b'IMFINZI (durvalumab) injection, Table 4. Recommended Dosage Modifications for AdverseIMFINZI in Combination with Other Products for intravenous use Reactions (contd) Administer all drug products as separate intravenous infusions.Initial U.S. Approval: 2017AdverseSeverity * DosageDo not co-administer other drugs through the same infusion line.Brief Summary of Prescribing InformationReaction Modification Forplatinum-basedchemotherapy,refertoPrescribing For complete prescribing information consultAST or ALT is more than 1 andInformation for administration information.official package insert. up to 3 times ULN at baselineFor pemetrexed therapy, refer to Prescribing Information for INDICATIONS AND USAGE and increases to more than administration information. 5 and up to 10 times ULN Combination Regimens: Order of InfusionsHepatocellular Carcinoma or Withhold IMFINZI in Combination with Tremelimumab-actlIMFINZI, in combination with tremelimumab-actl, is indicated forHepatitisAST or ALT is more thanthe treatment of adult patients with unresectable hepatocellularwith tumor3 and up to 5 times ULN atInfuse tremelimumab-actl first, followed by IMFINZI on the same carcinoma (uHCC). involvement ofbaseline and increases to moreday of dosing.DOSAGE AND ADMINISTRATION the liver than 8 and up to 10 times ULN IMFINZIinCombinationwithTremelimumab-actland Recommended Dosage AST or ALT increases to morePlatinum-Based ChemotherapyThe recommended dosages for IMFINZI as a single agent andthan 10 times ULNPermanentlyInfuse tremelimumab-actl first, followed by IMFINZI and then IMFINZIincombinationwithothertherapeuticagentsareor discontinue platinum-based chemotherapy on the day of dosing.presented in Table 1.total bilirubin increases toIMFINZI in Combination with Tremelimumab-actl and Pemetrexed Administer IMFINZI as an intravenous infusion after dilution asmore than 3 times ULN TherapyWithhold untilInfuse tremelimumab-actl first, followed by IMFINZI and then recommended [see Dosage and Administration (2.3) in the fullclinically stablepemetrexed therapy on the day of dosing.Prescribing Information]. Endocrinopathies Grade 3 or 4 or permanently Table 1. Recommended Dosages of IMFINZI discontinueCombination Regimens: Infusion InstructionsIndication Recommended IMFINZI Dosage Duration ofdepending IMFINZI in Combination with Tremelimumab-actlTherapy on severity Administer tremelimumab-actl over 60 minutes followed by a Combination with Other Therapeutic Agents Nephritis withGrade 2 or 3 increased Withhold 60 minute observation period. Then administer IMFINZI as a Renal blood creatinine separate intravenous infusion over 60 minutes.uHCC Patients with a body weight After Dysfunction Grade 4 increased PermanentlyIMFINZI in Combination with Tremelimumab-actl and Platinum- of30 kg: Cycle 1 ofblood creatinine discontinueIMFINZI 1,500 mg following acombinationSuspected SJS, TEN,Based Chemotherapy/ Pemetrexed Therapy single dose of tremelimumab-actl $ therapy,Exfoliativeor DRESS Withhold Cycle 1300 mg at Day 1 of Cycle 1; administerDermatologic Confirmed SJS, TEN, PermanentlyInfuse tremelimumab-actl over 1 hour. One to two hours after Continue IMFINZI 1,500 mg as IMFINZI as aConditions or DRESS discontinue completion of tremelimumab-actl infusion, infuse IMFINZI over a single agent every 4 weeks single agentPermanently1 hour. One to two hours after completion of IMFINZI infusion, every Myocarditis Grade 2, 3, or 4 discontinue administer platinum-based chemotherapy.Patients with a body weight 4 weeks Subsequent Cyclesof 30 kg: until diseaseNeurologicalGrade 2 WithholdIMFINZI 20 mg/kg following aprogression orToxicities Grade 3 or 4 PermanentlyIf there are no infusion reactions during cycle 1, subsequent single dose of tremelimumab-actl $ unacceptablediscontinue cycles of IMFINZI can be given immediately after tremelimumab- 4 mg/kg at Day 1 of Cycle 1; toxicity Other Adverse Reactions actl. The time between the end of the IMFINZI infusion and the Continue IMFINZI 20 mg/kg as aInfusion-relatedInterrupt or start of chemotherapy can be reduced to 30 minutes.single agent every 4 weeks reactions [seeGrade 1 or 2 slow the rate CONTRAINDICATIONS$Administer tremelimumab-actl prior to IMFINZI on the same day. WhenWarnings andof infusion None.tremelimumab-actl is administered in combination with IMFINZI, refer toPrecautionsWARNINGS AND PRECAUTIONS the Prescribing Information for tremelimumab-actl dosing information. (5.2) in the fullGrade 3 or 4 Permanently Prescribingdiscontinue Immune-Mediated Adverse ReactionsDosage Modifications for Adverse Reactions Information] IMFINZI is a monoclonal antibody that belongs to a class of drugs NodosereductionforIMFINZIisrecommended.Ingeneral,ALT = alanine aminotransferase, AST = aspartate aminotransferase, DRESS =that bind to either the programmed death-receptor 1 (PD-1) or the withhold IMFINZI for severe (Grade 3) immune-mediated adverseDrug Rash with Eosinophilia and Systemic Symptoms, SJS = Stevens JohnsonPD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby reactions.PermanentlydiscontinueIMFINZIforlife-threateningSyndrome, TEN = toxic epidermal necrolysis, ULN = upper limit normal. removing inhibition of the immune response, potentially breaking (Grade 4) immune-mediated adverse reactions, recurrent severe*Based on National Cancer Institute Common Terminology Criteria forperipheraltoleranceandinducingimmune-mediatedadverse Adverse Events, version 4.03.