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CALQUENCE ® (acalabrutinib) capsules, for oral use
Table 3: Hematologic Adverse Reactions Reported* in ≥ 20% of Patients with MCL
in Trial LY-004
Hematologic
Adverse Reactions
CALQUENCE 100 mg twice daily
N=124
All Grades (%) Grade ≥ 3 (%)
Hemoglobin decreased 46 10
Platelets decreased 44 12
Neutrophils decreased 36 15
* Per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03;
based on laboratory measurements and adverse reactions.
Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 4.8% of patients.
DRUG INTERACTIONS
Strong CYP3A Inhibitors
Clinical • Co-administration of CALQUENCE with a strong CYP3A inhibitor
Impact
(itraconazole) increased acalabrutinib plasma concentrations [see
Clinical Pharmacology (12.3) in the full Prescribing Information].
• Increased acalabrutinib concentrations may result in increased toxicity.
Prevention or • Avoid co-administration of strong CYP3A inhibitors with CALQUENCE.
Management • Alternatively, if the inhibitor will be used short-term, interrupt
CALQUENCE [see Dosage and Administration (2.2) in the full
Prescribing Information].
Moderate CYP3A Inhibitors
Clinical • Co-administration of CALQUENCE with a moderate CYP3A inhibitor
Impact
may increase acalabrutinib plasma concentrations [see Clinical
Pharmacology (12.3) in the full Prescribing Information].
• Increased acalabrutinib concentrations may result in increased toxicity.
Prevention or • When CALQUENCE is co-administered with moderate CYP3A inhibitors,
Management
reduce acalabrutinib dose to 100 mg once daily.
Strong CYP3A Inducers
Clinical • Co-administration of CALQUENCE with a strong CYP3A inducer
Impact
(rifampin) decreased acalabrutinib plasma concentrations [see
Clinical Pharmacology (12.3) in the full Prescribing Information].
• Decreased acalabrutinib concentrations may reduce
CALQUENCE activity.
Prevention or • Avoid co-administration of strong CYP3A inducers with CALQUENCE.
Management • If a strong CYP3A inducer cannot be avoided, increase the acalabrutinib
dose to 200 mg twice daily.
Gastric Acid Reducing Agents
• Co-administration of CALQUENCE with a proton pump inhibitor,
H2-receptor antagonist, or antacid may decrease acalabrutinib
plasma concentrations [see Clinical Pharmacology (12.3) in the
full Prescribing Information].
Clinical
• Decreased acalabrutinib concentrations may reduce
Impact
CALQUENCE activity.
• If treatment with a gastric acid reducing agent is required, consider
using a H2-receptor antagonist (e.g., ranitidine or famotidine) or an
antacid (e.g., calcium carbonate).
Antacids
H2-receptor
Prevention or
antagonists
Management
Proton pump
inhibitors
Separate dosing by at least 2 hours [see Dosage and
Administration (2.2) in the full Prescribing Information].
Take CALQUENCE 2 hours before taking the H2-receptor
antagonist [see Dosage and Administration (2.2) in the
full Prescribing Information].
Avoid co-administration. Due to the long-lasting
effect of proton pump inhibitors, separation of doses
may not eliminate the interaction with CALQUENCE.
USE IN SPECIFIC POPULATIONS
Pregnancy
Risk Summary
Based on findings in animals, CALQUENCE may cause fetal harm 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 pregnant
rabbits during organogenesis resulted in reduced fetal growth at maternal exposures (AUC)
approximately 4 times exposures in patients at the recommended dose of 100 mg twice daily
(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 2-4% and 15-20%, respectively.
2
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 16-times the AUC
in patients at the recommended dose of 100 mg twice daily. 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