LONSURF

After twice daily dosing of LONSURF, systemic exposure (AUC) of trifluridine increased more than dose-proportionally over the dose range of 15 mg/m 2 (0.43 times the recommended dose) to 35 mg/m 2 . The accumulation of trifluridine was 3-fold for AUC 0-12hr and 2-fold for C max at steady state while no accumulation was observed for tipiracil. Administration of a single dose of LONSURF 35 mg/m 2 increased the mean AUC 0-last of trifluridine by 37-fold and C max by 22-fold with reduced variability...

14.1 Metastatic Colorectal Cancer Previously treated metastatic colorectal cancer (single agent LONSURF) RECOURSE The efficacy of LONSURF was evaluated in RECOURSE (NCT01607957), an international, randomized, double-blind, placebo-controlled study conducted in patients with previously treated metastatic colorectal cancer (mCRC). Key eligibility criteria included prior treatment with at least 2 lines of standard chemotherapy for metastatic CRC, ECOG performance status (PS) 0-1, absence of brain metastasis, and absence of ascites requiring drainage in the past four weeks. Patients were randomize...

The following clinically significant adverse reactions are described elsewhere in the labeling: Severe Myelosuppression [see Warnings and Precautions (5.1) ] The most common adverse reactions or laboratory abnormalities for single agent LONSURF (≥10%) are neutropenia, anemia, thrombocytopenia, fatigue, nausea, decreased appetite, diarrhea, vomiting, abdominal pain, and pyrexia. ( 6.1 ) The most common adverse reactions or laboratory abnormalities for LONSURF in combination with bevacizumab (≥20%...

None. None. ( 4 )

Severe Myelosuppression: Obtain complete blood counts prior to and on Day 15 of each cycle. Withhold and resume at next lower LONSURF dosage as recommended. ( 2.1 , 5.1 ) Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus and to use effective contraception. ( 5.2 , 8.1 , 8.3 ) 5.1 Severe Myelosuppression In the 1114 patients who received LONSURF as a single agent, LONSURF caused severe or life-threatening myelosuppression (Grade...