trifluridine/tipiracil (Rx)

Brand and Other Names:Lonsurf
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

trifluridine/tipiracil

tablet

  • 15mg/6.14mg
  • 20mg/8.19mg

Metastatic Colorectal Cancer

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

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

Continue until disease progression or unacceptable toxicity

Metastatic Gastric Cancer or Gastroesophageal Junction Adenocarcinoma

Indicated for patients previously treated with ≥2 prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted 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

Continue 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 ≤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 after reducing dose by 5 mg/m²/dose from the previous dose level

  • 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 <1-1.5x ULN 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
  • End-stage renal disease: Not studied
  • Severe
    • CrCl 15-29 mL/min
    • Decrease to 20 mg/m2 PO BID on days 1-5 and 8-12 of each 28-day cycle
    • If unable to tolerate 15 mg/m2 PO BID on days 1-5 and 8-12 of each 28-day cycle
    • Permanently discontinue if unable to tolerate 15 mg/m2 PO BID

Safety and efficacy not established

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Adverse Effects

>10% (Metastatic Colorectal Cancer)

Anemia (77%)

Neutropenia (67%)

Asthenia/fatigue (52%)

Nausea (48%)

Thrombocytopenia (42%)

Decreased appetite (39%)

Neutropenia, Grade 3 or 4 (38%)

Diarrhea (32%)

Vomiting (28%)

Infections (27%)

Pyrexia (19%)

Anemia, Grade 3 or 4 (18%)

>10% (Metastatic Gastric Cancer)

Neutropenia (66%)

Anemia (63%)

Neutropenia, Grade 3 or 4 (38%)

Nausea (37%)

Decreased appetite (34%)

Thrombocytopenia (34%)

Vomiting (25%)

Diarrhea (23%)

Infections (23%)

Anemia, Grade 3 or 4 (19%)

1-10% (Metastatic Colorectal Cancer)

Stomatitis (8%)

Asthenia/fatigue, Grade 3 or 4 (7%)

Dysgeusia (7%)

Alopecia (7%)

Infections, Grade 3 or 4 (6%)

Thrombocytopenia, Grade 3 or 4 (5%)

Decreased appetite, Grade 3 or 4 (4%)

Diarrhea, Grade 3 or 4 (3%)

Nausea, Grade 3 or 4 (2%)

Vomiting, Grade 3 or 4 (2%)

Pyrexia, Grade 3 or 4 (1%)

1-10% (Metastatic Gastric Cancer)

Decreased appetite, Grade 3 or 4 (9%)

Thrombocytopenia, Grade 3 or 4 (6%)

Infections, Grade 3 or 4 (5%)

Vomiting, Grade 3 or 4 (4%)

Nausea, Grade 3 or 4 (3%)

Diarrhea, Grade 3 or 4 (3%)

<1%

Interstitial lung disease

Metastatic colorectal cancer

  • Stomatitis, Grade 3 or 4
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Warnings

Contraindications

None

Cautions

Severe and life-threatening myelosuppression reported, including anemia, neutropenia, thrombocytopenia, and febrile neutropenia; obtain CBC count prior to and on Day 15 of each cycle, or more frequently as indicated

Stomatitis may occur

Associated with a moderate emetic potential; antiemetics to prevent nausea and vomiting recommended; patient should report severe gastrointestinal toxicity to healthcare professional

Grade 3 or 4 bilirubin elevations reported in patients with hepatic impairment

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

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Pregnancy

Pregnancy

Based on animal data and its mechanism of action, drug can cause fetal harm

Embryo-fetal lethality and embryo-fetal toxicity occurred in pregnant rats when given during gestation at doses resulting in exposures lower than or similar to human exposures at the recommended clinical dose

There are no available data use in pregnant women

Verify pregnancy status in females of reproductive potential before initiating treatment

Contraception

  • Females of reproductive potential: Use effective contraception during treatment and for ≥6 months after final dose
  • Males with female partners of reproductive potential: Use condoms during treatment and for ≥ 3 months after final dose

Lactation

There are no data on the presence of trifluridine, tipiracil or its metabolites in human milk or its effects on the breastfed child or on milk production

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

Because of the potential for serious adverse reactions in breastfed children, 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.

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Pharmacology

Mechanism of Action

Trifluridine: Thymidine-based nucleoside analog that incorporates into DNA, interferes with DNA synthesis, and inhibits cell proliferation

Tipiracil: Thymidine phosphorylase inhibitor; inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase

Absorption

Peak plasma time (trifluridine): 2 hr

Food effect

  • A standardized high-fat, high-calorie meal decreased trifluridine peak plasma concentration, tipiracil peak plasma concentration and AUC by ~40%, but did not change trifluridine AUC compared to those in a fasting state in patients with cancer following single-dose administration

Distribution

Protein bound: >96% trifluridine (independent of drug concentration and presence of tipiracil); <8% tipiracil

Metabolism

Trifluridine and tipiracil are not metabolized by cytochrome P450 (CYP) enzymes

Trifluridine is mainly eliminated by metabolism via thymidine phosphorylase to form an inactive metabolite, 5-(trifluoromethyl) uracil (FTY)

