Calquence

acalabrutinib · Tablet, Film Coated · Oral

Uses

1 INDICATIONS AND USAGE CALQUENCE is a kinase inhibitor indicated:
• In combination with bendamustine and rituximab for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT). (1.1 )
• For the treatment of adult patients with MCL who have received at least one prior therapy. ( 1.2 )
• For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ( 1.3 ) 1.1 Previously Untreated Mantle Cell Lymphoma CALQUENCE in combination with bendamustine and rituximab is indicated for the treatment of adult patients with previously untreated mantle cell lymphoma (MCL) who are ineligible for autologous hematopoietic stem cell transplantation (HSCT). 1.2 Previously Treated Mantle Cell Lymphoma CALQUENCE is indicated for the treatment of adult patients with MCL who have received at least one prior therapy. 1.3 Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma CALQUENCE is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Dosage and administration

• Recommended dose is 100 mg orally approximately every 12 hours; swallow whole with water and with or without food. ( 2.1 )
• Advise patients not to chew, crush, dissolve, or cut tablets. ( 2.1 )
• Manage toxicities using treatment interruption, dose reduction, or discontinuation. ( 2.3 )
• Avoid CALQUENCE in patients with severe hepatic impairment. ( 8.6 ) 2.1 Recommended Dosage CALQUENCE Administration Instructions Advise patients to swallow tablet whole with water. Advise patients not to chew, crush, dissolve, or cut the tablets. CALQUENCE may be taken with or without food. If a dose of CALQUENCE is missed by more than 3 hours, it should be skipped, and the next dose should be taken at its regularly scheduled time. Extra tablets of CALQUENCE should not be taken to make up for a missed dose. CALQUENCE as Monotherapy For patients with MCL, CLL or SLL, the recommended dosage of CALQUENCE is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity. CALQUENCE in Combination with Bendamustine and Rituximab For patients with previously untreated MCL, the recommended dosage of CALQUENCE is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity. Start CALQUENCE on Day 1 of Cycle 1 (each cycle is 28 days) and administer until disease progression or unacceptable toxicity. Administer bendamustine 90 mg/m 2 on Days 1 and 2 and rituximab 375 mg/m 2 on Day 1 of Cycle 1 and continue for a total of 6 cycles. Patients achieving a response (PR or CR) after the first 6 cycles may receive maintenance rituximab on Day 1 of every other cycle for a maximum of 12 additional doses, starting on Cycle 8 up to Cycle 30 [see Clinical Studies (14.1) ] . CALQUENCE in Combination with Obinutuzumab For patients with previously untreated CLL or SLL, the recommended dosage of CALQUENCE is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity. Start CALQUENCE at Cycle 1 (each cycle is 28 days). Start obinutuzumab at Cycle 2 for a total of 6 cycles and refer to the obinutuzumab prescribing information for recommended dosing. Administer CALQUENCE prior to obinutuzumab when given on the same day. CALQUENCE in Combination with Venetoclax For patients with previously untreated CLL or SLL, the recommended dosage of CALQUENCE is 100 mg taken orally approximately every 12 hours until disease progression, unacceptable toxicity or completion of 14 cycles of treatment. Start CALQUENCE at Cycle 1 (each cycle is 28 days). Start venetoclax at Cycle 3 for total of 12 cycles. Start venetoclax at 20 mg daily for first week of treatment and increase weekly as per dosing schedule for 5-week ramp up (up to 400 mg daily) as described in the venetoclax USPI. Refer to the venetoclax USPI for additional details. 