Sprycel

Generic Name: Dasatinib
Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: N - (2 - Chloro - 6 - methylphenyl) - 2 - [[6 - [4 - (2 - hydroxyethyl) - 1 - piperazinyl] - 2 - methyl - 4 - pyrimidinyl]amino] - 5 - thiazolecarboxamide, monohydrate
Molecular Formula: C₂₂H₂₆C₁N₇O₂S • H₂O
CAS Number: 863127-77-9

Special Alerts:

[Posted 10/11/2011] ISSUE: FDA notified healthcare professionals that dasatinib (Sprycel) may increase the risk of a rare but serious condition in which there is abnormally high blood pressure in the arteries of the lungs (pulmonary arterial hypertension [PAH]). Symptoms of PAH may include shortness of breath, fatigue, and swelling of the body (such as the ankles and legs). In reported cases, patients developed PAH after starting dasatinib, including after more than one year of treatment.

Information about this risk has been added to the Warnings and Precautions section of the dasatinib drug label.

BACKGROUND: Dasatinib is used to treat certain adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

RECOMMENDATION:Healthcare professionals should evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to starting dasatinib and also during treatment. If PAH is confirmed, dasatinib should be permanently discontinued. For more information visit the FDA website at: and .

Introduction

Antineoplastic agent; a kinase inhibitor.^{1 2 3}

Uses for Sprycel

Chronic Myelogenous Leukemia (CML)

Treatment of CML in adults who are in myeloid or lymphoid blast crisis, in the accelerated phase, or in the chronic phase of the disease, after failure (secondary to resistance or intolerance) of prior therapy including imatinib (designated an orphan drug by FDA for this use).^{1 2 4 11 12 13 14 16 17}

Acute Lymphocytic (Lymphoblastic) Leukemia (ALL)

Treatment of Philadelphia chromosome-positive (Ph⁺) ALL in adults following failure (secondary to resistance or intolerance) of prior therapy (designated an orphan drug by FDA for this use).^{1 2 4 15}

Sprycel Dosage and Administration

General

• 
  

  Use under supervision of a qualified clinician.¹

  
  


• 
  

  Optimal duration of therapy has not been clearly established.¹ Effect of discontinuance of treatment after achievement of a complete cytogenetic response has not been established.¹

  
  

Administration

Oral Administration

Administer orally once daily (morning or evening) without regard to meals.¹

Administer at the same time each day.¹

Swallow tablets whole; do not cut, chew, or crush.^{1 10}

Dosage

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Adjustments may be necessary when used in conjunction with CYP3A4 inhibitors or inducers.¹ (See Drugs Affecting Hepatic Microsomal Enzymes under Interactions.)

Adults

CML

Chronic Phase

Oral

100 mg once daily.¹ If hematologic or cytogenetic response is not achieved, increase dosage to 140 mg once daily.¹

Continue treatment until evidence of disease progression or until no longer tolerated by the patient.¹

Accelerated Phase or Blast Crisis

Oral

140 mg once daily.¹ If hematologic or cytogenetic response is not achieved, increase dosage to 180 mg once daily.¹

Continue treatment until evidence of disease progression or until no longer tolerated by the patient.¹

ALL

Oral

140 mg once daily.¹ If hematologic or cytogenetic response is not achieved, increase dosage to 180 mg once daily.¹

Continue treatment until evidence of disease progression or until no longer tolerated by the patient.¹

Dosage Modification for Toxicity

Nonhematologic Adverse Effects

If a severe nonhematologic adverse reaction occurs, withhold dasatinib until the event has resolved or improved.¹ Thereafter, resume therapy, as appropriate, at a reduced dosage depending on the initial severity of the event.¹

Adverse Hematologic Effects

Temporary interruption, dosage reduction, or discontinuance is indicated in patients experiencing severe neutropenia and/or thrombocytopenia.^{1 10} Hematopoietic growth factor has been used in patients with resistant myelosuppression.¹

