Side Effects of Dasatinib (Sprycel)
Dasatinib has several significant side effects including pleural effusions affecting up to 37% of patients, pulmonary arterial hypertension, myelosuppression, and gastrointestinal disturbances, which require careful monitoring and management. 1
Major Side Effects
Pleuro-pulmonary Toxicity
- Recurrent pleural effusions occur in up to 37% of patients and may develop even after years of treatment 1
- Pulmonary arterial hypertension (PAH) is rare but serious 1, 2
- Respiratory failure and pre-existing pleuro-pulmonary or pericardial diseases are strong contraindications to dasatinib use 1
- Symptoms include shortness of breath, dry cough, and chest pain when breathing deeply 2
- Fluid retention can occur in multiple body compartments (lungs, heart sac, stomach cavity) 2, 3
Hematological Toxicity
- Myelosuppression affects all three blood cell lineages 1:
- Neutropenia (grade 3-4): 19.4% in first-line treatment
- Thrombocytopenia (grade 3-4): 17.4% in first-line treatment
- Anemia (grade 3-4): 11.5% in first-line treatment
- Higher rates of myelosuppression occur in advanced phases of CML 1
- Bleeding risk is increased, particularly gastrointestinal bleeding (17% across all phases) 1, 4
- Risk factors for bleeding include thrombocytopenia and advanced phase CML 4
Gastrointestinal Side Effects
- Generally well-tolerated compared to other TKIs 1
- Include nausea, vomiting, diarrhea, and abdominal pain 1
- Gastrointestinal bleeding risk is higher with dasatinib than other TKIs, especially in second-line treatment (2-5% in chronic phase) 1
Skin Reactions
- Rash occurs in 11% of patients in first-line treatment, increasing to 33% by 6 years 1
- Peripheral fluid retention occurs in approximately 26% of patients 1
- Severe skin reactions with fever, blistering or peeling may occur rarely 2
Cardiovascular Effects
- Can cause heart problems including abnormal heart rate and heart attack 2
- Risk of transient ischemic attacks (TIAs) 2
- Requires monitoring of potassium and magnesium levels 2
Other Notable Side Effects
- Fatigue and muscle pain are common 2
- Liver problems may occur, especially in those with prior liver issues 2
- Tumor lysis syndrome can cause kidney failure and abnormal heart rhythm 2
- Fertility problems in both males and females 2
- Growth and development effects in children 2
Management of Side Effects
Pleural Effusions
- Dose interruption until resolution 3
- Consider dose reduction to 50 mg daily which has similar efficacy with fewer side effects 1, 5
- Close monitoring of patients with risk factors for pleural effusion 3
Myelosuppression
- Regular blood count monitoring 1
- G-CSF and erythropoietic agents can be used transiently to facilitate recovery 1
- For grade 3 neutropenia: withhold therapy, treat infection if present, resume at lower dose when resolved 1
- For grade 4 neutropenia: consider G-CSF and switching to another TKI 1
Gastrointestinal Issues
- Mild symptoms: symptomatic relief and diet modification 1
- Severe symptoms: antiemetic and antidiarrheal medications 1
- For abdominal pain: rule out gastric and pancreatic problems 1
- Proton-pump inhibitors may help but should be taken 12 hours apart from dasatinib 1
Bleeding Management
- Careful use of antiplatelet therapy due to platelet dysfunction 1
- Dasatinib interruption (median 17 days) may be required 4
- Transfusions may be necessary (72% of bleeding cases) 4
Monitoring Recommendations
- Regular blood count monitoring for myelosuppression 1
- Cardiac function assessment, especially in patients with pre-existing conditions 1
- Liver function monitoring 2
- Patient education about symptoms of fluid retention and pleural effusion 3
- Close monitoring of patients with risk factors for pleural effusion 1, 3