Lonsurf Tablet 20

Adult dose

The dose of this medicine should be determined according to body surface area as shown in Table 1 below, and the maximum dose of trifluridine per administration should not exceed 80 mg. Administer orally with water within 1 hour after breakfast and dinner. 1. Lonsurf Tablets monotherapy Generally, the initial dose for adults (approximately 35 mg/m2/dose of trifluridine) is determined according to body surface area as shown in Table 1 below and administered twice daily, in the morning and evening, after meals for 5 consecutive days, followed by a 2-day rest period. Repeat this schedule twice, followed by a 14-day rest period. This constitutes 1 cycle, and treatment is repeated. Administration of this medicine should continue until disease progression or unacceptable toxicity occurs. 2. Lonsurf Tablets in combination with bevacizumab for the treatment of metastatic colorectal cancer Refer to the monotherapy dosage and administration for Lonsurf Tablets. Bevacizumab is administered by intravenous infusion at a dose of 5mg/Kg once every 2 weeks. (Administer on Days 1 and 15 of each cycle.) For details on the dosage and administration of bevacizumab, refer to its prescribing information. Instruct patients to swallow this medicine whole. If a patient vomits or misses a dose, do not administer another dose; instruct the patient to take the next dose at the next scheduled time. Table 1. Calculation of the initial dose according to body surface area Initial dose (trifluridine dose per administration) 35 mg/m2 Body surface area (m2) < 1.07: Dose 35 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 1 tablet, total daily dose 70 mg Body surface area (m2) 1.07 - 1.22: Dose 40 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 2 tablets, total daily dose 80 mg Body surface area (m2) 1.23 - 1.37: Dose 45 mg (twice daily), Lonsurf® 15-mg tablet 3 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 90 mg Body surface area (m2) 1.38 - 1.52: Dose 50 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 100 mg Body surface area (m2) 1.53 - 1.68: Dose 55 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 2 tablets, total daily dose 110 mg Body surface area (m2) 1.69 - 1.83: Dose 60 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 3 tablets, total daily dose 120 mg Body surface area (m2) 1.84 - 1.98: Dose 65 mg (twice daily), Lonsurf® 15-mg tablet 3 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 130 mg Body surface area (m2) 1.99 - 2.14: Dose 70 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 2 tablets, total daily dose 140 mg Body surface area (m2) 2.15 - 2.29: Dose 75 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 3 tablets, total daily dose 150 mg Body surface area (m2) ≥ 2.30: Dose 80 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 4 tablets, total daily dose 160 mg 3. Dose adjustment Reduce the dose as appropriate based on each patient's safety and tolerability. A maximum of 3 dose reductions is permitted, with a minimum dose of trifluridine 20 mg/m2 twice daily. Discontinue treatment in patients who cannot tolerate the dose of 20mg/m2 twice daily. Dose escalation after reduction is not permitted. A complete blood count should be performed before starting treatment in each cycle and on Day 15 of each cycle (see Precautions for Use, 1. Warnings). If hematologic and/or nonhematologic toxicity occurs, follow the interruption, resumption, and dose reduction criteria in Tables 2, 3, and 4. Table 2. Criteria for interruption and resumption for hematologic toxicities associated with bone marrow suppression Neutrophil count: Interruption criterion less than 0.5 × 109/L, resumption criterion at least 1.5 × 109/L Platelet count: Interruption criterion less than 50 × 109/L, resumption criterion at least 75 × 109/L a) Resumption criteria applicable at the start of the next cycle for all patients, regardless of whether the interruption criteria are met Table 3. Dose adjustment in the event of hematologic or nonhematologic adverse drug reactions ·Febrile neutropenia ·Delay of at least 1 week in starting the next cycle due to CTCAE* Grade 4 neutropenia (<0.5 × 109/L) or thrombocytopenia (<25 × 109/L) ·CTCAE* Grade 3 or Grade 4 nonhematologic adverse drug reactions (excluding Grade 3 nausea and/or vomiting controlled with antiemetics, or Grade 3 diarrhea responsive to antidiarrheal agents) ·Interrupt treatment until the toxicity recovers to Grade 1a) or lower, or to baseline. ·When treatment is resumed after recovery, reduce the previous dose by 5 mg/m2/dose. (See Table 4.) ·Dose reductions are permitted to a minimum of trifluridine 20 mg/m2/dose twice daily. (For patients with severe renal impairment, reduction to 15mg/m2/dose twice daily is permitted.) ·Do not increase the dose after reduction. *Common Terminology Criteria for Adverse Events a) For neutropenia, this means until recovery to at least 1.5× 109/L; for thrombocytopenia, until recovery to at least 75× 109/L. Table 4. Dose reduction according to body surface area Level 1: 35 mg/m2 → 30 mg/m2 30 mg/m2 Body surface area (m2) < 1.09: Dose 30 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 60 mg Body surface area (m2) 1.09 - 1.24: Dose 35 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 1 tablet, total daily dose 70 mg Body surface area (m2) 1.25 - 1.39: Dose 40 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 2 tablets, total daily dose 80 mg Body surface area (m2) 1.40 - 1.54: Dose 45 mg (twice daily), Lonsurf® 15-mg tablet 3 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 90 mg Body surface area (m2) 1.55 - 1.69: Dose 50 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 100 mg Body surface area (m2) 1.70 - 1.94: Dose 55 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 2 tablets, total daily dose 110 mg Body surface