Dosage Adjustments for Neutropenia and Thrombocytopenia

Use (Initial Dosage)	Hematologic Measurements	Dosage Adjustment
Chronic phase CML (initial dosage: 100 mg once daily)1	ANC <500/mm3 or platelets <50,000/mm3	1. Discontinue dasatinib until ANC ≥1000/mm3 and platelets ≥50,000/mm31 2. Resume treatment at original dosage (100 mg once daily) if cytopenia resolves within 7 days 1 3. If recurrence of ANC <500/mm3 lasting >7 days or platelets <25,000/mm3 occurs, repeat step 1 and resume therapy at a reduced dosage of 80 mg once daily (following a second episode); permanently discontinue dasatinib following a third episode1
Accelerated phase or blast phase CML and Ph+ ALL (initial dosage: 140 mg once daily1	ANC <500/mm3 or platelets <10,000/mm3	1. If cytopenia is unrelated to leukemia (as determined by marrow aspirate or biopsy), discontinue dasatinib until ANC ≥1000/mm3 and platelets ≥20,000/mm31 2. Resume treatment at original dosage (140 mg once daily)1 3. If recurrence of ANC <500/mm3 or platelets <10,000/mm3 occurs, repeat step 1 and resume therapy at a reduced dosage of 100 mg once daily (following a second episode) or 80 mg once daily (following a third episode)1 4. If cytopenia is related to leukemia (as determined by marrow aspirate or biopsy), consider increasing dosage to 180 mg once daily1

Special Populations

Hepatic Impairment

Dosage adjustment not necessary.¹ (See Hepatic Impairment under Cautions.)

Renal Impairment

No special dosage recommendations at this time.¹ (See Renal Impairment under Cautions.)

Geriatric Patients

No special dosage recommendations at this time.¹ (See Geriatric Use under Cautions.)

Cautions for Sprycel

Contraindications

• 
  

  No known contraindications.¹

  
  

Warnings/Precautions

Warnings

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; teratogenicity and embryolethality demonstrated in animals.¹ Avoid pregnancy during therapy.¹ If used during pregnancy or if patient becomes pregnant, apprise of potential fetal hazard.¹

Use adequate forms of contraception during therapy.¹

Major Toxicities

Hematologic Effects

Myelosuppression (principally severe neutropenia, anemia, and thrombocytopenia) occurs commonly and is usually reversible;¹ more frequent in patients in the accelerated or blast phase of CML and in those with Ph⁺ ALL than in patients in the chronic phase of CML.¹ In patients with chronic phase CML, less frequent with once-daily dosing (100 mg once daily) than with other (e.g., twice-daily) dosing regimens.^{1 11}

Temporary suspension of therapy or dosage reduction may be required if hematologic toxicity occurs.¹ (See Dosage Modification for Toxicity under Dosage and Administration.)

Perform CBCs weekly during the first 2 months of therapy and monthly (or as clinically indicated) thereafter.¹

Hemorrhage

Risk of severe hemorrhage, including potentially fatal CNS hemorrhage and GI hemorrhage; usually associated with severe thrombocytopenia.¹

Severe GI hemorrhage may require treatment interruption and transfusions.¹

Use with caution in patients receiving anticoagulants or drugs that inhibit platelet function.¹ (See Drugs Affecting Coagulation under Interactions.)

Fluid Retention

Risk of potentially severe fluid retention (i.e., pleural effusion, pericardial effusion, pulmonary edema, ascites, generalized edema).¹ Less common with once-daily dosing than with other dosing schedules (e.g., twice daily).¹

Fluid retention generally managed with supportive care (e.g., diuretics, short course of corticosteroids).¹

Evaluate symptoms suggestive of pleural effusion (e.g., dyspnea, dry cough) by chest radiograph.¹ Severe pleural effusion may require thoracentesis and oxygen therapy.¹

General Precautions

Prolongation of QT Interval

May cause prolongation of the QT interval.¹ Use with caution in patients who have or may develop prolongation of the QT interval (e.g., hypokalemia, hypomagnesemia, congenital long QT syndrome, use of drugs known to prolong QT interval, cumulative high-dose anthracycline therapy).¹

Correct preexisting hypokalemia or hypomagnesemia prior to administration of dasatinib.¹

Lactose Intolerance

140-mg daily dosage (two 70-mg tablets) contains 189 mg of lactose monohydrate; 100-mg daily dosage (one 100-mg tablet) contains 135 mg of lactose monohydrate¹

Specific Populations

Pregnancy

Category D.¹ (See Fetal/Neonatal Morbidity and Mortality under Cautions.)

