Trifluridine and tipiracil

Trifluridine and tipiracil
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Allison Tu [2]

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Overview

Trifluridine and tipiracil is a combination of a nucleoside metabolic inhibitor and a thymidine phosphorylase inhibitor that is FDA approved for the 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 if RAS wild-type, an anti-EGFR therapy. Common adverse reactions include fatigue, nausea, diarrhea, decreased appetite, abdominal pain, anemia, neutropenia, thrombocytopenia, weakness, and fever.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

LONSURF is indicated for the 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 if RAS wild-type, an anti-EGFR therapy.

Dosing Information

• The recommended starting dose of LONSURF is 35 mg/m2 up to a maximum of 80 mg per dose (based on the trifluridine component) orally twice daily within one hour of completion of morning and evening meals on Days 1 through 5 and Days 8 through 12 of each 28-day cycle until disease progression or unacceptable toxicity.
• Round dose to the nearest 5 mg increment.
• Do not take additional doses to make up for missed or held doses.
• Do not initiate the cycle of LONSURF until:
  • Absolute neutrophil count (ANC) is greater than or equal to 1,500/mm3 or febrile neutropenia is resolved
  • Platelets are greater than or equal to 75,000/mm3
  • Grade 3 or 4 non-hematological adverse reactions are resolved to Grade 0 or 1
• Within a treatment cycle, withhold LONSURF for any of the following:
  • Absolute neutrophil count (ANC) less than 500/mm3 or febrile neutropenia
  • Platelets less than 50,000/mm3
  • Grade 3 or 4 non-hematological adverse reactions
• After recovery, resume LONSURF 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 greater than or equal to 1,500/mm3) or thrombocytopenia (which has recovered to greater than or equal to 75,000/mm3) that results in more than 1 week delay in start of next cycle
  • Non-hematologic Grade 3 or Grade 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 of 20 mg/m2 twice daily. Do not escalate LONSURF dose after it has been reduced.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Trifluridine and tipiracil in adult patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Trifluridine and tipiracil in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Trifluridine and tipiracil FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information regarding Off-Label Guideline-Supported Use of Trifluridine and tipiracil in pediatric patients.

Non–Guideline-Supported Use

There is limited information regarding Off-Label Non–Guideline-Supported Use of Trifluridine and tipiracil in pediatric patients.

Contraindications

There is limited information regarding Trifluridine and tipiracil Contraindications in the drug label.

Warnings

• Severe Myelosuppression
  • In Study 1, LONSURF caused severe and life-threatening myelosuppression (Grade 3-4) consisting of anemia (18%), neutropenia (38%), thrombocytopenia (5%) and febrile neutropenia (3.8%). One patient (0.2%) died due to neutropenic infection. In Study 1, 9.4% of LONSURF-treated patients received granulocyte-colony stimulating factors.
  • Obtain complete blood counts prior to and on Day 15 of each cycle of LONSURF and more frequently as clinically indicated. Withhold LONSURF for febrile neutropenia, Grade 4 neutropenia, or platelets less than 50,000/mm3. Upon recovery resume LONSURF at a reduced dose.
• Embryo-Fetal Toxicity
  • Based on animal studies and its mechanism of action, LONSURF can cause fetal harm when administered to a pregnant woman. Trifluridine/tipiracil 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 twice daily.
  • Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with LONSURF.

Adverse Reactions

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The data described below are from Study 1, a randomized (2:1), double-blind, placebo-controlled trial in which 533 patients (median age 63 years; 61% men; 57% White, 35% Asian, 1% Black) with previously treated metastatic colorectal cancer received LONSURF as a single agent at a dose of 35 mg/m2/dose administered twice daily on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. The mean duration of LONSURF therapy was 12.7 weeks.

The most common adverse drug reactions or laboratory abnormalities (all Grades and greater than or equal to 10% in incidence) in patients treated with LONSURF at a rate that exceeds the rate in patients receiving placebo were anemia, neutropenia, asthenia/fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, and pyrexia.

In Study 1, 3.6% of patients discontinued LONSURF for an adverse event and 13.7% of patients required a dose reduction. The most common adverse reactions leading to dose reduction were neutropenia, anemia, febrile neutropenia, fatigue, and diarrhea.

This image is provided by the National Library of Medicine

This image is provided by the National Library of Medicine

In Study 1, infections occurred more frequently in LONSURF-treated patients (27%) compared to those receiving placebo (15%). The most commonly reported infections which occurred more frequently in LONSURF-treated patients were nasopharyngitis (4% versus 2%), and urinary tract infections (4% versus 2%).

In Study 1, pulmonary emboli occurred more frequently in LONSURF-treated patients (2%) compared to no patients on placebo.

Additional Clinical Experience:

Interstitial lung disease was reported in fifteen (0.2%) patients, three of which were fatal, among approximately 7,000 patients exposed to LONSURF in clinical studies and clinical practice settings in Asia.

Postmarketing Experience

There is limited information regarding Trifluridine and tipiracil Postmarketing Experience in the drug label.

Drug Interactions

There is limited information regarding Trifluridine and tipiracil Drug Interactions in the drug label.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Trifluridine and tipiracil in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Trifluridine and tipiracil in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Trifluridine and tipiracil during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Trifluridine and tipiracil in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Trifluridine and tipiracil in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Trifluridine and tipiracil in geriatric settings.

Gender

There is no FDA guidance on the use of Trifluridine and tipiracil with respect to specific gender populations.

Race

There is no FDA guidance on the use of Trifluridine and tipiracil with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Trifluridine and tipiracil in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Trifluridine and tipiracil in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Trifluridine and tipiracil in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Trifluridine and tipiracil in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Trifluridine and tipiracil Administration in the drug label.

Monitoring

There is limited information regarding Trifluridine and tipiracil Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Trifluridine and tipiracil and IV administrations.

Overdosage

There is limited information regarding Trifluridine and tipiracil overdosage. If you suspect drug poisoning or overdose, please contact the National Poison Help hotline (1-800-222-1222) immediately.

Pharmacology

There is limited information regarding Trifluridine and tipiracil Pharmacology in the drug label.

Mechanism of Action

There is limited information regarding Trifluridine and tipiracil Mechanism of Action in the drug label.

Structure

There is limited information regarding Trifluridine and tipiracil Structure in the drug label.

Pharmacodynamics

There is limited information regarding Trifluridine and tipiracil Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Trifluridine and tipiracil Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Trifluridine and tipiracil Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Trifluridine and tipiracil Clinical Studies in the drug label.

How Supplied

There is limited information regarding Trifluridine and tipiracil How Supplied in the drug label.

Storage

There is limited information regarding Trifluridine and tipiracil Storage in the drug label.

Images

Drug Images

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Patient Counseling Information

There is limited information regarding Trifluridine and tipiracil Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Trifluridine and tipiracil interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Trifluridine and tipiracil Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Trifluridine and tipiracil Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.