do not use if you are pregnant. Use effective birth control to prevent pregnancy while you are using this medicine.

If a man fathers a child while using tipiracil and trifluridine, the baby may have birth defects. Use a condom to prevent pregnancy during your treatment. Continue using condoms for at least 3 months after you stop receiving this medicine.

It is not known whether tipiracil and trifluridine passes into breast milk or if it could harm a nursing baby. You should not breast-feed while using this medicine, and for at least 24 hours after your last dose.

Tipiracil-trifluridine Interactions

Avoid being near people who are sick or have infections. Tell your doctor at once if you develop signs of infection.

This medicine can pass into body fluids (urine, feces, vomit). Caregivers should wear rubber gloves while cleaning up a patient's body fluids, handling contaminated trash or laundry or changing diapers. Wash hands before and after removing gloves. Wash soiled clothing and linens separately from other laundry.

Other drugs may interact with tipiracil and trifluridine, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Tipiracil-trifluridine Dosage

Before and during your treatment with tipiracil and trifluridine, you will need blood tests. The timing of these tests is very important. Do not miss any scheduled appointments.

Follow all directions on your prescription label. Do not use this medicine in larger or smaller amounts or for longer than recommended.

Tipiracil and trifluridine works best if you take it within 1 hour after your morning and evening meals.

Tipiracil and trifluridine is given in a 28-day treatment cycle. You may need to use the medicine only on certain days of each cycle. Your doctor will determine how long to treat you with this medicine.

Wash your hands after handling tipiracil and trifluridine tablets.

Caregivers who touch or handle the tablets should wear rubber gloves.

To get the correct dose, you may need to take 2 or more tablets that are different strengths and colors. Follow your doctor's dosing instructions very carefully.

Tipiracil and trifluridine can lower blood cells that help your body fight infections and help your blood to clot. Your blood will need to be tested often. Your cancer treatments may be delayed based on the results of these tests.

Store tablets in their original container at room temperature, away from moisture and heat.

Do not put tipiracil and trifluridine tablets into a daily pill box. If you do not store this medicine in the original container, you will need to throw away any unused tablets after 30 days.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

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