Lactation

Not known whether dasatinib is distributed into milk.¹ Discontinue nursing or the drug because of potential risk to nursing infants.¹

Pediatric Use

Safety and efficacy not established in patients <18 years of age.¹

Geriatric Use

No substantial differences in efficacy relative to younger adults; safety profile is similar to that in younger adults, but fluid retention and dyspnea are more common in patients ≥65 years of age.¹

Hepatic Impairment

Alterations in peak plasma concentrations and AUC reported but not considered clinically important (see Absorption: Special Populations under Pharmacokinetics).¹ Dosage adjustment is not necessary.¹ However, use with caution.¹

Renal Impairment

Not studied in patients with renal impairment; however, renal excretion of unchanged dasatinib and its metabolites is minimal (<4%).¹

Common Adverse Effects

Fluid retention (e.g., superficial and/or localized edema, generalized edema, pleural effusion, pericardial effusion, CHF or cardiac dysfunction, pulmonary edema),^{1 2} neutropenia,^{1 2} thrombocytopenia,^{1 2} anemia,¹ hemorrhage (e.g., GI or CNS hemorrhage),¹ diarrhea,^{1 2} vomiting,^{1 2} abdominal pain,¹ nausea,^{1 2} headache,^{1 2} fatigue,^{1 2} pyrexia,¹ musculoskeletal pain,¹ myalgia,¹ arthralgia,¹ rash,^{1 2} dyspnea,¹ hypophosphatemia,¹ hypokalemia,¹ hypocalcemia,¹ febrile neutropenia,¹ infection (e.g., bacterial, viral, fungal).^{1 2}

Interactions for Sprycel

Metabolized principally by CYP3A4; weak inhibitor of CYP3A4.¹

Does not inhibit CYP isoenzymes 1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6, or 2E1; does not induce human CYP isoenzymes.¹

Drugs Affecting Hepatic Microsomal Enzymes

Inhibitors of CYP3A4: Potential pharmacokinetic interaction (increased plasma dasatinib concentrations). ¹ Consider alternative drugs with no or less enzyme inhibition potential.¹ If concomitant use with a potent CYP3A4 inhibitor cannot be avoided, consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or to 40 mg daily (if current dosage is 140 mg daily) based on pharmacokinetic considerations (no clinical data with these dosage adjustments available).¹ If dasatinib is not tolerated following dosage reduction, discontinue the CYP3A4 inhibitor or interrupt dasatinib therapy until treatment with the CYP3A4 inhibitor is completed.¹ Upon discontinuance of a potent CYP3A4 inhibitor, allow approximately 1 week to elapse before increasing dasatinib dosage.¹

Inducers of CYP3A4: Potential pharmacokinetic interaction (decreased plasma dasatinib concentrations).¹ Avoid concomitant use of potent CYP3A4 inducers; consider alternative drugs with no or less enzyme induction potential.¹ If concomitant therapy cannot be avoided, consider increase in dasatinib dosage and closely monitor patient for toxicity.¹

Drugs Affecting Coagulation

Potential for bleeding; use anticoagulants and drugs that inhibit platelet function concomitantly with caution.¹ Initial clinical trials of dasatinib excluded patients receiving such drugs; subsequent trials permitted use of anticoagulants, aspirin, and NSAIAs if patient’s platelet count exceeded 50,000–75,000/mm³.¹

Drugs Metabolized by Hepatic Microsomal Enzymes

Substrates of CYP3A4: Potential pharmacokinetic interaction (increased plasma substrate concentrations).^{1 10}

