What are the side effects of Acalabrutinib (Bruton's tyrosine kinase inhibitor)?

Side Effects of Acalabrutinib (Bruton's Tyrosine Kinase Inhibitor)

Acalabrutinib commonly causes headache, diarrhea, and bleeding events, but has a more favorable cardiovascular safety profile compared to ibrutinib with lower rates of atrial fibrillation and hypertension. 1, 2

Common Side Effects

• Hematologic toxicities:

  • Neutropenia (19% overall, 12% grade 3/4) 1, 3, 4
  • Anemia (15%) 1, 3
  • Thrombocytopenia (9% grade 3/4) 4

• Gastrointestinal effects:

  • Diarrhea (58% of patients) 1, 4
  • Nausea (7-27%) 1, 4

• Constitutional symptoms:

  • Headache (39%) - typically resolves after 1-2 months and can be managed with acetaminophen and caffeine supplements 1, 4
  • Fatigue (10-18%) 1, 4
  • Pyrexia (12-21%) 1, 4

• Respiratory:

  • Cough (15-33%) 1, 4
  • Upper respiratory tract infection (24%) 4

• Musculoskeletal:

  • Arthralgia (8-21%) 3, 4

Cardiovascular Side Effects

• Atrial fibrillation:

  • 4-5% overall incidence 1, 2
  • 1% grade ≥3 1
  • Significantly lower than ibrutinib (5.8% vs 11.7%) 2

• Hypertension:

  • 3-5% overall incidence 1, 2
  • 2-3% grade ≥3 1
  • Significantly lower than ibrutinib (15% vs 26.3%) 2

Bleeding Events

• Overall bleeding risk:
  • 26-39% for any grade bleeding 1
  • 2% for grade ≥3 bleeding 1
  • Monitor patients requiring antiplatelet or anticoagulant therapies 1, 5
  • Avoid concomitant warfarin use 1, 5

Dermatologic Effects

• Skin manifestations:
  • Bruising and ecchymoses (>30% of patients) 6
  • Rash (9%) 3
  • Skin infections including herpes virus reactivations 6

Other Notable Side Effects

• Infections:

  • Overall infection rate of 65% 1
  • Grade ≥3 infections in 14% of patients 1
  • Pneumonia and upper respiratory tract infections are most common 1

• Secondary malignancies:

  • Overall incidence of 3% 1
  • Non-melanoma skin cancer (6%) 3

• Hepatic effects:

  • Transaminase elevations (ALT 15%, AST 13%) 3
  • Bilirubin increase (13%) 3

Management Considerations

• For headaches:

  • Usually self-limiting within 1-2 months 1
  • Manage with analgesics (acetaminophen) and caffeine supplements 1

• For cardiovascular events:

  • Monitor for atrial fibrillation and hypertension 1
  • Consider switching therapy if atrial fibrillation/hypertension is not medically controllable 1
  • Transition to alternate therapy should be done promptly as disease progression may accelerate when acalabrutinib is stopped 1

• For patients on anticoagulants:

  • Evaluate benefit and risk carefully 1
  • Avoid concomitant warfarin use 1, 5
  • Monitor for signs of bleeding 1

Special Considerations

• Ibrutinib intolerance:

  • Acalabrutinib is well-tolerated in patients previously intolerant to ibrutinib 1, 4
  • 72% of ibrutinib-related adverse events do not recur with acalabrutinib 4
  • 13% recur but at a lower grade 4

• Drug interactions:

  • Avoid strong CYP3A inhibitors or reduce acalabrutinib dose 3
  • Avoid strong CYP3A inducers or increase acalabrutinib dose 3

• Monitoring:

  • Regular blood count monitoring for cytopenias 3
  • Cardiac monitoring for patients with cardiovascular risk factors 1, 2