What are the adverse effects of Dasatinib (Sprycel)?

Dasatinib Adverse Effects

Dasatinib causes significant adverse effects across multiple organ systems, with myelosuppression, pleural effusions, and bleeding complications being the most clinically important concerns requiring vigilant monitoring and proactive management. 1, 2

Hematological Toxicity

Myelosuppression is the most common adverse effect, affecting all three blood cell lineages:

• Grade 3-4 neutropenia occurs in 19.4% of first-line chronic phase CML patients 1
• Grade 3-4 thrombocytopenia affects 17.4% of patients 1
• Grade 3-4 anemia develops in 11.5% of patients 1
• Advanced phase CML carries substantially higher rates of myelosuppression 1
• Thrombocytopenia is more clinically significant than neutropenia due to associated bleeding risk 3

Management of Myelosuppression:

• Withhold therapy for grade 3 neutropenia; for grade 4 neutropenia, consider G-CSF and switching to another TKI 1
• G-CSF and erythropoietic agents can be used transiently to facilitate recovery 1
• Regular blood count monitoring is mandatory throughout treatment 1, 2

Pulmonary and Pleural Complications

Pleural effusions represent a major toxicity unique to dasatinib:

• Pleural effusions occur in up to 37% of patients and may develop even after years of treatment 1, 4
• Fluid retention is the most common non-hematologic adverse event 4
• Pulmonary arterial hypertension (PAH) is rare but serious, occurring in approximately 5% of patients 5
• Patients with pre-existing pleuro-pulmonary or pericardial diseases are at significantly higher risk 1
• Respiratory failure and pre-existing pleuro-pulmonary disease are strong contraindications to dasatinib use 1

Management:

• Manage pleural effusions with supportive care measures and/or dose modification 2
• If PAH is confirmed, dasatinib must be permanently discontinued 1, 2
• Close monitoring of patients with risk factors for pleural effusion is necessary 1

Bleeding Complications

Dasatinib carries a significantly elevated bleeding risk compared to other TKIs:

• Gastrointestinal bleeding occurs in 17% of patients across all phases 6, 1
• Bleeding affects 23% of all patients (7% grade ≥3), with higher rates in advanced phase disease: 12% in chronic phase, 31% in accelerated phase, and 35% in blast phase 7
• 81% of bleeding episodes affect the gastrointestinal tract 7
• Thrombocytopenia and advanced phase CML are independent risk factors for bleeding 6, 7
• 63% of bleeding episodes occur with platelet counts ≤100 × 10⁹/L, though 37% occur with higher platelet counts 7
• Basic coagulation studies are normal in 97% of patients who develop bleeding 7

Management:

• Use extreme caution when combining with medications that inhibit platelet function or anticoagulants 2
• Interrupt dasatinib for median of 17 days when bleeding occurs 7
• Transfusions are required in 72% of bleeding episodes 7

Gastrointestinal Toxicity

Gastrointestinal side effects are common but generally well-tolerated:

• Diarrhea, nausea, vomiting, and abdominal pain are frequent (≥15% of patients) 2, 3
• Most gastrointestinal problems occur during the first month of therapy 6
• Gastrointestinal toxicity with dasatinib is generally better tolerated compared to other TKIs like bosutinib 6

Management:

• Proton-pump inhibitors may be helpful for abdominal pain, but dosing should be separated from dasatinib intake by 12 hours 6
• Mild symptoms require only symptomatic relief and diet modification unless they interfere with quality of life 6
• Rule out gastric and pancreatic problems in cases of abdominal pain 6

Dermatological Reactions

Skin reactions occur with moderate frequency:

• Rash occurs in 11% of first-line patients, increasing to 18% by 36 months and 33% by 6 years 6
• The incidence of rash is lower with dasatinib than with nilotinib 6
• Severe mucocutaneous dermatologic reactions have been reported in individual cases 2
• Other skin effects include pruritus and dry skin 6

Cardiovascular Toxicity

Cardiovascular complications require careful monitoring:

• QT prolongation can occur; use with caution in patients who have or may develop QT interval prolongation 2
• Cardiac function assessment is recommended, especially in patients with pre-existing conditions 1
• Patients with prior cardiac history, hypertension, and older age are at increased risk 5

Other Significant Adverse Effects

• Headache, dyspnea, fatigue, nausea, and musculoskeletal pain occur in ≥15% of patients 2
• Peripheral edema is common, though fluid retention is less apparent than with imatinib 6
• Tumor lysis syndrome has been reported; maintain adequate hydration and correct uric acid levels prior to initiating therapy 2
• Hepatotoxicity requires liver function assessment before initiation and monthly monitoring thereafter 2

Pediatric-Specific Concerns

Growth and development effects are critical in pediatric patients:

• Delayed epiphyseal fusion, osteopenia, growth retardation, and gynecomastia have been reported 2
• Monitor bone growth and development closely in pediatric patients 2

Dosing Optimization to Reduce Toxicity

Lower dosing may improve tolerability without compromising efficacy:

• Standard dose is 100 mg once daily for chronic phase CML, but 50 mg daily may be considered due to similar efficacy with fewer side effects 1
• 100 mg once daily is better tolerated than 70 mg twice daily, with lower incidences of pleural effusion and grade 3-4 thrombocytopenia 4