Specific Drugs and Foods

Drug or Food	Interaction	Comments
Alfentanil	Possible increased plasma concentrations and AUC of alfentanil1	Use concomitantly with caution1
Antacids (e.g., calcium carbonate, aluminum hydroxide/magnesium hydroxide)	Possible decreased plasma dasatinib concentrations, secondary to apparent pH-dependence of dasatinib solubility1	Administer antacids 2 hours before or 2 hours after a dose of dasatinib1
Anticoagulants (e.g., warfarin)	Possible increased risk of hemorrhage1	Use concomitantly with caution1
Anticonvulsants (carbamazepine, phenobarbital, phenytoin)	Possible decreased plasma dasatinib concentrations1	Avoid concomitant use if possible; if concomitant therapy necessary, consider increasing dasatinib dosage and closely monitor for toxicity1
Antifungals, azoles (i.e., itraconazole, ketoconazole, voriconazole)	Possible increased plasma dasatinib concentrations and increased exposure to dasatinib1	Avoid concomitant use if possible; if concomitant therapy necessary, closely monitor for toxicity and consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or 40 mg daily (if current dosage is 140 mg daily)1 (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions)
Antihistamines (terfenadine and astemizole [no longer commercially available])	Possible increased plasma concentrations of terfenadine and astemizole1 10
Cisapride	Possible increased plasma concentrations of cisapride1 10	Use concomitantly with caution1
Dexamethasone	Possible decreased plasma dasatinib concentrations1	Avoid concomitant use if possible; if concomitant therapy necessary, consider increasing dasatinib dosage and closely monitor for toxicity1
Ergot alkaloids (dihydroergotamine, ergotamine)	Possible increased plasma concentrations of ergot alkaloids1 10	Use concomitantly with caution1
Fentanyl	Possible increased plasma concentrations of fentanyl1 10	Use concomitantly with caution1
Grapefruit juice	Possible increased plasma dasatinib concentrations1	Avoid concomitant use1
Histamine H2-receptor antagonists (e.g., cimetidine, famotidine, ranitidine)	Possible decreased plasma dasatinib concentrations, secondary to apparent pH-dependence of dasatinib solubility1	Concomitant use not recommended1
HIV protease inhibitors (e.g., atazanavir, indinavir, nelfinavir, ritonavir, saquinavir)	Possible increased plasma dasatinib concentrations and increased exposure to dasatinib1	Avoid concomitant use if possible; if concomitant therapy necessary, closely monitor for toxicity and consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or 40 mg daily (if current dosage is 140 mg daily)1 (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions)
Immunosuppressive agents (cyclosporine, sirolimus, tacrolimus)	Possible increased plasma concentrations of immunosuppressive agents1 10	Use concomitantly with caution1
Macrolide antibiotics (i.e., clarithromycin, erythromycin, telithromycin)	Possible increased plasma dasatinib concentrations and increased exposure to dasatinib1	Avoid concomitant use if possible; if concomitant therapy necessary, closely monitor for toxicity and consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or 40 mg daily (if current dosage is 140 mg daily)1 (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions)
Nefazodone	Possible increased plasma dasatinib concentrations and increased exposure to dasatinib1	Avoid concomitant use if possible; if concomitant therapy necessary, closely monitor for toxicity and consider reducing dasatinib dosage to 20 mg daily (if current dosage is 100 mg daily) or 40 mg daily (if current dosage is 140 mg daily)1 (see Drugs Affecting Hepatic Microsomal Enzymes under Interactions)
NSAIAs (e.g., aspirin)	Possible increased risk of hemorrhage1	Use concomitantly with caution1
Pimozide	Possible increased plasma concentrations of pimozide1 10	Use concomitantly with caution1
Proton-pump inhibitors (e.g., esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)	Possible decreased plasma dasatinib concentrations, secondary to apparent pH-dependence of dasatinib solubility1	Concomitant use not recommended1
Quinidine	Possible increased plasma concentrations of quinidine1 10	Use concomitantly with caution1
Rifamycins (rifabutin, rifampin)	Possible decreased plasma dasatinib concentrations and AUC of dasatinib1	Avoid concomitant use if possible; if concomitant therapy necessary, consider increasing dasatinib dosage and closely monitor for toxicity1
St. John’s wort (Hypericum perforatum)	Potential for unpredictable decreases in plasma dasatinib concentrations1	Concomitant use not recommended1
Simvastatin	Possible increased plasma concentrations and AUC of simvastatin1	Use concomitantly with caution1

