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Severe Myelosuppression: In the 868 patients who received Lonsurf in the RECOURSE and TAGS studies, Lonsurf caused severe and life-threatening myelosuppression (Grade 3-4) consisting of anemia (18%), neutropenia (38%), thrombocytopenia (5%) and febrile neutropenia (3%). Two patients (0.2%) died due to neutropenic infection/sepsis and four other patients (0.5%) died due to septic shock. A total of 12% of Lonsurf-treated patients received granulocyte-colony stimulating factors.
Obtain complete blood counts prior to and on Day 15 of each cycle of Lonsurf and more frequently as clinically indicated. Withhold Lonsurf for severe myelosuppression and resume at the next lower dosage. [See Dosage Modifications for Adverse Reactions under Dosage & Administration.]
Embryo-Fetal Toxicity: Based on animal studies and its mechanism of action, Lonsurf can cause fetal harm when administered to a pregnant woman. Trifluridine/tipiracil caused embryo-fetal lethality and embryo-fetal toxicity in pregnant rats when orally administered during gestation at dosage levels resulting in exposures lower than those achieved at the recommended dosage of 35 mg/m2 twice daily.
Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use an effective method of contraception during treatment with Lonsurf and for at least 6 months after the final dose. [See Pregnancy and Females and Males of Reproductive Potential under Use in Pregnancy & Lactation.]
Renal Impairment: No dose adjustment is recommended for patients with mild or moderate renal impairment (CLcr of 30 to 89 mL/min as determined by the Cockcroft-Gault formula). Reduce the initial dose of Lonsurf for patients with severe renal impairment (CLcr of 15 to 29 mL/min). [See Recommended Dosage for Renal Impairment under Dosage & Administration.] The pharmacokinetics of trifluridine and tipiracil have not been studied in patients with end stage renal disease.
Hepatic Impairment: No adjustment to the starting dose of Lonsurf is recommended for patients with mild hepatic impairment. Do not initiate Lonsurf in patients with baseline moderate or severe (total bilirubin ˃1.5 times ULN and any AST) hepatic impairment. [See Pharmacology: Pharmacokinetics under Actions.]
Use in Children: Safety and effectiveness of Lonsurf in pediatric patients have not been established.
Juvenile Animal Toxicity Data: Dental toxicity including whitening, breakage, and malocclusion (degeneration and disarrangement in the ameloblasts, papillary layer cells and odontoblasts) were observed in rats treated with trifluridine/tipiracil at doses ≥50 mg/kg (approximately 0.33 times the exposure at the clinical dose of 35 mg/m2 twice daily).
Use in the Elderly: In the RECOURSE and TAGS studies, 868 patients received Lonsurf; 45% were 65 years of age or over, while 10% were 75 and over. No overall differences in effectiveness were observed in patients 65 years or older versus younger patients. Patients 65 years of age or older who received Lonsurf had a higher incidence of the following hematologic laboratory abnormalities compared to patients younger than 65 years: Grade 3 or 4 neutropenia (46% vs 32%), Grade 3 anemia (22% vs 16%), and Grade 3 or 4 thrombocytopenia (7% vs 4%).
