Trifluridine and Tipiracil (Oral)

Trifluridine and Tipiracil are a combination of drugs used to treat certain cancers by interfering with the spread and growth of cancer cells in the body. Below is detailed information on this combination of drugs.


Trifluridine and Tipiracil are a combination of metastatic cancer medicine given when other drugs have failed. Examples of dispensed drugs which may have been unable to work before this medication include oxaliplatin, fluoropyrimidine, irinotecan. The medicine is available in tablet form under the U.S. brand name, Lonsurf.

The drugs belong to the therapeutic class of Antineoplastic Agents, the chemical class - Pyrimidine Nucleoside Analog, and the pharmacologic class of Viral DNA Thymidylate Synthetase Inhibitors. Trifluridine is a nucleoside metabolic inhibitor that is thymidine-based, and is rapidly inactivated by thymidine phosphorylase: Tipiracil, on the other hand, is a thymidine phosphorylase inhibitor.

The mechanism of action of this combination is to arrest the growth and spread of cancerous cells in the body. Trifluridine once administered into the body is taken up into cancer cells, and incorporated into the DNA. It interferes with DNA synthesis and hinders cell proliferation. Administration by thymidine phosphorylase rapidly inactivates Trifluridine. Tipiracil slows down this administration by thymidine phosphorylase.

It is a prescription only medication.

Conditions Treated

Type of Medicine

  • Antineoplastic Agent

Side Effects

Medicines used to treat any cancer can be very strong and can have a lot of unwanted effects. Patients taking this drug must work closely with their doctor for the best chance of a successful outcome.

Most common unwanted effects of this medicine are the following:

A person on this drug may experience many side effects, some of which may be severe, while others are mild. The patient taking Tipiracil / trifluridine should check with their physician immediately if they see any one of the following unwanted effects.

These are more commonly observed:

  • Bleeding gums
  • Painful or difficult urination
  • Blood in stools or urine
  • Pinpoint red spots on the skin
  • Hoarseness or a cough
  • Side or lower back pain
  • Black, tarry stools
  • Pale skin
  • Fever or chills
  • Having to exert oneself while breathing and other troubles
  • White spots, ulcers, sores in the mouth
  • Unusual bruising or bleeding
  • Unusual weakness or tiredness

Others that are not commonly seen but require immediate medical attention are the following:

  • Bloody or cloudy urine
  • Pain in the bladder
  • Frequent urge to urinate
  • Muscle ache
  • Headache
  • Runny or stuffy nose

Not all the effects observed after administration of tipiracil / trifluridine constitute a medical emergency. Some symptoms may go away in time in the course of treatment as the patient's body adjusts to the medicine. A healthcare professional should, however, be notified of all observed side effects as he/she has the expertise to determine the seriousness of symptoms. The healthcare expert will give tips on how to prevent or reduce the impact of the side effects that are not a medical emergency if they have become bothersome.

The following are the more commonly seen side effects that are not severe:

  • Stomach or abdominal pain
  • Reduced appetite
  • Changes in taste, and at times losing it.
  • Diarrhea
  • Thinning or loss of hair
  • General weakness
  • Nausea
  • Vomiting
  • Inflammation or swelling of the mouth

A patient will not necessarily experience all the above adverse effects when taking the tipiracil / trifluridine combination. Moreover, other symptoms not listed here could be experienced. Medical attention must be sought, and side effects can be reported to the FDA.


The dosing for this medicine may not be the same for all patients. Dosage should not be adjusted or taken differently from what a doctor prescribed.

Adult doses

35mg per meter squared (m2) of body size based on trifluridine component, (maximum should be 80mg) taken orally in the morning and evening, within one hour of having a meal. This should be taken on days 1 to 5 and 8 to 12, repeated every 28 days until unacceptable toxicity or disease progression. The dose should be rounded to the nearest 5mg.

