b'Table 6: Select Laboratory Abnormalities (10%) in SUNLIGHT 8.4Pediatric Use Commander, DENTACChief of PharmacyLONSURF + LONSURFa Safety and effectiveness of LONSURF in pediatric patients have not beenMajor Yu-Sheng (David) ChenLaboratory parametersa established. Lt. Col. Marco OchoaBevacizumab Grade Juvenile Animal Toxicity Data Deputy Commander All Grade All Dental toxicity including whitening, breakage, and malocclusion (degeneration Grades 3 or 4 Grades 3 or 4 and disarrangement in the ameloblasts, papillary layer cells and odontoblasts)for Administration M A R Y L A N D(%) (%) (%) (%) were observed in rats treated with trifluridine/tipiracil at doses50 mg/kg Maj. Maxwell CarrollChemistry (approximately 0.33 times the exposure at the clinical dose of 35 mg/m2 Commander Kirk U.S. Army Health ClinicAspartate aminotransferase342.1281.2 twice daily).Deputy Commander for QualityCol. Samuel L Preston 6455 Machine Streetincreased 8.5Geriatric Use and Safety Alanine aminotransferase333.3230.4 Of the 1114 patients with metastatic colorectal cancer or gastric cancer whoMs. Tracy Wooten Command Sergeant MajorAberdeen Proving Groundincreased received single agent LONSURF in clinical studies, 45% were 65 years ofMaj. Gary D. PettyMD 21005-5163age or over, and 11% were 75 and over. In the 246 patients who receivedDeputy to the CDR for Quality410-278-5475Alkaline phosphatase increased310.8361.2 LONSURF in combination with bevacizumab; 41% were 65 years of age orand SafetyChief of PharmacySodium decreased252.1203.3 over, and 10% were 75 and over. While these studies were not designedLt. Col. Michele HudakPotassium increased170150 to detect a difference in efficacy, no overall differences were observed inMr. Tim Stevenspatients 65 or older versus younger patients with either LONSURF as a single Potassium decreased120.8122.5 agent or LONSURF in combination with bevacizumab. Chief of Pharmacy Ireland Army Health ClinicCreatinine increased120.8150 Patients 65 years of age or older who received LONSURF as a single agentMaj. Gregory Hare 871 Brule StreetaEach test incidence is based on the number of patients who had bothhad a higher incidence of the following hematologic laboratory abnormalitiesFort Knox, KY 40121-5111baseline and at least one on-study laboratory measurement available:compared to patients younger than 65 years: Grade 3 or 4 neutropenia (46%Irwin ArmyLONSURF + bevacizumab group (n=242 patients) and LONSURF groupvs 32%), Grade 3 anemia (20% vs 14%), and Grade 3 or 4 thrombocytopenia502-624-9333 Commander(range: 240 to 242 patients). (6% vs 3%). Patients 65 years of age or older who received LONSURF in Community Hospital8USE IN SPECIFIC POPULATIONS combination with bevacizumab had a higher incidence of the following650 Huebner Road Lt. Col. Lauris Trimble8.1Pregnancy hematologic laboratory abnormalities compared to patients younger than Fort Riley, KS 66442-5037 Senior Enlisted LeaderRisk Summary 65 years: Grade 3 or 4 neutropenia (60% vs 46%) and Grade 3 or 4 thrombocytopenia (5% vs 4%). 785-239-7000 MSG Jamika WilliamsBased on animal data and its mechanism of action [see Clinical Pharmacology(12.2) in the full Prescribing Information], LONSURF can cause fetal harm.8.6Renal Impairment Deputy Commander for NursingLONSURF caused embryo-fetal lethality and embryo-fetal toxicity in pregnantNo dose adjustment is recommended for patients with mild or moderate rats when given during gestation at doses resulting in exposures lower thanrenal impairment (CLcr of 30 to 89 mL/min as determined by the Cockcroft- Commander Maj. Julia Ryanor similar to human exposures at the recommended clinical dose (see Data).Gault formula). Reduce the dose of LONSURF for patients with severe renal There are no available data on LONSURF use in pregnant women. Adviseimpairment (CLcr of 15 to 29 mL/min) [see Dosage and Administration (2.3) Col. Scott M. Farley Deputy Commander pregnant women of the potential risk to a fetus. in the full Prescribing Information]. The pharmacokinetics of trifluridine and of Administration In the U.S. general population, the estimated background risk of major birthtipiracil have not been studied in patients with end stage renal disease. Command Sergeant MajorHipolito Garzadefects and miscarriage in clinically recognized pregnancies is 2-4% and8.7Hepatic Impairment Commander CSM Bradford Webster15-20%, respectively.No adjustment to the starting dosage of LONSURF is recommended for patients Data with mild hepatic impairment. Do not initiate LONSURF in patients withCol. Laudino M. Castillo-Rojas Deputy Commander forKimbrough AmbulatoryAnimal Data baseline moderate or severe (total bilirubin 1.5 times ULN and any AST)Command Sergeant Major AdministrationCare CenterTrifluridine/tipiracil was administered orally once daily to female rats duringhepatic impairment [see Clinical Pharmacology (12.3) in the full Prescribing organogenesis at dose levels of 15, 50, and 150 mg/kg [trifluridine (FTD)Information]. CSM Meredith R. Greene Lt. Col. Eun Choi 2480 Llewellyn Avenueequivalent]. Decreased fetal weight was observed at FTD doses 50 mg/kg2 17PATIENT COUNSELING INFORMATION Deputy Commander for ClinicalFort Meade, MD 20755-5129(approximately 0.33 times the