2.2 Recommended Dosage for Drug Interactions Dosage Modifications for Use with CYP3A Inhibitors or Inducers These are described in Table 1 [see Drug Interactions (7) ]. Table 1: Recommended Dosage Modifications for Use with CYP3A Inhibitors or Inducers CYP3A Co-administered Drug Recommended CALQUENCE use Inhibition Strong CYP3A inhibitor Avoid co-administration. If these inhibitors will be used short-term (such as anti‑infectives for up to seven days), interrupt CALQUENCE. After discontinuation of strong CYP3A inhibitor for at least 24 hours, resume previous dosage of CALQUENCE. Moderate CYP3A inhibitor Reduce the CALQUENCE 100 mg every 12 hours dosage to 100 mg once daily. Induction Strong CYP3A inducer Avoid co-administration. If co-administration is unavoidable, increase CALQUENCE dosage to 200 mg approximately every 12 hours. 2.3 Dosage Modifications for Adverse Reactions Recommended dosage modifications are provided in Table 2, 3 and 4. Table 2: Recommended Dosage Modifications for Adverse Reactions in Patients Receiving CALQUENCE Monotherapy and CALQUENCE in Combination with Obinutuzumab Event Adverse Reaction Occurrence Dosage Modification (Starting dose = 100 mg approximately every 12 hours) Grade 3 or greater non-hematologic toxicities, Grade 3 thrombocytopenia with bleeding, Grade 4 thrombocytopenia or Grade 4 neutropenia lasting longer than 7 days First and Second Interrupt CALQUENCE. Once toxicity has resolved to Grade 1 or baseline level, CALQUENCE may be resumed at 100 mg approximately every 12 hours. Third Interrupt CALQUENCE. Once toxicity has resolved to Grade 1 or baseline level, CALQUENCE may be resumed at a reduced frequency of 100 mg once daily. Fourth Discontinue CALQUENCE. Adverse reactions graded by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE). Table 3: Recommended Dosage Modifications for Adverse Reactions in Patients Receiving CALQUENCE in Combination with BR Adverse Reaction Severity a Dosage Modification (Starting dosage of CALQUENCE = 100 mg approximately every 12 hours) Neutropenia b [see Warnings and Precautions (5.3) ] Absolute neutrophil count less than 0.5 x 10 9 /L for greater than 7 days Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2, resume CALQUENCE at starting dosage. Upon 2nd or 3rd occurrence, reduce dosage of CALQUENCE to 100 mg once daily. c Discontinue CALQUENCE at 4th occurrence. For bendamustine b : Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2, resume bendamustine and consider dosage reduction to 70 mg/m 2.d,e Thrombocytopenia f [see Warnings and Precautions (5.3) ] Platelet count 25 to 50 x 10 9 /L with clinically significant bleeding or platelet count less than 25 x 10 9 /L Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2 or baseline, resume CALQUENCE at starting dosage. If recurrence, reduce dosage of CALQUENCE to 100 mg once daily. c Consider discontinuing CALQUENCE at 3rd occurrence. For bendamustinef : Interrupt bendamustine.

