Lonsurf Trifluridine and Tipiracil Hydrochloride Tablets

1. Indications and Usage
Metastatic Colorectal Cancer (mCRC):
Indicated for the treatment of patients with metastatic colorectal cancer previously treated with, or who are not considered candidates for, known regimens containing fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF biological therapy, and, if RAS wild-type, an anti-EGFR therapy.
Metastatic Gastric Cancer (mGC):
Indicated for the treatment of adult patients with metastatic gastric cancer (mGC), including metastatic gastroesophageal junction adenocarcinoma (mGEJC).
2. Dosage and Administration
Recommended Dosage:
Starting Dose: 35 mg/m²/dose orally twice daily (at a maximum dose of 80 mg per dose).
Cycling Schedule: On days 1–5 and days 8–12 of a 28-day cycle. Continue until disease progression or unacceptable toxicity.
Administration Instructions:
Administer orally within 1 hour after the morning and evening meals.
Do not substitute missed doses or take extra doses.
Dose Modifications:
Dose adjustments are required based on hematologic and non-hematologic toxicities.
3. Mechanism of Action
Fixed-Dose Combination:
Trifluridine: A nucleoside anticancer agent (thymidine analog). It is incorporated directly into tumor cell DNA, interfering with DNA synthesis and function, which inhibits tumor cell proliferation.
Tipiracil Hydrochloride: Inhibits thymidine phosphorylase (TPase), the enzyme responsible for the metabolic degradation of trifluridine. This inhibition increases the bioavailability and exposure of trifluridine.
Physiological Effect:
The combination exerts antitumor activity through two mechanisms: direct DNA incorporation (trifluridine) and inhibition of metabolic degradation (tipiracil).
4. Safety and Warnings
Bone Marrow Suppression:
Severe and life-threatening bone marrow suppression (Grade 3–4) consisting of anemia, neutropenia, thrombocytopenia, and febrile neutropenia has been observed. Monitor complete blood counts prior to the start of each cycle and on Day 15 of each cycle.
Embryo-Fetal Toxicity:
Based on animal studies and its mechanism of action, LONSURF can cause fetal harm when administered to a pregnant woman.
5. Adverse Reactions
Most Common:
Anemia, neutropenia, fatigue, nausea, thrombocytopenia, decreased appetite, diarrhea, vomiting, abdominal pain, and fever.
Laboratory Abnormalities:
Increased serum creatinine, increased aspartate aminotransferase (AST), and increased alanine aminotransferase (ALT).
6. Drug Interactions
Interaction with Uridine Acetyltransferase:
No clinically significant drug interactions have been identified involving uridine acetyltransferase.
General Considerations:
Caution is advised when co-administering with other myelosuppressive agents, which may exacerbate bone marrow suppression.
7. Pharmaceutical Information
Chemical Name:
Trifluridine: 5-Chloro-1-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)pyrimidine-2,4(1H,3H)-dione
Tipiracil Hydrochloride: 6-Benzyl-2-hydroxy-1,2-dihydropyridine-3-carboxylic acid hydrochloride
Storage:
Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F). Protect from moisture.