area (m2) 1.95 - 2.09: Dose 60 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 3 tablets, total daily dose 120 mg Body surface area (m2) 2.10 - 2.28: Dose 65 mg (twice daily), Lonsurf® 15-mg tablet 3 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 130 mg Body surface area (m2) ≥ 2.29: Dose 70 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 2 tablets, total daily dose 140 mg Level 2: 30 mg/m2 → 25 mg/m2 25 mg/m2 Body surface area (m2) < 1.10: Dose 25a) mg (twice daily), Lonsurf® 15-mg tablet 2a) tablets, Lonsurf® 20-mg tablet 1a) tablet, total daily dose 50a) mg Body surface area (m2) 1.10 - 1.29: Dose 30 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 60 mg Body surface area (m2) 1.30 - 1.49: Dose 35 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 1 tablet, total daily dose 70 mg Body surface area (m2) 1.50 - 1.69: Dose 40 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 2 tablets, total daily dose 80 mg Body surface area (m2) 1.70 - 1.89: Dose 45 mg (twice daily), Lonsurf® 15-mg tablet 3 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 90 mg Body surface area (m2) 1.90 - 2.09: Dose 50 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 100 mg Body surface area (m2) 2.10 - 2.29: Dose 55 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 2 tablets, total daily dose 110 mg Body surface area (m2) ≥ 2.30: Dose 60 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 3 tablets, total daily dose 120 mg Level 3: 25 mg/m2 → 20 mg/m2 20 mg/m2 Body surface area (m2) < 1.14: Dose 20 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 40 mg Body surface area (m2) 1.14 – 1.34: Dose 25a) mg (twice daily), Lonsurf® 15-mg tablet 2a) tablets, Lonsurf® 20-mg tablet 1a) tablet, total daily dose 50a) mg Body surface area (m2) 1.35 – 1.59: Dose 30 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 60 mg Body surface area (m2) 1.60 – 1.94: Dose 35 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 1 tablet, total daily dose 70 mg Body surface area (m2) 1.95 – 2.09: Dose 40 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 2 tablets, total daily dose 80 mg Body surface area (m2) 2.10 – 2.34: Dose 45 mg (twice daily), Lonsurf® 15-mg tablet 3 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 90 mg Body surface area (m2) ≥ 2.35: Dose 50 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 100 mg a) When administering 50 mg per day, take 1 Lonsurf 20 (20mg/8.19mg) tablet after breakfast and 2 Lonsurf 15 (15 mg/6.14 mg) tablets after dinner. <Special populations> 1) Patients with renal impairment • No initial dose adjustment is necessary in patients with mild renal impairment (CLcr 60 ~ 89 mL/min) or moderate renal impairment (CLcr 30 ~ 59 mL/min). • The recommended dose for patients with severe renal impairment (CLcr 15 ~ 29mL/min) is trifluridine 20mg/m2. Administer twice daily, in the morning and evening after meals, for 5 consecutive days, followed by a 2-day rest period. Repeat this schedule twice, followed by a 14-day rest period; 28 days constitutes 1 cycle. For patients with poor tolerability to the dose of 20mg/m2 twice daily, reduce the dose to 15mg/m2 twice daily. (Table 5) Discontinue treatment in patients who cannot tolerate the dose of 15mg/m2 twice daily. • Use in patients with end-stage renal disease has not been studied; therefore, administration of this medicine is not recommended in these patients. • Table 5 – Recommended dose according to BSA in patients with severe renal impairment 20mg/m2 twice daily Body surface area (m2) < 1.14: Dose 20 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 40 mg Body surface area (m2) 1.14 – 1.34: Dose 25a) mg (twice daily), Lonsurf® 15-mg tablet 2a) tablets, Lonsurf® 20-mg tablet 1a) tablet, total daily dose 50a) mg Body surface area (m2) 1.35 – 1.59: Dose 30 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 60 mg Body surface area (m2) 1.60 – 1.94: Dose 35 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 1 tablet, total daily dose 70 mg Body surface area (m2) 1.95 – 2.09: Dose 40 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 2 tablets, total daily dose 80 mg Body surface area (m2) 2.10 – 2.34: Dose 45 mg (twice daily), Lonsurf® 15-mg tablet 3 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 90 mg Body surface area (m2) ≥ 2.35: Dose 50 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 100 mg 15mg/m2 twice daily Body surface area (m2) < 1.15: Dose 15 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 0 tablets, total daily dose 30 mg Body surface area (m2) 1.15 – 1.49: Dose 20 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 1 tablet, total daily dose 40 mg Body surface area (m2) 1.50 – 1.84: Dose 25a) mg (twice daily), Lonsurf® 15-mg tablet 2a) tablets, Lonsurf® 20-mg tablet 1a) tablet, total daily dose 50a) mg Body surface area (m2) 1.85 – 2.09: Dose 30 mg (twice daily), Lonsurf® 15-mg tablet 2 tablets, Lonsurf® 20-mg tablet 0 tablets, total daily dose 60 mg Body surface area (m2) 2.10 – 2.34: Dose 35 mg (twice daily), Lonsurf® 15-mg tablet 1 tablet, Lonsurf® 20-mg tablet 1 tablet, total daily dose 70 mg Body surface area (m2) ≥ 2.35: Dose 40 mg (twice daily), Lonsurf® 15-mg tablet 0 tablets, Lonsurf® 20-mg tablet 2 tablets, total daily dose 80 mg a) When administering 50 mg per day, take 1 Lonsurf 20 (20mg/8.19mg) tablet after breakfast and 2 Lonsurf 15 (15mg/6.14mg) tablets after dinner. 2) Patients with hepatic impairment • No initial dose adjustment is necessary in patients with mild hepatic impairment. • Administration of this medicine is not recommended in patients with moderate to severe hepatic impairment (NCI criteria Group C, D with total bilirubin >1.5xULN). Although based on very limited data, the incidence of Grade 3 or 4 hyperbilirubinemia was higher in patients with moderate baseline hepatic impairment.

