b'CALQUENCE (acalabrutinib) tablets, for oral useInformation]. These infections predominantly occurred in the absence of Chronic Lymphocytic Leukemia CALQUENCE (acalabrutinib) tablets, for oral use 2Initial U.S. Approval: 2017 Grade 3 or 4 neutropenia, with neutropenic infection reported in 1.9% The safety data described below reflect exposure to CALQUENCE (100 mgBrief Summary of Prescribing Information.of all patients. Opportunistic infections in recipients of CALQUENCE approximatelyevery12hours,withorwithoutobinutuzumab)inIncludes any adverse reactions involving infection or febrile neutropenia Table 7: Common Adverse Reactions ( 15% Any Grade) withdata in pregnant women to inform the drug-associated risk. In animal For full Prescribing Information consult official package insert.have included, but are not limited to, hepatitis B virus reactivation, 511 patients with CLL from two randomized controlled clinical trialsIncludes 3 fatal cases in the CALQUENCE plus obinutuzumab arm, 3 fatal casesCALQUENCE in Patients with CLL (ASCEND) reproduction studies, administration of acalabrutinib to animals during fungalpneumonia,Pneumocystisjiroveciipneumonia,Epstein-Barr [see Clinical Studies (14.2) in the full Prescribing Information]. in the CALQUENCE monotherapy arm and 1 fatal case in the obinutuzumab plusorganogenesis resulted in dystocia in rats and reduced fetal growth in INDICATIONS AND USAGEvirusreactivation,cytomegalovirus,andprogressivemultifocal The most common adverse reactions ( 30%) of any grade in patients chlorambucil arm CALQUENCE IdelalisibBendamustinerabbits at maternal exposures (AUC) 2 times exposures in patients at the Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma leukoencephalopathy (PML). Consider prophylaxis in patients who are at with CLL were anemia, neutropenia, thrombocytopenia, headache, upperaIncludes upper respiratory tract infection, nasopharyngitis and sinusitis bronchiolitis,N=154 plus Rituximab plus Rituximabrecommended dose of 100 mg approximately every 12 hours (see Data). CALQUENCE is indicated for the treatment of adult patients with chronicincreased risk for opportunistic infections. Monitor patients for signs and respiratory tract infection, and diarrhea.Includes pneumonia, lower respiratory tract infection, bronchitis,Product N=118 Product N=35lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). symptoms of infection and treat promptly. b tracheitis, and lung infection Body System AllGrade AllGrade AllGrade Advise pregnant women of the potential risk to a fetus.ELEVATE-TN cDerived from adverse reaction and laboratory data The estimated background risk of major birth defects and miscarriage DOSAGE AND ADMINISTRATIONHemorrhageThesafetyofCALQUENCEplusobinutuzumab(CALQUENCE+G),dIncludes neutropenia, neutrophil count decreased, and related laboratory data AdverseGrades 3 Grades 3 Grades 3 for the indicated population is unknown. All pregnancies have a Recommended Dosage Fatal and serious hemorrhagic events have occurred in patients with CALQUENCE monotherapy, and obinutuzumab plus chlorambucil (GClb) eIncludes anemia, red blood cell count decreased, and related laboratory data Reaction* (%) (%) (%) (%) (%) (%) background risk of birth defect, loss, or other adverse outcomes. In hematologic malignancies treated with CALQUENCE. Major hemorrhageIncludes thrombocytopenia, platelet count decreased, and related laboratory data Infections CALQUENCE as Monotherapy (serious or Grade 3 or higher bleeding or any central nervous system wasevaluatedinarandomized,multicenter,open-label,activelyf Includes lymphocytosis, lymphocyte count increased, and related laboratory data Infection56 1565 2849 11 the U.S. general population, the estimated background risk of major For patients with CLL, or SLL, the recommended dosage of CALQUENCEbleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring in controlled trial in 526 patients with previously untreated CLL [seeg Includes back pain, bone pain, musculoskeletal chest pain, musculoskeletal pain,Upper respiratory29 1.9 26 3.4 17 2.9 birth defects and miscarriage in clinically recognized pregnancies is is 100 mg taken orally approximately every 12 hours until disease 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. Bleeding Clinical Studies (14.2) in the full Prescribing Information]. h musculoskeletal discomfort, myalgia, neck pain, pain in extremity and spinal pain tract infection 2 to 4% and 15 to 20%, respectively.progression or unacceptable toxicity. Patients randomized to the CALQUENCE+G arm were treated withiIncludes asthenia, fatigue, and lethargyevents of any grade, excluding bruising and petechiae, occurred in 22% ofIncludes bruise, contusion, and ecchymosis Lower respiratory23 6 26 15 14 6 Data CALQUENCE and obinutuzumab in combination for six cycles, thenj aCALQUENCE in Combination with Obinutuzumab patients [see Adverse Reactions (6.1) in the full Prescribing Information]. withCALQUENCEasmonotherapyuntildiseaseprogression orkIncludes rash, dermatitis, and other related terms tract infection b Animal DataFor patients with previously untreated CLL or SLL, the recommendedUse of antithrombotic agents concomitantly with CALQUENCE may further unacceptable toxicity. Patients initiated obinutuzumab on Day 1 ofIncludeshemorrhage,hematoma,hemoptysis,hematuria,menorrhagia,Blood and lymphatic system disorders Inacombinedfertilityandembryo-fetaldevelopmentstudyin dosage of CALQUENCE is 100 mg taken orally approximately everyincrease the risk of hemorrhage. In clinical trials, major hemorrhage Cycle 2, continuing for a total of 6 cycles. Patient randomized to hemarthrosis, and epistaxis Neutropeniac 48 23 79 53 80 40 female rats, acalabrutinib was administered orally at doses up to 12 hours until disease progression or unacceptable toxicity. Startoccurred in 2.7% of patients taking CALQUENCE without antithrombotic CALQUENCE monotherapy received CALQUENCE approximately everyOther clinically relevant adverse reactions (all grades incidence 15%)Anemiad 47 15 45 8 57 17 200 mg/kg/day starting 14 days prior to mating through gestational CALQUENCE at Cycle 1 (each cycle is 28 days). Start obinutuzumab at agents and 3.6% of patients taking CALQUENCE with antithrombotic 12 hours until disease progression or unacceptable toxicity. The trialinrecipientsofCALQUENCE(CALQUENCEincombinationwithe day [GD] 17. No effects on embryo-fetal development and survival were Cycle 2 for a total of 6 cycles and refer to the obinutuzumab prescribing agents. Consider the risks and benefits of antithrombotic agents when obinutuzumab and monotherapy) included: Thrombocytopenia33 6 41 13 54 6 observed. The AUC at 200 mg/kg/day in pregnant rats was approximately information for recommended dosing. Administer CALQUENCE prior to co-administered with CALQUENCE. Monitor patients for signs of bleeding. required age65 years of age or 18 to 65 years of age with a totalLymphocytosisf 26 19 23 18 2.9 2.9 9 times the AUC in patients at the recommended dose of 100 mg obinutuzumab when given on the same day. Cumulative Illness Rating Scale (CIRS) 6 or creatinine clearance ofNeoplasms: second primary malignancy (10%), non-melanoma skin Nervous system disorders approximately every 12 hours. The presence of acalabrutinib and its Consider the benefit-risk of withholding CALQUENCE for 3 to 7 days pre- and 30 to 69 mL/min, hepatic transaminases3 times ULN and totalcancer (5%)Advise patients to swallow tablet whole with water. Advise patients not post-surgery depending upon the type of surgery and the risk of bleeding. bilirubin 1.5 times ULN, and allowed