Version July 2025
Dosage guidance:
Safety: Use with caution in patients where fluid accumulation may be poorly tolerated, such as in cardiovascular disease (heart failure or hypertension) and pulmonary disease. Correct hypokalemia and hypomagnesemia prior to and during dasatinib therapy. Maintain adequate hydration and correct uric acid levels prior to treatment.
Clinical considerations : The effect of discontinuation on long-term disease outcome after achieving cytogenetic response (including complete cytogenetic response) or major molecular response is not known.
Acute lymphoblastic leukemia, Philadelphia chromosome positive (Ph+): Oral: 140 mg once daily until disease progression or unacceptable toxicity occurs. Consider a dose escalation to 180 mg once daily in patients not achieving hematologic or cytogenetic response at recommended initial dosage.
Off-label dosing/combinations:
Dasatinib in combination with low-intensity chemotherapy; EWALL-PH-01 (Ref): Patients ≥55 years of age: Oral: 140 mg once daily (100 mg once daily if ≥70 years) for 6 weeks during the induction period, followed by 100 mg once daily discontinuously during consolidation and maintenance, followed by postmaintenance of 100 mg once daily until relapse; dasatinib was administered in combination with chemotherapy; refer to protocol for further information.
Dasatinib in combination with Hyper- CVAD (Ref): Patients ≤60 years of age: Oral: 100 mg once daily for the first 14 days of the first Hyper-CVAD (high-intensity chemotherapy) cycle, followed by 70 mg once daily continuously during Hyper-CVAD cycles 2 through 8, followed by maintenance therapy with dasatinib 100 mg once daily (in combination with vincristine and prednisone) for 2 years, and then dasatinib was continued indefinitely thereafter. Patients who underwent hematopoietic cell transplant received dasatinib 100 mg once daily beginning on day 100 posttransplant and continued for up to 5 years. Refer to protocol for further information.
Dasatinib in combination with chemotherapy (Ref): Patients ≤65 years of age: Oral: 100 mg once daily for 4 weeks of each cycle for up to 4 cycles; for each cycle, chemotherapy was initiated first, followed by 4 weeks of dasatinib beginning when blood counts had recovered. Dasatinib was administered in combination with chemotherapy; refer to protocol for further information. Patients with a stem cell donor could receive up to 4 cycles total, followed by allogeneic stem cell transplant as early as possible. Patients unable to proceed to transplant could receive up to 4 cycles total, followed by dasatinib maintenance of 100 mg once daily for 2 years.
Protocol LAL1205 (Ref): Oral: Induction therapy: 70 mg twice daily for 84 days (in combination with prednisone and intrathecal methotrexate). Note: Patients received a 7-day steroid prephase prior to induction therapy.
GIMEMA LAL2116 (Ref): Oral: 140 mg once daily for 85 days in combination with glucocorticoid (induction therapy), followed by postinduction consolidation treatment with dasatinib 140 mg once daily in combination with blinatumomab. Therapy was continued for a minimum of 2 cycles; up to 3 additional cycles were allowed. Note: Patients received a 7-day steroid prephase prior to induction therapy.
Chronic myeloid leukemia (CML), Philadelphia chromosome positive:
Guideline recommendations (Ref): A British Society for Haematology guideline on the diagnosis and management of CML recommends considering a second-generation tyrosine kinase inhibitor (TKI) such as dasatinib as initial therapy for newly diagnosed chronic phase CML in patients with a high or intermediate EUTOS long-term survival (ELTS) or Sokal score; assess comorbidities and TKI toxicity profile to determine the appropriate TKI. An alternative TKI should be considered if treatment failure on first-line therapy occurs; the choice of second-line therapy should be guided by BCR-ABL mutational analysis as well as patient- and drug-specific characteristics. Patients with de novo accelerated phase CML should ideally be managed with a second generation TKI. Some patients may be candidates for a treatment-free remission (TFR); specific criteria and monitoring parameters must be met in order to discontinue treatment; refer to guideline for further information.
CML, Ph+, newly diagnosed in chronic phase: Oral: 100 mg once daily until disease progression or unacceptable toxicity occurs. Consider a dose escalation to 140 mg once daily in patients not achieving hematologic or cytogenetic response at recommended initial dosage.
CML, Ph+, resistant or intolerant:
Chronic phase: Oral: 100 mg once daily until disease progression or unacceptable toxicity occurs. Consider a dose escalation to 140 mg once daily in patients not achieving hematologic or cytogenetic response at recommended initial dosage.
Accelerated or blast phase: Oral: 140 mg once daily until disease progression or unacceptable toxicity occurs. Consider a dose escalation to 180 mg once daily in patients not achieving hematologic or cytogenetic response at recommended initial dosage.
Gastrointestinal stromal tumor (GIST), advanced (off-label use): Oral: 70 mg twice daily until disease progression or unacceptable toxicity; refer to protocols for further information (Ref).
Missed doses: If a dose is missed, take the next regularly scheduled dose; 2 doses should not be taken at the same time.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Altered kidney function: Oral: No dosage adjustment necessary for any degree of kidney impairment (Ref).
Hemodialysis, intermittent (thrice weekly): Not significantly dialyzed when administered after dialysis (Ref): Oral: No supplemental dose or dosage adjustment necessary; when scheduled dose falls on dialysis days, administer after hemodialysis (Ref). Note: Monitor for fluid accumulation and cardiotoxicity, as patients on dialysis may be at higher risk of developing and/or tolerating these adverse effects (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzed (highly protein bound, large Vd): Oral: No dosage adjustment necessary (Ref).
CRRT: Oral: No dosage adjustment necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): Oral: No dosage adjustment necessary (Ref).
Altered hepatic function at treatment initiation : No initial dosage adjustment is necessary (Ref).
Hepatotoxicity during treatment : Transaminase or bilirubin elevations during treatment may be managed with treatment interruption, dose reduction, or permanent discontinuation.
Hematologic toxicity:
| Indication and starting dosage | Laboratory parameters | Adjustment |
|---|---|---|
|
a Growth factor support may be considered in patients with resistant myelosuppression. b ALL = acute lymphoblastic leukemia; CML= chronic myeloid leukemia. | ||
| Chronic phase CML (starting dosage 100 mg once daily) | ANC <500/mm3 or platelets <50,000/mm3 |
|
| Accelerated phase CML, blast phase CML, and Philadelphia chromosome-positive (Ph+) ALL (starting dosage 140 mg once daily) | ANC <500/mm3 or platelets <10,000/mm3 |
|
Nonhematologic toxicity:
Adults with Ph+ CML and ALL: Severe nonhematologic toxicity: Withhold treatment until toxicity improvement or resolution; if appropriate, resume treatment at a reduced dose based on the event severity and recurrence.
Management of other nonhematologic toxicities:
Dermatologic toxicities: Manage rash with antihistamines or topical or systemic steroids (Ref), or treatment interruption, dose reduction, or discontinuation. Discontinue if dasatinib-related severe mucocutaneous reaction occurs.
