Version May 2024
Note: The effect of discontinuation on long-term disease outcome after achieving cytogenetic response (including complete cytogenetic response) or major molecular response is not known. 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.
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.
No dosage adjustment is necessary (Ref).
Hemodialysis: No need for dosage adjustment is expected (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 (eg, dyspnea, fatigue, hypoxia, fluid retention) and interrupt therapy if symptoms are severe. Discontinue dasatinib for confirmed pulmonary arterial hypertension.
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: Oral:
10 to <20 kg: 40 mg once daily.
20 to <30 kg: 60 mg once daily.
30 to <45 kg: 70 mg once daily.
≥45 kg: 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: Oral:
10 to <20 kg: Initial: 40 mg once daily; may escalate to 50 mg once daily if hematologic or cytogenetic response is not achieved.
20 to <30 kg: Initial: 60 mg once daily; may escalate to 70 mg once daily if hematologic or cytogenetic response is not achieved.
30 to <45 kg: Initial: 70 mg once daily; may escalate to 90 mg once daily if hematologic or cytogenetic response is not achieved.
≥45 kg: 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: Children and Adolescents: Adjustments are specific for indications. Note: Growth factor support may be considered in patients with resistant myelosuppression.
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.
Chronic myelogenous leukemia, Philadelphia chromosome-positive (Ph+ CML):
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.
If cytopenia recurs, repeat marrow aspirate/biopsy and resume dasatinib at a reduced dose.
Note: If ≥ grade 3 neutropenia or thrombocytopenia recurs during complete hematologic response, interrupt dasatinib therapy and resume at a reduced dose. Temporary dose reductions for intermediate degrees of cytopenia and disease response may be used as needed.
Recommended dose reductions for neutropenia and thrombocytopenia in Ph+ CML:
If the original starting dose is 40 mg daily, may reduce dose to 20 mg once daily (one-level dose reduction); further dose reductions cannot be made due to available tablet sizes.
If the original starting dose is 60 mg once daily, may reduce dose to 40 mg once daily (one-level dose reduction), and then to 20 mg once daily (two-level dose reduction).
If the original starting dose is 70 mg once daily, may reduce dose to 60 mg once daily (one-level dose reduction), and then to 50 mg once daily (two-level dose reduction).
If the original starting dose is 100 mg once daily, may reduce dose to 80 mg once daily (one-level dose reduction), and then to 70 mg once daily (two-level dose reduction).
Nonhematologic toxicity: Recommendations exclude altered liver enzymes (see Dosing: Hepatic Impairment: Pediatric).
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 (see the following dose reductions).
Grade ≥3 toxicity: Withhold dasatinib until recovered to grade 1 or lower, and then resume at a reduced dose (see the following dose reductions).
Recommended dose reductions for non-hematologic toxicities Ph+ ALL:
If the original starting dose is 40 mg daily, may reduce dose to 20 mg once daily (one-level dose reduction); further dose reductions cannot be made due to available tablet sizes.
If the original starting dose is 60 mg once daily, may reduce dose to 40 mg once daily (one-level dose reduction), and then to 20 mg once daily (two-level dose reduction).
If the original starting dose is 70 mg once daily, may reduce dose to 60 mg once daily (one-level dose reduction), and then to 50 mg once daily (two-level dose reduction).
If the original starting dose is 100 mg once daily, may reduce dose to 80 mg once daily (one-level dose reduction), and then to 70 mg once daily (two-level dose reduction).
Ph+ CML: 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.
All indications: 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.
Pleural effusion: 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) when effusion resolves; if pleural effusion recurs, initiate supportive therapy, withhold therapy, and resume at next lower dose level (two-level dose reduction) or discontinue therapy (Ref).
Pulmonary arterial hypertension: Discontinue with confirmed pulmonary arterial hypertension.
There are no dosage adjustments provided in the manufacturer's labeling; however, <4% of dasatinib and metabolites are renally excreted.
Children and Adolescents: Oral:
Baseline (prior to therapy initiation): No initial dosage adjustment is necessary; use with caution.
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 the following:
If the original starting dose is 40 mg daily, may reduce dose to 20 mg once daily (one-level dose reduction); further dose reductions cannot be made due to available tablet sizes.
If the original starting dose is 60 mg once daily, may reduce dose to 40 mg once daily (one-level dose reduction), and then to 20 mg once daily (two-level dose reduction).
If the original starting dose is 70 mg once daily, may reduce dose to 60 mg once daily (one-level dose reduction), and then to 50 mg once daily (two-level dose reduction).
If the original starting dose is 100 mg once daily, may reduce dose to 80 mg once daily (one-level dose reduction), and then to 70 mg once daily (two-level dose reduction).