Renal dose adjustments

For patients with mild renal dysfunction, no dose adjustment is recommended.

For patients with moderate renal dysfunction, dose adjustments may be recommended for increased toxicity. There are no specific guidelines on the dose adjustments necessary, though caution is advised.

There is no data available on dose adjustments for patients with severe renal dysfunction.


No data is available on the safety of this drug for patients undergoing dialysis.

Liver Dose Adjustments

There are no recommended dose adjustments for patients with mild liver dysfunction. For patients with moderate liver dysfunction and severe liver dysfunction, no data is available on dose adjustments.

Adolescents, children, infants and neonates

Safety and efficacy of this drug have not been established for persons under the age of 18 years.


A maximum dose of 160mg, based on trifluridine component PO total daily dose (80mg PO given twice daily) on days 1-5, and 8-12 every 28 days.

Missed Dose

If a dose of this medicine is missed, a double treatment should not be taken. The missed dose should be wholly skipped and regular dosing resumed.


There is no known antidote for this medicine. The highest dose ever administered for this drug was 180mg/m2 per day.

NOTE: when handling the medicine, gloves should be worn, and hands washed afterward.


A total of 156 drugs (839 generic and brand names) are known to interact with tipiracil / trifluridine.

  • 31 drugs (82 generic and brand names) have major interactions with tipiracil / trifluridine.
  • 125 drugs (757 generic and brand names) have moderate interactions with tipiracil / trifluridine.

Significant interactions are highly significant clinically, and combinations of such drugs are to be avoided as the risks outweigh the benefits of using the two medicines together.

Moderate interactions are moderately clinically important and such drugs should be used together in exceptional circumstances. Combinations should be avoided.

Tipiracil / trifluridine have major interactions with the following drugs and should never be prescribed together.

  • ACAM2000 (smallpox vaccine)
  • Adalimumab
  • Amjevita (adalimumab)
  • Arava (leflunomide)
  • Attenuvax (measles virus vaccine)
  • Aubagio (teriflunomide)
  • BCG
  • Biavax II (mumps / rubella virus vaccine)
  • Certolizumab
  • Cimzia (certolizumab)
  • Clopine (clozapine)
  • Clozapine
  • Clozapine Synthon (clozapine)
  • Clozaril (clozapine)
  • Cyltezo (adalimumab)
  • Deferiprone
  • Denzapine (clozapine)
  • Dryvax (smallpox vaccine)
  • Enbrel (etanercept)
  • Erelzi (etanercept)
  • Etanercept
  • FazaClo (clozapine)
  • Ferriprox (deferiprone)
  • Fingolimod
  • FluMist (influenza virus vaccine, live, trivalent)
  • FluMist Quadrivalent (influenza virus vaccine, live, trivalent)
  • Gilenya (fingolimod)
  • Golimumab
  • Humira (adalimumab)
  • Imlygic (talimogene laherparepvec)
  • Inflectra (infliximab)
  • Infliximab
  • Influenza virus vaccine, h1n1, live
  • Influenza virus vaccine, live, trivalent
  • Leflunomide
  • M-M-R II (measles / mumps / rubella virus vaccine)
  • M-R-Vax II (measles / rubella virus vaccine)
  • Measles virus vaccine
  • Measles / mumps / rubella virus vaccine
  • Measles e / mumps / rubella / varicella virus vaccine
  • Measles virus vaccine / rubella virus vaccine
  • Meruvax II (rubella virus vaccine)
  • Mumps virus vaccine
  • Mumps virus vaccine / rubella virus vaccine
  • Mumpsvax (mumps virus vaccine)
  • Natalizumab
  • Orimune (poliovirus vaccine, live, trivalent)
  • Poliovirus vaccine, live, trivalent
  • ProQuad (measles / mumps / rubella / varicella virus vaccine)
  • Quadramet (samarium sm 153 lexidronam)
  • Remicade (infliximab)
  • Renflexis (infliximab)
  • Rotarix (rotavirus vaccine)
  • RotaShield (rotavirus vaccine)
  • RotaTeq (rotavirus vaccine)
  • Rotavirus vaccine
  • Rubella virus vaccine
  • Samarium sm 153 lexidronam
  • Simponi (golimumab)
  • Simponi Aria (golimumab)
  • Smallpox vaccine
  • Stamaril (yellow fever vaccine)
  • Talimogene laherparepvec
  • Teriflunomide
  • TheraCys (bcg)
  • Tice BCG (bcg)
  • Tice BCG Vaccine (bcg)
  • Tofacitinib
  • Typhoid vaccine, live
  • Tysabri (natalizumab)
  • Varicella virus vaccine
  • Varivax (varicella virus vaccine)
  • Versacloz (clozapine)
  • Vivotif Berna (typhoid vaccine, live)
  • Vivotif Berna Vaccine (typhoid vaccine, live)
  • Xeljanz (tofacitinib)
  • Xeljanz XR (tofacitinib)
  • Yellow fever vaccine
  • YF-Vax (yellow fever vaccine)
  • Zaponex (clozapine)
  • Zostavax (zoster vaccine live)
  • Zoster vaccine live


