Trifluridine and tipiracil are two active pharmaceutical agents that are combined to form a drug used primarily in the treatment of metastatic colorectal cancer that has not responded to other chemotherapy treatments. This combination drug is commonly known by the brand name Lonsurf.

Lonsurf (Trifluridine and tipiracil) is an oral combination pill containing two chemotherapeutic drugs used in the treatment of patients with metastatic gastric and metastatic colorectal cancer.

Trifluridine and tipiracil Uses:

• Metastatic Colorectal cancer:
  • Used in the treatment of metastatic colorectal cancer 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.
• Metastatic Gastric cancer:
  • Also used for treating metastatic gastric or gastroesophageal junction adenocarcinoma in adults previously treated with at least two prior lines of chemotherapy which included a fluoropyrimidine, platinum, either a taxane or irinotecan, and if appropriate, HER2/neu-targeted therapy.

Lonsurf (Trifluridine and tipiracil) Dose in Adults

 Note:

• Trifluridine/tipiracil is a medicine used to treat certain types of cancer.
• When giving doses, round to the closest 5 mg.
• Before starting and halfway through each treatment cycle, get a blood test.
• Only start a new cycle if blood counts are safe: no high fever with low white blood cells, enough platelets, and any severe side effects have improved.
• This medicine can make people feel sick, so it's a good idea to take anti-sickness medicine to help with nausea and vomiting.

Lonsurf (Trifluridine and tipiracil) Dose in the treatment of metastatic colorectal cancer:

• Take by mouth.
• Dosage: 35 mg/m (based on the trifluridine part).
• Take it twice a day.
• Use it on days 1-5 and days 8-12 in a 28-day cycle.
• Don't take more than 80 mg of trifluridine at once.
• Keep using until the disease gets worse or side effects are too strong.

Lonsurf (Trifluridine and tipiracil) Dose in the treatment of metastatic gastric cancer:

• Take it by mouth.
• The dosage is 35 mg/m (based on the trifluridine part).
• Take it twice a day.
• Use it on days 1-5 and days 8-12 in a 28-day cycle.
• Don't take more than 80 mg of trifluridine at once.
• Keep using it until the disease gets worse or side effects are too strong.

Missed dose:

• If you miss a dose or vomit after taking it, don't take that missed dose again. Just continue with the next scheduled dose.

Use in Children:

Not indicated. 

Pregnancy Risk Category: X

• Trifluridine and tipiracil may potentially harm a developing fetus based on animal studies and its mechanism of action.
• Therefore, it's crucial to determine if a female is pregnant before starting this therapy.
• If a female of reproductive age is undergoing this treatment, she should use reliable birth control methods while taking the medication and for at least 6 months after the last dose.
• For males who have female partners of reproductive potential, using condoms is recommended during the treatment period and for at least 3 months after the final dose to avoid potential exposure to the drug.
• These precautions are essential to reduce the risk of harm to a developing fetus.

Use while breastfeeding

• Trifluridine and tipiracil might be in breast milk, but we're not sure.
• Because of the possible serious side effects in a breastfed baby, the company that makes the drug recommends not breastfeeding while taking the medication and for one day after the last dose.

Dose in Kidney Disease:

• If your kidney function (CrCl) is 30 mL/minute or more: You don't need to change the starting dose of the medicine.
• If your kidney function is less than 30 mL/minute or you have end-stage kidney disease: The manufacturer hasn't given any guidance on dose changes (because it hasn't been studied).

Dose in Liver disease:

• Mild issues (either normal bilirubin with elevated AST or bilirubin slightly raised): You don't need to change the starting dose.
• Moderate issues (bilirubin raised a bit more) or severe issues (bilirubin significantly raised): Don't start the therapy at all.

Common Side Effects of Lonsurf (Trifluridine and tipiracil):

• Central Nervous System:
  • Fatigue
• Gastrointestinal:
  • Nausea
  • Decreased Appetite
  • Diarrhea
  • Vomiting
  • Abdominal Pain
• Hematologic & Oncologic:
  • Anemia
  • Neutropenia
  • Thrombocytopenia
  • Febrile Neutropenia
• Infection:
  • Infection
• Neuromuscular & Skeletal:
  • Asthenia
• Miscellaneous:
  • Fever

Less Common Side Effects of Lonsurf (Trifluridine and tipiracil):

• Cardiovascular:
  • Pulmonary Embolism
• Dermatologic:
  • Alopecia
• Gastrointestinal:
  • Stomatitis
  • Dysgeusia

Contraindications to Lonsurf (Trifluridine and tipiracil):

• The manufacturer doesn't list any specific reasons or conditions under which you shouldn't use the medication.

Warnings and precautions

Suppression of bone marrow

• Bone marrow suppression can happen when taking this medication.
• This means there's a risk of severe, even life-threatening, low blood cell counts, which can cause conditions like anemia, low white blood cells, and low platelets.
• Rarely, this has led to deaths due to infections or septic shock.
• In research trials, just over 10% of people needed extra support to boost their cell growth.
• It's important to check blood counts before starting each treatment cycle and again on day 15, or even more often if needed.
• If counts are too low, treatment might need to be paused or the dose might need to be lowered.

Gastrointestinal toxicities:

• Trifluridine/tipiracil can upset the stomach.
• It can make people feel like throwing up, so taking medicine to prevent nausea and vomiting is a good idea.
• Common side effects include feeling sick, throwing up, diarrhea, and stomach pain.
• Mouth sores can also happen.

Hepatic impairment

• People with serious liver problems (where the bilirubin is more than 3 times the normal limit, along with any level of AST) weren't tested in the studies.
• So, those with moderate or severe liver problems shouldn't start this treatment.
• In a study looking at how the drug works in the body, some patients with moderate liver problems saw their bilirubin levels rise to concerning levels.

Trifluridine and tipiracil: Drug Interaction

Monitoring parameters:

Blood Tests

• Check complete blood counts before each treatment cycle.
• Also check on day 15 of each cycle.
• Do these tests even more often if the doctor thinks it's needed.

Pregnancy Check

• Make sure females who could get pregnant are not pregnant before starting the treatment.

Stomach Issues

• Watch for signs of stomach problems.

Taking the Medicine

• Keep track to make sure the patient is taking the medicine as directed.

How to administer Lonsurf (Trifluridine and tipiracil)?

Trifluridine/Tipiracil and Stomach Upset

• This medicine might make people feel like throwing up.
• It's a good idea to take medicine that stops nausea and vomiting (Hesketh 2017).

How to Take It

• Take the medicine by mouth two times a day.
• Eat something when you take it.
• Don't chew or crush the tablets; swallow them whole.

Mechanism of action of Lonsurf (Trifluridine and tipiracil):

Trifluridine's Role

• Trifluridine is a powerful component in this medicine.
• It's kind of like a building block for DNA.
• When it turns into its active form (triphosphate), it joins the DNA and messes up its growth.
• This slows down or stops the cells from multiplying.

Tipiracil's Role

• Tipiracil is another important part.
• It stops an enzyme called thymidine phosphorylase from breaking down trifluridine.
• This keeps trifluridine around longer in the body.
• That's good because it helps the medicine work better.

Protein Binding:

• Trifluridine: Most of it (over 96%) attaches to proteins in the blood, mainly albumin.
• Tipiracil: Very little (less than 8%) attaches to blood proteins.

Metabolism (How it's broken down):

• Neither trifluridine nor tipiracil are changed by the usual enzymes (CYP enzymes) that alter many drugs.
• Trifluridine is mostly changed into an inactive form called 5-(trifluoromethyl) uracil (FTY) by an enzyme named thymidine phosphorylase.

How Long They Last (Half-life):

• Trifluridine: About 2.1 hours when the amount in the body is stable.
• Tipiracil: About 2.4 hours when stable.

Peak Time (When levels are highest in blood):

• Around 2 hours after taking.

How They Leave the Body (Excretion):

• Trifluridine:
  • Urine: 55% leaves as inactive forms, less than 3% as the unchanged drug.
  • Feces: Less than 3% as the unchanged drug.
  • Breathed out: Less than 3%.
• Tipiracil:
  • Urine: 27% as tipiracil and another form called 6-HMU.
  • Feces: Half (50%) leaves as tipiracil and 6-HMU.

International Brand Names of Trifluridine and tipiracil:

• Lonsurf

Trifluridine and Tipiracil Brand Names in Pakistan:

Not available.