Fluid retention: Manage with diuretics, short courses of corticosteroids, and/or supportive care. Severe pleural effusions may require thoracentesis and oxygen therapy; consider dose reduction or treatment interruption. For grade 3 pleural effusion, withhold treatment until resolves to grade 1 or lower and consider corticosteroids (eg, prednisone 20 to 40 mg/day for 3 to 4 days), diuretics, thoracentesis and/or pleurodesis; may resume dasatinib at a decreased dose when effusion resolves (Ref).
Hypertension: If indicated, initiate appropriate antihypertensive treatment to reduce the risk for cardiotoxicity (Ref).
Pulmonary arterial hypertension: Evaluate and rule out alternative etiologies in patients with symptoms suggestive of pulmonary arterial hypertension (PAH) (eg, dyspnea, fatigue, hypoxia, fluid retention) (Ref).
Normal peak tricuspid regurgitation velocity or mild peak tricuspid regurgitation velocity elevation on serial monitoring (eg, tricuspid regurgitation velocity ≤2.8 meters/second): May continue dasatinib with transthoracic echocardiography (TTE) monitoring every 3 months; if tricuspid regurgitation velocity (TRV) continues to rise, conduct right heart catheterization (Ref).
Asymptomatic increase in peak tricuspid regurgitation velocity of 2.9 to 3.4 meters/second: Consider reducing the dasatinib dose and monitor peak TRV with TTE every 4 weeks (Ref).
Asymptomatic increase in peak tricuspid regurgitation velocity >3.4 meters/second or symptomatic pulmonary arterial hypertension: Discontinue dasatinib; switch to an alternative BCR-ABL tyrosine kinase inhibitor after peak TRV recovery to <2.8 meters/second; conduct right heart catheterization (Ref).
Confirmed pulmonary arterial hypertension: Discontinue dasatinib; switch to an alternative BCR-ABL tyrosine kinase inhibitor after peak TRV recovery to <2.8 meters/second; consider medications for management of PAH (Ref).
Refer to adult dosing.
(For additional information see "Dasatinib: Pediatric drug information")
Acute lymphoblastic leukemia (ALL), Philadelphia chromosome positive (Ph+), newly diagnosed:
Note: Use in combination with chemotherapy; dose escalation is not recommended; initiate dasatinib on or before day 15 of induction chemotherapy. Continue treatment for 2 years. Recalculate the dose every 3 months or as clinically necessary based on changes in body weight.
Children weighing ≥10 kg and Adolescents: Sprycel:
10 to <20 kg: Oral: 40 mg once daily.
20 to <30 kg: Oral: 60 mg once daily.
30 to <45 kg: Oral: 70 mg once daily.
≥45 kg: Oral: 100 mg once daily.
Chronic myelogenous leukemia (CML), Philadelphia chromosome positive (Ph+), chronic phase:
Note: Continue dasatinib until disease progression or unacceptable toxicity. Recalculate the dose every 3 months or as clinically necessary based on changes in body weight.
Children weighing ≥10 kg and Adolescents: Sprycel:
10 to <20 kg: Oral: Initial: 40 mg once daily; may escalate to 50 mg once daily if hematologic or cytogenetic response is not achieved.
20 to <30 kg: Oral: Initial: 60 mg once daily; may escalate to 70 mg once daily if hematologic or cytogenetic response is not achieved.
30 to <45 kg: Oral: Initial: 70 mg once daily; may escalate to 90 mg once daily if hematologic or cytogenetic response is not achieved.
≥45 kg: Oral: Initial: 100 mg once daily; may escalate to 120 mg once daily if hematologic or cytogenetic response is not achieved.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Dosing adjustment for toxicity:
Hematologic toxicity: Adjustments are indication-specific.
Children and Adolescents: Sprycel: Oral:
Acute lymphoblastic leukemia, Philadelphia chromosome-positive (Ph+ ALL): If neutropenia and/or thrombocytopenia result in a delay of the next block of treatment by >14 days, interrupt dasatinib treatment and resume at the same level once the next block of treatment is started. If neutropenia and/or thrombocytopenia persist and the next block of treatment is delayed another 7 days, perform a bone marrow assessment to assess cellularity and blast percentage. If marrow cellularity is <10%, interrupt dasatinib treatment until ANC >500/mm3 and then resume dasatinib at the full dose. If marrow cellularity is >10%, consider resuming dasatinib. Note: Growth factor support may be considered in patients with resistant myelosuppression.
Chronic myelogenous leukemia, Philadelphia chromosome-positive (Ph+ CML):
Dosage reduction levels:
|
Original starting once-daily dose |
One-level dose reduction – once-daily dose |
Two-level dose reduction – once-daily dose |
|---|---|---|
|
40 mg |
20 mg |
No further reductions possible |
|
60 mg |
40 mg |
20 mg |
|
70 mg |
60 mg |
50 mg |
|
100 mg |
80 mg |
70 mg |
Dosage adjustments:
Note: Growth factor support may be considered in patients with resistant myelosuppression.
• If cytopenia (eg, neutropenia, thrombocytopenia) persists for >3 weeks, determine if cytopenia is due to leukemia by performing a marrow aspirate or biopsy.
• If cytopenia is unrelated to leukemia, withhold dasatinib until ANC ≥1,000/mm3 and platelets ≥75,000/mm3 and resume dasatinib at the original starting dose or at a reduced dose based on dosage reduction table.
• If cytopenia recurs, repeat marrow aspirate/biopsy and resume dasatinib at a reduced dose based on dosage reduction table.
Note: If ≥ grade 3 neutropenia or thrombocytopenia recurs during complete hematologic response, interrupt dasatinib therapy and resume at a reduced dose based on dosage reduction table. Temporary dose reductions for intermediate degrees of cytopenia and disease response may be used as needed.
Nonhematologic toxicity:
Children and Adolescents: Sprycel: Oral:
Dosage reduction levels:
|
Original starting once-daily dose |
One-level dose reduction – once-daily dose |
Two-level dose reduction – once-daily dose |
|---|---|---|
|
40 mg |
20 mg |
No further reductions possible |
|
60 mg |
40 mg |
20 mg |
|
70 mg |
60 mg |
50 mg |
|
100 mg |
80 mg |
70 mg |
Dosage adjustments for nonhematologic toxicities:
Ph+ ALL:
Grade 2 toxicity: If no recovery despite symptomatic management, consider interrupting dasatinib therapy; once recovered to ≤ grade 1, resume at the original starting dose. For recurrent events, resume dasatinib at a reduced dose based on dosage reduction table.
Grade ≥3 toxicity: Withhold dasatinib until recovered to grade 1 or lower, and then resume at a reduced dose based on dosage reduction table.
Ph+ CML:
Grade 2 toxicity (first occurrence): Interrupt dasatinib therapy until toxicity improvement or resolution; once recovered to ≤ grade 1, resume at the same dose (Ref).
Grade 2 toxicity (recurrent): Interrupt dasatinib therapy until toxicity improvement or resolution; once recovered to ≤ grade 1, resume reduced dose based on dosage reduction table (Ref).
Grade ≥3 toxicity: Withhold dasatinib until recovered to grade 1 or lower, and then resume at a reduced dose based on dosage reduction table (Ref).
