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 |
| 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).