SPRYCEL® (dasatinib) 100-mg tablets SPRYCEL® (dasatinib) 100-mg tablets

INDICATIONS

SPRYCEL® (dasatinib) is indicated for the treatment of adults with:

  • Newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase
  • Chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib
  • Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy

SPRYCEL is indicated for the treatment of pediatric patients with:

  • Ph+ CML in chronic phase

Close

banner clouds and book
banner clouds and book

Efficacy in Adults With Imatinib-Resistant or -Intolerant Ph+ CML in CP

Full Study Design

Study Design1,2:

  • Phase III, randomized, open-label, international, multicenter, dose-optimization trial of CP Ph+ CML adult patients (N=670) resistant or intolerant to imatinib randomized to one of four dosing schedules:
    • SPRYCEL 100 mg once daily (n=167), SPRYCEL 140 mg once daily (n=167), SPRYCEL 50 mg twice daily (n=168), SPRYCEL 70 mg twice daily (n=168)
  • The median duration of treatment was 22 months
  • The primary endpoint in chronic phase Ph+ CML was Major Cytogenetic Response (MCyR). MCyR combines both complete (0% Ph+ metaphases) and partial (>0%–35%) responses
  • Secondary endpoints included rates of MCyR in imatinib-intolerant patients, rates of complete hematological response (CHR), time to and duration of MCyR and CHR, progression-free survival (PFS), overall survival, and safety evaluations

SPRYCEL Is the Only TKI for Imatinib-Resistant or -Intolerant CP Ph+ CML With 7-Year Efficacy Data in the PI1

Image shows the response rate CML patients resistant or intolerant to Imatinib taking SPRYCEL 100 mg once daily (n=167) at a minimum follow up of 2 years. MCyR=63% (95% Cl, 56%-71%), CHR 92% (95% CL, (86%-95%), CCyCR 50% (95% Cl, 42%-58%). MMR was achieved in 44% (n=73/167) of patients taking SPRYCEL 100 mg once daily within 7 years.

Image shows the response rate CML patients resistant or intolerant to Imatinib taking SPRYCEL 100 mg once daily (n=167) at a minimum follow up of 2 years. MCyR=63% (95% Cl, 56%-71%), CHR 92% (95% CL, (86%-95%), CCyCR 50% (95% Cl, 42%-58%). MMR was achieved in 44% (n=73/167) of patients taking SPRYCEL 100 mg once daily within 7 years.

  • Dasatinib does not appear to be active against the T315I mutation, based on in vitro data1

Based on data 7 years after the last patient was enrolled in the trial1:

  • 44% of patients were known to be alive
  • 25% of patients had an unknown survival status and 31% of patients were known to have died

SELECTED IMPORTANT SAFETY INFORMATION

  • In Ph+ CML patients resistant or intolerant to prior imatinib therapy:
    • Drug-related SARs were reported for 26.1% of SPRYCEL-treated patients treated at the recommended dose of 100 mg once daily in the randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy. Serious adverse reactions reported in ≥5% of patients included pleural effusion (10%)
    • The most common adverse reactions (≥15%) included myelosuppression, fluid retention events, diarrhea, headache, fatigue, dyspnea, skin rash, nausea, hemorrhage and musculoskeletal pain
    • Grade 3/4 hematologic laboratory abnormalities in chronic phase CML patients resistant or intolerant to prior imatinib therapy who received SPRYCEL 100 mg once daily with a minimum follow up of 60 months included neutropenia (36%), thrombocytopenia (24%), and anemia (13%). Other grade 3/4 laboratory abnormalities included: hypophosphatemia (10%), and hypokalemia (2%)
    • Among chronic phase CML patients with resistance or intolerance to prior imatinib therapy, cumulative grade 3/4 cytopenias were similar at 2 and 5 years including: neutropenia (36% vs 36%), thrombocytopenia (23% vs 24%), and anemia (13% vs 13%)

 CHR=Complete Hematological Response; CCyR=Complete Cytogenetic Response; MCyR=Major Cytogenetic Response; MMR=Major Molecular Response; TKI=Tyrosine Kinase Inhibitor; PI=Prescribing Information.

* Resistance to imatinib was defined as failure to achieve a complete hematologic response (CHR; after 3 months), major cytogenetic response (MCyR; after 6 months), or complete cytogenetic response (CCyR; after 12 months); or loss of a previous molecular response (with concurrent ≥10% increase in Ph+ metaphases), cytogenetic response, or hematologic response.

