Acalabrutinib

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). • 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).

Acalabrutinib is a small-molecule inhibitor of BTK. Acalabrutinib and its active metabolite, ACP-5862, form a covalent bond with a cysteine residue in the BTK active site, leading to inhibition of BTK enzymatic activity. BTK is a signaling molecule of the B cell antigen receptor (BCR) and cytokine receptor pathways. In B cells, BTK signaling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion. In nonclinical studies, acalabrutinib inhibited BTK-mediated activation of downstream signaling proteins CD86 and CD69 and inhibited malignant B-cell proliferation and tumor growth in mouse xenograft models.

Recommended dose is 100 mg orally approximately every 12 hours, swallow whole with water and with or without food. • Advise patients not to break, open, or chew capsules. • Manage toxicities using treatment interruption, dose reduction, or discontinuation. • Avoid CALQUENCE in patients with severe hepatic impairment

None. None.

• Serious and Opportunistic Infections: Monitor for signs and symptoms of infection and treat promptly. • Hemorrhage: Monitor for bleeding and manage appropriately. • Cytopenias: Monitor complete blood counts regularly. • Second Primary Malignancies: Other malignancies have occurred, including skin cancers and other solid tumors. Advise patients to use sun protection. • Cardiac Arrhythmias: Monitor for symptoms of arrhythmias and manage. • Hepatotoxicity, Including Drug-Induced Liver Injury: Monitor hepatic function throughout treatment.

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: • Serious and Opportunistic Infections • Hemorrhage • Cytopenias • Second Primary Malignancies • Cardiac Arrhythmias • Hepatotoxicity, including DILI The most common adverse reactions (≥ 30%), excluding laboratory abnormalities, are upper respiratory tract infection, diarrhea, headache, and musculoskeletal pain. The most common Grade 3 or 4 laboratory abnormalities (≥ 10%) are absolute neutrophil count decreased, uric acid increase, absolute lymphocyte count decreased, and platelets decreased.

• CYP3A Inhibitors: Avoid co-administration with strong CYP3A inhibitors. Dose adjustments may be recommended. • CYP3A Inducers: Avoid co-administration with strong CYP3A inducers. Dose adjustments may be recommended. • Gastric Acid Reducing Agents: Avoid co-administration with proton pump inhibitors (PPIs). Stagger dosing with H2-receptor antagonists and antacids.

Storage Store at 20°C-25°C (68°F-77°F), excursions permitted to 15°C-30°C (59°F-86°F).