patients to receive antithromboticCardiac disorders: atrial fibrillation or flutter (3.6%), hypertension (5%) Headache 22 0.6 6 0 0 0 active metabolite were confirmed in fetal rat plasma.to chew, crush, dissolve, or cut the tablets. CALQUENCE may be taken with Cytopeniasagents other than warfarin or equivalent vitamin K antagonists. Infection: herpesvirus infection (6%) Gastrointestinal disorders In an embryo-fetal development study in rabbits, pregnant animals were or without food. If a dose of CALQUENCE is missed by more than 3 hours, Grade 3 or 4 cytopenias, including neutropenia (23%), anemia (8%), throm- Duringrandomizedtreatment,themediandurationofexposureto Table 6: Select Non-Hematologic Laboratory Abnormalities ( 15%Diarrhea g 18 1.3 49 25 14 0 administered acalabrutinib orally at doses up to 200 mg/kg/day during the it should be skipped and the next dose should be taken at its regularly bocytopenia (7%), and lymphopenia (7%), developed in patients with hemato- CALQUENCEintheCALQUENCE+GandCALQUENCEmonotherapy Vascular disorders period of organogenesis (from GD 6-18). Administration of acalabrutinib scheduled time. Extra tablets of CALQUENCE should not be taken to make logic malignancies treated with CALQUENCE. Grade 4 neutropenia developed arms was 27.7 months (range 0.3 to 40 months), with 95% and 92% Any Grade), New or Worsening from Baseline in Patients ReceivingHemorrhageh 16 1.3 5 1.7 6 2.9 at doses100 mg/kg/day produced maternal toxicity and 100 mg/kg/day up for a missed dose. in 12% of patients [see Adverse Reactions (6.1) in the full Prescribing and 89% and 86% of patients with at least 6 months and 12 months of CALQUENCE (ELEVATE-TN)General disordersresulted in decreased fetal body weights and delayed skeletal ossification. Recommended Dosage for Drug Interactions Information]. Monitor complete blood counts regularly during treatment. exposure, respectively. In the obinutuzumab and chlorambucil arm theCALQUENCECALQUENCE ObinutuzumabFatiguei 15 1.9 13 0.8 31 6 The AUC at 100 mg/kg/day in pregnant rabbits was approximately 2 times Dosage Modifications for Use with CYP3A Inhibitors or InducersInterrupt treatment, reduce the dose, or discontinue treatment as warranted median number of cycles was 6 with 84% of patients receiving at leastplus Monotherapy plus Musculoskeletal and connective tissue disorders the AUC in patients at 100 mg approximately every 12 hours.These are described in Table 1 [see Drug Interactions (7) in the full[see Dosage and Administration (2.3) in the full Prescribing Information]. 6 cycles of obinutuzumab, 70% of patients received at least 6 cycles ofLaboratory Obinutuzumab N=179 Chlorambucil Musculoskeletal painj 15 1.3 15 1.7 2.9 0 In a pre- and postnatal development study in rats, acalabrutinib was Prescribing Information].Second Primary Malignancieschlorambucil. Eighty-five percent of patients in the CALQUENCE+G armAbnormality* , a N=178 N=169 *Per NCI CTCAE version 4.03 administeredorallytopregnantanimalsduringorganogenesis, Table 1:Recommended Dosage Modifications for Use with CYP3A Second primary malignancies, including skin cancers and other solid received at least 6 cycles of obinutuzumab. AllGradeAllGradeAllGrade Includes any adverse reactions involving infection or febrile neutropenia parturition and lactation, at doses of 50, 100, and 150 mg/kg/day. Dystocia Inhibitors or Inducers tumors, occurred in 12% of 1029 patients exposed to CALQUENCEIn the CALQUENCE+G and CALQUENCE monotherapy arms, fatal adverseGrades 3Grades 3Grades 3Includes 1 fatal case in the CALQUENCE monotherapy arm and 1 fatal case in the(prolonged or difficult labor) and mortality of offspring were observed Co-administeredin clinical trials [see Adverse Reactions (6.1) in the full Prescribingreactions that occurred in the absence