This drug is an anticancer chemotherapy agent and must be administered under the guidance of an experienced physician in chemotherapy. Before starting treatment, the patient and family must be thoroughly informed of the benefits and risks of this medication and consent obtained. This medication can cause myelosuppression, leading to a reduction in white blood cells, platelets, and red blood cells in the blood, hence regular blood tests should be performed to closely monitor the patient’s condition. If blood counts drop severely, measures such as stopping or reducing the dosage of the drug may be necessary. In particular, the risk of infection due to neutropenia may increase, so treatment should be initiated immediately if infection symptoms appear. Caution should be exercised when used with other anticancer agents, certain antifungal agents, or folate antagonists as side effects may worsen. Patients with severely impaired kidney function may need dose adjustments, and it is not to be used in patients with end-stage renal disease. Patients with allergies to this medication, pregnant women, nursing mothers, and patients with specific genetic metabolic disorders should not receive this drug. Careful administration is required in patients with myelosuppression or infection, moderate to severe renal impairment, and the elderly. During administration, gastrointestinal disturbances, fatigue, fever, loss of appetite, vomiting, diarrhea, and other side effects may commonly occur, so symptoms should be closely monitored. It is advisable to take this medication after meals rather than on an empty stomach, and contraception is recommended as it may affect fertility. Women of childbearing potential and their partners should use effective contraception during treatment and for a certain period after the treatment ends. If nursing, breastfeeding should be discontinued. This medication may cause symptoms such as fatigue and dizziness, which require caution when driving or operating dangerous machinery. In case of overdose, there is no specific antidote, so the patient's condition should be closely monitored, and appropriate treatment should be provided. When taking the medication, care should be taken not to swallow the packaging sheet and to keep it out of reach of children. There might be a reduction in efficacy when used with other antiviral agents, hence consultation with a physician is necessary.

• Anemia
• neutropenia
• leukopenia
• thrombocytopenia
• febrile neutropenia
• infections
• sepsis
• septic shock
• nausea
• diarrhea

This medication should be stored in a tightly sealed container, protected from air and moisture. It is advisable to maintain a storage temperature between 1 and 30 degrees Celsius. This method of storage helps preserve the medication's efficacy.

Appearance

Pale red, round film-coated tablet, biconvex on both sides

Package unit

20 tablets/bottle, 40 tablets/bottle, 60 tablets/bottle, 20 tablets/box [10 tablets/PTP X 2 sheets], 60 tablets/box [10 tablets/PTP X 2 sheets X 3]