CALQUENCE

/ Astra Zeneca

Recommended Dosage
Monotherapy
For patients with MCL, CLL or SLL, the recommended is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity.
Combination with Bendamustine and Rituximab
For patients with previously untreated MCL, the recommended dosage is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity.
Start this medical product on Day 1 of Cycle 1 (each cycle is 28 days) and administer until disease progression or unacceptable toxicity. Administer bendamustine 90 mg/m2 on Days 1 and 2 and rituximab 375 mg/m2 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.
Combination with Obinutuzumab
For patients with previously untreated CLL or SLL, the recommended dosage is 100 mg taken orally approximately every 12 hours until disease progression or unacceptable toxicity. Start this medical treatment 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 this medical product prior to obinutuzumab when given on the same day.
See prescribing information for full details.

Previously Untreated Mantle Cell Lymphoma
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).
Mantle Cell Lymphoma
Treatment of adult patients with mantle cell lymphoma (MCL) who have received at least one prior therapy.
Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Treatment of adult patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

Hypersensitivity to the active substance or to any of the excipients

Serious and Opportunistic Infections
Fatal and serious infections, including opportunistic infections, have occurred in patients with hematologic malignancies.
Serious or Grade 3 or higher infections (bacterial, viral, or fungal) occurred in 32% of patients exposed to acalabrutinib in clinical trials, most often due to respiratory tract infections (19% of all patients, including pneumonia in 9%). These infections predominantly occurred in the absence of Grade 3 or 4 neutropenia, with neutropenic infection reported in 2.7% of all patients. Opportunistic infections 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.
Hemorrhage
Fatal and serious hemorrhagic events have occurred in patients treated with acalabrutinib. Major hemorrhage (serious or Grade 3 or higher bleeding or any central nervous system bleeding) occurred in 4.4% of patients, with fatal hemorrhage occurring in 0.2%. patients exposed in clinical trials. Bleeding events of any grade, excluding bruising and petechiae, occurred in 40% of patients.
Use of antithrombotic agents concomitantly may further increase the risk of hemorrhage. In clinical trials, major hemorrhage occurred in 7% of patients taking acalabrutinib without antithrombotic agents and 4% of patients taking acalabrutinib with antithrombotic agents. Consider the risks and benefits of antithrombotic agents when co-administered with acalabrutinib. Monitor patients for signs of bleeding.
Consider the benefit-risk of withholding this medical product for 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.
Cytopenias
Grade 3 or 4 cytopenias included absolute neutrophil count decreased (26%), platelets decreased (10%), hemoglobin decreased (10%), and absolute lymphocyte count decreased (10%) in patients treated with acalabrutinib alone or in combination with obinutuzumab; Grade 4 neutropenia developed in 14%.
Monitor complete blood counts regularly during treatment. Interrupt treatment, reduce the dose, or discontinue treatment as warranted
Second Primary Malignancies
Second primary malignancies, including skin cancers and other solid tumors, occurred in 18% of patients exposed to acalabrutinib in clinical trials. The most frequent second primary malignancy was non-melanoma skin cancer, reported in 10% of patients, followed by other solid tumors in 9% (including melanoma, lung cancer, gastrointestinal cancers, and genitourinary cancers) and hematologic malignancies (1%). Monitor patients for the development of second cancers and advise protection from sun exposure.
Cardiac Arrhythmias
Fatal and serious cardiac arrhythmias have occurred in patients treated with acalabrutinib. Grade 3 or 4 atrial fibrillation or flutter was reported in 2.6% of patients treated with acalabrutinib, with all grades of atrial fibrillation or flutter reported in 7% of all patients. Grade 3 or higher ventricular arrhythmia events were reported in 0.6% 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.
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 acalabrutinib.
Evaluate bilirubin and transaminases at baseline and throughout treatment. For patients who develop abnormal liver tests after this treatment, monitor more frequently for liver test abnormalities and clinical signs and symptoms of hepatic toxicity. If DILI is suspected, withhold treatment. Upon confirmation of DILI, discontinue acalabrutinib.

See prescribing information for full details.

Effect of Other Drugs on Obinutuzumab
Strong CYP3A Inhibitors

with a strong CYP3A inhibitor increased acalabrutinib plasma concentrations. Increased acalabrutinib concentrations may result in increased toxicity.
Avoid co-administration with strong CYP3A inhibitors. Alternatively, if the inhibitor will be used short-term, interrupt acalabrutinib.
Moderate CYP3A Inhibitors
Co-administration with a moderate CYP3A inhibitor may increase acalabrutinib plasma concentration. Increased acalabrutinib concentrations may result in increased toxicity. Reduce the dosage of acalabrutinib when co-administered with a moderate CYP3A inhibitor.
Strong CYP3A Inducers
Co-administration with a strong CYP3A inducer decreased acalabrutinib plasma concentration. Decreased acalabrutinib concentrations may reduce acalabrutinib activity. Avoid co-administration with strong CYP3A inducers. If co-administration is unavoidable, increase the dosage of acalabrutinib.

Pregnancy: There are no available data in pregnant women to inform the drug-associated risk.
Lactation: 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. Due to the potential for adverse reactions in a breastfed child acalabrutinib, advise lactating women not to breastfeed while taking acalabrutinib and for 2 weeks after the last dose.
Reproductive Potential: acalabrutinib may cause embryo-fetal harm and dystocia when administered to pregnant women
Pregnancy Testing
Pregnancy testing is recommended for females of reproductive potential prior to initiating therapy.
Contraception
Advise female patients of reproductive potential to use effective contraception during treatment and for 1 week following the last dose. 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.