Ph+ CML: Transaminase or bilirubin elevations during treatment may be managed with treatment interruption or dose reduction.
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%)
Endocrine & metabolic: Fluid retention (19% to 48%; cardiac-related: 9%), hypocalcemia (grades 3/4: ≤12%), hypokalemia (grades 3/4: 2% to 15%), hypophosphatemia (grades 3/4: 7% to 18%)
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%), febrile neutropenia (4% to 12%; grades 3/4: 4% to 12%), hemorrhage (8% to 26%; grades 3/4: 1% to 9%), neutropenia (grades 3/4: 29% to 79%), thrombocytopenia (grades 3/4: 22% to 85%)
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%)
Miscellaneous: Fever (6% to 18%)
1% to 10%:
Cardiovascular: Cardiac conduction disturbance (7%; including cardiac arrhythmias [tachycardia, ventricular arrhythmia, ventricular tachycardia] and palpitations), cardiac disorder (≤4%; including cardiomyopathy, heart failure, left ventricular dysfunction, ischemic heart disease, reduced ejection fraction), chest pain, edema (1% to 4%), flushing, hypertension, pericardial effusion (1% to 4%), prolonged QT interval on ECG (≤1%)
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%), stomatitis
Hematologic & oncologic: Bruise
Hepatic: Increased serum alanine aminotransferase (grades 3/4: ≤5%), increased serum aspartate aminotransferase (grades 3/4: ≤4%), increased serum bilirubin (grades 3/4: ≤6%)
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 (1% to 5%), pulmonary infiltrates, upper respiratory tract infection
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: Renal failure syndrome, renal insufficiency
Respiratory: Acute respiratory distress syndrome, asthma, bronchospasm, cor pulmonale
Miscellaneous: Fibrosis (dermal)
Postmarketing:
Cardiovascular: Atrial fibrillation, atrial flutter
Dermatologic: Erythema multiforme, Stevens-Johnson syndrome
Hematologic & oncologic: Thrombotic microangiopathy
Hepatic: Hepatotoxicity
Infection: Reactivation of HBV
Renal: Nephrotic syndrome
Respiratory: Interstitial lung disease
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
No
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: Administer once daily (morning or evening). May be taken without regard to food. Swallow whole; do not break, crush, or chew tablets. Take with a meal if GI upset occurs (Ref). Do not administer proton pump inhibitors and H2 blockers concomitantly with dasatinib. If needed, may consider antacid administration, separated by at least 2 hours before or 2 hours after the dasatinib dose. Note: Crushing and dispersing a tablet in juice showed 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 (see Extemporaneous Preparations).
Hazardous agent (NIOSH 2016 [group 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 2016; 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.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Acetaminophen: May enhance the hepatotoxic effect of Dasatinib. Dasatinib may increase the 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 Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): Dasatinib may enhance the anticoagulant effect of Agents with Antiplatelet Properties. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Androgens: Hypertension-Associated Agents may enhance the hypertensive effect of Androgens. Risk C: Monitor therapy
Antacids: May decrease the serum concentration of Dasatinib. Management: Simultaneous administration of dasatinib and antacids should be avoided. Administer antacids 2 hours before or 2 hours after dasatinib. Risk D: Consider therapy modification
Anticoagulants: Dasatinib may enhance the anticoagulant effect of Anticoagulants. Risk C: Monitor therapy
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Azithromycin (Systemic): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Risk X: Avoid combination
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of BCG Products. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Chikungunya Vaccine (Live). Risk X: Avoid combination
Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Risk C: Monitor therapy
Chloramphenicol (Systemic): Myelosuppressive Agents may enhance the myelosuppressive effect of Chloramphenicol (Systemic). Risk X: Avoid combination
Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk X: Avoid combination
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Clofazimine: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk C: Monitor therapy
CloZAPine: May enhance the QTc-prolonging effect 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 therapy
Coccidioides immitis Skin Test: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. 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 (Adenovirus Vector): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Adenovirus Vector). Management: Administer a 2nd dose using an mRNA COVID-19 vaccine (at least 4 weeks after the primary vaccine dose) and a bivalent booster dose (at least 2 months after the additional mRNA dose or any other boosters). Risk D: Consider therapy modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor therapy
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 diminish the therapeutic effect of COVID-19 Vaccine (Subunit). Risk C: Monitor therapy
COVID-19 Vaccine (Virus-like Particles): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of COVID-19 Vaccine (Virus-like Particles). Risk C: Monitor therapy
CYP3A4 Inducers (Moderate): May increase the serum concentration of Dasatinib. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the 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 the serum concentration of Dasatinib. Risk C: Monitor therapy
CYP3A4 Inhibitors (Strong): May increase the 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 enhance the QTc-prolonging effect 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 therapy
Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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 enhance the adverse/toxic effect of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Dengue Tetravalent Vaccine (Live). Risk X: Avoid combination
Denosumab: May enhance the immunosuppressive effect 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Risk X: Avoid combination
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Encorafenib: May enhance the QTc-prolonging effect of Dasatinib. Encorafenib may decrease the 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 enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fexinidazole: May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Fexinidazole: Myelosuppressive Agents may enhance the myelosuppressive effect of Fexinidazole. Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Fluorouracil Products: May enhance the QTc-prolonging effect 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 therapy