Dosage forms and strengths

Tablets:100 mg acalabrutinib, orange, oval, film-coated, biconvex, debossed with ‘ACA 100’ on one side and plain on the other. Tablets: 100 mg. ( 3 )

Contraindications

None. None. ( 4 )

Warnings and precautions

• Serious and Opportunistic Infections: Monitor for signs and symptoms of infection and treat promptly. ( 5.1 )
• Hemorrhage: Monitor for bleeding and manage appropriately. ( 5.2 )
• Cytopenias: Monitor complete blood counts regularly. ( 5.3 )
• Second Primary Malignancies: Other malignancies have occurred, including skin cancers and other solid tumors. Advise patients to use sun protection. ( 5.4 )
• Cardiac Arrhythmias: Monitor for symptoms of arrhythmias and manage. ( 5.5 )
• Hepatotoxicity, Including Drug Induced Liver Injury: Monitor hepatic function throughout treatment. ( 5.6 ) 5.1 Serious and Opportunistic Infections Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies treated with CALQUENCE. Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 29% of 2,055 patients exposed to CALQUENCE in clinical trials, most often due to respiratory tract infections (18% of all patients, including pneumonia in 14%) [see Adverse Reactions (6.1) ] . These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 8% of all patients. Opportunistic infections in recipients of CALQUENCE have included, but are not limited to, hepatitis B virus reactivation, fungal pneumonia, Pneumocystis jirovecii pneumonia, Epstein-Barr virus reactivation, cytomegalovirus, and progressive multifocal leukoencephalopathy (PML). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Monitor patients for signs and symptoms of infection and treat promptly. In an additional cohort of patients receiving CALQUENCE in combination with venetoclax with obinutuzumab (AVO) (an unapproved regimen for previously untreated CLL/SLL in AMPLIFY), serious or Grade 3 or higher infections occurred in 25% receiving AVO compared to 14% in patients receiving AV. Fatal infections occurred in 6% receiving AVO compared to 3.1% of patients receiving AV, most commonly due to COVID-19. The safety and effectiveness of AVO has not been established in patients with previously untreated CLL/SLL [see Clinical Studies (14.3) ]. 5.2 Hemorrhage Fatal and serious hemorrhagic events have occurred in patients treated with CALQUENCE. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 4.7% of patients, with fatal hemorrhage occurring in 0.1% of 2,055 patients exposed to CALQUENCE in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 39% of patients [ see Adverse Reactions (6.1) ] . Use of antithrombotic agents concomitantly with CALQUENCE may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 5% of patients taking CALQUENCE without antithrombotic agents and 3.2% of patients taking CALQUENCE with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with CALQUENCE. Monitor patients for signs of bleeding. Consider the benefit-risk of withholding CALQUENCE for 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding. 5.3 Cytopenias CALQUENCE can cause Grade 3 or 4 cytopenias. Grade 3 or 4 cytopenias included absolute neutrophil count decreased (28%), absolute lymphocyte count decreased (10%), hemoglobin decreased (9%), and platelets decreased (9%) in 1,758 patients treated with CALQUENCE alone and in combination with obinutuzumab or venetoclax; Grade 4 neutropenia developed in 14% [see Adverse Reactions (6.1) ] . Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted [see Dosage and Administration (2.3) ] . 5.4 Second Primary Malignancies Second primary malignancies, including skin cancers and other solid tumors, occurred in 16% of 2,055 patients exposed to CALQUENCE in clinical trials [see Adverse Reactions (6.1) ] . The most frequent second primary malignancy was non-melanoma skin cancer, reported in 9% of patients, followed by other solid tumors in 8% (including melanoma, lung cancer, gastrointestinal cancers, and genitourinary cancers) and hematologic malignancies (1.1%). Fatal second primary malignancies occurred in 0.8% of patients. Monitor patients for the development of second cancers and advise protection from sun exposure. 5.5 Cardiac Arrhythmias Fatal and serious cardiac arrhythmias have occurred in patients treated with CALQUENCE. Grade 3 or 4 atrial fibrillation or flutter was reported in 2.2% of 2,055 patients treated with CALQUENCE, with all grades of atrial fibrillation or flutter reported in 7% of all patients [see Adverse Reactions (6.1) ] . Grade 3 or higher ventricular arrhythmia events were reported in 0.5% of patients, including fatal cases in 0.3% of all patients. The risk of arrhythmias may be increased in patients with cardiac risk factors, hypertension, previous arrhythmias, and acute infection. Monitor for symptoms of arrhythmia (e.g., palpitations, dizziness, syncope, dyspnea) and manage as appropriate. 5.6 Hepatotoxicity, Including Drug-Induced Liver Injury Hepatotoxicity, including severe, life-threatening, and potentially fatal cases of drug-induced liver injury (DILI), has occurred in patients treated with Bruton tyrosine kinase inhibitors, including CALQUENCE. Evaluate bilirubin and transaminases at baseline and throughout treatment with CALQUENCE. For patients who develop abnormal liver tests after CALQUENCE, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold CALQUENCE. Upon confirmation of DILI, discontinue CALQUENCE.