Management of other nonhematologic toxicities: All indications:
Cardiac adverse reactions, signs, or symptoms (eg, chest pain, diaphoresis, shortness of breath): Withhold treatment and perform functional assessment; results may determine continuation of therapy (refer to individual protocols). If dasatinib therapy continued, for mild/moderate adverse reactions (eg, ≤ grade 2), resume at original dose; for severe adverse reactions (eg, ≥ grade 3), resume at a reduced dose (one-level dose reduction, see nonhematologic dosage reduction table) (Ref).
Dermatologic toxicities: Manage rash with antihistamines or topical or systemic steroids (Ref), or treatment interruption, dose reduction, or discontinuation. Discontinue if dasatinib-related severe mucocutaneous reaction occurs.
Fluid retention: Manage with diuretics, short courses of corticosteroids, and/or supportive care. Severe pleural effusions may require thoracentesis and oxygen therapy; consider dose reduction or treatment interruption (see nonhematologic dosage reduction table).
Pleural effusion: If resolution does not occur within ~1 week, consider corticosteroids and/or diuretics. For first occurrence ≤ grade 2 effusion, following resolution, resume at the same dose (Ref). For first episode of grade 3 pleural effusion, withhold treatment until resolves to grade 1 or lower and consider corticosteroids (eg, prednisone for 3 to 4 days), diuretics, thoracentesis, and/or pleurodesis; may resume dasatinib at a decreased dose (one-level dose reduction, see nonhematologic dosage reduction table) when effusion resolves; if pleural effusion recurs, initiate supportive therapy, withhold therapy, and resume at next lower dose level (two-level dose reduction, see nonhematologic dosage reduction table) or discontinue therapy (Ref).
Pulmonary arterial hypertension: Discontinue with confirmed pulmonary arterial hypertension.
Thrombotic microangiopathy: Withhold treatment and evaluate ADAMTS13 and anti-ADAMTS13-antibody activity; do not resume if anti-ADAMTS13-antibody is elevated in conjunction with low ADAMTS13 activity (Ref).
Children and Adolescents: Sprycel: Oral: There are no dosage adjustments provided in the manufacturer's labeling; however, <4% of dasatinib and metabolites are renally excreted.
Children and Adolescents: Sprycel: Oral:
Baseline (prior to therapy initiation): No initial dosage adjustment is necessary.
Hepatic impairment during therapy:
Ph+ ALL:
If direct bilirubin >5 times ULN or ALT/AST >15 times ULN, first episode: Hold dasatinib; once recovered to ≤ grade 1, resume therapy at the original starting dose.
If direct bilirubin >5 times ULN or ALT/AST >15 times ULN recur, reduce dasatinib dose based on dosage reduction tables for nonhematologic toxicity.
Ph+ CML: Transaminase or bilirubin elevations during treatment may be managed with treatment interruption or dose reduction.
Bone marrow suppression, including grade ≥3 incidence of anemia, neutropenia, and thrombocytopenia, has occurred during therapy with dasatinib for chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL) (Ref). Bone marrow suppression occurred earlier and more frequently in advanced-phase CML and ALL than chronic-phase CML. Hematologic toxicity is a significant cause of dose reductions and interruptions but rarely permanent discontinuation (Ref). Hematologic parameters generally recover within 2 to 3 weeks following dose interruption/reduction (Ref).
Mechanism: Dose-related; related to the pharmacologic action. Inhibition of multiple kinases by dasatinib leads to suppression of hematopoiesis by the leukemic clone. Hematopoiesis of healthy progenitor stem cells eventually recovers after tyrosine kinase inhibitor-induced suppression of the leukemic process (Ref). May also occur due to inhibition of SRC kinases that are involved in megakaryocytopoiesis, erythropoiesis, and B-cell and myeloid cell survival (Ref).
Onset: Varied; most common in the first weeks to 3 months of treatment (Ref). For treatment of CML, the median is 3 to 6 weeks (Ref). Hematologic toxicity after the first year of therapy is rare (Ref).
Risk factors:
• Advanced phases of CML
• Twice daily dosing (Ref)
Rare but potentially life-threatening cardiovascular adverse events have been reported in patients receiving dasatinib, including cases of ischemic heart disease, transient ischemic attacks, acute myocardial infarction, and cardiac arrhythmia involving prolonged QT interval on ECG (Ref). Cases of prolongation of the QTc values >500 msec (<1%) or a change of >60 msec from baseline (<3%) have been reported (Ref). In the 5-year follow-up of a randomized, prospective trial of dasatinib for first-line treatment of chronic-phase CML, 70% of patients experiencing a cardiovascular event receiving dasatinib restarted therapy without recurrence (Ref).
Mechanism: Not clearly established; may be related to pharmacological action of kinase inhibition leading to altered signaling pathways and ultimate cardiotoxicity (Ref).
Onset: Varied; most cardiac events occurred within the first 6 months, and events were rare after the first year (Ref).
Risk factors:
• Age ≥75 years (Ref)
• Prior history of atherosclerosis (Ref)
• Presence of atherosclerosis risk factors (eg, current/former smoker, hypertension, diabetes, hypercholesterolemia) (Ref)
Cases of varied and severe dermatologic reactions have occurred during dasatinib therapy, including erythema multiforme, maculopapular skin rash, palmar-plantar erythrodysthesia, panniculitis, and Stevens-Johnson syndrome (Ref). Episodes commonly and promptly resolved upon discontinuation, but rechallenge often resulted in rapid reappearance of symptoms (Ref). Grade ≥3 events may require permanent discontinuation (Ref).
Mechanism: Unknown (Ref).
Onset: Varied (Ref).
Risk factors:
• Cross-reactivity between imatinib, nilotinib, and/or dasatinib may occur, although some patients have been able to tolerate alternative tyrosine kinase inhibitors (Ref)
Dasatinib is associated with fluid retention, such as generalized and superficial edema, pleural effusion, and pericardial effusion. Pleural effusion, including grade ≥3 events, has occurred during first and later lines of dasatinib treatment for chronic myeloid leukemia and acute lymphoblastic leukemia (Ref). Overall incidence of pleural effusion is higher in adults compared to pediatric patients (Ref). Concurrent pericardial effusion was present in ~20% to 30% of cases (Ref). Most cases of pleural effusion can be clinically managed with dose interruption, dose reduction, and/or pharmacologic intervention, although 20% to 50% experienced recurrent effusion (Ref). Median time to resolution of symptoms in clinical trials was 3 to 4 weeks (Ref). Pleural effusion led to permanent discontinuation in ~6% to 7% of patients (Ref).
Mechanism: Pleural effusion: Not clearly established; possibly multifactorial, including immunologic and dose-related mechanisms. May be related to dose-dependent alterations to endothelial barriers via an increase in reaction oxygen species production or activation of Rho-associated coiled-coil kinase 1, ultimately resulting in increased pulmonary vascular endothelial permeability and subsequent development of pleural effusion (Ref). May be related to inhibition of platelet-derived growth factor receptor-β leading to dysregulated angiogenesis and reduced interstitial fluid pressure (Ref).
Onset: Pleural effusion: Varied; median is 5 to 11 months (may be delayed until 3 years) (Ref). Long-term follow-up of prospective clinical trials demonstrated an ongoing risk of pleural effusion throughout the duration of therapy (Ref).