A healthcare provider should be informed of all allergies that a patient has before prescribing any medicine. Every known hypersensitivity that a patient has should be listed so the physician can be able to assess the safety of giving a particular prescription.

  • Pregnancy warnings

There are no well-controlled and adequate studies on pregnant women using this medicine, but animal studies suggest trifluridine / tipiracil can harm a fetus. Women receiving treatment with the drug should avoid getting pregnant. Further, females who have partners who are on trifluridine/tipiracil should avoid getting pregnant during treatment and until three months after the last dose.

Men and women in relationships and one of the partners is taking trifluridine/tipiracil should ensure adequate contraception to ensure conception does not take place while any one of them is in treatment. Where pregnancy does occur, the potential risk to the fetus should be carefully assessed by a trained healthcare professional.

  • Breastfeeding Warnings

It is not known if trifluridine/tipiracil is passed into human milk. Most drugs are passed into human milk, and because of the potential harm to a nursing infant, women should not breastfeed their babies at least until after one day since the last dose.


This medicine should be kept safe and very far from children and pets.

The medicine should be stored in a well-sealed container, away from direct light, moisture and heat. This drug should not be frozen.

All expired medicines should be discarded using procedures deemed safe for disposal of cytotoxic agents.

Any medicine that is stored away from the original container should be disposed of safely after thirty days.


Trifluridine and Tipiracil is a drug administered to treat Metastatic Colorectal Cancer after other medications have failed. Cancer drugs, even those not given as a last resort like Trifluridine and Tipiracil can be potent. The side effects of this drug can be major.

A patient using any drug, and not just this strong cancer drugs must work with their healthcare provider. To achieve successful outcomes using this or any drug, the patient must follow the doctor's advice and discuss any issues or concerns with the doctor. Only a doctor, nurse or pharmacist understands the myriad issues involved in determining the safety and effectiveness of a drug and the steps to take to achieve the desired outcome.

Trifluridine and Tipiracil interact with very many medications, and for this reason, a patient using this drug should never use any other medicine without notifying their doctor. Even vitamins, minerals, and any other natural products should not be taken without informing the doctor. These natural products which appear otherwise safe may have high concentrations of nutrients which may result in unexpected interactions.

Similarly, despite the severity of cancer, a patient should not seek all sorts of alternative therapies unless working with a trained medical professional. A physician can prescribe effective natural products which won't interact with any prescribed medications.

The information contained here on Trifluridine and Tipiracil is by no means complete. It should not be used as prescribing information, nor should it replace the advice of a trained doctor. This information should be used for general purposes only.

Last Reviewed:
December 23, 2017
Last Updated:
April 05, 2018
Content Source: