Lonsurf Trifluridine and Tipiracil Hydrochloride Tablets

1. Indications and Usage
Metastatic Colorectal Cancer: Indicated for the treatment of adult patients with metastatic colorectal cancer who have received or are not candidates for fluoropyrimidine-based regimens, an anti-VEGF agent, and, if RAS wild-type, an anti-EGFR agent.
2. Dosage and Administration
Route of Administration: Oral administration.
Recommended Dosage: 35 mg/m² administered orally twice daily on Days 1-5 and Days 8-12 of each 28-day cycle.
Administration Details: Tablets should be swallowed whole with water. Do not take with food. Administer at approximately the same times each day.
Dose Modifications: Dose reductions to 26 mg/m² or 18 mg/m² may be required for hematologic and non-hematologic toxicities according to severity.
3. Mechanism of Action
Nucleoside Analogue: Trifluridine is a thymidine analogue that incorporates into DNA, inhibiting DNA synthesis and causing cell death.
Enzyme Inhibition: Tipiracil inhibits thymidine phosphorylase, the enzyme that degrades trifluridine. This increases the plasma concentration and duration of active trifluridine, enhancing its antitumor effects.
4. Safety and Warnings
Neutropenia: Severe neutropenia and febrile neutropenia can occur. Complete blood counts (CBC) must be monitored regularly before each cycle.
Diarrhea: Severe diarrhea may occur. Prompt management with antidiarrheal agents and dose modification may be required.
Embryo-Fetal Toxicity: Can cause fetal harm; effective contraception is required during and for 6 months after the last dose.
Hepatotoxicity: Monitor liver function tests; dose delays or reductions may be necessary for hepatic impairment.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: Neutropenia, anemia, leukopenia, fatigue, diarrhea, nausea, vomiting, abdominal pain, and anorexia.
Clinical Research Highlights: Clinical trials (e.g., RECOURSE) demonstrated significant improvements in overall survival and progression-free survival compared to placebo in previously treated metastatic colorectal cancer patients.
6. Drug Interactions
UGT1A1 Inhibitors: Concomitant use with drugs that inhibit UGT1A1 may increase the risk of severe neutropenia.
Other Oral Antineoplastics: Caution is advised when co-administering other oral chemotherapy agents due to potential overlapping toxicities.
Probenecid: May interfere with the renal excretion of tipiracil and increase its plasma concentration.
7. Pharmaceutical Information
Chemical Composition: Active ingredients: Trifluridine and tipiracil hydrochloride.
Appearance: Film-coated tablets (various strengths available).
Packaging: Available in blister packs.
Storage: Store at controlled room temperature; protect from moisture and light.