b'IMFINZI (durvalumab) injection, for intravenous use 4Table 13 summarizes the adverse reactions that occurred in patientsEach test incidence is based on the number of patients who had bothGeriatric Usetreated with IMFINZI in combination with tremelimumab-actl in thebaseline and at least one on-study laboratory measurement available:Of the 476 patients treated with IMFINZI in the PACIFIC study, HIMALAYA study. IMFINZIwithtremelimumab-actl(range:367-378)andsorafenib45% were 65 years or older, while 7.6% were 75 years or older. Table 13. Adverse Reactions Occurring in10% of Patients in(range: 344-352). No overall differences in safety or effectiveness were observed the HIMALAYA study USE IN SPECIFIC POPULATIONS between patients 65 years or older and younger patients. The Pregnancy PACIFIC study did not include sufficient numbers of patients aged IMFINZI andSorafenib75 years and over to determine whether they respond differently Tremelimumab-actl (N = 374) Risk Summary fromyounger patients.(N = 388) Based on findings from animal studies and its mechanism ofOf the 393 patients with uHCC treated with IMFINZI in combination action, IMFINZI can cause fetal harm when administered to awith tremelimumab-actl, 50% of patients were 65 years of age AdverseAll Grades Grade 3-4 All Grades Grade 3-4pregnant woman [see Clinical Pharmacology (12.1) in the fullor older and 13% of patients were 75 years of age or older. No Reaction (%) (%) (%) (%) Prescribing Information]. There are no available data on the useoverall differences in safety or effectiveness of IMFINZI have been Gastrointestinal disorders of IMFINZI in pregnant women. observed between patients 65 years of age and older and younger Diarrhea* 27 6 45 4.3 Inanimalreproductionstudies,administrationofdurvalumabadult patients.Abdominal pain* 20 1.8 24 4 topregnantcynomolgusmonkeysfromtheconfirmationofPATIENT COUNSELING INFORMATION Nausea 12 0 14 0 pregnancythroughdeliveryatexposurelevelsapproximatelyAdvisethepatienttoreadtheFDA-approvedpatientlabeling 6 to 20 times higher than those observed at the clinical dose Skin and subcutaneous tissue disorders of 10 mg/kg based on area under the curve (AUC), resulted(Medication Guide in the full Prescribing Information).Rash* 32 2.8 57 12 in an increase in premature delivery, fetal loss, and prematureImmune-Mediated Adverse ReactionsPruritus 23 0 6 0.3 neonatal death (see Data). Human immunoglobulin G1 (IgG1) isInform patients of the risk of immune-mediated adverse reactions Metabolism and nutrition disorders known to cross the placental barrier; therefore, durvalumab hasthatmayrequirecorticosteroidtreatmentandinterruptionor the potential to be transmitted from the mother to the developingdiscontinuation of IMFINZI [see Warnings and Precautions (5.1) in Decreased 17 1.3 18 0.8 fetus. Apprise pregnant women of the potential risk to a fetus. the full Prescribing Information], including:appetite In the U.S. general population, the estimated background risk ofPneumonitis:Advisepatientstocontacttheirhealthcare General disorders and administration site conditions majorbirthdefectsandmiscarriageinclinicallyrecognizedprovider immediately for any new or worsening cough, chest Fatigue* 26 3.9 30 6 pregnancies is 2 to 4% and 15 to 20%, respectively. pain, or shortness of breath.Pyrexia* 13 0.3 9 0.3 Data Hepatitis: Advise patients to contact their healthcare provider Psychiatric disorders Animal Data immediately for jaundice, severe nausea or vomiting, pain As reported in the literature, the PD-1/PD-L1 pathway plays aon the right side of abdomen, lethargy, or easy bruising Insomnia 10 0.3 4.3 0 centralroleinpreservingpregnancybymaintainingmaternalor bleeding.Endocrine disorders immune tolerance to the fetus. In mouse allogeneic pregnancyColitis: Advise patients to contact their healthcare provider Hypothyroidism* 14 0 6 0 models, disruption of PD-L1 signaling was shown to result in animmediatelyfordiarrhea,bloodormucusinstools,or Musculoskeletal and Connective Tissue Disorders increase in fetal loss. The effects of durvalumab on prenatal andsevere abdominal pain.Musculoskeletal22 2.6 17 0.8 postnatal development were evaluated in reproduction studies inEndocrinopathies:Advisepatientstocontacttheir pain* cynomolgus monkeys. Durvalumab was administered from thehealthcare provider immediately for signs or symptoms of confirmation of pregnancy through delivery at exposure levelshypothyroidism,hyperthyroidism,adrenalinsufficiency, * Represents a composite of multiple related terms. approximately 6 to 20 times higher than those observed at atype 1 diabetes mellitus, or hypophysitis.Table 14 summarizes the laboratory abnormalities that occurred inclinical dose of 10mg/kg (based on AUC). Administration ofNephritis: Advise patients to contact their healthcare provider patients treated with IMFINZI in combination with tremelimumab-durvalumab resulted in premature delivery, fetal loss (abortionimmediately for signs or symptoms of nephritis.actl in the HIMALAYA study. and stillbirth), and increase