Trifluridine and tipiracil: Drug information

(For additional information see "Trifluridine and tipiracil: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

Brand Names: US

Lonsurf

Brand Names: Canada

Lonsurf

Pharmacologic Category

Antineoplastic Agent, Antimetabolite;
Antineoplastic Agent, Antimetabolite (Pyrimidine Analog);
Thymidine Phosphorylase Inhibitor

Dosing: Adult

Note: The manufacturer recommends rounding each dose to the nearest 5 mg increment. Obtain blood counts prior to starting each cycle and on day 15 of each cycle. Do not initiate a cycle until ANC ≥1,500/mm³ or febrile neutropenia is resolved, platelets are ≥75,000/mm³, and/or grade 3 or 4 nonhematologic reactions are ≤ grade 1. Trifluridine/tipiracil is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).

Colorectal cancer, metastatic

Colorectal cancer, metastatic:

Colorectal cancer, metastatic (single-agent therapy): Oral: 35 mg/m²/dose (based on the trifluridine component) twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle (maximum per dose: trifluridine 80 mg); continue until disease progression or unacceptable toxicity (Ref).

Colorectal cancer, metastatic (combination therapy): Oral: 35 mg/m²/dose (based on the trifluridine component) twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle (in combination with bevacizumab; maximum per dose: trifluridine 80 mg); continue until disease progression or unacceptable toxicity (Ref).

Note: Refer to specific protocol or to bevacizumab monograph for bevacizumab dosing when used in combination with trifluridine/tipiracil.

**Recommended Trifluridine/Tipiracil Metastatic Colorectal Cancer Dosage^a According to BSA**
BSA	Dose^a administered twice daily	Total daily dose^a
35 mg/m²/dose^a twice daily:
^a Total daily dose (in mg) and dose (in mg) based on the trifluridine component.
<1.07 m²	35 mg	70 mg
1.07 to 1.22 m²	40 mg	80 mg
1.23 to 1.37 m²	45 mg	90 mg
1.38 to 1.52 m2	50 mg	100 mg
1.53 to 1.68 m²	55 mg	110 mg
1.69 to 1.83 m²	60 mg	120 mg
1.84 to 1.98 m²	65 mg	130 mg
1.99 to 2.14 m²	70 mg	140 mg
2.15 to 2.29 m²	75 mg	150 mg
≥2.3 m²	80 mg	160 mg

Off-label combination/dosing: Oral: 35 mg/m²/dose (based on the trifluridine component) twice daily on days 1 to 5 every 2 weeks (in combination with bevacizumab); continue until disease progression or unacceptable toxicity (Ref).

Gastric cancer, metastatic

Gastric cancer, metastatic: Oral: 35 mg/m²/dose (based on the trifluridine component) twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle (maximum per dose: trifluridine 80 mg); continue until disease progression or unacceptable toxicity (Ref).

**Recommended Trifluridine/Tipiracil Metastatic Gastric Cancer Dosage^a According to BSA**
BSA	Dose^a administered twice daily	Total daily dose^a
35 mg/m²/dose^a twice daily:
^a Total daily dose (in mg) and dose (in mg) based on the trifluridine component.
<1.07 m²	35 mg	70 mg
1.07 to 1.22 m²	40 mg	80 mg
1.23 to 1.37 m²	45 mg	90 mg
1.38 to 1.52 m²	50 mg	100 mg
1.53 to 1.68 m²	55 mg	110 mg
1.69 to 1.83 m²	60 mg	120 mg
1.84 to 1.98 m²	65 mg	130 mg
1.99 to 2.14 m²	70 mg	140 mg
2.15 to 2.29 m²	75 mg	150 mg
≥2.3 m²	80 mg	160 mg

Missed dose: Do not re-administer doses that are missed or vomited; continue with the next scheduled dose.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

Kidney function may be estimated by the Cockcroft-Gault equation.

CrCl ≥30 mL/minute: No initial dosage adjustment is necessary.

CrCl 15 to 29 mL/minute: 20 mg/m²/dose (based on the trifluridine component) twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle.

If unable to tolerate 20 mg/m²/dose: Further reduce the dose to 15 mg/m²/dose(based on the trifluridine component) twice daily on days 1 to 5 and days 8 to 12 of a 28-day cycle.

If unable to tolerate 15 mg/m²/dose: Permanently discontinue trifluridine/tipiracil.

