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HELP HEMATOLOGY PATIENTS FIND YOU! ASH members can help patients find their hematology practice by signing up to be included in ASH’s Find a Hematologist directory. Visit www.hematology.org/ Patients/FAH.aspx to add your information! WORK AND PLAY ON MAUI, HAWAII Pacific Permanente Group is seeking a BC/BE Hematologist/Oncologist for its Oncology Department at Maui Memorial Medical Center in Wailuku, Maui, Hawaii. POSITION HIGHLIGHTS: • Join a 1 MD and 1 APRN Oncology practice. • Broad spectrum practice with approximately 75% Medical Oncology and 25% Hematology. • Shared call. • Infusion center at Maui Memorial Medical Center. • Collaboration with Radiation Oncology Group. • Opportunity to help build Cancer Center of Excellence on Maui. POSITION QUALIFICATIONS: • Board certified in Hematology and Medical Oncology. • 5+ years of experience preferred. Please email CV TRIM and cover letter to: x [email protected] SIZE: 8.5” 11” Learn more at careers.pacificpermanente.com 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 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