Side effects

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling:
• Serious and Opportunistic Infections [see Warnings and Precautions (5.1) ]
• Hemorrhage [see Warnings and Precautions (5.2) ]
• Cytopenias [see Warnings and Precautions (5.3) ]
• Second Primary Malignancies [see Warnings and Precautions (5.4) ]
• Cardiac Arrhythmias [see Warnings and Precautions (5.5) ]
• Hepatotoxicity, including DILI [see Warnings and Precautions (5.6) ] The most common adverse reactions (≥ 30%), excluding laboratory abnormalities, are upper respiratory tract infection, diarrhea, headache, and musculoskeletal pain. The most common Grade 3 or 4 laboratory abnormalities (≥ 10%) are absolute neutrophil count decreased, uric acid increased, absolute lymphocyte count decreased, and platelets decreased. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data in the Warnings and Precautions reflect exposure to CALQUENCE 100 mg approximately every 12 hours in 2,055 patients with hematologic malignancies. Treatment includes CALQUENCE monotherapy in 1258 patients in 9 trials, and CALQUENCE combinations in 797 patients in 4 trials. Among these recipients of CALQUENCE, 89% were exposed for at least 6 months and 82% were exposed for at least one year. In this pooled safety population, adverse reactions in ≥ 30% of 2,055 patients, excluding laboratory abnormalities, were upper respiratory tract infection (37%), diarrhea (36%), headache (35%), and musculoskeletal pain (32%). The most common Grade 3 or 4 laboratory abnormalities (≥ 10%) were absolute neutrophil count decreased (32%), uric acid increased (27%), absolute lymphocyte count decreased (21%) and platelets decreased (10%). Previously Untreated Mantle Cell Lymphoma The safety data described below reflect exposure to CALQUENCE (100 mg approximately every 12 hours, with or without BR) in patients with MCL [see Clinical Studies (14.1) ] . ECHO The safety of CALQUENCE in combination with bendamustine and rituximab (CALQUENCE plus BR) was evaluated in 297 patients with previously untreated MCL in ECHO [see Clinical Studies (14.1) ] . The trial enrolled patients with previously untreated MCL, ≥ 65 years of age with no intention for transplant, total bilirubin ≤ 1.5 × ULN, AST or ALT ≤ 2.5 × ULN, and estimated creatinine clearance of > 50 mL/min. Patients received 6 cycles (as 28-day cycles) of CALQUENCE 100 mg orally twice daily (n = 297) or placebo (n = 297) in combination with bendamustine and rituximab. Patients then received CALQUENCE 100 mg orally twice daily or placebo continuously until progressive disease or unacceptable toxicity, with 12 additional dosages of rituximab every other cycle up to Cycle 30. The median duration of treatment with CALQUENCE was 28.6 months. A total of 171 (57.6%) patients were treated with CALQUENCE for ˃ 24 months and 122 (41.1%) patients were treated for ˃ 36 months. Serious adverse reactions occurred in 69% of patients who received CALQUENCE plus BR. Serious adverse reactions reported in ≥ 2% of patients were pneumonia (23%; includes COVID-19 pneumonia), COVID-19 (20%; includes COVID-19 pneumonia), pyrexia (6%), second primary malignancy (7%), rash (3.4%), febrile neutropenia (3.4%), atrial fibrillation (3%), sepsis (2.7%), and anemia (2.4%). Fatal adverse reactions that occurred within 30 days of the last study treatment were reported in 12% who received CALQUENCE plus BR including COVID-19 (6%; includes COVID-19 pneumonia), pneumonia (1%), sepsis (0.3%), second primary malignancy (0.7%), and pneumonitis (0.3%). Adverse reactions led to permanent discontinuation of CALQUENCE in 43%, dosage interruptions in 74%, and dosage reductions in 10% of patients. Adverse reactions that resulted in dosage modification in > 10% included infections, cytopenias, rashes, and gastrointestinal toxicity. Adverse reactions which resulted in permanent discontinuation of CALQUENCE in ≥ 4% of patients included COVID-19 (includes COVID-19 pneumonia) and neutropenia. Table 5 and Table 6 summarize select adverse reactions and laboratory abnormalities observed in patients treated in ECHO. Table 5: Adverse Reactions* (≥ 15%) in Patients with Previously Untreated MCL Who Received CALQUENCE plus BR in ECHO Body System Adverse Reactions* CALQUENCE plus BR N = 297 Placebo plus BR N = 297 All Grades (%) Grade 3 or 4 (%) All Grades (%) Grade 3 or 4 (%) Skin and subcutaneous tissue disorders Rash a 47 12 31 3 Infections COVID-19 b 38 13 27 11 Upper respiratory tract infection c 30 0.7 29 1 Pneumoniad d 31 17 25 14 Gastrointestinal disorders Diarrhea 37 3 28 2.4 Vomiting 26 0.7 14 1 Constipation 25 1 25 0.3 General disorders Fatigue 37 3.7 32 4.4 Pyrexia 29 2.4 24 1.3 Edema 20 1.3 19 0 Nervous system disorders Headache 31 1.7 14 0.7 Dizziness 18 1 17 0.3 Respiratory, thoracic and mediastinal disorders Cough 27 0 20 0.3 Dyspnea 17 1 11 2.7 Neoplasms Secondary primary malignancy e 19 7 15 7 Musculoskeletal and connective tissue disorders Arthralgia 18 0.7 16 1 Vascular disorders Hemorrhage f 20 1.7 11 3 *Excludes laboratory terms. a Includes rash, dermatitis, and other related terms. b Includes the following fatal adverse reactions: n=24 for COVID-19. c Includes upper respiratory tract infection, sinusitis, pharyngitis, and related terms. d Includes pneumonia, terms containing pneumonia, and related infections. COVID-19 pneumonia is represented under both Pneumonia and COVID-19. e Includes terms related to malignant neoplasms including cutaneous neoplasms.