(Grade3)immune-mediatedreactionsthatrequiresystemic Resume in patients with complete or partial resolution (Grade 0 to 1)reactions.Importantimmune-mediatedadversereactionslisted immunosuppressive treatment, or an inability to reduce cortico-after corticosteroid taper. Permanently discontinue if no complete or partialunder Warnings and Precautions may not include all possible severe steroid dose to 10 mg or less of prednisone or equivalent per dayresolution within 12 weeks of initiating corticosteroids or an inability to reduceand fatal immune-mediated reactions.within 12 weeks of initiating corticosteroids. corticosteroid dose to 10 mg of prednisone or less per day (or equivalent)The incidence and severity of immune-mediated adverse reactions within 12 weeks of initiating corticosteroids.Dosage modifications for IMFINZI or IMFINZI in combination were similar when IMFINZI was administered as a single agent Permanently discontinue IMFINZI for Grade 3 colitis when administered as with tremelimumab-actl and platinum-based chemotherapy forpart of a tremelimumab-actl containing regimen. orincombinationwithchemotherapyorincombinationwith adverse reactions that require management different from theseIf AST and ALT are less than or equal to ULN at baseline in patients withtremelimumab-actlandplatinum-basedchemotherapy,unless general guidelines are summarized in Table 4. liver involvement, withhold or permanently discontinue IMFINZI based onotherwise noted.Table 4. Recommended Dosage Modifications for Adverserecommendations for hepatitis with no liver involvement. Immune-mediated adverse reactions, which may be severe or fatal, Reactions Preparation and Administration can occur in any organ system or tissue. Immune-mediated adverse AdverseSeverity * DosagePreparation reactions can occur at any time after starting treatment with a PD-1/Reaction Modification VisuallyinspectdrugproductforparticulatematterandPD-L1 blocking antibody. While immune-mediated adverse reactions Immune-Mediated Adverse Reactions [see Warnings anddiscoloration prior to administration, whenever solution andusuallymanifestduringtreatmentwithPD-1/PD-L1blocking Precautions (5.1) in the full Prescribing Information] container permit. Discard the vial if the solution is cloudy,antibodies, immune-mediated adverse reactions can also manifest Grade 2 Withhold discolored, or visible particles are observed. after discontinuation of PD-1/PD-L1 blocking antibodies.Pneumonitis PermanentlyDo not shake the vial. Early identification and management of immune-mediated adverse Grade 3 or 4 discontinue Withdraw the required volume from the vial(s) of IMFINZIreactions are essential to ensure safe use of PD-1/PD-L1 blocking Grade 2 Withhold and transfer into an intravenous bag containing 0.9% Sodiumantibodies. Monitor patients closely for symptoms and signs that Chloride Injection, USP or 5% Dextrose Injection, USP. Mixmay be clinical manifestations of underlying immune-mediated Withhold ordilutedsolutionbygentleinversion.Donotshaketheadversereactions.Evaluateliverenzymes,creatinine,and Colitis Grade 3 permanentlysolution. The final concentration of the diluted solution shouldthyroid function at baseline and periodically during treatment. In discontinuebe between 1 mg/mL and 15 mg/mL. cases of suspected immune-mediated adverse reactions, initiate Grade 4 PermanentlyDiscard partially used or empty vials of IMFINZI. appropriateworkuptoexcludealternativeetiologies,including discontinue Storage of Infusion Solution infection.Institutemedicalmanagementpromptly,including IntestinalAny grade PermanentlyIMFINZI does not contain a preservative.specialty consultation as appropriate.perforation discontinue Administer infusion solution immediately once prepared. If theWithholdorpermanentlydiscontinueIMFINZIdependingon ALT or AST increases to moreinfusion solution is not administered immediately and needsseverity [see Dosage and Administration (2.2) in the full Prescribing than 3 and up to 8 timesto be stored, the time from preparation until the completionInformation].Ingeneral,ifIMFINZIrequiresinterruptionor the ULN of the infusion should not exceed: discontinuation, administer systemic corticosteroid therapy (1 mg or Withhold o28 days in a refrigerator at 2C to 8C (36F to 46F) to 2 mg/kg/day prednisone or equivalent) until improvement to Hepatitis withtotal bilirubin increases too8 hours at room temperature up to 25C (77F) Grade 1 or less. Upon improvement to Grade 1 or less, initiate no tumormore than 1.5 and up to Do not freeze. corticosteroid taper and continue to taper over at least 1 month. involvement 3 times ULN Do not shake. Consider administration of other systemic immunosuppressants of the liver ALT or AST increases to moreAdministration in patients whose immune-mediated adverse reactions are not than 8 times ULN PermanentlyAdminister infusion solution intravenously over 60 minutescontrolled with corticosteroid therapy.ordiscontinue through an intravenous line containing a sterile, low-proteinToxicity management guidelines for adverse reactions that do not total bilirubin increases tobinding 0.2 or 0.22 micron in-line filter. necessarily require systemic steroids (e.g., endocrinopathies and more than 3 times the ULN Use separate infusion bags and filters for each drug product. dermatologic reactions) are discussed below.US-76417_US-77669_US-77951 Imfinzi-Imjudo US Medicine - The Compendium.indd 3 12/6/23 3:45 PM'