Tipiracil

LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil, at a molar ratio 1:0.5 (weight ratio, 1:0.471). Inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase.

• LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of adult patients with: metastatic colorectal cancer as a single agent or in combination with bevacizumab 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. ( 1.1 ) metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.ICD-10: C18.9

• None. None.contraindicated

Recommended Dosage : 35 mg/m 2 /dose orally twice daily with food on Days 1 through 5 and Days 8 through 12 of each 28-day cycle. ( 2.1 ) 2.1 Recommended Dosage The recommended dosage of LONSURF as a single agent or in combination with bevacizumab is 35 mg/m 2 up to a maximum of 80 mg per dose (based on the trifluridine component) orally twice daily with food 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. Refer to the Prescribing Information for bevacizumab dosing information. Instruct patients to swallow LONSURF tablets whole. Instruct patients not to retake doses of LONSURF that are vomited or missed and to continue with the next scheduled dose. LONSURF is a cytotoxic drug. Follow applicable special handling and disposal procedures. 1 Table 1 shows the calculated initial daily dose based on body surface area (BSA). Table 1: Recommended Dosage According to Body Surface Area (BSA) BSA (m2) Total daily dose (mg) Dose (mg) administered twice daily Tablets per dose 15 mg 20 mg < 1.07 70 35 1 1 1.07 – 1.22 80 40 0 2 1.23 – 1.37 90 45 3 0 1.38 – 1.52 100 50 2 1 1.53 – 1.68 110 55 1 2 1.69 – 1.83 120 60 0 3 1.84 – 1.98 130 65 3 1 1.99 – 2.14 140 70 2 2 2.15 – 2.29 150 75 1 3 ≥2.30 160 80 0 4 2.2 Dosage Modifications for Adverse Reactions Obtain complete blood cell counts prior to and on Day 15 of each cycle [see Warnings and Precautions (5.1) ] .

Severe Myelosuppression: Obtain complete blood counts prior to and on Day 15 of each cycle. Withhold and resume at next lower LONSURF dosage as recommended. ( 2.1 , 5.1 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.2 , 8.1 , 8.3 ) 5.1 Severe Myelosuppression In the 1114 patients who received LONSURF as a single agent, LONSURF caused severe or life-threatening myelosuppression (Grade 3-4) consisting of neutropenia (38%), anemia (17%), thrombocytopenia (4%) and febrile neutropenia (3%). Three patients (0.3%) died due to neutropenic infection/sepsis; four other patients (0.5%) died due to septic shock. A total of 14% of patients received granulocyte-colony stimulating factors. In the 246 patients who received LONSURF in combination with bevacizumab, LONSURF caused severe or life-threatening myelosuppression (Grade 3-4) consisting of neutropenia (52%), anemia (5%), thrombocytopenia (4%) and febrile neutropenia (0.4%). One patient (0.4%) died due to abdominal sepsis and two other patients (0.8%) died due to septic shock. A total of 29% of 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 severe myelosuppression and resume at the next lower dosage [see Dosage and Administration (2.2) ] .

The following clinically significant adverse reactions are described elsewhere in the labeling: Severe Myelosuppression [see Warnings and Precautions (5.1) ] The most common adverse reactions or laboratory abnormalities for single agent LONSURF (≥10%) are neutropenia, anemia, thrombocytopenia, fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, and pyrexia. ( 6.1 ) The most common adverse reactions or laboratory abnormalities for LONSURF in combination with bevacizumab (≥20%) are neutropenia, anemia, thrombocytopenia, fatigue, nausea, increased AST, increased ALT, increased alkaline phosphatase, decreased sodium, diarrhea, abdominal pain, and decreased appetite. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Taiho Oncology, Inc. at 1-844-878-2446 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 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 in the WARNINGS AND PRECAUTIONS section and below reflect exposure to LONSURF at the recommended dose in 533 patients with metastatic colorectal cancer in RECOURSE, 246 patients with metastatic colorectal cancer treated with LONSURF as monotherapy in SUNLIGHT and 335 patients with metastatic gastric cancer in TAGS.

Lactation : Advise not to breastfeed. ( 8.2 ) Geriatric Use : For LONSURF as a single agent, Grade 3 or 4 neutropenia, Grade 3 anemia and Grade 3 or 4 thrombocytopenia occurred more commonly in patients 65 years or older. ( 8.5 ) For LONSURF in combination with bevacizumab Grade 3 or 4 neutropenia and Grade 3 or 4 thrombocytopenia occurred more commonly in patients 65 years or older. ( 8.5 ) Hepatic Impairment : Do not initiate LONSURF in patients with baseline moderate or severe hepatic impairment. ( 8.7 ) Renal Impairment : Reduce LONSURF dose in patients with severe renal impairment. ( 8.6 ) 8.1 Pregnancy Risk Summary Based on animal data and its mechanism of action [see Clinical Pharmacology (12.2) ] , LONSURF can cause fetal harm. LONSURF caused embryo-fetal lethality and embryo-fetal toxicity in pregnant rats when given during gestation at doses resulting in exposures lower than or similar to human exposures at the recommended clinical dose (see Data ) . There are no available data on LONSURF use in pregnant women. Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Metabolism

After twice daily dosing of LONSURF, systemic exposure (AUC) of trifluridine increased more than dose-proportionally over the dose range of 15 mg/m 2 (0.43 times the recommended dose) to 35 mg/m 2 . The accumulation of trifluridine was 3-fold for AUC 0-12hr and 2-fold for C max at steady state while no accumulation was observed for tipiracil.