Drug interactions

• Strong CYP3A Inhibitors : Avoid co-administration with CALQUENCE. ( 2.2 , 7 )
• Moderate CYP3A Inhibitors : Reduce the dosage of CALQUENCE. ( 2.2 , 7 )
• Strong CYP3A Inducers : Avoid co-administration with CALQUENCE. If co-administration is unavoidable, increase the dosage of CALQUENCE. ( 2.2 , 7 ) 7.1 Effect of Other Drugs on CALQUENCE Strong CYP3A Inhibitors Clinical Effect Co-administration of CALQUENCE with a strong CYP3A inhibitor increased acalabrutinib plasma concentrations [see Clinical Pharmacology (12.3) ] . Increased acalabrutinib concentrations may result in increased toxicity. Prevention or Management Avoid co-administration of CALQUENCE with strong CYP3A inhibitors. Alternatively, if the inhibitor will be used short-term, interrupt CALQUENCE [see Dosage and Administration (2.2) ]. Moderate CYP3A Inhibitors Clinical Effect Co-administration of CALQUENCE with a moderate CYP3A inhibitor may increase acalabrutinib plasma concentration [see Clinical Pharmacology (12.3) ] . Increased acalabrutinib concentrations may result in increased toxicity. Prevention or Management Reduce the dosage of CALQUENCE when co-administered with a moderate CYP3A inhibitor [see Dosage and Administration (2.2) ]. Strong CYP3A Inducers Clinical Effect Co-administration of CALQUENCE with a strong CYP3A inducer decreased acalabrutinib plasma concentration [see Clinical Pharmacology (12.3) ] . Decreased acalabrutinib concentrations may reduce CALQUENCE activity. Prevention or Management Avoid co-administration of CALQUENCE with strong CYP3A inducers. If co-administration is unavoidable, increase the dosage of CALQUENCE [see Dosage and Administration (2.2) ].

