Table 2.

Management of adverse events associated with BTK inhibitor therapy.

Adverse Event	Management Strategy	References
Atrial fibrillation	Monitor for atrial fibrillation during treatment Administer direct oral anticoagulants Discontinue BTK inhibitor therapy if atrial fibrillation is not medically controllable	(7, 39)
Bleeding events	Monitor for signs of bleeding Use direct oral anticoagulants if anticoagulation therapy is needed Withhold BTK inhibitor for 3 to 7 days before and after surgery, depending upon the type of surgery, and the risk of a bleeding event	(7)
Diarrhea	Use antidiarrheal medication (e.g., loperamide) as needed	(40)
Headache	Prior to treatment initiation: advise patients that headaches should abate quickly, are easily managed, and are not a long-term consequence of treatment After treatment initiation: recommend the use of acetaminophen or caffeine and avoid NSAIDs if possible	(39)
Hypertension	Monitor for treatment-emergent hypertension Manage with antihypertensive medication Reduce antihypertensive medication dose once BTK inhibitors are discontinued
Infection	Consider prophylaxis for patients at increased risk of opportunistic infection Monitor for signs and symptoms Treat as needed	(1, 7, 9)
Musculoskeletal pain (myalgia, arthralgia, etc)	Grade 1 myalgias/arthralgias may not need intervention Dose reduction or dose interruption should be used as appropriate	(41)
Neutropenia	First to third occurrence of grade 3 or 4: dose interruptions are recommended Fourth occurrence: discontinuation of BTK inhibitor is recommended	(7, 9)
Thrombocytopenia	First to third occurrence of grade 3 or 4: dose interruptions are recommended Fourth occurrence: discontinuation of BTK inhibitor is recommended (unless thrombocytopenia is related to CLL infiltration of the bone marrow)	(7)

BTK, Bruton tyrosine kinase; CLL, chronic lymphocytic leukemia; NSAID, nonsteroidal anti-inflammatory drug.