of disease progression and with(%) (%) (%) (%) (%) (%)Idelalisib plus Rituximab arm at doses100 mg/kg/day. The AUC at 100 mg/kg/day in pregnant rats CYP3A Recommended CALQUENCE use Information]. The most frequent second primary malignancy was skinonset within 30 days of the last study treatment were reported in 2% forUric acid increase 29 29 22 22 37 37 aIncludes upper respiratory tract infection, rhinitis and nasopharyngitis was approximately 2 times the AUC in patients at 100 mg approximately Drug cancer, reported in 6% of patients. Monitor patients for skin cancerseach treatment arm, most often from infection. Serious adverse reactions Includes pneumonia, lower respiratory tract infection, bronchitis, bronchiolitis,every 12 hours. Underdeveloped renal papilla was also observed in Avoid co-administration. and advise protection from sun exposure. were reported in 39% of patients in the CALQUENCE+G arm and 32%ALT increase 30 7 20 1.1 36 6 b tracheitis, and lung infection F1 generation offspring at 150 mg/kg/day with an AUC approximately If these inhibitors will be used short- AST increase 38 5 17 0.6 60 8 cDerived from adverse reaction and laboratory data 5 times the AUC in patients at 100 mg approximately every 12 hours.Cardiac Arrhythmias in the CALQUENCE monotherapy arm, most often due to events of Includes neutropenia, neutrophil count decreased, and related laboratory dataStrong CYP3Aterm (such as anti-infectives for up toSeriouscardiacarrhythmiashaveoccurredinpatientstreatedwith pneumonia (2.8% to 7%). Bilirubin increase 13 0.6 15 0.6 11 0.6 d Includes anemia, red blood cell decreased, and related laboratory data Lactationinhibitor seven days), interrupt CALQUENCE.CALQUENCE. Grade 3 atrial fibrillation or flutter occurred in 1.1% of In the CALQUENCE+G arm, adverse reactions led to treatment discontin- *Per NCI CTCAE version 4.03 e f Includes thrombocytopenia, platelet count decreased, and related laboratory data Risk SummaryInhibition After discontinuation of strong CYP3A1029 patients treated with CALQUENCE, with all grades of atrial fibrillation uation in 11% of patients and a dose reduction of CALQUENCE in 7% ofaExcludes electrolytes gIncludes lymphocytosis, lymphocyte count increased and related laboratory data No data are available regarding the presence of acalabrutinib or its inhibitor for at least 24 hours, resumeh Includes colitis, diarrhea, and enterocolitisprevious dosage of CALQUENCE. or flutter reported in 4.1% of all patients [see Adverse Reactions (6.1) in patients. In the CALQUENCE monotherapy arm, adverse reactions led toIncreases in creatinine to 1.5 to 3 times ULN occurred in 3.9% and 2.8% Includeshemorrhage,hematoma,hemoptysis,hematuria,menorrhagia,active metabolite in human milk, its effects on the breastfed child, or on the full Prescribing Information]. Grade 3 or higher ventricular arrhythmia discontinuation in 10% and dose reduction in 4% of patients. of patients in the CALQUENCE combination arm and monotherapy arm,hemarthrosis, and epistaxis milk production. Acalabrutinib and its active metabolite were present Moderate CYP3AReduce the CALQUENCE 100 mg everyevents were reported in 0.9% of patients. The risk may be increased in Tables 5 and 6 present adverse reactions and laboratory abnormalitiesrespectively. i j Includes asthenia, fatigue, and lethargy in the milk of lactating rats. Due to the potential for adverse reactions inhibitor 12 hours dosage to 100 mg once daily. patients with cardiac risk factors, hypertension, previous arrhythmias, and identified in the ELEVATE-TN trial.Includesbackpain,musculoskeletalchestpain,musculoskeletalpain,in a breastfed child from CALQUENCE, advise lactating women not to Avoid co-administration. acute infection. Monitor for symptoms of arrhythmia (e.g., palpitations, Table5:CommonAdverseReactions(15%AnyGrade)withASCEND musculoskeletal discomfort, pain in extremity, myalgia, spinal pain and bone pain breastfeed while taking CALQUENCE and for 2 weeks after the last dose.Induction Strong CYP3AIf co-administration is unavoidable,dizziness, syncope, dyspnea) and manage as appropriate. CALQUENCE in Patients with CLL (ELEVATE-TN) The safety of CALQUENCE in patients with relapsed or refractory CLL wasOther clinically relevant adverse reactions (all grades incidence 15%) inFemales and Males of Reproductive Potentialinducer increase CALQUENCE dosage toHepatotoxicity, Including Drug-Induced Liver Injury evaluated in a randomized, open-label study (ASCEND) [see Clinical Studiesrecipients of CALQUENCE included: CALQUENCEmaycauseembryo-fetalharmanddystociawhen 200 mg approximately every 12 hours. Hepatotoxicity, including severe, life-threatening, and potentially fatal CALQUENCE CALQUENCE Obinutuzumab(14.2) in the full Prescribing Information]. The trial enrolled patients with Skin and subcutaneous disorders: bruising (10%), rash (9%) administered to pregnant women [see Use in Specific Populations (8.1) cases of drug-induced liver injury (DILI), has occurred in patients treatedplus Monotherapyplus relapsed or refractory CLL after at least one prior therapy and required Neoplasms: second primary malignancy (12%),in the full Prescribing Information].Dosage Modifications for Adverse Reactions with Bruton tyrosine kinase inhibitors, including CALQUENCE. Body SystemObinutuzumab N=179 Chlorambucil hepatic transaminases2 times ULN, total bilirubin1.5 times ULN, andnon-melanoma skin cancer (6%)Recommended dosage modifications of CALQUENCE for Grade 3 orEvaluate bilirubin and transaminases at baseline and throughout treatment Adverse Reaction* N=178 N=169 an estimated creatinine clearance30 mL/min. The trial excluded patientsMusculoskeletal and connective tissue disorders: arthralgia (8%) Pregnancy Testinggreater adverse reactions are provided in Table 2.with CALQUENCE. For patients who develop abnormal liver tests after AllGrade AllGrade AllGradehaving an absolute neutrophil count 500/L, platelet count 30,000/L, Cardiac disorders: atrial fibrillation or flutter (5%), hypertension (3.2%) Pregnancy testing is recommended for females of reproductive potential Table 2:Recommended Dosage Modifications for Adverse Reactions CALQUENCE, monitor more frequently for liver test abnormalities and Grades3 Grades3 Grades3 prothrombin time or activated partial thromboplastin time 2 times ULN,Infection: herpesvirus infection (4.5%) prior to initiating CALQUENCE therapy.Adverse Dosage Modification clinical signs and symptoms of hepatic toxicity. If DILI is suspected, (%) (%) (%) (%) (%) (%) significant cardiovascular disease, or a requirement for strong CYP3ATable 8: Select Non-Hematologic Laboratory Abnormalities( 10%Contraception Infections inhibitors or inducers. Patients were allowed to receive antithrombotic Event Reaction(Starting dose = 100 mgwithhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE. Infection69 2265 1446 13agents other than warfarin or equivalent vitamin K antagonist. Any Grade), New or Worsening from Baseline in Patients ReceivingFemalesOccurrence approximately every 12 hours) ADVERSE REACTIONSUpper respiratory 39 2.8 35 0 17 1.2 In ASCEND, 154 patients received CALQUENCE (100 mg approximatelyCALQUENCE (ASCEND) Advisefemalepatientsofreproductivepotentialtouseeffective Grade 3 or greaterInterrupt CALQUENCE.The following clinically significant adverse reactions are discussed in IdelalisibBendamustinecontraception during treatment with CALQUENCE and for 1 week following non-hematologicgreater detail in other sections of the labeling: tract infection every 12 hours until disease progression or unacceptable toxicity), 118CALQUENCEplus