Dosing and uses of Sprycel (dasatinib)
Adult dosage forms and strengths
tablet
- 20mg
- 50mg
- 70mg
- 80mg
- 100mg
- 140mg
CML, Chronic Phase (Newly Diagnosed)
Indicated for newly diagnosed adults with Philadelphia chromosome-positive chronic phase chronic myeloid leukemia (Ph+ CP-CML)
Start 100 mg PO qDay (morning or evening)
May increase to 140 mg qDay if inadequate response
CML, Advanced
Indicated for treatment of chronic, accelerated, or myeloid or lymphoid blast phase Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) with resistance or intolerance to prior therapy including imatiniB
Start 140 mg PO qDay
May increase to 180 mg qDay if inadequate response
ALL, Ph+
Indicated for Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy
Start 140 mg PO qDay
May increase to 180 mg PO qDay if inadequate response
Hepatic Impairment
Dose adjustment not necessary
Administration
Take with or without meals
Swallow tablet whole; do not cut, crush, or chew
Dose Modification
Myelosuppression: Reduce/interrupt dose, see Manufacturer's PI
Monitor: CBC qWeek for 2 months, THEN qMonth
Concomitant Strong CYP3A4 Inducers/Inhibitors
- Avoid or modify dose
- Concomitant strong CYP3A4 inducers: May decrease dasatinib plasma concentrations; consider increasing dose (monitor for toxicity)
- Concomitant strong CYP3A4 inhibitors: May increase dasatinib plasma concentrations; decrease to 20 mg/day if taking 100 mg/day; decrease to 40 mg/day if taking 140 mg/day
- If not tolerated despite dose reduction, discontinue strong CYP3A4 inhibitor and allow washout of 1 week before dasatinib dose increased, OR
- Discontinue dasatinib until treatment with CYP3A4 inhibitor ceased
Pediatric dosage forms and strengths
<18 years: Safety and efficacy not established
Sprycel (dasatinib) adverse (side) effects
>10%
Fluid retention, incl CHF, pulm edema, pleural effusion (50%)
Diarrhea (49%)
Headache (40%)
Hemorrhage (40%)
Fatigue (39%)
Pyrexia (39%)
Skin rash (35%)
Infection (34%)
Nausea (34%)
Dyspnea (32%)
Cough (28%)
Pain (26%)
Abdominal pain (25%)
Vomiting (22%)
Anorexia (19%)
Arthralgia (19%)
Asthenia (19%)
Constipation (14%)
Dizziness (14%)
Musculoskeletal pain (14%)
Weight loss (14%)
Chest pain (13%)
Neuropathy (13%)
Myalgia (12%)
Abdominal distention (11%)
Arrhythmia (11%)
Chills (11%)
Pneumonia (11%)
Pruritus (11%)
Weight gain (11%)
1-10% (selected)
Anemia
Febrile neutropenia
Thrombocytopenia
Mucosal inflammation
Postmarketing Reports
Cardiac disorders: Atrial fibrillation/atrial flutter
Vascular disorders: Thrombosis/embolism (including pulmonary embolism, deep vein thrombosis)
Respiratory, thoracic, and mediastinal disorders: Interstitial lung disease, pulmonary arterial hypertension
Dermatologic reactions: Stevens-Johnson syndrome, erythema multiforme
Infections: Hepatitis B virus reactivation
Warnings
Contraindications
None
Cautions
Myelosuppression including severe thrombocytopenia, neutropenia and anemia may occur; may manage by dose interruption, dose reduction, or discontinuation of therapy; hematopoietic growth factor has been used with resistant myelosuppression
In patients with chronic phase CML, perform complete blood counts (CBCs) every 2 weeks for 12 weeks, then every 3 months thereafter, or as clinically indicated; perform CBCs weekly for the first 2 months and then monthly thereafter, or as clinically indicated in patients with advanced phase CML or Ph+ ALL
CNS and gastrointestinal hemorrhages, including fatalities have occurred; severe hemorrhage may require treatment interruption and transfusion
Increased risk of developing pulmonary arterial hypertension (PAH); may be reversible on discontinuation; evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiation and during treatment; if PAH confirmed permanently discontinue therapy
Hypokalemia, hypomagnesemia, congenital QT interval prolongation, hepatic impairment
Use with caution in patients who have or may develop prolongation of QT intervaL
Cardiac adverse reactions were reported in 5.8% of 258 patients including cardiomyopathy (1.6%), congestive heart failure, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction; monitor patients for signs or symptoms and treat appropriately
Cases of severe mucocutaneous dermatologic reactions, including Stevens-Johnson syndrome and erythema multiforme, reported; discontinue permanently in patients who experience severe mucocutaneous reaction during treatment if no other etiology can be identified
Tumor lysis syndrome reported; maintain adequate hydration and correct uric acid levels prior to initiating therapy
Risk of fluid retention and pleural/pericardial effusion; manage with supportive care measures and/or dose modification
Embryofetal toxicity reported; advise female patients of reproductive potential to avoid pregnancy during treatment
Avoid concomitant CYP3A4 inducers/inhibitors
- If unavoidable, consider dose modification as appropriate
- Decrease from 100 mg/day to 20 mg/day if concomitant strong CYP3A4 inhibitor
- Decrease from 140 mg/day to 40 mg/day if concomitant strong CYP3A4 inhibitor
Pregnancy and lactation
Pregnancy category: d
Transplacental transfer of dasatinib reported; dasatinib has been measured in fetal plasma and amniotic fluid and concentrations were found to be comparable to those in maternal plasma
Hydrops fetalis and fetal bicytopenia have been reported with maternal exposure to dasatiniB
Lactation: not known if excreted in breast milk; do not nurse
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Sprycel (dasatinib)
Mechanism of action
Multi-kinase inhibitor that inhibits BCR-ABL, SRC family (SRC, LCK, YES, FYN), c-Kit, EPHA2 and PDGFR-beta kinases; tyrosine kinase inhibition possibly blocks angiogenesis and cellular proliferation
Absorption
Peak Plasma Time: 0.5-6 hr
Distribution
Protein Bound: 96%
Vd: 2505 L
Metabolism
Metabolism: extensively metabolized primarily by CYP3A4
Enzymes inhibited: CYP3A4 (weak)
Elimination
Half-Life: 3-5 hr
Excretion: Feces 85%; urine 4%
Pharmacogenomics
Tyrosine kinase inhibitors (TKIs) inhibit activity of BCR-ABL fusion protein, resulting in both hematologic response (ie, normal cell counts in the peripheral blood and normal bone marrow morphology), as well as cytogenetic response (ie, disappearance or reduction of the Philadelphia [Ph] chromosome)
NCCN clinical practice guidelines recommends TKIs in CML with confirmed BCR-ABL transcripts in bone marrow or evidence of translocation on cytogenetics
Genetic testing laboratories
- The following companies currently offer FISH and/or transcript quantification testing for BCR-ABL
- Asuragen (https://www.asuragen.com/)
- Dako (https://www.dakousa.com/)
- Invitrogen (https://www.invitrogen.com/)
- Ipsogen (https://www.ipsogen.com)