CrCl <15 mL/minute and end-stage kidney disease: There are no dosage adjustments provided in the manufacturer's labeling (has not been studied).

**Recommended Trifluridine/Tipiracil Dosage^a for Altered Kidney Function According to BSA**
BSA	Dose^a administered twice daily	Total daily dose^a
^a Total daily dose (in mg) and dose (mg) based on the trifluridine component.
20 mg/m²/dose^a twice daily:
<1.14 m²	20 mg	40 mg
1.14 to 1.34 m²	25 mg	50 mg
1.35 to 1.59 m²	30 mg	60 mg
1.6 to 1.94 m²	35 mg	70 mg
1.95 to 2.09 m²	40 mg	80 mg
2.1 to 2.34 m²	45 mg	90 mg
≥2.35 m²	50 mg	100 mg
15 mg/m²/dose^a twice daily:
<1.15 m²	15 mg	30 mg
1.15 to 1.49 m²	20 mg	40 mg
1.5 to 1.84 m²	25 mg	50 mg
1.85 to 2.09 m²	30 mg	60 mg
2.1 to 2.34 m²	35 mg	70 mg
≥2.35 m²	40 mg	80 mg

Dosing: Hepatic Impairment: Adult

Mild impairment (total bilirubin ≤ ULN and AST >ULN or total bilirubin <1 to 1.5 times ULN and any AST): No dosage adjustment necessary.

Moderate impairment (total bilirubin >1.5 to 3 times ULN and any AST) or severe impairment (total bilirubin >3 times ULN and any AST): Do not initiate therapy.

Dosing: Obesity: Adult

American Society of Clinical Oncology guidelines for appropriate systemic therapy dosing in adults with cancer with a BMI ≥30 kg/m² : Utilize patient's actual body weight for calculation of BSA- or weight-based dosing; manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m² (Ref). Note: According to the prescribing information, if a dose is reduced due to toxicity, do not re-escalate the dose.

Dosing: Adjustment for Toxicity: Adult

A maximum of 3 dose reductions are allowed (to a minimum dose of 20 mg/m²/dose); permanently discontinue in patients unable to tolerate 20 mg/m²/dose. Do not re-escalate dose after it has been reduced. Other concomitant combination therapy medications may also require treatment interruption, dosage reduction, and/or discontinuation.

Hematologic toxicity:

ANC <500/mm³ (uncomplicated or resulting in >1 week delay in the start of the next cycle) or febrile neutropenia: Interrupt therapy; following recovery to ANC ≥1,500/mm³ or resolution of febrile neutropenia, may resume therapy with the dose reduced by 5 mg/m²/dose from the previous dose. May require WBC growth factor support.

Platelets <50,000/mm³ (or resulting in >1 week delay in the start of the next cycle): Interrupt therapy; following recovery to platelets ≥75,000/mm³, may resume therapy with the dose reduced by 5 mg/m²/dose from the previous dose.

Nonhematologic toxicity: Grade 3 or 4 toxicity: Interrupt therapy until recovery to ≤ grade 1; following recovery, may resume with the dose reduced by 5 mg/m²/dose from the previous dose (excludes dose reduction for grade 3 nausea and/or vomiting controlled by antiemetic therapy or grade 3 diarrhea responsive to antidiarrheal treatment).

Dosing: Older Adult

Refer to adult dosing.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults administered monotherapy.

>10%:

Gastrointestinal: Abdominal pain (21%), decreased appetite (34% to 39%), diarrhea (23% to 32%; grades 3/4: 3%), nausea (37% to 48%; grades 3/4: 2%), vomiting (25% to 28%; grades 3/4: 2% to 4%)

Hematologic & oncologic: Anemia (63% to 77%; grades 3/4: 17% to 19%), neutropenia (66% to 67%; grades 3/4: 38%;), thrombocytopenia (34% to 42%; grades 3/4: 4% to 6%)

Infection: Infection (23% to 27%)

Nervous system: Asthenia (≤52%), fatigue (≤52%)

Miscellaneous: Fever (19%)

1% to 10%:

Cardiovascular: Pulmonary embolism (2% to 3%)

Dermatologic: Alopecia (7%)

Gastrointestinal: Dysgeusia (7%), stomatitis (8%; grades 3/4: <1%)

Hematologic & oncologic: Febrile neutropenia (grades 3/4: 3%)

<1%: Respiratory: Interstitial lung disease

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Additional contraindication (not in the US labeling): Hypersensitivity to trifluridine, tipiracil, or any component of the formulation.

