b'CALQUENCE (acalabrutinib) tablets, for oral useInformation]. These infections predominantly occurred in the absence ofChronic Lymphocytic LeukemiaInitial 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 mg Brief Summary of Prescribing Information. of all patients. Opportunistic infections in recipients of CALQUENCEapproximatelyevery12hours,withorwithoutobinutuzumab)in 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 trials fungalpneumonia,Pneumocystisjiroveciipneumonia,Epstein-Barr[see Clinical Studies (14.2) in the full Prescribing Information].INDICATIONS AND USAGEvirusreactivation,cytomegalovirus,andprogressivemultifocalThe most common adverse reactions ( 30%) of any grade in patients Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma leukoencephalopathy (PML). Consider prophylaxis in patients who are atwith CLL were anemia, neutropenia, thrombocytopenia, headache, upper CALQUENCE is indicated for the treatment of adult patients with chronicincreased risk for opportunistic infections. Monitor patients for signs andrespiratory tract infection, and diarrhea.lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). symptoms of infection and treat promptly. ELEVATE-TNDOSAGE AND ADMINISTRATIONHemorrhageThesafetyofCALQUENCEplusobinutuzumab(CALQUENCE+G), Recommended Dosage Fatal and serious hemorrhagic events have occurred in patients withCALQUENCE monotherapy, and obinutuzumab plus chlorambucil (GClb) CALQUENCE as Monotherapy hematologic malignancies treated with CALQUENCE. Major hemorrhagewasevaluatedinarandomized,multicenter,open-label,actively For patients with CLL, or SLL, the recommended dosage of CALQUENCE(serious or Grade 3 or higher bleeding or any central nervous systemcontrolled trial in 526 patients with previously untreated CLL [see is 100 mg taken orally approximately every 12 hours until diseasebleeding) occurred in 3.0% of patients, with fatal hemorrhage occurring inClinical Studies (14.2) in the full Prescribing Information].progression or unacceptable toxicity. 0.1% of 1029 patients exposed to CALQUENCE in clinical trials. BleedingPatients randomized to the CALQUENCE+G arm were treated with events of any grade, excluding bruising and petechiae, occurred in 22% ofCALQUENCE and obinutuzumab in combination for six cycles, then CALQUENCE in Combination with Obinutuzumab patients [see Adverse Reactions (6.1) in the full Prescribing Information]. withCALQUENCEasmonotherapyuntildiseaseprogressionor For patients with previously untreated CLL or SLL, the recommendedUse of antithrombotic agents concomitantly with CALQUENCE may furtherunacceptable toxicity. Patients initiated obinutuzumab on Day 1 of dosage of CALQUENCE is 100 mg taken orally approximately everyincrease the risk of hemorrhage. In clinical trials, major hemorrhageCycle 2, continuing for a total of 6 cycles. Patient randomized to 12 hours until disease progression or unacceptable toxicity. Startoccurred in 2.7% of patients taking CALQUENCE without antithromboticCALQUENCE monotherapy received CALQUENCE approximately every CALQUENCE at Cycle 1 (each cycle is 28 days). Start obinutuzumab atagents and 3.6% of patients taking CALQUENCE with antithrombotic12 hours until disease progression or unacceptable toxicity. The trial Cycle 2 for a total of 6 cycles and refer to the obinutuzumab prescribingagents. Consider the risks and benefits of antithrombotic agents whenrequired age65 years of age or 18 to 65 years of age with a total information for recommended dosing. Administer CALQUENCE prior toco-administered with CALQUENCE. Monitor patients for signs of bleeding. Cumulative Illness Rating Scale (CIRS) 6 or creatinine clearance of obinutuzumab when given on the same day. Consider the benefit-risk of withholding CALQUENCE for 3 to 7 days pre- and30 to 69 mL/min, hepatic transaminases3 times ULN and total Advise patients to swallow tablet whole with water. Advise patients notpost-surgery depending upon the type of surgery and the risk of bleeding. bilirubin 1.5 times ULN, and allowed patients to receive antithrombotic to chew, crush, dissolve, or cut the tablets. CALQUENCE may be taken withCytopeniasagents other than warfarin or equivalent vitamin K antagonists.