Rituximab plus Rituximabthe last dose of CALQUENCE. If this drug is used during pregnancy, or Once toxicity has resolved to Lower respiratory24 8 18 4.5 7 1.8 received idelalisib (150 mg approximately every 12 hours until diseaseN=154 if the patient becomes pregnant while taking this drug, the patient toxicities,First andSerious and Opportunistic Infections [see Warnings and Precautionsa Laboratory Product N=118 Product N=35SecondGrade 1 or baseline level, CALQUENCE tract infection progression or unacceptable toxicity) with up to 8 infusions of a rituximaba should be informed of the potential hazard to a fetus.Grade 3 may be resumed at 100 mg (5.1) in the full Prescribing Information] Urinary tract infection 15 1.7 15 2.8 5 0.6 product, and 35 received up to 6 cycles of bendamustine and a rituximabAbnormalityAllGradeAllGradeAllGrade thrombocytopenia approximately every 12 hours.Hemorrhage[seeWarningsandPrecautions(5.2)inthefullBlood and lymphatic system disorders b product. The median age overall was 68 years (range: 32-90); 67% wereGrades 3Grades 3Grades 3Pediatric Use with bleeding,Interrupt CALQUENCE.Prescribing Information] Neutropenia c 53 37 23 13 78 50 male; 92% were white; and 88% had an ECOG performance status of 0 or 1. (%) (%) (%) (%) (%) (%) The safety and efficacy of CALQUENCE in pediatric patients have not Grade 4 Once toxicity has resolved toCytopenias [see Warnings and Precautions (5.3) in the full PrescribingAnemiad 52 12 53 10 54 14 In the CALQUENCE arm, serious adverse reactions occurred in 29% ofUric acid increase 15 15 11 11 23 23 been established.thrombocytopenia Third Grade 1 or baseline level, CALQUENCE Information] e patients. Serious adverse reactions in 5% of patients who receivedALT increase 15 1.9 59 23 26 2.9 Geriatric UseSecond Primary Malignancies [see Warnings and Precautions (5.4) inThrombocytopenia 51 12 32 3.4 61 16 Of the 929 patients in clinical trials of CALQUENCE, 68% were 65 years or may be resumed at a reducedf CALQUENCEincludedlowerrespiratorytractinfection(6%).FatalAST increase 13 0.6 48 13 31 2.9Grade 4 frequency of 100 mg once daily. the full Prescribing Information] Lymphocytosis 12 11 16 15 0.6 0.6 adverse reactions within 30 days of the last dose of CALQUENCEBilirubin increase 13 1.3 16 1.7 26 11 of age or older, and 24% were 75 years of age or older. Among neutropenia lasting Cardiac Arrhythmias [see Warnings and Precautions (5.5) in the fullNervous system disorders occurredin2.6%ofpatients,includingfromsecondprimaryPer NCI CTCAE version 5 patients 65 years of age or older, 59% had Grade 3 or higher adverse longer than 7 daysFourth Discontinue CALQUENCE. Prescribing Information] Headache 40 1.1 39 1.1 12 0 malignancies and infection. a Excludes electrolytes reactionsand39%hadseriousadversereactions.Amongpatients Adverse reactions graded by the National Cancer Institute Common Terminology Hepatotoxicity, including DILI [see Warnings and Precautions (5.6) inDizziness 20 0 12 0 7 0 Increases in creatinine to 1.5 to 3 times ULN occurred in 1.3% ofyounger than age 65, 45% had Grade 3 or higher adverse reactions and Criteria for Adverse Events (NCI CTCAE). the full Prescribing Information] Gastrointestinal disorders In recipients of CALQUENCE, permanent discontinuation due to an25% had serious adverse reactions. No clinically relevant differences in Clinical Trials ExperienceDiarrhea 39 4.5 35 0.6 21 1.8 adverse reaction occurred in 10% of patients, most frequently due topatients who received CALQUENCE. efficacy were observed between patients65 years and younger.Refer to the obinutuzumab prescribing information for management of As clinical trials are conducted under widely varying conditions, adverseNausea 20 0 22 0 31 0 second primary malignancies followed by infection. Adverse reactionsPostmarketing