Warnings/Precautions

Concerns related to adverse effects:

• Bone marrow suppression: Severe and life-threatening (grade 3 or 4) bone marrow suppression (anemia, neutropenia, thrombocytopenia) has occurred with single-agent therapy and in combination with bevacizumab, including fatalities (rare) related to neutropenic infection, sepsis, or septic shock. In clinical trials, slightly over 10% of patients and ~30% of patients with single-agent and combination treatment, respectively, received growth factor support.

• Gastrointestinal toxicity: Nausea, vomiting, diarrhea, and abdominal pain have been commonly reported. Stomatitis may also occur. Advise patients to report severe gastrointestinal toxicity to their health care provider.

Disease-related concerns:

• Hepatic impairment: Patients with severe hepatic impairment (total bilirubin >3 times ULN and any AST) were not included in studies. In a pharmacokinetic study in patients with hepatic impairment, several patients with moderate impairment (total bilirubin >1.5 to 3 times ULN and any AST) experienced grade 3 or 4 bilirubin elevations.

Special populations:

• Older age: Patients ≥65 years of age experienced a higher incidence of grade 3 and grade 4 neutropenia and thrombocytopenia with single-agent and combination therapy, as well as increased grade 3 anemia with single-agent therapy, compared to patients <65 years of age.

Dosage form specific issues:

• Tablet strength: Trifluridine/tipiracil is available in two tablet strengths (trifluridine 15 mg/tipiracil 6.14 mg and trifluridine 20 mg/tipiracil 8.19 mg); both tablet strengths may be necessary to provide the correct dose. Read labels carefully in order to ensure the appropriate dose is administered. Dosing is based on the trifluridine component. The manufacturer recommends rounding doses to the nearest 5 mg increment.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Lonsurf: Trifluridine 15 mg and tipiracil 6.14 mg, Trifluridine 20 mg and tipiracil 8.19 mg

Generic Equivalent Available: US

Pricing: US

Tablets (Lonsurf Oral)

15-6.14 mg (per each): $249.19

20-8.19 mg (per each): $332.25

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Lonsurf: Trifluridine 15 mg and tipiracil 6.14 mg, Trifluridine 20 mg and tipiracil 8.19 mg

Administration: Adult

Trifluridine/tipiracil is associated with a moderate or high emetic potential; antiemetics are recommended to prevent nausea and vomiting (Ref).

Oral: Administer with food. Swallow tablets whole.

Hazardous Drugs Handling Considerations

Hazardous agent (NIOSH 2016 [group 1]).

Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).

Use: Labeled Indications

Colorectal cancer, metastatic: Treatment of metastatic colorectal cancer, as a single agent or in combination with bevacizumab, in adults previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and if RAS wild-type, an anti-EGFR therapy.

Gastric cancer, metastatic: Treatment of metastatic gastric or gastroesophageal junction adenocarcinoma in adults previously treated with at least two prior lines of chemotherapy which included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

Medication Safety Issues

Sound-alike/look-alike issues:

Trifluridine may be confused with trifluoperazine.

High alert medication:

This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its lists of drug classes which have a heightened risk of causing significant patient harm when used in error.

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Antithymocyte Globulin (Equine): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of cytotoxic chemotherapy is reduced. Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy

Baricitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination

BCG Products: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination

Brincidofovir: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy

Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Chikungunya Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy

Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination

Cladribine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor therapy

Coccidioides immitis Skin Test: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing cytotoxic chemotherapy several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification

COVID-19 Vaccine (Adenovirus Vector): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification

COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy

COVID-19 Vaccine (mRNA): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider therapy modification

COVID-19 Vaccine (Subunit): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy

COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider therapy modification

Dengue Tetravalent Vaccine (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination

Denosumab: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and cytotoxic chemotherapy. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider therapy modification

Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination

Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination

Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Inebilizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy

Influenza Virus Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating chemotherapy if possible. If vaccination occurs less than 2 weeks prior to or during chemotherapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider therapy modification

Leflunomide: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents, such as cytotoxic chemotherapy. Risk D: Consider therapy modification

Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination

Nadofaragene Firadenovec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination

Natalizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination

Ocrelizumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy

Ofatumumab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy

Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy

Pidotimod: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy

Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Pneumococcal Vaccines: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy

Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination

Polymethylmethacrylate: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy

Rabies Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider therapy modification

Ritlecitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination

Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider therapy modification

Ruxolitinib (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination

Sipuleucel-T: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants, such as cytotoxic chemotherapy, prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification

Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk C: Monitor therapy

Tacrolimus (Topical): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination

Talimogene Laherparepvec: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination

Tertomotide: Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination

Tofacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination

Typhoid Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination

Ublituximab: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy

Upadacitinib: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination

Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of chemotherapy when possible. Patients vaccinated less than 14 days before initiating or during chemotherapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider therapy modification

Vaccines (Live): Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Vaccines (Live) may diminish the therapeutic effect of Immunosuppressants (Cytotoxic Chemotherapy). Risk X: Avoid combination

Yellow Fever Vaccine: Immunosuppressants (Cytotoxic Chemotherapy) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Cytotoxic Chemotherapy) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination

Reproductive Considerations

Verify pregnancy status prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should use effective contraception during therapy and for at least 6 months after the final trifluridine and tipiracil dose. Patients with partners who could become pregnant should use condoms during therapy and for at least 3 months following the final dose.

Pregnancy Considerations

Based on the mechanism of action and data from animal reproduction studies, in utero exposure to trifluridine/tipiracil may cause fetal harm.

Breastfeeding Considerations

It is not known if trifluridine or tipiracil are present in breast milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during therapy and for one day following the last trifluridine/tipiracil dose.

Monitoring Parameters

CBCs prior to each cycle and on day 15 of each cycle (or more frequently if clinically necessary); liver and renal function tests. Verify pregnancy status prior to treatment in patients who could become pregnant. Monitor for signs/symptoms of GI toxicity. Monitor adherence.

The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.

Mechanism of Action

Trifluridine, the active cytotoxic component of trifluridine/tipiracil, is a thymidine-based nucleic acid analogue; the triphosphate form of trifluridine is incorporated into DNA which interferes with DNA synthesis and inhibits cell proliferation. Tipiracil is a potent thymidine phosphorylase inhibitor which prevents the rapid degradation of trifluridine, allowing for increased trifluridine exposure (Mayer 2015).

Pharmacokinetics (Adult Data Unless Noted)

Protein binding: Trifluridine: >96% (primarily to albumin); Tipiracil: <8%

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)

Half-life elimination: Trifluridine: 2.1 hours (at steady state); Tipiracil: 2.4 hours (at steady state)

Time to peak, plasma: ~2 hours

Excretion:

Trifluridine: Urine (55% [as inactive metabolite FTY and trifluridine glucuronide isomers]; <3% [as unchanged drug]); feces (<3% [as unchanged drug]); expired air (<3%)

Tipiracil: Urine (27% [as tipiracil and 6-HMU]); feces (50% [as tipiracil and 6-HMU])

Pharmacokinetics: Additional Considerations (Adult Data Unless Noted)

Altered kidney function: In a study of patients who received a trifluridine/tipiracil dose of 35 mg/m²/dose twice daily (except patients with CrCl 15 to 29 mL/minute who received a dose of 20 mg/m²/dose twice daily), the steady-state AUC_0-last of trifluridine was 56% and 140% higher in patients with CrCl 30 to 59 mL/minute and CrCl 15 to 29 mL/minute, respectively, as compared to patients with normal kidney function. The steady-state AUC_0-last of tipiracil was 139% and 614% higher in patients with CrCl 30 to 59 mL/minute and CrCl 15 to 29 mL/minute, respectively, as compared to patients with normal kidney function.

Hepatic function impairment: In a pharmacokinetic study of patients with hepatic impairment, grade 3 or 4 bilirubin elevations were seen in patients with moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment (compared to patients with normal hepatic function). No clinically important differences in mean exposures were noted.