 Imatinib intolerance was defined as inability to tolerate 400 mg or more of imatinib per day or discontinuation of imatinib because of toxicity.

 MCyR combines both complete (0% Ph+ metaphases) and partial (>0%–35%) responses.1

§ CHR (response confirmed after 4 weeks): WBC ≤ institutional ULN, platelets <450,000/mm3, no blasts or promyelocytes in peripheral blood, <5% myelocytes plus metamyelocytes in peripheral blood, basophils in peripheral blood <20%, and no extramedullary involvement.1

ǁ CCyR = 0% Ph+ metaphases.1

Graphic shows Philadelphia positive Chronic myeloid leukemia patients who transformed to Accelerated Phase (AP) or Blast Crisis (BC) while on the study by year 7. Ninety-five % of SPRYCEL-treated patients on study did not transform to AP or BC (158 out of 167). Dasatinib does not appear to be active against the T315I mutation, based on in vitro studies.

Graphic shows Philadelphia positive Chronic myeloid leukemia patients who transformed to Accelerated Phase (AP) or Blast Crisis (BC) while on the study by year 7. Ninety-five % of SPRYCEL-treated patients on study did not transform to AP or BC (158 out of 167). Dasatinib does not appear to be active against the T315I mutation, based on in vitro studies.

Dasatinib does not appear to be active against the T315I mutation, based on in vitro studies.1

SELECTED IMPORTANT SAFETY INFORMATION

  • In Ph+ CML patients resistant or intolerant to prior imatinib therapy:
    • Drug-related SARs were reported for 26.1% of SPRYCEL-treated patients treated at the recommended dose of 100 mg once daily in the randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy. Serious adverse reactions reported in ≥5% of patients included pleural effusion (10%)
    • The most common adverse reactions (≥15%) included myelosuppression, fluid retention events, diarrhea, headache, fatigue, dyspnea, skin rash, nausea, hemorrhage and musculoskeletal pain
    • Grade 3/4 hematologic laboratory abnormalities in chronic phase CML patients resistant or intolerant to prior imatinib therapy who received SPRYCEL 100 mg once daily with a minimum follow up of 60 months included neutropenia (36%), thrombocytopenia (24%), and anemia (13%). Other grade 3/4 laboratory abnormalities included: hypophosphatemia (10%), and hypokalemia (2%)
    • Among chronic phase CML patients with resistance or intolerance to prior imatinib therapy, cumulative grade 3/4 cytopenias were similar at 2 and 5 years including: neutropenia (36% vs 36%), thrombocytopenia (23% vs 24%), and anemia (13% vs 13%)

 MMR=Major Molecular Response; CHR=Complete Hematological Response; CCyR=Complete Cytogenetic Response; MCyR=Major Cytogenetic Response; AP=Accelerated Phase; BC=Blast Crisis.

References:

  1. SPRYCEL® (dasatinib) full Prescribing Information. Bristol-Myers Squibb Company.
  2. Shah NP, Kantarjian HM, Kim D-W, 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(19):3204–3212.
SPRYCEL Assist program
Expand

SPRYCEL® (dasatinib) SELECTED IMPORTANT SAFETY INFORMATION

  • SPRYCEL is associated with the following warnings and precautions: myelosuppression, bleeding-related events, fluid retention, cardiovascular events, pulmonary arterial hypertension, QT prolongation, severe dermatologic reactions, tumor lysis syndrome, embryo-fetal toxicity, and effects on growth and development in pediatric patients.
 
Expand

SPRYCEL® (dasatinib) IMPORTANT SAFETY INFORMATION

Myelosuppression:
Treatment with SPRYCEL is associated with severe (NCI CTCAE Grade 3/4) thrombocytopenia, neutropenia, and anemia, which occur earlier and more frequently in patients with advanced phase CML or Ph+ ALL than in patients with chronic phase CML. Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities.

  • 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
  • In patients with advanced phase CML or Ph+ ALL, perform CBCs weekly for the first 2 months and then monthly thereafter, or as clinically indicated
  • Myelosuppression is generally reversible and usually managed by withholding SPRYCEL temporarily and/or dose reduction
    • In clinical studies, myelosuppression may have also been managed by discontinuation of study therapy
    • Hematopoietic growth factor has been used in patients with resistant myelosuppression

Bleeding-Related Events:
SPRYCEL can cause serious and fatal bleeding. In all CML or Ph+ ALL clinical studies, Grade ≥3 central nervous system (CNS) hemorrhages, including fatalities, occurred in <1% of patients receiving SPRYCEL. The incidence of Grade 3/4 hemorrhage, occurred in 5.8% of adult patients and generally required treatment interruptions and transfusions. The incidence of Grade 5 hemorrhage occurred in 0.4% of adult patients. The most frequent site of hemorrhage was gastrointestinal.

  • Most bleeding events in clinical studies were associated with severe thrombocytopenia
  • In addition to causing thrombocytopenia in human subjects, dasatinib caused platelet dysfunction in vitro
  • Concomitant medications that inhibit platelet function or anticoagulants may increase the risk of hemorrhage

Fluid Retention:
SPRYCEL may cause fluid retention. After 5 years of follow-up in the adult randomized newly diagnosed chronic phase CML study (n=258), Grade 3/4 fluid retention was reported in 5% of patients, including 3% of patients with Grade 3/4 pleural effusion. In adult patients with newly diagnosed or imatinib resistant or intolerant chronic phase CML, grade 3/4 fluid retention occurred in 6% of patients treated with SPRYCEL at the recommended dose (n=548). In adult patients with advanced phase CML or Ph+ ALL treated with SPRYCEL at the recommended dose (n=304), grade 3/4 fluid retention was reported in 8% of patients, including grade 3/4 pleural effusion reported in 7% of patients. In pediatric patients with chronic phase CML cases of Grade 1 or 2 fluid retention were reported in 10.3% of patients.

  • Patients who develop symptoms of pleural effusion or other fluid retention, such as new or worsened dyspnea on exertion or at rest, pleuritic chest pain, or dry cough should be evaluated promptly with a chest x-ray or additional diagnostic imaging as appropriate
  • Fluid retention events were typically managed by supportive care measures that may include diuretics or short courses of steroids
  • Severe pleural effusion may require thoracentesis and oxygen therapy
  • Consider dose reduction or treatment interruption

Cardiovascular Events:
SPRYCEL can cause cardiac dysfunction. After 5 years of follow-up in the randomized newly diagnosed chronic phase CML trial in adults (n=258), the following cardiac adverse reactions occurred:

  • Cardiac ischemic events (3.9% dasatinib vs 1.6% imatinib), cardiac related fluid retention (8.5% dasatinib vs 3.9% imatinib), and conduction system abnormalities, most commonly arrhythmia and palpitations (7.0% dasatinib vs 5.0% imatinib). Two cases (0.8%) of peripheral arterial occlusive disease occurred with imatinib and 2 (0.8%) transient ischemic attacks occurred with dasatinib

Monitor patients for signs or symptoms consistent with cardiac dysfunction and treat appropriately.

Pulmonary Arterial Hypertension (PAH):
SPRYCEL may increase the risk of developing PAH in adult and pediatric patients, which may occur any time after initiation, including after more than 1 year of treatment. Manifestations include dyspnea, fatigue, hypoxia, and fluid retention. PAH may be reversible on discontinuation of SPRYCEL.

  • Evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to initiating SPRYCEL and during treatment. If PAH is confirmed, SPRYCEL should be permanently discontinued

QT Prolongation:
SPRYCEL may increase the risk of prolongation of QTc in patients including those with hypokalemia or hypomagnesemia, patients with congenital long QT syndrome, patients taking antiarrhythmic medicines or other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy

  • Correct hypokalemia or hypomagnesemia prior to and during SPRYCEL administration

Severe Dermatologic Reactions:
Cases of severe mucocutaneous dermatologic reactions, including Stevens-Johnson syndrome and erythema multiforme, have been reported in patients treated with SPRYCEL.

  • Discontinue permanently in patients who experience a severe mucocutaneous reaction during treatment if no other etiology can be identified

Tumor Lysis Syndrome (TLS):
TLS has been reported in patients with resistance to prior imatinib therapy, primarily in advanced phase disease.