ExperienceHepatic Impairmentobinutuzumab toxicities. reaction rates observed in the clinical trials of a drug cannot be directlyMusculoskeletal and connective tissue disorders led to dosage interruptions of CALQUENCE in 34% of patients, mostThe following adverse reactions have been identified during postapprovalAvoid use of CALQUENCE in patients with severe hepatic impairment CONTRAINDICATIONScompared to rates in the clinical trials of another drug and may notMusculoskeletal pain g 37 2.2 32 1.1 16 2.4 often due to respiratory tract infections followed by neutropenia, anduse of CALQUENCE. Because these reactions are reported voluntarily(Child-Pugh class C). No dosage adjustment of CALQUENCE is None. reflect the rates observed in practice. Arthralgia 22 1.1 16 0.6 4.7 1.2 dose reduction in 3.9% of patients. from a population of uncertain size, it is not always possible to reliablyrecommended in patients with mild (Child-Pugh class A) or moderate WARNINGS AND PRECAUTIONSThe data in the Warnings and Precautions reflect exposure to CALQUENCEGeneral disorders and administration site conditions Selected adverse reactions are described in Table 7 and non-hematologicestimate their frequency or establish a causal relationship to drug exposure. (Child-Pugh class B) hepatic impairment. The safety of CALQUENCE has 100 mg approximately every 12 hours in 1029 patients with hematologic Fatigueh 34 2.2 23 1.1 24 1.2 laboratory abnormalities are described in Table 8. These tables reflectCardiac disorders: ventricular arrhythmias not been evaluated in patients with moderate or severe hepatic impairment Serious and Opportunistic Infections malignancies. Treatment includes CALQUENCE monotherapy in 820exposure to CALQUENCE with median duration of 15.7 months withHepatobiliary disorders: drug-induced liver injury [see Clinical Pharmacology (12.3) in the full Prescribing Information].Fatal and serious infections, including opportunistic infections, have occurred patients in 6 trials, and CALQUENCE with obinutuzumab in 209 patientsSkin and subcutaneous tissue disorders i 94% of patients on treatment for greater than 6 months and 86% of in patients with hematologic malignancies treated with CALQUENCE. in 2 trials. Among these recipients of CALQUENCE, 88% were exposedBruising j 31 0 21 0 5 0 patients on treatment for greater than 12 months. The median durationUSE IN SPECIFIC POPULATIONSDistributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred for at least 6 months and 79% were exposed for at least one year. InRash 26 2.2 25 0.6 9 0.6 of exposure to idelalisib was 11.5 months with 72% of patients onPregnancyCALQUENCE is a registered trademark of the AstraZeneca group of in 19% of 1029 patients exposed to CALQUENCE in clinical trials, most this pooled safety population, adverse reactions in30% of 1029Vascular disorders treatment for greater than 6 months and 48% of patients on treatmentRisk Summarycompanies. AstraZeneca 2022often due to respiratory tract infections (11% of all patients, including patients were anemia, neutropenia, upper respiratory tract infection,Hemorrhage k 20 1.7 20 1.7 6 0 for greater than 12 months. Eighty-three percent of patients completedBased on findings in animals, CALQUENCE may cause fetal harm and pneumonia in 6%) [see Adverse Reactions (6.1) in the full Prescribing thrombocytopenia, headache, diarrhea, and musculoskeletal pain. * Per NCI CTCAE version 4.03 6 cycles of bendamustine and rituximab product. dystocia when administered to a pregnant woman. There are no available06/24 US-91538 7/24US-91257_US-91538 Calquence U.S. Medicine 2025 Directory of Federal Medical Treatment Facilities.indd 3 11/21/24 9:44AM US-91257_US-91538 Calquence U.S. Medicine 2025 Directory of Federal Medical Treatment Facilities.indd 4 11/21/24 9:44AM'