Use in specific populations

• Pregnancy: May cause fetal harm and dystocia. ( 8.1 )
• Lactation: Advise not to breastfeed. ( 8.2 )
• Severe Hepatic Impairment: Avoid use of CALQUENCE. ( 8.6 ) 8.1 Pregnancy Risk Summary Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of acalabrutinib to animals during organogenesis resulted in dystocia in rats and reduced fetal growth in rabbits at maternal exposures (AUC) 2 times exposures in patients at the recommended dose of 100 mg approximately every 12 hours ( see Data ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In a combined fertility and embryo-fetal development study in female rats, acalabrutinib was administered orally at doses up to 200 mg/kg/day starting 14 days prior to mating through gestational day [GD] 17. No effects on embryo-fetal development and survival were observed. The AUC at 200 mg/kg/day in pregnant rats was approximately 9 times the AUC in patients at the recommended dose of 100 mg approximately every 12 hours. The presence of acalabrutinib and its active metabolite were confirmed in fetal rat plasma. In an embryo-fetal development study in rabbits, pregnant animals were administered acalabrutinib orally at doses up to 200 mg/kg/day during the period of organogenesis (from GD 6-18). Administration of acalabrutinib at doses ≥ 100 mg/kg/day produced maternal toxicity and 100 mg/kg/day resulted in decreased fetal body weights and delayed skeletal ossification. The AUC at 100 mg/kg/day in pregnant rabbits was approximately 2 times the AUC in patients at 100 mg approximately every 12 hours. In a pre- and postnatal development study in rats, acalabrutinib was administered orally to pregnant animals during organogenesis, parturition and lactation, at doses of 50, 100, and 150 mg/kg/day. Dystocia (prolonged or difficult labor) and mortality of offspring were observed at doses ≥ 100 mg/kg/day. The AUC at 100 mg/kg/day in pregnant rats was approximately 2 times the AUC in patients at 100 mg approximately every 12 hours. Underdeveloped renal papilla was also observed in F1 generation offspring at 150 mg/kg/day with an AUC approximately 5 times the AUC in patients at 100 mg approximately every 12 hours. 8.2 Lactation Risk Summary No data are available regarding the presence of acalabrutinib or its active metabolite in human milk, its effects on the breastfed child, or on milk production. Acalabrutinib and its active metabolite were present in the milk of lactating rats. Due to the potential for adverse reactions in a breastfed child from CALQUENCE, advise lactating women not to breastfeed while taking CALQUENCE and for 2 weeks after the last dose. 8.3 Females and Males of Reproductive Potential CALQUENCE may cause embryo-fetal harm and dystocia when administered to pregnant women [see Use in Specific Populations (8.1) ] . Pregnancy Testing Pregnancy testing is recommended for females of reproductive potential prior to initiating CALQUENCE therapy. Contraception Females Advise female patients of reproductive potential to use effective contraception during treatment with CALQUENCE and for 1 week following the last dose of CALQUENCE. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be informed of the potential hazard to a fetus. 8.4 Pediatric Use The safety and efficacy of CALQUENCE in pediatric patients have not been established. 8.5 Geriatric Use CLL and Previously Treated MCL Of the 1,758 CALQUENCE-treated patients with B-cell malignancies (excluding previously untreated MCL) in clinical trials, 1,074 (61%) were 65 years of age or older, and 341 (19%) were 75 years of age or older. Among patients 65 years of age or older, 73% had Grade 3 or higher adverse reactions and 55% had serious adverse reactions. Among patients younger than age 65, 58% had Grade 3 or higher adverse reactions and 35% had serious adverse reactions. No clinically relevant differences in efficacy were observed between patients ≥ 65 years and younger. Of patients that received CALQUENCE in combination with venetoclax in AMPLIFY, 33% (97/291) were ≥ 65 years of age, and 4.5% (13/291) were ≥ 75 years of age. In patients 65 years of age or older and younger than age 65, the fatal adverse reactions were 5% and 2.6% respectively. No clinically relevant differences in efficacy were observed between patients ≥ 65 years of age and younger adults. Previously Untreated MCL Of the 297 CALQUENCE-treated patients with previously untreated MCL, 214 (72%) were 65 to 74 years of age and 83 (28%) were 75 years of age and older. No clinically relevant differences in safety or efficacy were observed between patients ages 65 to 74 years and those who were 75 years of age and older. 8.6 Hepatic Impairment Avoid use of CALQUENCE in patients with severe hepatic impairment (Child-Pugh class C). No dosage adjustment of CALQUENCE is recommended in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment. The safety of CALQUENCE has not been evaluated in patients with moderate or severe hepatic impairment [see Clinical Pharmacology (12.3) ] .

