Tipiracil and trifluridine

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 ever had:

• kidney disease;

• liver disease; or

• if you are pregnant or may become pregnant.

Tipiracil and trifluridine can harm an unborn baby. Use effective birth control to prevent pregnancy while you are using this medicine, whether you are a man or a woman. Men should use condoms. The use of tipiracil and trifluridine by either parent may cause birth defects.

If you are a man, keep using condoms for at least 3 months after your last dose. Tell your doctor right away if a pregnancy occurs while either the mother or the father is using tipiracil and trifluridine.

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.

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 should be taken 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.

If you do not store this medicine in the original container, you will need to throw away any unused tablets after 30 days.

Applies to tipiracil / trifluridine: oral tablet

Hematologic

Very common (10% or more): Anemia (77%), neutropenia (67%), thrombocytopenia (42%)
Common (1% to 10%): Febrile neutropenia[Ref]

Other

Very common (10% or more): Asthenia/fatigue (52%), infections (27%), pyrexia (19%)[Ref]

Gastrointestinal

Very common (10% or more): Nausea (48%), diarrhea (32%), vomiting (28%), abdominal pain (21%)
Common (1% to 10%): Stomatitis (8%)[Ref]

General

3.6% of patients discontinued treatment for an adverse event; 13.7% required a dose reduction, most commonly for neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea.[Ref]

Respiratory

Common (1% to 10%): Nasopharyngitis, pulmonary emboli
Uncommon (0.1% to 1%): Interstitial lung disease[Ref]

Metabolic

Very common (10% or more): Decreased appetite (39%)[Ref]

Cardiovascular

Common (1% to 10%): QTc interval prolongation[Ref]

Nervous system

Common (1% to 10%): Dysgeusia[Ref]

Genitourinary

Common (1% to 10%): Urinary tract infections[Ref]

Dermatologic

Common (1% to 10%): Alopecia[Ref]

Some side effects of tipiracil / trifluridine may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

-Initial dose: 35 mg/m2 orally twice a day on Days 1 through 5 and Days 8 through 12 of each 28-day cycle (based on trifluridine component)
-Maximum dose: 80 mg per dose (based on trifluridine component)
-Duration of therapy: Until disease progression or unacceptable toxicity

Comments:
-Dose should be taken within 1 hour of completion of morning and evening meals.
-The dose should be rounded to the nearest 5 mg increment.
-Do not initiate a cycle of this drug until absolute neutrophil count (ANC) is 1,500/mm3 or greater or febrile neutropenia is resolved; platelets are 75,000/mm3 or greater; and Grade 3 or 4 non-hematological adverse reactions are resolved to Grade 0 or 1.

Use: Treatment of patients with metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and an anti-EGFR therapy (if RAS wild-type).

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Administration Advice:
-Additional doses should not be taken to make up for missed or held doses.
-Handling and disposal of this drug should be performed in a manner consistent with safe procedures for cytotoxic agents.

Storage Requirements:
-This drug should be discarded after 30 days if stored outside of original bottle.

General:
-This drug consists of trifluridine and tipiracil at a molar ratio of 1:0.5.
-There is no known antidote for overdosage with this drug; the highest dose administered in studies was 180 mg/m2 per day.

Monitoring:
-CBC prior to and on Day 15 of each cycle

Patient Advice:
-This drug is available in two strengths; you may receive both strength tablets to provide your prescribed dose.
-Patients and caregivers need to wear gloves or wash hands when handling this drug.