• Sep 22, 2015NDANDA207981Taiho Oncology

1. 1Death3,07929%
2. 2Disease Progression1,79517%
3. 3Fatigue1,37113%
4. 4Nausea1,15011%
5. 5Diarrhoea9879.4%
6. 6Decreased Appetite6796.5%
7. 7Vomiting6175.9%
8. 8Asthenia4854.6%
9. 9White Blood Cell Count Decreased4824.6%
10. 10Drug Ineffective3603.4%
11. 11Anaemia3523.4%
12. 12Weight Decreased3293.1%
13. 13Constipation3273.1%
14. 14Neutropenia3223.1%
15. 15Dehydration3203.0%

The 10 most recently updated of 193 ClinicalTrials.gov registrations naming Tipiracil as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study of Denikitug (GS-1811) Given Alone or With Nivolumab or With Chemotherapy in Adults With Advanced Colorectal Cancer
  Recruiting · Phase 2 · Interventional · 170 enrolled · Gilead Sciences
  NCT07527858updated 2026-06-12
• ASCEND-CRC: Profiling and Targeting Dynamic Tumor Resistance in Patients With Metastatic Colorectal Cancer
  Not yet recruiting · Early phase 1 · Interventional · 100 enrolled · M.D. Anderson Cancer Center
  NCT07318389updated 2026-06-11
• A Study of ASP1570 Taken by Itself, or ASP1570 Taken Together With Either Pembrolizumab, Standard Therapies, or Both, in Adults With Solid Tumors
  Terminated · Phase 1 · Phase 2 · Interventional · 226 enrolled · Astellas Pharma Global Development, Inc.
  NCT05083481updated 2026-06-10
• RegoNivo vs Standard of Care Chemotherapy in AGOC
  Completed · Phase 3 · Interventional · 462 enrolled · Australasian Gastro-Intestinal Trials Group
  NCT04879368updated 2026-06-10
• Efficacy and Safety of Trifluridine/Tipiracil (TAS-102) Combined With Bevacizumab and Serplulimab in Patients With Metastatic Colorectal Cancer Undergoing Cytoreductive Surgery: A Single-Arm, Single-Center Clinical Study
  Not yet recruiting · Phase 1 · Interventional · 20 enrolled · Second Affiliated Hospital, School of Medicine, Zhejiang University
  NCT06882915updated 2026-06-08
• Evaluation of the Safety and Efficacy of Treatment w/High Dose Melphalan Given Directly Into the Liver Followed by Treatment w/Approved Cancer Treatment or Approved Cancer Treatment Alone in Patients w/ Metastatic Colorectal Cancer w/Liver Dominant Disease
  Recruiting · Phase 2 · Interventional · 90 enrolled · Delcath Systems Inc.
  NCT06607458updated 2026-06-01
• FOG-001 in Locally Advanced or Metastatic Solid Tumors
  Recruiting · Phase 1 · Phase 2 · Interventional · 595 enrolled · Parabilis Medicines, Inc.
  NCT05919264updated 2026-05-28
• AZD0901 Compared With Investigator's Choice of Therapy in Participants With Second- or Later-line Advanced or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma Expressing Claudin18.2
  Active not recruiting · Phase 3 · Interventional · 592 enrolled · AstraZeneca
  NCT06346392updated 2026-05-27
• A Study of Coformulated Favezelimab/Pembrolizumab (MK-4280A) Versus Standard of Care in Subjects With Previously Treated Metastatic PD-L1 Positive Colorectal Cancer (MK-4280A-007)
  Completed · Phase 3 · Interventional · 441 enrolled · Merck Sharp & Dohme LLC
  NCT05064059updated 2026-05-26
• Investigate the Efficacy of Chemotherapy in Patients With Positive ctDNA After Surgery and Adjuvant Chemotherapy for a Stage III Colorectal Cancer
  Recruiting · Phase 3 · Interventional · 1,660 enrolled · Centre Hospitalier Universitaire Dijon
  NCT06197425updated 2026-05-22

Frequently asked questions

How does Tipiracil work?

LONSURF consists of a thymidine-based nucleoside analog, trifluridine, and the thymidine phosphorylase inhibitor, tipiracil, at a molar ratio 1:0.5 (weight ratio, 1:0.471). Inclusion of tipiracil increases trifluridine exposure by inhibiting its metabolism by thymidine phosphorylase.

What is Tipiracil used for?

According to FDA labeling, Tipiracil carries indications including: LONSURF is a combination of trifluridine, a nucleoside metabolic inhibitor, and tipiracil, a thymidine phosphorylase inhibitor, indicated for the treatment of adult patients with: metastatic colorectal cancer as a single agent or in combination with bevacizumab 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. ( 1.1 ) metastatic gastric or gastroesophageal junction adenocarcinoma previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Tipiracil?

Tipiracil is classified as Thymidine Phosphorylase Inhibitor, Thymidine Phosphorylase Inhibitors.

What are the brand names for Tipiracil?

Tipiracil is marketed under brand names including Lonsurf.

What are the contraindications for Tipiracil?

Tipiracil labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.