in neonatal deaths. Durvalumab wasDermatological Reactions: Advise patients to contact their detected in infant serum on postpartum Day 1, indicating thehealthcare provider immediately for signs or symptoms of Table 14. Laboratory Abnormalities Worsening from Baselinepresenceofplacentaltransferofdurvalumab.Basedonitssevere dermatological reactions.Occurring in20% of Patients in the HIMALAYA study mechanism of action, fetal exposure to durvalumab may increasePancreatitis:Advisepatientstocontacttheirhealthcare IMFINZI and Sorafenib the risk of developing immune-mediated disorders or altering theprovider immediately for signs or symptoms of pancreatitis.Tremelimumab-actl normal immune response and immune-mediated disorders haveOther Immune-Mediated Adverse Reactions: Advise patients Laboratory Any Grade 3Any Grade 3 been reported in PD-1 knockout mice. to contact their healthcare provider immediately for signs or Abnormality gradeor 4 gradeor 4 Lactation symptoms of pancreatitis, aseptic meningitis, encephalitis, (%)(%)(%)(%)Risk Summary immune thrombocytopenia, myocarditis, hemolytic anemia, Chemistry There are no data on the presence of durvalumab in human milk,myositis, uveitis, keratitis, and myasthenia gravis.its effects on the breastfed child, or the effects on milk production.Infusion-Related Reactions: Aspartate 63 27 55 21 Maternal IgG is known to be present in human milk. The effectsAdvisepatientstocontacttheirhealthcareprovider Aminotransferaseof local gastrointestinal exposure and limited systemic exposureimmediatelyforsignsorsymptomsofinfusion-related increased in the breastfed child to IMFINZI are unknown. Durvalumab wasreactions [see Warnings and Precautions (5.2) in the full Alanine 56 18 53 12 present in the milk of lactating cynomolgus monkeys and wasPrescribing Information].Aminotransferaseassociated with premature neonatal death (see Data).Complications of Allogeneic HSCT: increased Because of the potential for adverse reactions in a breastfed child,Advisepatientsofpotentialriskofpost-transplant Sodium 46 15 40 11 advise women not to breastfeed during treatment with IMFINZIcomplications [see Warnings and Precautions (5.3) in the decreased and for 3 months after the last dose. Refer to the Prescribingfull Prescribing Information].Bilirubin 41 8 47 11 Informationfortheagentsadministeredincombinationwith increased IMFINZI for recommended duration to not breastfeed, as appropriate. Embryo-Fetal Toxicity: Data AdvisefemalesofreproductivepotentialthatIMFINZI Alkaline 41 8 44 5 In lactating cynomolgus monkeys, durvalumab was present incan cause harm to a fetus and to inform their healthcare Phosphatasebreast milk at about 0.15% of maternal serum concentrations afterprovider of a known or suspected pregnancy [see Warnings increased administration of durvalumab from the confirmation of pregnancyandPrecautions(5.4)andUseinSpecificPopulations Glucose increased 39 14 29 4 through delivery at exposure levels approximately 6 to 20 times(8.1, 8.3) in the full Prescribing Information].Calcium 34 0 43 0.3 higher than those observed at the recommended clinical dose ofAdvise females of reproductive potential to use effective decreased 10mg/kg (based on AUC). Administration of durvalumab resultedcontraception during treatment and for 3 months after the Albumin 31 0.5 37 1.7 in premature neonatal death. last dose of IMFINZI [see Use in Specific Populations (8.3) decreased Females and Males of Reproductive Potential in the full Prescribing Information].Potassium 28 3.8 21 2.6 Pregnancy testing Lactation: increased Verify pregnancy status of females of reproductive potential priorAdvise female patients not to breastfeed while taking IMFINZI Creatinine 21 1.3 15 0.9 to initiating treatment with IMFINZI.and for 3 months after the last dose [see Warnings and Precautions (5.4) and Use in Specific Populations (8.2) inincreased Contraception the full Prescribing Information].Hematology FemalesHemoglobin 52 4.8 40 6 IMFINZI can cause fetal harm when administered to a pregnantManufactured for:decreased woman [see Use in Specific Populations (8.1) in the full PrescribingAstraZeneca Pharmaceuticals LP, Wilmington, DE 19850Information]. Advise females of reproductive potential to use effectiveBy: AstraZeneca UK Limited Lymphocytes 41 11 39 10 contraception during treatment with IMFINZI and for 3 months1 Francis Crick Ave., Cambridge, England CB2 0AA decreased following the last dose of IMFINZI. Refer to the PrescribingUS License No. 2043Platelets 29 1.6 35 3.1 Information for the agents administered in combination with IMFINZIIMFINZI is a registered trademark of the AstraZenecadecreased for recommended contraception duration, as appropriate. group of companies.Leukocytes 20 0.8 30 1.1 Pediatric UseAstraZeneca 2022 decreased The safety and effectiveness of IMFINZI have not been established Graded according to NCI CTCAE version 4.03. in pediatric patients. 6/23 US-77669 7/23US-76417_US-77669_US-77951 Imfinzi-Imjudo US Medicine - The Compendium.indd 6 12/6/23 3:45 PM'