Risk factors:
• Older age (Ref)
• Higher doses, including total daily dose >100 mg (Ref)
• Twice daily dosing (Ref)
• Hypertension (Ref)
• Concurrent cardiac disease (Ref)
• Hyperlipidemia (Ref)
• Concurrent pulmonary disease (Ref)
• Lymphocytosis during therapy (Ref)
• Autoimmune disease (Ref)
• Skin rash during therapy (Ref)
Dasatinib may cause severe and fatal hemorrhage, including grade ≥3 CNS hemorrhage and subdural hematoma (Ref). The most common site of bleeding is gastrointestinal hemorrhage (Ref). Median duration of bleeding was 8 days, and ~40% experienced recurrent bleeding upon continuation (Ref). Although thrombocytopenia was identified as a risk factor, bleeding has occurred in patients with normal platelet values and coagulation parameters (Ref). Bleeding episodes were managed with dose interruption (median duration: 17 days), dose reduction, and/or permanent discontinuation (Ref).
Mechanism: Dose-related; related to pharmacologic action. In addition to suppression of hematopoiesis caused by kinase inhibition, may impair platelet signaling and aggregation leading to hemostasis defects likely via inhibition of SRC family kinases (Ref).
Onset: Varied; median is 6 to 11 weeks (range: 0.5 weeks to >9 months) (Ref). Almost all hemorrhagic events occurred during the first 24 months of therapy in a long-term clinical trial follow-up for treatment of chronic-phase chronic myeloid leukemia (CML) (Ref).
Risk factors:
• Advanced phases of CML (Ref)
• Thrombocytopenia (platelet count <100 x 109/L) (Ref)
• Age ≥60 years (Ref)
• Females (Ref)
Dasatinib has been associated with hepatotoxicity (eg, increased serum bilirubin, increased serum aspartate aminotransferase, increased serum alanine aminotransferase, increased serum alkaline phosphatase, acute hepatitis) during treatment of chronic myeloid leukemia and acute lymphoblastic leukemia (Ref). Grade ≥3 events occurred in <5% of patients and rarely led to permanent discontinuation (Ref).
Mechanism: Not clearly established; may upregulate bile acid synthesis and alter bile acid uptake and excretion (Ref).
Onset: Not clearly established (Ref).
Cases of pulmonary hypertension, including pulmonary arterial hypertension, have been reported during dasatinib therapy for treatment of chronic myeloid leukemia and acute lymphoblastic leukemia (Ref). Pulmonary hypertension is a rare but serious disease of the pulmonary vasculature commonly characterized by dyspnea, fatigue, and syncope (Ref). If diagnosed, management includes permanent discontinuation of dasatinib. Although improvement of signs and symptoms of pulmonary hypertension occurred within months in most cases upon discontinuation, complete resolution of hemodynamic parameters was uncommon (Ref). Rapid recurrence of symptoms occurred in 1 case of dasatinib rechallenge (Ref).
Mechanism: Not clearly established; may cause direct endothelial toxicity, which increases the susceptibility to develop pulmonary hypertension. May increase the intracellular reactive oxygen species in pulmonary endothelial cells, leading to endothelial cell apoptosis (Ref). The relationship between pleural effusion and pulmonary hypertension is unknown (Ref).
Onset: Delayed; median is 2 to 3 years (range: 1 month to >6 years) (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Cardiovascular: Peripheral edema
Dermatologic: Pruritus (12%), skin rash (11% to 21%) (table 1)
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
19% |
N/A |
Children and adolescents |
91 of 97 patients treated with 60 mg/m2 once daily (maximum dose of 100 mg once daily for patients with high BSA) |
Chronic phase chronic myeloid leukemia |
97 |
N/A |
N/A |
|
15% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
21% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
16% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
18% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
14% |
18% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
14% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 5 years follow-up |
|
11% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 1 year follow-up |
|
24% |
N/A |
Adults |
140 mg daily |
Philadelphia chromosome-positive acute lymphoblastic leukemia |
135 |
N/A |
N/A |
Endocrine & metabolic: Fluid retention (19% to 48%; cardiac related: 9%) (table 2), hypocalcemia (grades 3/4: ≤12%), hypokalemia (grades 3/4: 2% to 15%), hypophosphatemia (grades 3/4: 7% to 18%)
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
35% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
21% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
34% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
48% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
42% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 5 years follow-up |
|
34% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 2 years follow-up |
|
38% |
45% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
38% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 5 years follow-up |
|
19% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 1 year follow-up |
|
9% |
4% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Cardiac-related fluid retention |
Gastrointestinal: Abdominal pain (7% to 16%), diarrhea (17% to 31%; grades 3/4: ≤5%), nausea (8% to 24%; grades 3/4: 1% to 3%), vomiting (5% to 16%; grades 3/4: 1%)
Hematologic & oncologic: Anemia (grades 3/4: 13% to 74%) (table 3), febrile neutropenia (4% to 12%; grades 3/4: 4% to 12%), hemorrhage (8% to 26%; grades 3/4: 1% to 9%) (table 4), neutropenia (grades 3/4: 29% to 79%) (table 5), thrombocytopenia (grades 3/4: 22% to 85%) (table 6)
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
Grades 3/4: 47% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
Grades 3/4: 52% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
Grades 3/4: 74% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
Grades 3/4: 13% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
Grades 3/4: 13% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
N/A |
N/A |
Minimum of 2 years follow-up |
|
Grades 3/4: 13% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
N/A |
N/A |
Minimum of 5 years follow-up |
|
Grades 3/4: 13% |
Grades 3/4: 9% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
All grades: 26% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
Grades 3/4: 8% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
All grades: 24% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
Grades 3/4: 9% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
All grades: 19% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
Grades 3/4: 9% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
All grades: 12% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
All grades: 11% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 2 years follow-up |
|
All grades: 11% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 5 years follow-up |
|
Grades 3/4: 1% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 2 years follow-up |
|
Grades 3/4: 1% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 5 years follow-up |
|
Grades 3/4: 1% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
All grades: 8% |
All grades: 8% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
Grades 3/4: 1% |
Grades 3/4: 1% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
All grades: 19% |
N/A |
Adults |
140 mg daily |
Philadelphia chromosome-positive acute lymphoblastic leukemia |
135 |
N/A |
N/A |
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
Grades 3/4: 58% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
Grades 3/4: 79% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
Grades 3/4: 77% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
Grades 3/4: 36% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
Grades 3/4: 36% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
N/A |
N/A |
Minimum of 2 years follow-up |
|
Grades 3/4: 36% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
N/A |
N/A |
Minimum of 5 years follow-up |
|
Grades 3/4: 29% |
Grades 3/4: 24% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
Grades 3/4: 63% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
Grades 3/4: 85% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
Grades 3/4: 78% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
Grades 3/4: 24% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
Grades 3/4: 24% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
N/A |
N/A |
Minimum of 5 years follow-up |
|
Grades 3/4: 23% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
N/A |
N/A |
Minimum of 2 years follow-up |
|
Grades 3/4: 22% |
Grades 3/4: 14% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
Hypersensitivity: Facial edema
Infection: Infection (9% to 14%; serious infection: 5%)
Local: Localized edema (3% to 22%; superficial)
Nervous system: Fatigue (8% to 26%), headache (12% to 33%), pain (11%)
Neuromuscular & skeletal: Arthralgia (5% to 13%), limb pain (19%), musculoskeletal pain (8% to 22%), myalgia (7% to 13%)
Respiratory: Dyspnea (3% to 24%), pleural effusion (10% to 28%; serious: 5% to 11%) (table 7)
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
21% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
21% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
20% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
28% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
24% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 5 years follow-up |
|
18% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 2 years follow-up |
|
28% |
1% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
28% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 5 years follow-up |
|
10% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 1 year follow-up |
|
24% |
N/A |
Adults |
140 mg daily |
Philadelphia chromosome-positive acute lymphoblastic leukemia |
135 |
N/A |
N/A |
Miscellaneous: Fever (6% to 18%)
1% to 10%:
Cardiovascular: Cardiac conduction disturbance (7%; including cardiac arrhythmias [tachycardia, ventricular arrhythmia, ventricular tachycardia], palpitations), cardiac disorder (≤4%; including cardiomyopathy, heart failure, left ventricular dysfunction, ischemic heart disease [4%] (table 8), reduced ejection fraction), chest pain, edema (1% to 4%), flushing, hypertension, pericardial effusion (0% to 4%) (table 9), prolonged QT interval on ECG (≤1%)
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|
|
4% |
2% |
Adults |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
3% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
0% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
0% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
3% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
2% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 2 years follow-up |
|
2% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 5 years follow-up |
|
4% |
1% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
4% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 5 years follow-up |
|
1% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 1 year follow-up |
Dermatologic: Acne vulgaris, alopecia, dermatitis, eczema, hyperhidrosis, urticaria, xeroderma
Endocrine & metabolic: Hyperuricemia, weight gain, weight loss
Gastrointestinal: Abdominal distention, change in appetite, colitis (including neutropenic colitis), constipation (10%), dysgeusia, dyspepsia, enterocolitis, gastritis, gastrointestinal hemorrhage (2% to 9%) (table 10), stomatitis
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
8% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
9% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
9% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
2% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 2 years follow-up |
|
2% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 5 years follow-up |
|
2% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
2% |
2% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
7% |
N/A |
Adults |
140 mg daily |
Philadelphia chromosome-positive acute lymphoblastic leukemia |
135 |
N/A |
N/A |
Hematologic & oncologic: Bruise
Hepatic: Increased serum alanine aminotransferase (grades 3/4: 0% to 5%) (table 11), increased serum aspartate aminotransferase (grades 3/4: 0% to 4%) (table 12), increased serum bilirubin (grades 3/4: <1% to 6%) (table 13)
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
Grades 3/4: 2% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
Grades 3/4: 3% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
Grades 3/4: 5% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
Grades 3/4: 0% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
Grades 3/4: <1% |
Grades 3/4: 2% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
Grades 3/4: 0% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
Grades 3/4: 3% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
Grades 3/4: 4% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
Grades 3/4: <1% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
Grades 3/4: <1% |
Grades 3/4: 1% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
Grades 3/4: 1% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Accelerated |
157 |
N/A |
N/A |
|
Grades 3/4: 6% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Lymphoid blast |
33 |
N/A |
N/A |
|
Grades 3/4: 3% |
N/A |
Adults |
140 mg once daily |
Advanced phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy: Myeloid blast |
74 |
N/A |
N/A |
|
Grades 3/4: <1% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
Grades 3/4: 1% |
Grades 3/4: 0% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
Infection: Herpes virus infection, sepsis
Nervous system: Asthenia, chills, depression, dizziness, drowsiness, insomnia, intracranial hemorrhage (≤3%), myasthenia, neuropathy, peripheral neuropathy
Neuromuscular & skeletal: Abnormal bone growth (children: 5%; including epiphyses delayed fusion, growth suppression, osteopenia), muscle spasm (5%), stiffness
Ophthalmic: Blurred vision, decreased visual acuity, dry eye syndrome, visual disturbance
Otic: Tinnitus
Renal: Increased serum creatinine (grades 3/4: 1% to 8%)
Respiratory: Cough, pneumonia, pneumonitis, pulmonary edema (≤4%), pulmonary hypertension (0% to 5%) (table 14), pulmonary infiltrates, upper respiratory tract infection
|
Drug (Dasatinib) |
Comparator (Imatinib) |
Population |
Dose |
Indication |
Number of Patients (Dasatinib) |
Number of Patients (Imatinib) |
Comments |
|---|---|---|---|---|---|---|---|
|
2% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 7 years follow-up |
|
0% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 2 years follow-up |
|
0% |
N/A |
Adults |
100 mg once daily |
Chronic phase chronic myeloid leukemia resistant or intolerant to prior imatinib therapy |
165 |
N/A |
Minimum of 5 years follow-up |
|
5% |
<1% |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
258 |
Minimum of 5 years follow-up |
|
5% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 5 years follow-up |
|
1% |
N/A |
Adults |
100 mg once daily |
Newly diagnosed chronic phase chronic myeloid leukemia |
258 |
N/A |
Minimum of 1 year follow-up |
Miscellaneous: Soft tissue injury (oral)
<1%:
Cardiovascular: Abnormal T waves on ECG, acute coronary syndrome, angina pectoris, cardiomegaly, coronary artery disease, deep vein thrombosis, embolism, hypotension, livedo reticularis, myocarditis, pericarditis, pleuropericarditis, prolongation P-R interval on ECG, pulmonary embolism, syncope, thrombophlebitis, thrombosis, troponin increased in blood specimen
Dermatologic: Bullous skin disease, dermal ulcer, dyschromia, erythema nodosum, hair disease, nail disease, palmar-plantar erythrodysesthesia, skin photosensitivity, Sweet syndrome
Endocrine & metabolic: Decreased libido, dehydration, diabetes mellitus, gynecomastia, hypercholesterolemia, hyperthyroidism, hypoalbuminemia, hypothyroidism, menstrual disease, thyroiditis
Gastrointestinal: Anal fissure, cholecystitis, cholestasis, dysphagia, esophagitis, gastroesophageal reflux disease, gastrointestinal disease (protein wasting), intestinal obstruction, pancreatitis (including acute pancreatitis), rectal fistula, upper gastrointestinal tract ulcer
Genitourinary: Proteinuria, urinary frequency
Hematologic & oncologic: Lymphadenopathy, lymphocytopenia, pure red cell aplasia, tumor lysis syndrome
Hepatic: Ascites, hepatitis, increased gamma-glutamyl transferase
Hypersensitivity: Hypersensitivity angiitis, hypersensitivity reaction
Nervous system: Abnormal gait, amnesia, anxiety, ataxia, balance impairment, Bell palsy, cerebrovascular accident, confusion, dementia, emotional lability, malaise, seizure, transient ischemic attacks, tremor, vertigo, voice disorder
Neuromuscular & skeletal: Arthritis, increased creatine phosphokinase in blood specimen, myositis, osteonecrosis, panniculitis, rhabdomyolysis, tendinopathy
Ophthalmic: Conjunctivitis, increased lacrimation, optic neuritis, photophobia, visual impairment
Otic; Hearing loss
Renal: Kidney failure, kidney impairment
Respiratory: Acute respiratory distress syndrome, asthma, bronchospasm, cor pulmonale
Miscellaneous: Fibrosis (dermal)
Postmarketing:
Cardiovascular: Acute myocardial infarction (Ref), atrial fibrillation, atrial flutter
Dermatologic: Erythema multiforme, hair discoloration (Ref), madarosis of eyebrows (Ref), Stevens-Johnson syndrome
Gastrointestinal: Clostridioides difficile-associated diarrhea (Ref)
Hematologic & oncologic: Aplastic anemia (Ref), lymphocytosis (large granular) (Ref), thrombotic microangiopathy (Ref), thrombotic thrombocytopenic purpura (Ref)
Hepatic: Hepatotoxicity (Ref), increased serum alkaline phosphatase (Ref)
Infection: Reactivation of HBV
Renal: Nephrotic syndrome (Ref)
Respiratory: Interstitial lung disease (Ref), pulmonary alveolar hemorrhage (Ref), respiratory system disorder (chylothorax) (Ref)
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to dasatinib or any other component of the formulation; breast-feeding
Concerns related to adverse effects:
• Bone marrow suppression: Severe dose-related bone marrow suppression (thrombocytopenia, neutropenia, anemia) is associated with dasatinib. Hematologic toxicity is usually reversible with dosage adjustment and/or temporary treatment interruption. The incidence of myelosuppression is higher in patients with advanced phases of chronic myeloid leukemia (CML) and Ph+ acute lymphoblastic leukemia (ALL).
