Acalabrutinib

Indications

Acalabrutinib is a kinase inhibitor indicated for the treatment of adult patients with:
  • Mantle cell lymphoma (MCL) who have received at least one prior therapy
  • This indication is approved under accelerated approval based on overall response rate Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials
  • Chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL)

Pharmacology

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.

Dosage & Administration

The 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 Acalabrutinib in patients with severe hepatic impairment.

Interaction

  • 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

Side Effects

Most common adverse reactions (incidence ≥30%) were: anemia, neutropenia, upper respiratory tract infection, thrombocytopenia, headache, diarrhea, and musculoskeletal pain.

Pregnancy & Lactation

Based on findings in animals, Acalabrutinib may cause fetal harm and dystocia when administered to a pregnant woman. There are no available data in pregnant women to inform the drug-associated risk. 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.

Precautions & Warnings

  • 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
  • Atrial Fibrillation and Flutter: Monitor for symptoms of arrhythmias and manage

Therapeutic Class

Tyrosine Kinase Inhibitor

Storage Conditions

Do not store above 30⁰C. Keep away from light and out of the reach of children.

Available Brand Names