Table 2.

Our approach to management of common adverse events with TKIs in CML

Adverse events	Management
Nonhematologic adverse events
Nausea and vomiting	Take imatinib with food; antiemetics if necessary
Diarrhea	Loperamide or diphenoxylate atropine
Fluid retention
Peripheral edema	Diuretics as needed (usually furosemide)
Periorbital edema	Steroid-containing cream
Pleural effusion	Observation if minimal; when intervention is required, stop TKI, use diuretics, corticosteroids may help in occasional patients; resume TKI with dose reduction when the effusion has significantly improved; thoracentesis if effusion not resolving or large and symptomatic
Skin rash	Symptomatic therapy (eg, antihistamines); topical steroids; occasionally systemic steroids; minimize sun exposure
Muscle cramps	Tonic water or quinine; calcium gluconate may sometimes help; electrolyte replacement if needed (eg, potassium)
Arthralgia, bone pain	NSAID (should be used with caution if platelet dysfunction is suspected, eg, with dasatinib)
Elevated transaminases	Monitor if grade 1 or 2; interrupt therapy if grade 3; restart a lower dose when recovered to grade ≤ 1; corticosteroids may help some patients if recurrent
Elevated bilirubin	Monitor if grade 1 or 2; interrupt therapy if grade 3; restart a lower dose when recovered to grade ≤ 1; elevation of bilirubin common with nilotinib, particularly among patients with Gilbert syndrome; in those instances, may allow continuation of therapy in some instances with grade 3
Elevated lipase, amylase (asymptomatic)	Monitor if grade 1 or 2; interrupt therapy if grade 3; restart at lower dose when recovered to grade ≤ 1
Hyperglycemia	More common with nilotinib; stop therapy if grade ≥ 3; restart therapy when recovered to grade ≤ 1 with reduced dose; no contraindication to use nilotinib in patients with diabetes mellitus; close monitoring and adjustment of hypoglycemic agents as needed
Hematologic adverse events
Neutropenia	Hold therapy if grade ≥ 4 (ie, ANC < 0.5 × 109/L);† restart at the same dose if recovery to ANC ≥ 0.75 × 109/L within 2 wks; restart at lower dose if recovery after 2 wks; consider filgrastim if recurrent/persistent, or sepsis72*
Thrombocytopenia	Hold therapy if platelets < 40 × 109/L†; restart at the same dose if recovery within 2 wks to ≥ 75 × 109/L; restart at lower dose if recovery after 2 wks; consider IL-11 10 μg/kg 3-7 d/wk73*
Anemia	Treatment interruption/dose reduction usually not indicated; consider erythropoietin or darbepoetin74*; transfusions rarely needed

NSAID indicates nonsteroidal anti-inflammatory drug; and ANC, absolute neutrophil count.

^*The use of erythropoietin, darbepoietin, filgrastim, and IL-11 in this setting is not standard and should be considered investigational.

^†The standard recommendation is to hold if grade ≥ 3 (ie, ANC < 1 × 10⁹/L, platelets < 50 × 10⁹/L).