• Cardiovascular adverse events: Dasatinib may cause cardiac dysfunction; cardiac ischemic events, cardiac fluid retention-related events, and conduction abnormalities (arrhythmia and palpitations) have been reported. Cases of transient ischemic attacks have been reported with dasatinib; there have also been cases of peripheral arterial occlusive disease with another BCR-ABL tyrosine kinase inhibitor.
• Dermatologic toxicity: Cases of severe mucocutaneous dermatologic reactions (including Stevens-Johnson syndrome and erythema multiforme) have been reported with dasatinib.
• Fluid retention: Dasatinib may cause fluid retention, including pleural and pericardial effusions, pulmonary hypertension, and generalized or superficial edema. A prompt chest x-ray (or other appropriate diagnostic imaging) is recommended for symptoms suggestive of effusion (new or worsening dyspnea on exertion or at rest, pleuritic chest pain, or dry cough). Utilizing once-daily dosing has been associated with a decreased frequency of fluid retention; the risk for pleural effusion was increased in patients with hypertension, prior cardiac history and a twice a day administration schedule (Quintás-Cardama 2007). Grade 3 or 4 fluid retention/pleural effusion was observed in adults and grade 1 or 2 fluid retention was observed in pediatric patients.
• Hemorrhage: Dasatinib may cause serious and fatal bleeding, including grades 3 and higher CNS hemorrhage. The most frequent hemorrhage site was GI. Grades 3 or 4 hemorrhage usually required treatment interruptions and transfusions. Most bleeding events in clinical studies were associated with severe thrombocytopenia, although dasatinib may also cause platelet dysfunction. Concomitant medications that inhibit platelet function or anticoagulants may increase the risk of bleeding.
• Hepatotoxicity: Dasatinib may cause hepatotoxicity (eg, increased bilirubin, AST, ALT, alkaline phosphatase). Transaminase elevation and hyperbilirubinemia have been observed when dasatinib was administered in combination with chemotherapy.
• Pulmonary arterial hypertension: Dasatinib may increase the risk for pulmonary arterial hypertension (PAH) in both adult and pediatric patients. PAH may occur at any time after starting treatment, including after >12 months of therapy; may be reversible following dasatinib discontinuation.
• QT prolongation: Dasatinib may increase the risk for QT interval prolongation; there are rare reports of patients with QTcF >500 msec. The risk for QT prolongation is increased in patients with long QT syndrome, patients taking antiarrhythmic medications or other medications that lead to QT prolongation or potassium-wasting diuretics, patients with cumulative high-dose anthracycline therapy, and conditions which cause hypokalemia or hypomagnesemia.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS) has been reported in patients with resistance to prior imatinib therapy, usually in patients with advanced phase disease. Risk for TLS is higher in patients with advanced stage disease and/or a high tumor burden.
Concurrent drug therapy issues:
• Drugs that affect gastric pH: Elevated gastric pH may reduce dasatinib bioavailability.
Special populations:
• Older adult: Patients ≥65 years of age are more likely to experience toxicity (compared with patients <65 years of age).
• Pediatric: Adverse reactions associated with bone growth and development have been reported in pediatric studies of chronic phase CML (including a report of severe [grade 3] growth retardation). Cases have included epiphyses delayed fusion, osteopenia, growth retardation, and gynecomastia; some cases resolved during treatment.
Phyrago tablets: FDA approved December 2023; anticipated availability currently unknown. Information pertaining to this product within the monograph is pending revision. Phyrago is indicated for the treatment of adult patients with of newly diagnosed Philadelphia chromosome-positive (Ph+) CML in chronic phase or treatment of chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib or Ph+ ALL with resistance or intolerance to prior therapy. Consult the prescribing information for additional information.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Sprycel: 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg
Generic: 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg
Yes
Tablets (Dasatinib Oral)
20 mg (per each): $192.35
50 mg (per each): $384.70
70 mg (per each): $384.70
80 mg (per each): $693.33 - $693.36
100 mg (per each): $693.33 - $693.36
140 mg (per each): $693.33 - $693.36
Tablets (Sprycel Oral)
20 mg (per each): $202.48
50 mg (per each): $404.95
70 mg (per each): $404.95
80 mg (per each): $729.85
100 mg (per each): $729.85
140 mg (per each): $729.85
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet, Oral:
Sprycel: 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg
Generic: 20 mg, 50 mg, 70 mg, 80 mg, 100 mg, 140 mg
Oral: Administer either in the morning or the evening (for once-daily dosing); has also been administered twice daily (in off-label uses). Swallow whole; do not break, cut, crush, or chew tablets. Administer with or without meals. Administer with a meal if GI upset occurs (Ref).
Oral: Sprycel tablets: Administer once daily (morning or evening); may be administered without regard to food. Swallow whole; do not break, crush, or chew tablets. Administer with a meal if GI upset occurs (Ref). Note: Crushing and dispersing a tablet in juice showed a decreased exposure to dasatinib (36% lower) in pediatric patients (n=5, age range: 2 to 10 years); safety and efficacy of this administration method are undetermined; an extemporaneous suspension can be prepared.
Missed doses: If a dose is missed, skip the dose and administer the next regularly scheduled dose; do not double or administer 2 doses at the same time.
Hazardous agent (NIOSH 2024 [table 1]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Acute lymphoblastic leukemia:
Adults: Treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) in adult patients with resistance or intolerance to prior therapy.
Pediatric patients: Treatment of newly diagnosed Ph+ ALL (in combination with chemotherapy) in pediatric patients ≥1 year of age.
Chronic myeloid leukemia:
Adults:
Treatment of newly diagnosed Ph+ chronic myeloid leukemia (CML) in chronic phase.
Treatment of chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy, including imatinib.