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 it should be skipped and the next dose should be taken at its regularlybocytopenia (7%), and lymphopenia (7%), developed in patients with hemato- CALQUENCEintheCALQUENCE+GandCALQUENCEmonotherapy scheduled time. Extra tablets of CALQUENCE should not be taken to makelogic malignancies treated with CALQUENCE. Grade 4 neutropenia developedarms was 27.7 months (range 0.3 to 40 months), with 95% and 92% up for a missed dose.in 12% of patients [see Adverse Reactions (6.1) in the full Prescribingand 89% and 86% of patients with at least 6 months and 12 months of Recommended Dosage for Drug Interactions Information]. Monitor complete blood counts regularly during treatment.exposure, respectively. In the obinutuzumab and chlorambucil arm the Dosage Modifications for Use with CYP3A Inhibitors or InducersInterrupt treatment, reduce the dose, or discontinue treatment as warrantedmedian number of cycles was 6 with 84% of patients receiving at least 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 of Prescribing Information].Second Primary Malignancieschlorambucil. Eighty-five percent of patients in the CALQUENCE+G arm Table 1:Recommended Dosage Modifications for Use with CYP3ASecond primary malignancies, including skin cancers and other solidreceived at least 6 cycles of obinutuzumab.Inhibitors or Inducers tumors, occurred in 12% of 1029 patients exposed to CALQUENCEIn the CALQUENCE+G and CALQUENCE monotherapy arms, fatal adverse Co-administeredin clinical trials [see Adverse Reactions (6.1) in the full Prescribingreactions that occurred in the absence of disease progression and with CYP3A Drug Recommended CALQUENCE use Information]. The most frequent second primary malignancy was skinonset within 30 days of the last study treatment were reported in 2% for Avoid co-administration. cancer, reported in 6% of patients. Monitor patients for skin cancerseach treatment arm, most often from infection. Serious adverse reactions If these inhibitors will be used short- and advise protection from sun exposure. were reported in 39% of patients in the CALQUENCE+G arm and 32% term (such as anti-infectives for up toCardiac Arrhythmias in the CALQUENCE monotherapy arm, most often due to events of Strong CYP3Aseven days), interrupt CALQUENCE.Seriouscardiacarrhythmiashaveoccurredinpatientstreatedwithpneumonia (2.8% to 7%).Inhibition inhibitor After discontinuation of strong CYP3ACALQUENCE. Grade 3 atrial fibrillation or flutter occurred in 1.1% ofIn the CALQUENCE+G arm, adverse reactions led to treatment discontin- inhibitor for at least 24 hours, resume1029 patients treated with CALQUENCE, with all grades of atrial fibrillationuation in 11% of patients and a dose reduction of CALQUENCE in 7% of previous dosage of CALQUENCE. or flutter reported in 4.1% of all patients [see Adverse Reactions (6.1) inpatients. In the CALQUENCE monotherapy arm, adverse reactions led to the full Prescribing Information]. Grade 3 or higher ventricular arrhythmiadiscontinuation in 10% and dose reduction in 4% of patients.Moderate CYP3AReduce the CALQUENCE 100 mg everyevents were reported in 0.9% of patients. The risk may be increased inTables 5 and 6 present adverse reactions and laboratory abnormalities inhibitor 12 hours dosage to 100 mg once daily. patients with cardiac risk factors, hypertension, previous arrhythmias, andidentified in the ELEVATE-TN trial.Avoid co-administration. acute infection. Monitor for symptoms of arrhythmia (e.g., palpitations,Table5:CommonAdverseReactions(15%AnyGrade)with Induction Strong CYP3AIf co-administration is unavoidable,dizziness, syncope, dyspnea) and manage as appropriate. CALQUENCE in Patients with CLL (ELEVATE-TN)inducer increase CALQUENCE dosage to Hepatotoxicity, Including Drug-Induced Liver Injury CALQUENCE CALQUENCE Obinutuzumab 200 mg approximately every 12 hours. Hepatotoxicity, including severe, life-threatening, and potentially fatalplus MonotherapyplusDosage Modifications for Adverse Reactions cases of drug-induced liver injury (DILI), has occurred in patients treatedObinutuzumab N=179 ChlorambucilRecommended dosage modifications of CALQUENCE for Grade 3 orwith Bruton tyrosine kinase inhibitors, including CALQUENCE. Body SystemN=178 N=169greater adverse reactions are provided in Table 2.Evaluate bilirubin and transaminases