  • Due to potential for TLS, maintain adequate hydration, correct uric acid levels prior to initiating therapy with SPRYCEL, and monitor electrolyte levels
  • Patients with advanced stage disease and/or high tumor burden may be at increased risk and should be monitored more frequently

Embryo-Fetal Toxicity:
Based on limited human data, SPRYCEL can cause fetal harm when administered to a pregnant woman. Hydrops fetalis, fetal leukopenia and fetal thrombocytopenia have been reported with maternal exposure to SPRYCEL. Transplacental transfer of dasatinib has been measured in fetal plasma and amniotic fluid at concentrations comparable to those in maternal plasma.

  • Advise females of reproductive potential to avoid pregnancy, which may include the use of effective contraception, during treatment with SPRYCEL and for 30 days after the final dose

Effects on Growth and Development in Pediatric Patients:
In pediatric trials of SPRYCEL in chronic phase CML after at least 2 years of treatment, adverse reactions associated with bone growth and development were reported in 5 (5.2%) patients, one of which was severe in intensity (Growth Retardation Grade 3). These 5 cases included cases of epiphyses delayed fusion, osteopenia, growth retardation, and gynecomastia. Of these 5 cases, 1 case of osteopenia and 1 case of gynecomastia resolved during treatment.

Lactation:
No data are available regarding the presence of dasatinib in human milk, the effects of the drug on the breastfed child or the effects of the drug on milk production. However, dasatinib is present in the milk of lactating rats.

  • Because of the potential for serious adverse reactions in nursing children from SPRYCEL, breastfeeding is not recommended during treatment with SPRYCEL and for 2 weeks after the final dose

Drug Interactions:
Effect of Other Drugs on Dasatinib

  • Strong CYP3A4 inhibitors: The coadministration with strong CYP3A inhibitors may increase dasatinib concentrations. Increased dasatinib concentrations may increase the risk of toxicity. Avoid concomitant use of strong CYP3A4 inhibitors. If concomitant administration of a strong CYP3A4 inhibitor cannot be avoided, consider a SPRYCEL dose reduction
    • Grapefruit juice may increase plasma concentrations of SPRYCEL and should be avoided
  • Strong CYP3A4 inducers: The coadministration of SPRYCEL with strong CYP3A inducers may decrease dasatinib concentrations. Decreased dasatinib concentrations may reduce efficacy. Consider alternative drugs with less enzyme induction potential. If concomitant administration of a strong CYP3A4 inducer cannot be avoided, consider a SPRYCEL dose increase
    • St. John's wort may decrease plasma concentrations of SPRYCEL and should be avoided
  • Gastric Acid Reducing Agents: The coadministration of SPRYCEL with a gastric acid reducing agent may decrease the concentrations of dasatinib. Decreased dasatinib concentrations may reduce efficacy.

Do not administer H2 antagonists or proton pump inhibitors with SPRYCEL. Consider the use of antacids in place of H2 antagonists or proton pump inhibitors. Administer the antacid at least 2 hours prior to or 2 hours after the dose of SPRYCEL. Avoid simultaneous administration of SPRYCEL with antacids.

Adverse Reactions:
The safety data reflects exposure to SPRYCEL at all doses tested in clinical studies (n=2809) including 324 adult patients with newly diagnosed chronic phase CML, 2388 adult patients with imatinib resistant or intolerant chronic or advanced phase CML or Ph+ ALL, and 97 pediatric patients with chronic phase CML.

The median duration of therapy in a total of 2712 SPRYCEL-treated adult patients was 19.2 months (range 0–93.2 months). Median duration of therapy in:

  • 1618 adult patients with chronic phase CML was 29 months (range 0–92.9 months)
    • Median duration for 324 adult patients in the newly diagnosed chronic phase CML trial was approximately 60 months
  • 1094 adult patients with advanced phase CML or Ph+ ALL was 6.2 months (range 0–93.2 months)

In two non-randomized trials in 97 pediatric patients with chronic phase CML (51 patients newly diagnosed and 46 patients resistant or intolerant to previous treatment with imatinib), the median duration of therapy was 51.1 months (range 1.9 to 99.6 months).

In the newly diagnosed adult chronic phase CML trial, after a minimum of 60 months of follow-up, the cumulative discontinuation rate for 258 patients was 39%.

In the overall population of 2712 adult SPRYCEL-treated patients, 88% of patients experienced adverse reactions at some time and 19% experienced adverse reactions leading to treatment discontinuation.

