Acalabrutinib

Grade 3 or 4 cytopenias including neutropenia, anemia, and thrombocytopenia have occurred in patients with hematologic malignancies treated with acalabrutinib (as a single agent). In studies, CBC was monitored monthly.

Atrial fibrillation and atrial flutter (any grade) occurred in a small percentage of patients with hematologic malignancies treated with acalabrutinib (as a single agent); grade 3 events were reported. Monitor for atrial fibrillation and atrial flutter and manage as appropriate.

Diarrhea, nausea, and vomiting may commonly occur, although generally mild.

Serious hemorrhagic events (some fatal) have been reported in patients with hematologic malignancies who received acalabrutinib. Overall, bleeding events, including bruising and petechiae (any grade), occurred in approximately half of patients with hematological malignancies who received acalabrutinib. Grade 3 or higher bleeding events (including GI, intracranial, and epistaxis) have been reported rarely. While the mechanism for bleeding events is not well understood, acalabrutinib may further increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies; monitor these patients for signs of bleeding. Depending upon the type of surgery and the risk of bleeding, consider the benefit-risk of withholding acalabrutinib treatment for 3 to 7 days before and after surgery.

Serious bacterial, viral, or fungal infections (including fatal events and opportunistic infections) have occurred in patients with hematologic malignancies treated with acalabrutinib (as a single agent). Consider prophylaxis in patients who are at increased risk for opportunistic infections. Grade 3 or higher infections occurred in about one-fifth of these patients; pneumonia was the most frequent grade 3 or 4 infection. Infections due to hepatitis B virus (HBV) reactivation and progressive multifocal leukoencephalopathy (PML) have also occurred. Monitor for signs and symptoms of infection and manage as medically appropriate.

Second primary malignancies, including non-skin carcinomas, have occurred in about one-tenth of patients with hematologic malignancies treated with acalabrutinib (as a single agent); the most frequent second primary malignancy was skin cancer. Advise patients to utilize protection from sun exposure. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Avoid concomitant use with proton pump inhibitors; administer acalabrutinib 2 hours prior to H2-receptor antagonists; separate acalabrutinib from antacids by at least 2 hours.