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AE) United Arab Emirates: Lonsurf;
(AR) Argentina: Flonurise | Friracil | Limustac | Lonsurf | Suprol | Temaste | Terfun;
(AT) Austria: Lonsurf;
(BE) Belgium: Lonsurf;
(BG) Bulgaria: Lonsurf;
(BR) Brazil: Lonsurf;
(CH) Switzerland: Lonsurf;
(CN) China: Lonsurf | Trifluridine and Tipiracil Hydrochloride;
(CZ) Czech Republic: Lonsurf;
(DE) Germany: Lonsurf;
(EE) Estonia: Lonsurf;
(EG) Egypt: Lonsurf;
(ES) Spain: Lonsurf;
(FI) Finland: Lonsurf;
(FR) France: Lonsurf;
(GB) United Kingdom: Lonsurf;
(GR) Greece: Lonsurf;
(HK) Hong Kong: Lonsurf;
(HR) Croatia: Lonsurf;
(HU) Hungary: Lonsurf;
(IE) Ireland: Lonsurf;
(IN) India: Tipanat;
(IT) Italy: Lonsurf;
(JO) Jordan: Lonsurf;
(KR) Korea, Republic of: Lonsurf;
(KW) Kuwait: Lonsurf;
(LB) Lebanon: Lonsurf;
(LT) Lithuania: Lonsurf;
(LV) Latvia: Lonsurf;
(MY) Malaysia: Lonsurf;
(NL) Netherlands: Lonsurf;
(NO) Norway: Lonsurf;
(NZ) New Zealand: Lonsurf;
(PK) Pakistan: Lonsurf;
(PL) Poland: Lonsurf;
(PT) Portugal: Lonsurf;
(QA) Qatar: Lonsurf;
(RO) Romania: Lonsurf;
(RU) Russian Federation: Lonsurf;
(SA) Saudi Arabia: Lonsurf;
(SE) Sweden: Lonsurf;
(SG) Singapore: Lonsurf;
(SI) Slovenia: Lonsurf;
(SK) Slovakia: Lonsurf;
(TH) Thailand: Lonsurf;
(TW) Taiwan: Lonsurf;
(UA) Ukraine: Lansurf

<800> Hazardous Drugs—Handling in Healthcare Settings. United States Pharmacopeia and National Formulary (USP 43-NF 38). Rockville, MD: United States Pharmacopeia Convention; 2020:74-92.
Griggs JJ, Bohlke K, Balaban EP, et al. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J Clin Oncol. 2021;39(18):2037-2048. doi:10.1200/JCO.21.00471 [PubMed 33939491]
Hesketh PJ, Kris MG, Basch E, et al. Antiemetics: ASCO guideline update. J Clin Oncol. 2020;38(24):2782-2797. doi:10.1200/JCO.20.01296 [PubMed 32658626]
Hwang JP, Feld JJ, Hammond SP, et al. Hepatitis B virus screening and management for patients with cancer prior to therapy: ASCO provisional clinical opinion update. J Clin Oncol. 2020;38(31):3698-3715. doi:10.1200/JCO.20.01757 [PubMed 32716741]
Lonsurf (trifluridine and tipiracil) [prescribing information]. Princeton, NJ: Taiho Oncology; August 2023.
Lonsurf (trifluridine and tipiracil) [product monograph]. Oakville, Ontario, Canada: Taiho Pharma Canada, Inc; October 2020.
Mayer RJ, Van Cutsem E, Falcone A, et al. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015;372(20):1909-1919. [PubMed 25970050]
Pfeiffer P, Yilmaz M, Möller S, et al. TAS-102 with or without bevacizumab in patients with chemorefractory metastatic colorectal cancer: an investigator-initiated, open-label, randomised, phase 2 trial. Lancet Oncol. 2020;21(3):412-420. doi:10.1016/S1470-2045(19)30827-7 [PubMed 31999946]
Prager GW, Taieb J, Fakih M, et al; SUNLIGHT Investigators. Trifluridine-tipiracil and bevacizumab in refractory metastatic colorectal cancer. N Engl J Med. 2023;388(18):1657-1667. doi:10.1056/NEJMoa2214963 [PubMed 37133585]
Refer to manufacturer's labeling.
Satake H, Kato T, Oba K, et al. Phase Ib/II study of biweekly TAS-102 in combination with bevacizumab for patients with metastatic colorectal cancer refractory to standard therapies (BiTS study). Oncologist. 2020;25(12):e1855-e1863. doi:10.1634/theoncologist.2020-0643 [PubMed 32666647]
Shitara K, Doi T, Dvorkin M, et al. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018;19(11):1437-1448. doi: 10.1016/S1470-2045(18)30739-3. [PubMed 30355453]
US Department of Health and Human Services; Centers for Disease Control and Prevention; National Institute for Occupational Safety and Health. NIOSH list of antineoplastic and other hazardous drugs in healthcare settings 2016. https://www.cdc.gov/niosh/docs/2016-161/. Accessed April 14, 2017.

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Trifluridine and tipiracil: Drug information