Suyuan Trifluridine and Tipiracil Hydrochloride Tablets

1. Indications and Usage
Metastatic Colorectal Cancer (mCRC):
Indicated for the treatment of adult patients with mCRC who have been previously treated with, or are not eligible for, fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, anti-VEGF therapy, and anti-EGFR therapy (if RAS wild-type).
Metastatic Gastric Cancer (mGC):
Indicated for the treatment of adult patients with mGC (including metastatic gastroesophageal junction adenocarcinoma) who have been previously treated with two or more lines of chemotherapy.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY. Must be taken within 1 hour after a meal to reduce the risk of toxicity.
Recommended Dosage:
Dose Calculation: Based on body surface area (BSA). The recommended starting dose is approximately 35 mg/m² (based on trifluridine component) twice daily.
Schedule: Administered on Days 1–5 and Days 8–12 of a 28-day cycle.
Maximum Dose: 80 mg per dose.
Dose Modifications:
Dose adjustments (decrements of 10 mg/day) are required based on hematologic toxicity (neutropenia, thrombocytopenia) and non-hematologic adverse reactions.
3. Mechanism of Action
Dual-Component Mechanism:
Trifluridine (TFT): A thymidine-based nucleoside antiviral agent. It is incorporated directly into tumor cell DNA during DNA synthesis, interfering with DNA function and inhibiting cell proliferation.
Tipiracil Hydrochloride: A thymidine phosphorylase inhibitor. It inhibits the degradation of trifluridine, thereby improving its systemic exposure and bioavailability.
4. Safety and Warnings
Bone Marrow Suppression:
Severe and potentially fatal bone marrow suppression (neutropenia, thrombocytopenia, anemia) can occur. Baseline and periodic monitoring of complete blood counts (CBC) is required.
Embryo-Fetal Toxicity:
Based on its mechanism, trifluridine can cause fetal harm. Effective contraception is recommended for women of reproductive potential and males with female partners of reproductive potential.
Interstitital Lung Disease (ILD):
ILD has been reported. Patients should be monitored for respiratory symptoms.
5. Adverse Reactions
Most Common:
Hematologic: Neutropenia, anemia, leukopenia, thrombocytopenia.
Gastrointestinal: Nausea, vomiting, diarrhea, decreased appetite, abdominal pain.
General: Fatigue, pyrexia, rash.
6. Drug Interactions
Metabolic Pathway:
Trifluridine is a substrate of thymidine phosphorylase and is not metabolized by CYP enzymes. Tipiracil is not metabolized in the liver.
Interaction Potential:
Uracil: Co-administration with uracil (e.g., in tegafur-uracil) is contraindicated as it may inhibit the metabolism of trifluridine and increase toxicity.
CYP Enzymes: No clinically significant interactions are expected with CYP substrates.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredients: Trifluridine (FTD) and Tipiracil Hydrochloride (TPI) in a molar ratio of 1:0.5.
Appearance:
15 mg: White to off-white, flat, oval-shaped film-coated tablets.
20 mg: Pale red, flat, oval-shaped film-coated tablets.
Storage: Store at 20°C–25°C (68°F–77°F).