Elimination

Half-life (steady-state): 2.1 hr trifluridine; 2.4 hr tipiracil

Urinary excretion: 1.5% unchanged trifluridine; 19.2% FTY; 29.3% unchanged tipiracil

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Administration

Oral Administration

Dose is based on trifluridine component rounded to nearest 5-mg increment

Administer with food; swallow whole

Do not take additional doses to make up for missed or held doses

Cytotoxic drug; follow applicable special handling and disposal procedures

Storage

Store at controlled room temperature 20-25°C (68-77°F); excursions are permitted from 15-30°C (59-86°F)

If stored outside of original bottle, discard after 30 days

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Images

BRAND FORM. UNIT PRICE PILL IMAGE
Lonsurf oral
-
15-6.14 mg tablet
Lonsurf oral
-
20-8.19 mg tablet

Copyright © 2010 First DataBank, Inc.

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Patient Handout

Patient Education
trifluridine-tipiracil oral

TRIFLURIDINE/TIPIRACIL - ORAL

(trye-FLURE-i-deen/tye-PIR-a-sil)

COMMON BRAND NAME(S): Lonsurf

USES: This medication is used to treat certain cancers (such as stomach, colon/rectum). It works by slowing or stopping the growth of cancer cells.

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking this medication and each time you get a refill. If you have any questions, ask your doctor or pharmacist.This drug is not taken every day. On the days you are supposed to take this medication, take it by mouth as directed by your doctor, usually twice in one day. Take your dose within 1 hour after eating your morning and evening meals. Swallow the tablets whole. Do not crush or chew. Follow your doctor's directions exactly.The dosage is based on your body size, medical condition, and response to treatment. Do not increase your dose or use this drug more often or for longer than prescribed. Your condition will not improve any faster, and your risk of side effects will increase.Take this medication regularly to get the most benefit from it. To help you remember, take it at the same times on the days your doctor directs.If you vomit after taking a dose, do not take another dose at that time. Take your next dose at the regular time.Since this drug can be absorbed through the skin and lungs and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication or breathe the dust from the tablets. You and your caregiver should wear gloves when handling this medication. Wash your hands after handling the tablets.

SIDE EFFECTS: Nausea, diarrhea, vomiting, change in taste, or hair loss may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.People using this medication may have serious side effects. However, you have been prescribed this drug because your doctor has judged that the benefit to you is greater than the risk of side effects. Careful monitoring by your doctor may decrease your risk.This medication decreases bone marrow function, an effect that may lead to a low number of blood cells such as red cells, white cells, and platelets. This effect can cause anemia, decrease your body's ability to fight an infection, or cause easy bruising/bleeding. Tell your doctor right away if you develop any of the following symptoms: unusual tiredness, pale skin, signs of infection (such as sore throat that doesn't go away, fever, chills), easy bruising/bleeding.Get medical help right away if you have any very serious side effects, including: chest pain, trouble breathing.A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088 or at www.fda.gov/medwatch.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking trifluridine/tipiracil, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.Before using this medication, tell your doctor or pharmacist your medical history, especially of: kidney problems, liver problems.Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).This product can make you more likely to get infections or may worsen any current infections. Avoid contact with people who have infections that may spread to others (such as chickenpox, measles, flu). Consult your doctor if you have been exposed to an infection or for more details.Do not have immunizations/vaccinations without the consent of your doctor. Avoid contact with people who have recently received live vaccines (such as flu vaccine inhaled through the nose).To lower the chance of getting cut, bruised, or injured, use caution with sharp objects like razors and nail cutters, and avoid activities such as contact sports.Older adults may be more sensitive to the side effects of this drug, especially decreased bone marrow function.Tell your doctor if you are pregnant or plan to become pregnant. You should not become pregnant while using trifluridine/tipiracil. Trifluridine/tipiracil may harm an unborn baby. Your doctor should order a pregnancy test before you start this medication. Men and women using this medication should ask about reliable forms of birth control during treatment and for 6 months after stopping treatment. Men taking this medication should use condoms during sex with women who are pregnant or of childbearing age. Consult your doctor for more details. If you or your partner become pregnant, talk to your doctor right away about the risks and benefits of this medication.It is unknown if this medication passes into breast milk. Because of the possible risk to the infant, breast-feeding is not recommended while using this drug and for one day after the end of treatment. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

OVERDOSE: If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.Lab and/or medical tests (such as complete blood counts) must be done while you are taking this medication. Keep all medical and lab appointments. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, skip the missed dose. Take your next dose at the regular time. Do not double the dose to catch up.

STORAGE: Store at room temperature in its original bottle away from light and moisture. If stored outside of the original bottle, then throw away any unused tablets after 30 days. Do not store in the bathroom. Keep all medications away from children and pets.Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-888-633-4298 (US) or 1-800-668-1507 (Canada).

Information last revised August 2021. Copyright(c) 2021 First Databank, Inc.

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

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Formulary

FormularyPatient Discounts

Adding plans allows you to compare formulary status to other drugs in the same class.

To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

Adding plans allows you to:

  • View the formulary and any restrictions for each plan.
  • Manage and view all your plans together – even plans in different states.
  • Compare formulary status to other drugs in the same class.
  • Access your plan list on any device – mobile or desktop.

The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.