Pregnancy

8.1 Pregnancy Risk Summary Based on findings in animals, CALQUENCE may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. In animal reproduction studies, administration of acalabrutinib to animals during organogenesis resulted in dystocia in rats and reduced fetal growth in rabbits at maternal exposures (AUC) 2 times exposures in patients at the recommended dose of 100 mg approximately every 12 hours ( see Data ) . Advise pregnant women of the potential risk to a fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Data Animal Data In a combined fertility and embryo-fetal development study in female rats, acalabrutinib was administered orally at doses up to 200 mg/kg/day starting 14 days prior to mating through gestational day [GD] 17. No effects on embryo-fetal development and survival were observed. The AUC at 200 mg/kg/day in pregnant rats was approximately 9 times the AUC in patients at the recommended dose of 100 mg approximately every 12 hours. The presence of acalabrutinib and its active metabolite were confirmed in fetal rat plasma. In an embryo-fetal development study in rabbits, pregnant animals were administered acalabrutinib orally at doses up to 200 mg/kg/day during the period of organogenesis (from GD 6-18). Administration of acalabrutinib at doses ≥ 100 mg/kg/day produced maternal toxicity and 100 mg/kg/day resulted in decreased fetal body weights and delayed skeletal ossification. The AUC at 100 mg/kg/day in pregnant rabbits was approximately 2 times the AUC in patients at 100 mg approximately every 12 hours. In a pre- and postnatal development study in rats, acalabrutinib was administered orally to pregnant animals during organogenesis, parturition and lactation, at doses of 50, 100, and 150 mg/kg/day. Dystocia (prolonged or difficult labor) and mortality of offspring were observed at doses ≥ 100 mg/kg/day. The AUC at 100 mg/kg/day in pregnant rats was approximately 2 times the AUC in patients at 100 mg approximately every 12 hours. Underdeveloped renal papilla was also observed in F1 generation offspring at 150 mg/kg/day with an AUC approximately 5 times the AUC in patients at 100 mg approximately every 12 hours.

Pediatric use

8.4 Pediatric Use The safety and efficacy of CALQUENCE in pediatric patients have not been established.

Geriatric use

8.5 Geriatric Use CLL and Previously Treated MCL Of the 1,758 CALQUENCE-treated patients with B-cell malignancies (excluding previously untreated MCL) in clinical trials, 1,074 (61%) were 65 years of age or older, and 341 (19%) were 75 years of age or older. Among patients 65 years of age or older, 73% had Grade 3 or higher adverse reactions and 55% had serious adverse reactions. Among patients younger than age 65, 58% had Grade 3 or higher adverse reactions and 35% had serious adverse reactions. No clinically relevant differences in efficacy were observed between patients ≥ 65 years and younger. Of patients that received CALQUENCE in combination with venetoclax in AMPLIFY, 33% (97/291) were ≥ 65 years of age, and 4.5% (13/291) were ≥ 75 years of age. In patients 65 years of age or older and younger than age 65, the fatal adverse reactions were 5% and 2.6% respectively. No clinically relevant differences in efficacy were observed between patients ≥ 65 years of age and younger adults. Previously Untreated MCL Of the 297 CALQUENCE-treated patients with previously untreated MCL, 214 (72%) were 65 to 74 years of age and 83 (28%) were 75 years of age and older. No clinically relevant differences in safety or efficacy were observed between patients ages 65 to 74 years and those who were 75 years of age and older.

Description

(acalabrutinib) is a kinase inhibitor. The molecular formula for acalabrutinib maleate is C 26 H 23 N 7 O 2
• C 4 H 4 O 4 .H 2 O, and the molecular weight is 599.59. The chemical name is 4-{8-Amino-3-[(2 S )-1-(but-2-ynoyl) pyrrolidin-2-yl] imidazo[1,5- a ]pyrazin-1-yl}- N -(pyridin-2-yl)benzamide (2 Z )-2-butenedioic acid hydrate. The chemical structure of acalabrutinib is shown below: Acalabrutinib maleate is a white to pale brown powder with pH-dependent solubility. It is freely soluble in water at pH values below 3 and practically insoluble at pH values above 6. CALQUENCE tablets are for oral administration. Each tablet contains 100 mg of acalabrutinib (equivalent to 129 mg of acalabrutinib maleate). Inactive ingredients in the tablet core are low-substituted hydroxypropyl cellulose, mannitol, microcrystalline cellulose, and sodium stearyl fumarate. The tablet coating consists of copovidone, ferric oxide yellow, ferric oxide red, hypromellose, medium-chain triglycerides, polyethylene glycol 3350, purified water, and titanium dioxide. chemical_structure

Mechanism of action

12.1 Mechanism of Action Acalabrutinib is a small-molecule inhibitor of Bruton tyrosine kinase (BTK). Acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B cell antigen receptor (BCR) and cytokine receptor pathways. In B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. In nonclinical studies, acalabrutinib inhibited BTK‑mediated activation of downstream signaling proteins CD86 and CD69 and inhibited malignant B-cell proliferation and tumor growth in mouse xenograft models.