Pediatric patients: Treatment of Ph+ CML in chronic phase in pediatric patients ≥1 year of age.
Gastrointestinal stromal tumor, advanced
Dasatinib may be confused with asciminib, bosutinib, cabozantinib, dabrafenib, dacomitinib, duvelisib, enasidenib, fedratinib, imatinib, lapatinib, neratinib, nilotinib, pacritinib, PONATinib, SUNItinib, tucatinib.
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of CYP3A4 (Major); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Acetaminophen: May increase hepatotoxic effects of Dasatinib. Dasatinib may increase serum concentration of Acetaminophen. Management: Avoid coadministration of acetaminophen and dasatinib if possible. If coadministration is unavoidable, monitor for signs/symptoms of hepatotoxicity, particularly in patients with greater acetaminophen exposure. Risk D: Consider Therapy Modification
Agents with Antiplatelet Effects: Dasatinib may increase antiplatelet effects of Agents with Antiplatelet Effects. Risk C: Monitor
Amisulpride (Oral): May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk C: Monitor
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Antacids: May decrease serum concentration of Dasatinib. Management: Simultaneous administration of dasatinib and antacids should be avoided. If combined, administer antacids 2 hours before or 2 hours after dasatinib. Risk D: Consider Therapy Modification
Anticoagulants: Dasatinib may increase anticoagulant effects of Anticoagulants. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Azithromycin (Systemic): QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Azithromycin (Systemic). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
Clofazimine: May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor
CloZAPine: May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
CYP3A4 Inducers (Moderate): May increase serum concentration of Dasatinib. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Dasatinib. Management: Avoid concurrent use of dasatinib with strong CYP3A4 inducers when possible. If such a combination cannot be avoided, consider increasing dasatinib dose and monitor clinical response and toxicity closely. Risk D: Consider Therapy Modification
CYP3A4 Inhibitors (Moderate): May increase serum concentration of Dasatinib. Risk C: Monitor
CYP3A4 Inhibitors (Strong): May increase serum concentration of Dasatinib. Management: This combination should be avoided if possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or 70 mg to 20 mg. For patients taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is discontinued. Risk D: Consider Therapy Modification
Dabrafenib: QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Dabrafenib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Domperidone: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Domperidone. Risk X: Avoid
Encorafenib: May increase QTc-prolonging effects of Dasatinib. Encorafenib may decrease serum concentration of Dasatinib. Management: Consider alternatives to this drug combination. If combined, consider increasing the dasatinib dose and monitor clinical response and toxicity. Additionally, monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes. Risk D: Consider Therapy Modification
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fluorouracil Products: May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Fusidic Acid (Systemic): May increase serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Management: Consider avoiding this combination if possible. If required, monitor patients closely for increased adverse effects of the CYP3A4 substrate. Risk D: Consider Therapy Modification
Grapefruit Juice: May increase serum concentration of Dasatinib. Risk X: Avoid
Haloperidol: QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of Haloperidol. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Histamine H2 Receptor Antagonists: May decrease absorption of Dasatinib. Management: Do not administer H2RAs with dasatinib. Antacids (taken 2 hours before or after dasatinib) can be used in place of H2-antagonists if some acid-reducing therapy is needed. No interaction is expected with the Phyrago brand of dasatinib. Risk X: Avoid
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Inhibitors of the Proton Pump (PPIs and PCABs): May decrease serum concentration of Dasatinib. Management: Do not administer PPIs/PCABs with dasatinib. Antacids (taken 2 hours before or after dasatinib) can be used instead if some acid-reducing therapy is needed. No interaction is expected with the Phyrago brand of dasatinib. Risk X: Avoid
Lefamulin: May increase QTc-prolonging effects of QT-prolonging CYP3A4 Substrates. Management: Do not use lefamulin tablets with QT-prolonging CYP3A4 substrates. Lefamulin prescribing information lists this combination as contraindicated. Risk X: Avoid
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Levoketoconazole: QT-prolonging CYP3A4 Substrates may increase QTc-prolonging effects of Levoketoconazole. Levoketoconazole may increase serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Midostaurin: May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
OLANZapine: May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Ondansetron: May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
PAZOPanib: QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of PAZOPanib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Pentamidine (Systemic): May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pimozide: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Piperaquine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Piperaquine. Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Posaconazole: May increase serum concentration of QT-prolonging CYP3A4 Substrates. Such increases may lead to a greater risk for proarrhythmic effects and other similar toxicities. Risk X: Avoid
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Propacetamol: Dasatinib may increase hepatotoxic effects of Propacetamol. Dasatinib may increase active metabolite exposure of Propacetamol. Specifically, acetaminophen concentrations may increase. Management: Consider less frequent or lower daily doses of propacetamol in patients taking dasatinib. Patients receiving dasatinib and propacetamol concomitantly, particularly those with greater propacetamol exposure, should be monitored for hepatotoxicity. Risk D: Consider Therapy Modification
QT-prolonging Agents (Highest Risk): May increase QTc-prolonging effects of Dasatinib. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider Therapy Modification
QT-prolonging Antidepressants (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Antipsychotics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-Prolonging Inhalational Anesthetics (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Kinase Inhibitors (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Risk C: Monitor
QT-prolonging Quinolone Antibiotics (Moderate Risk): May increase QTc-prolonging effects of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May increase QTc-prolonging effects of Dasatinib. QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase serum concentration of Dasatinib. Management: Avoid this combination if possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or 70 mg to 20 mg. If taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is discontinued. Monitor for prolonged QT interval Risk D: Consider Therapy Modification
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): Dasatinib may increase QTc-prolonging effects of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase serum concentration of Dasatinib. Management: Avoid this combination if possible. If combined, decrease dasatinib dose from 140 mg to 40 mg, 100 mg to 20 mg, or 70 mg to 20 mg. If taking 60 mg or 40 mg daily, stop dasatinib until the CYP3A4 inhibitor is discontinued. Monitor for prolonged QT interval Risk D: Consider Therapy Modification
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
RisperiDONE: QT-prolonging Kinase Inhibitors (Moderate Risk) may increase QTc-prolonging effects of RisperiDONE. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Saquinavir: Dasatinib may increase QTc-prolonging effects of Saquinavir. Saquinavir may increase serum concentration of Dasatinib. Risk X: Avoid
Sertindole: May increase QTc-prolonging effects of QT-prolonging Agents (Moderate Risk). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
St John's Wort: May decrease serum concentration of Dasatinib. Risk X: Avoid
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Therapeutic Antiplatelets: Dasatinib may increase antiplatelet effects of Therapeutic Antiplatelets. Risk C: Monitor
Thioridazine: QT-prolonging Agents (Moderate Risk) may increase QTc-prolonging effects of Thioridazine. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Dasatinib serum concentrations may be increased when taken with grapefruit or grapefruit juice. Management: Avoid concurrent use.
Patients who could become pregnant or who could father a child should use effective contraception during treatment and for 30 days after the last dasatinib dose.
Changes in menstrual patterns have been reported with tyrosine kinase inhibitor (TKI) therapy (Yu 2019).
