Calquence Tablets
(Acalabrutinib)Dosage & Administration
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Calquence Tablets Prescribing Information
Indications and Usage, Mantle Cell Lymphoma (
Dosage and Administration, Recommended Dosage (
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.
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.
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
Dosage and Administration, Dosage Modifications for Adverse Reactions (
Recommended dosage modifications of are provided in Table 2 and 3.
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). | ||
Adverse Reaction | Severitya | Dosage Modification (Starting dosage of CALQUENCE = 100 mg approximately every 12 hours) |
|---|---|---|
Neutropeniab [see Warnings and Precautions (5.4)] | Absolute neutrophil count less than 0.5 x 109/L for greater than 7 days | Interrupt CALQUENCE. Once toxicity has resolved to Grade ≤ 2, resume CALQUENCE at starting dosage. Upon 2ndor 3rdoccurrence, reduce dosage of CALQUENCE to 100 mg once daily.c Discontinue CALQUENCE at 4thoccurrence. For bendamustine b:Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2, resume bendamustine and consider dosage reduction to 70 mg/m2.d,e |
Thrombocytopeniaf [see Warnings and Precautions (5.4)] | Platelet count 25 to 50 x 109/L with clinically significant bleeding or platelet count less than 25 x 109/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 3rdoccurrence. For bendamustinef :Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline, resume bendamustine and consider dose reduction to 70 mg/m2.e |
Non‑hematologic adverse reactions [see Warnings and Precautions (5)] | Grade 3 or higher | 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 Discontinue CALQUENCE at 3rdoccurrence of Grade 4 toxicity. For Grade 3 toxicity, consider the risks and benefits of continuing CALQUENCE. For bendamustine :Interrupt bendamustine. Once toxicity has resolved to Grade ≤ 2 or baseline, resume bendamustine and consider dose reduction to 70 mg/m2.e |
a Graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. b For neutropenia with ANC less than 1 x 109/L, consideration for bendamustine dose interruption and dosage reduction to 70 mg/m2 may be appropriate in certain circumstances. c Dose may be re-escalated at the discretion of the physician if patient tolerates a reduced dose for ≥4 weeks. d Consider use of myeloid growth factors before bendamustine dosage reduction. e Consider discontinuing bendamustine if additional dosage reduction is required. f For thrombocytopenia, a platelet count below 50 x 109/L should prompt bendamustine dose interruption even in the absence of clinically significant bleeding . | ||
Warnings and Precautions, Second Primary Malignancies (
Warnings and Precautions, Cardiac Arrythmias (
Warnings and Precautions, Hepatotoxicity, Including Drug-Induced Liver Injury (
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 Previously Untreated Mantle Cell LymphomaCALQUENCE 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).• For the treatment of adult patients with MCL who have received at least one prior therapy. ()1.2 Previously Treated Mantle Cell LymphomaCALQUENCE is indicated for the treatment of adult patients with MCL who have received at least one prior therapy.
• For the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). ()1.3 Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaCALQUENCE is indicated for the treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
• Recommended dose is 100 mg orally approximately every 12 hours; swallow whole with water and with or without food. ()2.1 Recommended DosageCALQUENCE Administration InstructionsAdvise 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 MonotherapyFor 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 RituximabFor 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/m2on Days 1 and 2 and rituximab 375 mg/m2on 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 ObinutuzumabFor 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
• Advise patients not to chew, crush, dissolve, or cut tablets. ()2.1 Recommended DosageCALQUENCE Administration InstructionsAdvise 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 MonotherapyFor 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 RituximabFor 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/m2on Days 1 and 2 and rituximab 375 mg/m2on 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 ObinutuzumabFor 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
• Manage toxicities using treatment interruption, dose reduction, or discontinuation. ()2.2 Recommended Dosage for Drug InteractionsDosage Modifications for Use with CYP3A Inhibitors or InducersThese are described in Table 1
[seeDrug Interactions (7)].Table 1: Recommended Dosage Modifications for Use with CYP3A Inhibitors or Inducers CYP3ACo-administered DrugRecommended CALQUENCE useInhibition
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.
• Avoid CALQUENCE in patients with severe hepatic impairment. ()8.6 Hepatic ImpairmentAvoid 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)]
Tablets:100 mg acalabrutinib, orange, oval, film-coated, biconvex, debossed with ‘ACA 100’ on one side and plain on the other.
• Pregnancy: May cause fetal harm and dystocia. ()8.1 PregnancyRisk SummaryBased 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.
DataAnimal DataIn 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.
• Lactation: Advise not to breastfeed. ()8.2 LactationRisk SummaryNo 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.
• Severe Hepatic Impairment: Avoid use of CALQUENCE. ()8.6 Hepatic ImpairmentAvoid 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)]
None.