at baseline and throughout treatmentAdverse Reaction* AllGradeAllGradeAllGrade with CALQUENCE. For patients who develop abnormal liver tests afterGrades3 Grades3 Grades3Table 2:Recommended Dosage Modifications for Adverse Reactions CALQUENCE, monitor more frequently for liver test abnormalities and(%) (%) (%) (%) (%) (%)Adverse Dosage Modification clinical signs and symptoms of hepatic toxicity. If DILI is suspected,InfectionsEvent Reaction(Starting dose = 100 mgwithhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE. Infection69 2265 1446 13 Occurrence approximately every 12 hours) ADVERSE REACTIONSUpper respiratory 39 2.8 35 0 17 1.2Grade 3 or greaterInterrupt CALQUENCE.The following clinically significant adverse reactions are discussed intract infectionnon-hematologicOnce toxicity has resolved to greater detail in other sections of the labeling: Lower respiratory24 8 18 4.5 7 1.8toxicities,First and Grade 1 or baseline level, CALQUENCESerious and Opportunistic Infections [see Warnings and Precautionstract infection aGrade 3 Secondmay be resumed at 100 mg (5.1) in the full Prescribing Information] Urinary tract infection 15 1.7 15 2.8 5 0.6thrombocytopenia approximately every 12 hours. Hemorrhage[seeWarningsandPrecautions(5.2)inthefull Blood and lymphatic system disorders bwith bleeding,Interrupt CALQUENCE.Prescribing Information] Neutropenia c 53 37 23 13 78 50Grade 4 Once toxicity has resolved to Cytopenias [see Warnings and Precautions (5.3) in the full PrescribingAnemiad 52 12 53 10 54 14thrombocytopenia Third Grade 1 or baseline level, CALQUENCEInformation] eSecond Primary Malignancies [see Warnings and Precautions (5.4) inThrombocytopenia 51 12 32 3.4 61 16or may be resumed at a reducedthe full Prescribing Information] Lymphocytosis f 12 11 16 15 0.6 0.6Grade 4 frequency of 100 mg once daily. Cardiac Arrhythmias [see Warnings and Precautions (5.5) in the fullNervous system disordersneutropenia lastingFourth Discontinue CALQUENCE. Prescribing Information] Headache 40 1.1 39 1.1 12 0longer than 7 daysHepatotoxicity, including DILI [see Warnings and Precautions (5.6) inDizziness 20 0 12 0 7 0Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). the full Prescribing Information] Gastrointestinal disordersRefer to the obinutuzumab prescribing information for management ofClinical Trials ExperienceDiarrhea 39 4.5 35 0.6 21 1.8obinutuzumab toxicities. As clinical trials are conducted under widely varying conditions, adverseNausea 20 0 22 0 31 0reaction rates observed in the clinical trials of a drug cannot be directlyMusculoskeletal and connective tissue disordersCONTRAINDICATIONScompared to rates in the clinical trials of another drug and may notMusculoskeletal pain g 37 2.2 32 1.1 16 2.4None. reflect the rates observed in practice. Arthralgia 22 1.1 16 0.6 4.7 1.2WARNINGS AND PRECAUTIONSThe data in the Warnings and Precautions reflect exposure to CALQUENCEGeneral disorders and administration site conditionsSerious and Opportunistic Infections 100 mg approximately every 12 hours in 1029 patients with hematologicFatigueh 34 2.2 23 1.1 24 1.2Fatal and serious infections, including opportunistic infections, have occurredmalignancies. Treatment includes CALQUENCE monotherapy in 820Skin and subcutaneous tissue disordersin patients with hematologic malignancies treated with CALQUENCE. patients in 6 trials, and CALQUENCE with obinutuzumab in 209 patientsBruising i 31 0 21 0 5 0in 2 trials. Among these recipients of CALQUENCE, 88% were exposedjSerious or Grade 3 or higher infections (bacterial, viral, or fungal) occurredfor at least 6 months and 79% were exposed for at least one year. InRash 26 2.2 25 0.6 9 0.6in 19% of 1029 patients exposed to CALQUENCE in clinical trials, mostthis pooled safety population, adverse reactions in30% of 1029Vascular disordersoften due to respiratory tract infections (11% of all patients, includingpatients were anemia, neutropenia, upper respiratory tract infection,Hemorrhage k 20 1.7 20 1.7 6 0pneumonia in 6%) [see Adverse Reactions (6.1) in the full Prescribingthrombocytopenia, headache, diarrhea, and musculoskeletal pain. *Per NCI CTCAE version 4.03US-91257_US-91538 Calquence U.S. Medicine 2025 Directory of Federal Medical Treatment Facilities.indd 3 11/21/24 9:44AM'