Fusidic Acid (Systemic): May increase the serum concentration of CYP3A4 Substrates (High risk with Inhibitors). Risk X: Avoid combination
Grapefruit Juice: May increase the serum concentration of Dasatinib. Risk X: Avoid combination
Haloperidol: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
Histamine H2 Receptor Antagonists: May decrease the absorption of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of H2-antagonists if some acid-reducing therapy is needed. Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 the serum concentration of Dasatinib. Management: Antacids (taken 2 hours before or after dasatinib administration) can be used in place of PPIs or PCABs if some acid-reducing therapy is needed. Risk X: Avoid combination
Lefamulin: May enhance the QTc-prolonging effect 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 combination
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect 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 enhance the QTc-prolonging effect of Levoketoconazole. Levoketoconazole may increase the serum concentration of QT-prolonging CYP3A4 Substrates. Risk X: Avoid combination
Midostaurin: May enhance the QTc-prolonging effect 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 therapy
Mumps- Rubella- or Varicella-Containing Live Vaccines: May enhance the adverse/toxic effect of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Mumps- Rubella- or Varicella-Containing Live Vaccines. Risk X: Avoid combination
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
OLANZapine: May enhance the QTc-prolonging effect 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 therapy
Olaparib: Myelosuppressive Agents may enhance the myelosuppressive effect of Olaparib. Risk C: Monitor therapy
Ondansetron: May enhance the QTc-prolonging effect 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 therapy
PAZOPanib: QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
Pentamidine (Systemic): May enhance the QTc-prolonging effect 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 therapy
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid combination
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Pneumococcal Vaccines. Risk C: Monitor therapy
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Poliovirus Vaccine (Live/Trivalent/Oral). Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the potential for allergic or hypersensitivity reactions to 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 the 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 combination
Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Risk C: Monitor therapy
Propacetamol: Dasatinib may enhance the hepatotoxic effect of Propacetamol. Dasatinib may increase serum concentrations of the active metabolite(s) 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 enhance the QTc-prolonging effect 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 enhance the QTc-prolonging effect 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 therapy
QT-prolonging Antipsychotics (Moderate Risk): May enhance the QTc-prolonging effect 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 therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect 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 therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of other 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 therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Kinase Inhibitors (Moderate Risk) may enhance the QTc-prolonging effect 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 therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk) may increase the serum concentration of QT-prolonging Kinase Inhibitors (Moderate Risk). Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect 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 therapy
QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk): May enhance the QTc-prolonging effect of Dasatinib. QT-prolonging Strong CYP3A4 Inhibitors (Highest Risk) may increase the 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 enhance the QTc-prolonging effect of QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk). QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk) may increase the 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 diminish the therapeutic effect 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 enhance the QTc-prolonging effect 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 therapy
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ropeginterferon Alfa-2b: Myelosuppressive Agents may enhance the myelosuppressive effect 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 enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Saquinavir: Dasatinib may enhance the QTc-prolonging effect of Saquinavir. Saquinavir may increase the serum concentration of Dasatinib. Risk X: Avoid combination
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect 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 enhance the hypertensive effect of Hypertension-Associated Agents. Risk C: Monitor therapy
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor therapy
St John's Wort: May decrease the serum concentration of Dasatinib. Risk X: Avoid combination
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect 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 combination
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Tofacitinib. Risk X: Avoid combination
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Typhoid Vaccine. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Vaccines (Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Inactivated/Non-Replicating). Management: Give inactivated vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before initiating or during therapy should be revaccinated at least 3 after therapy is complete. Risk D: Consider therapy modification
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Vaccines (Live). Risk X: Avoid combination
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may enhance the adverse/toxic effect of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may diminish the therapeutic effect of Yellow Fever Vaccine. Risk X: Avoid combination
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]). Consider a baseline echocardiography; repeat every 3 months for high- and very high-risk patients (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.
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