FTD exposure at the clinical dose of 35 mg/m Advise the patient to read the FDA-approved patient labeling (Patient Information). Deputy Commander Services301-677-8800twice daily). At the FTD dose of 150 mg/kg (approximately 0.92 times theSevere Myelosuppression for Administration FTD exposure at the clinical dose of 35 mg/m2 twice daily) embryolethalityAdvise patients to immediately contact their healthcare provider if theyLt. Col. Michael Crivello Lt. Col. Juan C. Saaverdraand structural anomalies (kinked tail, cleft palate, ectrodactyly, anasarca,experience signs or symptoms of infection and advise patients to keep all alterations in great vessels, and skeletal anomalies) were observed. appointments for blood tests [see Warnings and Precautions (5.1)]. Deputy Commander Deputy Commander for Nursing 8.2Lactation Gastrointestinal Toxicity for Nursing and Patient ServicesServicesRisk Summary Advise patients to contact their healthcare provider for severe or persistentLt. Col. Monica LooneyThere are no data on the presence of trifluridine, tipiracil or its metabolitesCol. Hyun Kangin human milk or its effects on the breastfed child or on milk production.nausea, vomiting, diarrhea, or abdominal pain [see Adverse Reactions (6.1)]. Chief, Clinical SupportIn nursing rats, trifluridine and tipiracil or their metabolites were present inAdministration Instructions Deputy Commander Commanderbreast milk (see Data). Because of the potential for serious adverse reactionsAdvise patients that LONSURF is available in two strengths and they mayfor Clinical ServicesMaj. Mallory Pinger Col. Darryl M. Metcalfin breastfed children, advise women not to breastfeed during treatment withreceive both strength tablets to provide the prescribed dosage. Lt. Col. Jarett SkinnerLONSURF and for 1 day following the final dose.Advise patients to take LONSURF with food [see Dosage and AdministrationCommand Sergeant Major Data (2.1) in the full Prescribing Information]. Deputy Commander L O U I S I A N A CSM Kathleen HedgesRadioactivity was excreted in the milk of nursing rats dosed with trifluridine/ Advise patients not to retake doses of LONSURF that are vomited or missedfor Quality and Safety tipiracil containing 14C-FTD or 14C-tipiracil (TPI). Levels of FTD-derivedand to continue with the next scheduled dose. Bayne-Jones Army Deputy Commanderradioactivity were as high as approximately 50% of the exposure in maternalAdvise patients that anyone else who handles their medication should wearMr. Reynold Mosier Community Hospital for Clinical Services plasma an hour after dosing with trifluridine/tipiracil and were approximately gloves [see References (15) in the full Prescribing Information].the same as those in maternal plasma for up to 12 hours following dosing.1585 3rd Street Col. Nkemakonam I. OkpokwasiliExposure to TPI-derived radioactivity was higher in milk than in maternalEmbryo-Fetal Toxicity K E N T U C K Y Building 285 plasma beginning 2 hours after dosing and continuing for at least 12 hoursAdvise pregnant women and females of reproductive potential of the potentialDeputy Commander for Nursing following administration of trifluridine/tipiracil.risk to the fetus. Advise females to inform their healthcare provider of aBlanchfield Army Fort Polk, LA 71459-5110 Col. Jimmie J. Tolvert8.3Females and Males of Reproductive Potential known or suspected pregnancy [see Warnings and Precautions (5.2), Use 337-531-3118Pregnancy Testing in Specific Populations (8.3)].Community Hospital Pharmacy ChiefVerify pregnancy status in females of reproductive potential prior to initiatingAdvise female patients of reproductive potential to use effective contraception650 Joel Drive Sarah ShearinLONSURF [see Use in Specific Populations (8.1)]. during treatment with LONSURF and for at least 6 months after the final doseFort Campbell, KY 42223-5349Contraception [see Warnings and Precautions (5.2), Use in Specific Populations (8.3)]. 270-798-8400 Barquist Detrick U.S. Army LONSURF can cause fetal harm when administered to a pregnant womanAdvise males with female partners of reproductive potential to use condoms [see Use in Specific Populations (8.1)]. during treatment with LONSURF and for at least 3 months after the final doseHealth ClinicFemales [see Use in Specific Populations (8.3), Nonclinical Toxicology (13.1) in the 1434 Porter StreetAdvise females of reproductive potential to use effective contraception duringfull Prescribing Information]. Commander Frederick, MD 21702-9210treatment with LONSURF and for at least 6 months after the final dose. LactationAdvise women not to breastfeed during treatment with LONSURF and for 1 dayCol. Alisa R. Wilma 301-619-7175Males following the final dose [see Use in Specific Populations (8.2)].Because of the potential for genotoxicity, advise males with female partnersCommand Sergeant Major of reproductive potential to use condoms during treatment with LONSURFLarry D. White IIand for at least 3 months after the final dose [see Nonclinical Toxicology(13.1) in the full Prescribing Information].TAIHO ONCOLOGY, INC.08/2023LON-PM-US-1722U.S. ARMY MEDICAL TREATMENT FACILITIESTHEDIRECTORYTaiho_Directory_USMed_Dec2023_FullAd_NAout_7.875x10.75_L09.indd 5 11/27/23 6:17 PM'