Based on the mechanism of action, TKIs have the potential to adversely affect fertility by acting on receptors in the ovaries or testis, primarily when administered prior to puberty in males. Although there are cases showing difficulty conceiving, successful pregnancies have also been reported. Fertility data related to long-term TKI use are limited. Recommendations are available for fertility preservation prior to TKI treatment (ASCO [Oktay 2018]; Madabhavi 2019; Rambhatla 2021).
Patients planning to become pregnant but currently receiving a TKI should minimize the risk of first-trimester exposure (Rambhatla 2021). Discontinuing TKI therapy for chronic myeloid leukemia (CML) can be considered if the patient is eligible for a tumor-free remission, allowing a washout period before attempting to conceive (Baccarani 2019; ELN [Hochhaus 2020]; Madabhavi 2019). Because the time to conception can be highly variable, treatment may also be discontinued at the first positive pregnancy test, prior to organogenesis in select patients (Abruzzese 2020).
Outcome data following male use of dasatinib prior to conception are available (Cortes 2015; Rambhatla 2021; Szakács 2020). Based on available data, dasatinib does not need to be stopped prior to conception in patients diagnosed with CML planning to father a child (Abruzzese 2020; Baccarani 2019; BSH [Smith 2020]; ELN [Hochhaus 2020]).
Dasatinib crosses the placenta, with fetal plasma and amniotic concentrations comparable to maternal concentrations (Berveiller 2012).
Outcome data following use of dasatinib for the treatment of chronic myeloid leukemia (CML) or of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) during pregnancy are available (Assi 2021; Barkoulas 2018; Cortes 2015; Hermel 2019). Adverse effects, including hydrops fetalis and fetal leukopenia and thrombocytopenia have been reported following in utero exposure to dasatinib (Berveiller 2012; Cortes 2015).
Persons who are pregnant are advised to avoid exposure to crushed or broken tablets.
Treatment of CML in pregnant patients should be individualized based on gestational age, hematologic parameters, and clinical condition at presentation. If pregnancy is detected in the first trimester in patients already on a tyrosine kinase inhibitor (TKI), treatment should be discontinued as soon as pregnancy is confirmed. Treatments other than a TKI are recommended in pregnant patients not eligible for a tumor-free remission. If a TKI is needed, use of dasatinib is not recommended (Abruzzese 2020; BSH [Smith 2020]; ELN [Hochhaus 2020]; Madabhavi 2019).
The European Society for Medical Oncology has published guidelines for diagnosis, treatment, and follow-up of cancer during pregnancy. The guidelines recommend referral to a facility with expertise in cancer during pregnancy and encourage a multidisciplinary team (obstetrician, neonatologist, oncology team) approach (ESMO [Peccatori 2013]).
A long-term observational research study is collecting information about the diagnosis and treatment of cancer during pregnancy. For additional information about the pregnancy and cancer registry or to become a participant, contact Cooper Health (877-635-4499).
It is not known if dasatinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment and for 2 weeks following the last dasatinib dose. Patients diagnosed with chronic myeloid leukemia requiring a tyrosine kinase inhibitor may consider short-term breastfeeding for the first 2 to 5 days postpartum to provide the benefits of colostrum to the newborn prior to starting or restarting therapy (Abruzzese 2020; Madabhavi 2019).
Avoid grapefruit juice.
CBC with differential every 2 weeks for 12 weeks and then every 3 months thereafter or as clinically indicated (for chronic phase chronic myeloid leukemia [CML]) or weekly for 2 months, then monthly or as clinically necessary (for accelerated or blast phase CML and for acute lymphoblastic leukemia [ALL]); CBC with differential prior to initiation of each block of chemotherapy and then as clinically indicated and every 2 days until recovery during consolidation blocks of chemotherapy (pediatric patients with Ph+ ALL); transaminases at baseline and then monthly or as clinically necessary during treatment (also monitor LFTs when dasatinib is administered in combination with chemotherapy); bone marrow biopsy; electrolytes including calcium, phosphorus, magnesium. Monitor for fluid retention and bleeding. Chest x-ray (or other appropriate diagnostic imaging) is recommended (promptly) for symptoms suggestive of pleural effusion (eg, cough, dyspnea, pleuritic chest pain). Monitor for signs/symptoms of tumor lysis syndrome and dermatologic reactions. Monitor bone growth/development in pediatric patients. Monitor adherence.
Cardiovascular monitoring recommendations: Evaluate for underlying cardiopulmonary disease prior to dasatinib initiation and during therapy. Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking; repeat assessment every 3 months for the first year and then every 6 to 12 months thereafter (ASCO [Armenian 2017]; ESC [Lyon 2022]; Moslehi 2015). ECG at baseline. Monitor BP routinely (ASCO [Armenian 2017]). Conduct baseline transthoracic echocardiography (TTE); repeat every 3 months for 1 year for high- and very high-risk patients; then consider TTE every 6 to 12 months for patients who require long-term therapy (>12 months). Repeat TTE every 3 months for patients with mild peak tricuspid regurgitation velocity (TRV) on serial monitoring or every 4 weeks for asymptomatic patients with peak TRV increase of 2.9 to 3.4 meters/second; if TRV continues to rise and/or for TRV >3.4 meters/second, conduct right heart catheterization to confirm presence of pulmonary arterial hypertension (ESC [Lyon 2022]).
Thyroid function testing recommendations (Hamnvik 2011):
Preexisting levothyroxine therapy: Obtain baseline TSH levels, then monitor every 4 weeks until levels and levothyroxine dose are stable, then monitor every 2 months.
Without preexisting thyroid hormone replacement: TSH at baseline, then monthly for 4 months, then every 2 to 3 months.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Dasatinib is a BCR-ABL tyrosine kinase inhibitor that targets most imatinib-resistant BCR-ABL mutations (except the T315I and F317V mutants) by distinctly binding to active and inactive ABL-kinase. Kinase inhibition halts proliferation of leukemia cells. It also inhibits SRC family (including SRC, LKC, YES, FYN); c-KIT, EPHA2 and platelet derived growth factor receptor (PDGFRβ).
Distribution: 2,505 L.
Protein binding: Dasatinib: ~96%; metabolite (active): 93%.
Bioavailability: The adjusted geometric mean ratio was 0.84 for AUC in healthy adults who received tablets dispersed in juice (compared with intact tablets).
Metabolism: Hepatic (extensive); metabolized by CYP3A4 (primarily), flavin-containing mono-oxygenase-3 (FOM-3) and uridine diphosphate-glucuronosyltransferase (UGT) to an active metabolite and other inactive metabolites (the active metabolite plays only a minor role in the pharmacology of dasatinib).
Half-life elimination: Terminal: 3 to 5 hours (adults); 2 to 5 hours (pediatrics).
Time to peak, plasma: 0.5 to 6 hours.
Excretion: Feces (~85%, 19% as unchanged drug); urine (~4%, 0.1% as unchanged drug).
Clearance: 363.8 L/hour.
Hepatic function impairment: Patients with moderate hepatic impairment (Child-Pugh class B) had decreases in mean Cmax and AUC by 47% and 8%, respectively, compared to subjects with normal hepatic function. Patients with severe hepatic impairment (Child-Pugh class C) had decreases in mean Cmax and AUC of 43% and 28%, respectively, compared with healthy controls.