Among the 1618 adult SPRYCEL-treated patients with chronic phase CML, drug-related adverse reactions leading to discontinuation were reported in 329 (20.3%) patients.

  • In the adult newly diagnosed chronic phase CML trial, drug was discontinued for adverse reactions in 16% of SPRYCEL-treated patients with a minimum of 60 months of follow-up

Among the 1094 SPRYCEL-treated patients with advanced phase CML or Ph+ ALL, drug-related adverse reactions leading to discontinuation were reported in 191 (17.5%) patients.

Among the 97 pediatric subjects, drug-related adverse reactions leading to discontinuation were reported in 1 patient (1%).

Patients ≥65 years are more likely to experience the commonly reported adverse reactions of fatigue, pleural effusion, diarrhea, dyspnea, cough, lower gastrointestinal hemorrhage, and appetite disturbance, and more likely to experience the less frequently reported adverse reactions of abdominal distention, dizziness, pericardial effusion, congestive heart failure, hypertension, pulmonary edema and weight decrease, and should be monitored closely.

  • In adult newly diagnosed chronic phase CML patients:
    • Drug-related serious adverse reactions (SARs) were reported for 16.7% of patients. Serious adverse reactions reported in ≥5% of patients included pleural effusion (5%)
    • Grade 3/4 laboratory abnormalities included neutropenia (29%), thrombocytopenia (22%), anemia (13%), hypophosphatemia (7%), hypocalcemia (4%), elevated bilirubin (1%), and elevated creatinine (1%)
  • In adult patients resistant or intolerant to prior imatinib therapy:
    • Drug-related SARs were reported for 26.1% of SPRYCEL-treated patients treated at the recommended dose of 100 mg once daily in the randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy. Serious adverse reactions reported in ≥5% of patients included pleural effusion (10%)
    • Grade 3/4 hematologic laboratory abnormalities in chronic phase CML patients resistant or intolerant to prior imatinib therapy who received SPRYCEL 100 mg once daily with a minimum follow up of 60 months included neutropenia (36%), thrombocytopenia (24%), and anemia (13%). Other grade 3/4 laboratory abnormalities included: hypophosphatemia (10%), and hypokalemia (2%)
    • Among chronic phase CML patients with resistance or intolerance to prior imatinib therapy, cumulative grade 3/4 cytopenias were similar at 2 and 5 years including: neutropenia (36% vs 36%), thrombocytopenia (23% vs 24%), and anemia (13% vs 13%)
  • Grade 3/4 elevations of transaminases or bilirubin and Grade 3/4 hypocalcemia, hypokalemia, and hypophosphatemia were reported in patients with all phases of CML
    • Elevations in transaminases or bilirubin were usually managed with dose reduction or interruption
    • Patients developing Grade 3/4 hypocalcemia during the course of SPRYCEL therapy often had recovery with oral calcium supplementation
  • In pediatric subjects with Ph+ CML in chronic phase
    • Drug-related SARs were reported for 14.4% of pediatric patients
    • In the pediatric studies, the rates of laboratory abnormalities were consistent with the known profile for laboratory parameters in adults

Most common adverse reactions (≥15%) in patients included myelosuppression, fluid retention events, diarrhea, headache, skin rash, hemorrhage, dyspnea, fatigue, nausea, and musculoskeletal pain.

Please see full Prescribing Information.

729US1704207-01-01 01/18

Close

Please verify that you are a US Healthcare Professional

This information is intended for US Healthcare Professionals.

I am a US Healthcare/Medical
Professional

Continue

I am not a US Healthcare/Medical
Professional

Return

Close

You are now leaving this Bristol-Myers Squibb site.

This Internet site may provide links or references to other sites.
BMS has no responsibility for the content of such other sites and is not
liable for any damages or injury arising from that content. Any links to
other sites are provided merely as a convenience to the users of this Internet site.

Close

You are about to leave the Bristol-Myers Squibb Company and
Otsuka America Pharmaceutical, Inc. SPRYCEL-HCP.com site.
You are being redirected to the Otsuka America Pharmaceutical, Inc. Corporate Web site.
Your linking to any other off-site pages or other sites is at your own risk.

Would you like to leave this site?

Yes

No

Close

You are about to leave this Bristol-Myers Squibb Company site.
You are being redirected to another Bristol-Myers Squibb Company site.

Would you like to leave this site?

Yes

No