Sprycel Pharmacokinetics

Absorption

Onset

Following oral administration, peak plasma concentrations are attained within 0.5–6 hours.¹

Special Populations

In patients with moderate or severe hepatic impairment (Child-Pugh class B or C), peak plasma concentrations and AUC (normalized for differences in administered doses) are lower than in healthy individuals; differences not considered clinically important.¹

Distribution

Extent

Extensively distributed into the extravascular space.¹

Plasma Protein Binding

Approximately 96 and 93% for dasatinib and active metabolite, respectively.¹

Elimination

Metabolism

Metabolized in the liver, principally by CYP3A4, to an active metabolite and several inactive metabolites.¹

Elimination Route

Eliminated principally in feces (85%) mainly as metabolites and to a lesser extent in urine (4%). ¹

Half-life

3–5 hours.¹

Special Populations

No clinically relevant effects of age and gender on pharmacokinetics.¹

Stability

Storage

Oral

Tablets

25° C (may be exposed to 15–30°C).¹

Actions

• 
  

  Inhibits multiple tyrosine kinases including Bcr-Abl, the Src family (Src, Lck, Yes, Fyn), c-Kit, EphA-2, and platelet-derived growth factor (PDGFR)-β; predicted to bind to multiple conformations of the Abl kinase.¹

  
  


• 
  

  Inhibits Bcr-Abl tyrosine kinase, an abnormal protein created by the Philadelphia chromosome abnormality in CML and Ph⁺ ALL that exhibits enhanced tyrosine kinase activity (i.e., increased phosphorylation of tyrosine residues).^{5 6 7 8 9}

  
  


• 
  

  Overcomes imatinib resistance resulting from Bcr-Abl kinase domain mutations, activation of alternate signaling pathways involving the Src family kinases (Lyn, Hck), and multidrug-resistance gene overexpression.¹

  
  

Advice to Patients

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

• 
  

  Importance of taking only as prescribed.¹ Take at about the same time each day; do not discontinue therapy without first consulting clinician.¹

  
  


• 
  

  Importance of advising patients to swallow dasatinib tablets whole with water and not to break, chew, cut, or crush the tablets.¹ Importance of not drinking grapefruit juice while taking the drug.¹

  
  


• 
  

  Risk of severe fluid retention, bleeding, and cytopenia.¹ Importance of immediately informing clinician if fever, any bleeding or bruising, swelling, weight gain, or increasing shortness of breath occurs.¹

  
  


• 
  

  Importance of close medical supervision in patients receiving dasatinib.¹

  
  


• 
  

  Importance of informing clinicians if patient is lactose intolerant.¹

  
  


• 
  

  Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed; necessity for clinicians to advise women to avoid pregnancy during therapy, advise pregnant women of risk to the fetus, and advise both males and females to utilize effective contraception during therapy.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.¹

  
  


• 
  

  Importance of informing patients of other important precautionary information.¹ (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Dasatinib

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	20 mg	Sprycel	Bristol Myers-Squibb
		50 mg	Sprycel	Bristol Myers-Squibb
		70 mg	Sprycel	Bristol Myers-Squibb
		100 mg	Sprycel	Bristol Myers-Squibb

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 10/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Sprycel 20MG Tablets (B-M SQUIBB U.S. (PRIMARY CARE)): 30/$2,304.00 or 90/$6,777.22

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions October 14, 2011. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Bristol Myers-Squibb Company. Sprycel (dasatinib) tablets prescribing information and patient information. Princeton, NJ; 2009 May.