How supplied

How Supplied Pack Size Contents NDC Number 60-count bottle Bottle containing 60 tablets with a child-resistant closure 100 mg, orange, oval, biconvex tablet, with debossment ‘ACA100’ on one side and plain on the reverse 0310-3512-60 Storage Store at 20°C-25°C (68°F-77°F); excursions permitted to 15°C-30°C (59°F-86°F) [see USP Controlled Room Temperature].

Patient information

Advise the patient to read the FDA-approved patient labeling (Patient Information). Serious and Opportunistic Infections Inform patients of the possibility of serious infection and to immediately report signs or symptoms suggestive of infection [see Warnings and Precautions (5.1) ] . Hemorrhage Inform patients to immediately report signs or symptoms of bleeding. Inform patients that CALQUENCE may need to be interrupted for major surgeries [see Warnings and Precautions (5.2) ] . Cytopenias Inform patients that they will need periodic blood tests to check blood counts during treatment with CALQUENCE [see Warnings and Precautions (5.3) ] . Second Primary Malignancies Inform patients that other malignancies have been reported in patients who have been treated with CALQUENCE, including skin cancer and other solid tumors. Advise patients to use sun protection [see Warnings and Precautions (5.4) ] . Cardiac Arrhythmias Counsel patients to immediately report any signs of palpitations, dizziness, fainting, chest discomfort, and shortness of breath [see Warnings and Precautions (5.5) ] . Hepatotoxicity, Including Drug-Induced Liver Injury: Inform patients that liver problems, including drug-induced liver injury and abnormalities in liver tests, may develop during CALQUENCE treatment. Advise patients to contact their healthcare provider immediately if they experience abdominal discomfort, dark urine, or jaundice [see Warnings and Precautions (5.6) ]. Pregnancy Complication CALQUENCE may cause fetal harm and dystocia. Advise women to use effective contraception during treatment and for 1 week after the last dose of CALQUENCE [see Use in Specific Populations (8.3) ] . Lactation Advise females not to breastfeed during treatment with CALQUENCE and for 2 weeks after the last dose [see Use in Specific Populations (8.2) ] . Dosing Instructions Instruct patients to take CALQUENCE orally twice daily, about 12 hours apart. CALQUENCE may be taken with or without food. Advise patients that CALQUENCE tablets should be swallowed whole with a glass of water, without chewing, crushing, dissolving, or cutting [see Dosage and Administration (2.1) ] . Missed Dose Advise patients that if they miss a dose of CALQUENCE, they may still take it up to 3 hours after the time they would normally take it. If more than 3 hours have elapsed, they should be instructed to skip that dose and take their next dose of CALQUENCE at the usual time. Warn patients they should not take extra tablets to make up for the dose that they missed [see Dosage and Administration (2.1) ] . Drug Interactions Advise patients to inform their healthcare providers of all concomitant medications, including over‑the‑counter medications, vitamins and herbal products [see Drug Interactions (7) ] . Distributed by: AstraZeneca Pharmaceuticals LP Wilmington, DE 19850 CALQUENCE is a registered trademark of the AstraZeneca group of companies. ©AstraZeneca 2026

Label text from the FDA structured product label by AstraZeneca Pharmaceuticals LP (revised Feb 19, 2026). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Acalabrutinib in 3 products

Calquence NDC products (3)

NDC	Strength & form	Labeler	Type
0310-0512	Acalabrutinib 100 mg/1 Capsule, Gelatin Coated	AstraZeneca Pharmaceuticals LP	NDA
0310-3512	Acalabrutinib 100 mg/1 Tablet, Film Coated	AstraZeneca Pharmaceuticals LP	NDA
0310-4513	Acalabrutinib 100 mg/1 Tablet, Film Coated	AstraZeneca Pharmaceuticals LP	NDA

Frequently asked questions

What is Calquence used for?

What are the side effects of Calquence?

Who makes Calquence?

Calquence is listed by 1 labeler in the FDA NDC directory, including AstraZeneca Pharmaceuticals LP.