ASH Clinical News ACN_5.4_Full Issue_web | Page 43

BACK of the BOOK
ASH
Daniel Gih, MD
@ASH_hematology
Zackary Berger, MD, PhD
@DrDanielGih
ASH President @RSilversteinMD and
the 2019 officers are on Capitol
Hill today advocating for issues
important to hematology, including
the @CDCgov #sicklecell disease
data collection program and patient
access to CAR-T therapy.
@ZackBergerMDPhD
I wish came up with this, but credit
@annegalloway on best advice on
entering #academia, “We’re all smart.
Distinguish yourself by being kind.”
TRIM SIZE: 8.5” x 11”
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
(itraconazole) increased acalabrutinib plasma concentrations [see
Impact
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
may increase acalabrutinib plasma concentrations [see Clinical
Impact
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,
reduce acalabrutinib dose to 100 mg once daily.
Management
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
My favorite faxes are Epic notes
printed out
faxed to me
then scanned
into Epic
2
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.
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 and delayed skeletal
ossification. The AUC at 100 mg/kg/day in pregnant rabbits was approximately 4-times the
AUC in patients at 100 mg twice daily.
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 at least 2 weeks after the final dose.
Pediatric Use
The safety and efficacy of CALQUENCE in pediatric patients have not been established.
Geriatric Use
Eighty (64.5%) of the 124 MCL patients in clinical trials of CALQUENCE were 65 years of
age or older, and 32 patients (25.8%) were 75 years of age or older. No clinically relevant
differences in safety or efficacy were observed between patients ≥ 65 years and younger.
PATIENT COUNSELING INFORMATION
Advise the patient to read the FDA-approved patient labeling (Patient Information).
Hemorrhage
Inform patients to report signs or symptoms of severe bleeding. Inform patients that
CALQUENCE may need to be interrupted for major surgeries [see Warnings and Precautions
(5.1) in the full Prescribing Information].
Infections
Inform patients to report signs or symptoms suggestive of infection [see Warnings and
Precautions (5.2) in the full Prescribing Information].
Cytopenias
Inform patients that they will need periodic blood tests to check blood counts during
treatment with CALQUENCE [see Warnings and Precautions (5.3) in the full Prescribing
Information].
Second Primary Malignancies
Inform patients that other malignancies have been reported in patients who have been treated
with CALQUENCE, including skin cancer. Advise patients to use sun protection [see Warnings
and Precautions (5.4) in the full Prescribing Information].
Atrial Fibrillation and Flutter
Counsel patients to report any signs of palpitations, lightheadedness, dizziness, fainting,
shortness of breath, and chest discomfort [see Warnings and Precautions (5.5) in the full
Prescribing Information].
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 capsules should be
swallowed whole with a glass of water, without being opened, broken, or chewed [see
Dosage and Administration (2.1) in the full Prescribing Information].
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 capsules to make up for the dose that they
missed [see Dosage and Administration (2.1) in the full Prescribing Information].
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) in the
full Prescribing Information].
Lactation
Advise women not to breastfeed during treatment with CALQUENCE and for at least 2 weeks
after the final dose [see Use in Specific Populations (8.2) in the full Prescribing Information].
Distributed by: AstraZeneca Pharmaceuticals LP, Wilmington, DE 19850
CALQUENCE is a registered trademark of the AstraZeneca group of companies.
©AstraZeneca 2017
11/17 US-17859 2/18