2. Talpaz M, Shah NP, Kantarjian H et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006; 354:2531-41. [PubMed 16775234]

3. Shah NP. Loss of response to imatinib: mechanisms and management. Hematology Am Soc Hematol Educ Program. 2005; :183-7. [PubMed 16304378]

4. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414). Rockville, MD; 2006 Mar 21. From FDA website. Accessed 2006 Jul 19.

5. Druker BJ, Lydon NB. Lessons learned from the development of an Abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Investig. 2000; 105:3-7. [PubMed 10619854]

6. McGuire TR, Kazakoff PW. Chronic leukemias. In: DiPiro JT, Talbert RL, Yee GC et al., eds. Pharmacotherapy: a pathophysiologic approach. 4th ed. Stamford: Appleton and Lange; 1999:2169-80.

7. Druker BJ, Talpaz M, Resta DJ et al. Efficacy and safety of a specific inhibitor of the Bcr-Abl tyrosine kinase in chronic myeloid leukemia. N Engl J Med. 2001; 344:1031-7. [IDIS 461596] [PubMed 11287972]

8. Anon. Gleevec (STI-571) for chronic myeloid leukemia. Med Lett Drugs Ther. 2001; 43:49-50. [PubMed 11402258]

9. Weisberg E, Griffin J. Mechanisms of resistance imatinib (STI-571) in preclinical models and in leukemia patients. Drug Resistance Updates. 2001; 4:22-8. [PubMed 11512149]

10. Bristol-Myers Squibb, Plainsboro, NJ: Personal communication.

11. Shah NP, Kantarjian HM, Kim DW et al. Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and -intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol. 2008; 26:3204-12. [PubMed 18541900]

12. Kantarjian H, Cortes J, Kim DW et al. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in patients with chronic myeloid leukemia in accelerated phase resistant or intolerant to imatinib: 15-month median follow-up. Blood. 2009; 113:6322-9. [PubMed 19369231]

13. Kantarjian H, Pasquini R, Hamerschlak N et al. Dasatinib or high-dose imatinib for chronic-phase chronic myeloid leukemia after failure of first-line imatinib: a randomized phase 2 trial. Blood. 2007; 109:5143-50. [PubMed 17317857]

14. Hochhaus A, Baccarani M, Deininger M et al. Dasatinib induces durable cytogenetic responses in patients with chcronic myelogenous leukemia in chronic phase with resistance or intolerance to imatinib. Leukemia. 2008; 22:1200-6. [PubMed 18401416]

15. Ottmann O, Dombret H, Martinelli G et al. Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study. Blood. 2007; 110:2309-15. [PubMed 17496201]

16. Cortes J, Kim DW, Raffoux E et al. Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase. Leukemia. 2008; 22:2176-83. [PubMed 18754032]

17. Guilhot F, Apperley J, Kim DW et al. Dasatinib induces significant hematologic and cytogenetic responses in patients with imatinib-resistant or -intolerant chronic myeloid leukemia in accelerated phase. Blood. 2007; 109:4143-50. [PubMed 17264298]

18. Food and Drug Administration. Center for Drug Evaluation and Research: Application number 21-986 and 22-072: Medical Review(s). From FDA website.

More Sprycel resources

• Sprycel Side Effects (in more detail)
• Sprycel Dosage
• Sprycel Use in Pregnancy & Breastfeeding
• Drug Images
• Sprycel Drug Interactions
• Sprycel Support Group
• 4 Reviews for Sprycel - Add your own review/rating

• Sprycel Prescribing Information (FDA)


• Sprycel Consumer Overview


• Sprycel Advanced Consumer (Micromedex) - Includes Dosage Information


• Sprycel MedFacts Consumer Leaflet (Wolters Kluwer)


• Dasatinib Professional Patient Advice (Wolters Kluwer)

Compare Sprycel with other medications

• Acute Lymphoblastic Leukemia
• Chronic Myelogenous Leukemia
• Leukemia