Sprycel
(dasatinib)Dosage & Administration
Sprycel Prescribing Information
SPRYCEL (dasatinib) is indicated for the treatment of adult patients with
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- newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.
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- chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib.
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- Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
SPRYCEL (dasatinib) is indicated for the treatment of pediatric patients 1 year of age and older with
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- Ph+ CML in chronic phase.
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- newly diagnosed Ph+ ALL in combination with chemotherapy.
Duration of Treatment
In clinical studies, treatment with SPRYCEL in adults and in pediatric patients with chronic phase CML was continued until disease progression or until no longer tolerated by the patient. The effect of stopping treatment on long-term disease outcome after the achievement of a cytogenetic response (including complete cytogenetic response [CCyR]) or major molecular response (MMR and MR4.5) has not been established.
In clinical studies, treatment with SPRYCEL in pediatric patients with Ph+ ALL was administered for a maximum duration of 2 years [see Dosage and Administration (2.2) and Clinical Studies (14.4)].
SPRYCEL is a hazardous product. Follow applicable special handling and disposal procedures.1
SPRYCEL (dasatinib) Tablets are available as 20-mg, 50-mg, 70-mg, 80-mg, 100-mg, and 140-mg white to off-white, biconvex, film-coated tablets.
Pregnancy
Risk Summary
Based on limited human data, SPRYCEL can cause fetal harm when administered to a pregnant woman. Adverse pharmacologic effects including hydrops fetalis, fetal leukopenia, and fetal thrombocytopenia have been reported with maternal exposure to SPRYCEL. Animal reproduction studies in rats have demonstrated extensive mortality during organogenesis, the fetal period, and in neonates. Skeletal malformations were observed in a limited number of surviving rat and rabbit conceptuses. These findings occurred at dasatinib plasma concentrations below those in humans receiving therapeutic doses of dasatinib [see Data]. Advise a pregnant woman of the potential risk to a fetus.
The estimated background risk in the U.S. general population of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies.
Clinical Considerations
Fetal/Neonatal Adverse Reactions
Transplacental transfer of dasatinib has been reported. Dasatinib has been measured in fetal plasma and amniotic fluid at concentrations comparable to those in maternal plasma. Hydrops fetalis, fetal leukopenia, and fetal thrombocytopenia have been reported with maternal exposure to dasatinib. These adverse pharmacologic effects on the fetus are similar to adverse reactions observed in adult patients and may result in fetal harm or neonatal death [see Warnings and Precautions (5.1, 5.3)].
Data
Human Data
Based on human experience, dasatinib is suspected to cause congenital malformations, including neural tube defects, and harmful pharmacological effects on the fetus when administered during pregnancy.
Animal Data
In nonclinical studies at plasma concentrations below those observed in humans receiving therapeutic doses of dasatinib, embryo-fetal toxicities were observed in rats and rabbits. Fetal death was observed in rats. In both rats and rabbits, the lowest doses of dasatinib tested (rat: 2.5 mg/kg/day [15 mg/m2/day] and rabbit: 0.5 mg/kg/day [6 mg/m2/day]) resulted in embryo-fetal toxicities. These doses produced maternal AUCs of 105 ng•h/mL and 44 ng•h/mL (0.1-fold the human AUC) in rats and rabbits, respectively. Embryo-fetal toxicities included skeletal malformations at multiple sites (scapula, humerus, femur, radius, ribs, and clavicle), reduced ossification (sternum; thoracic, lumbar, and sacral vertebrae; forepaw phalanges; pelvis; and hyoid body), edema, and microhepatia. In a pre- and postnatal development study in rats, administration of dasatinib from gestation day (GD) 16 through lactation day (LD) 20, GD 21 through LD 20, or LD 4 through LD 20 resulted in extensive pup mortality at maternal exposures that were below the exposures in patients treated with dasatinib at the recommended labeling dose.
Lactation
Risk Summary
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 last dose.
Females and Males of Reproductive Potential
SPRYCEL can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)].
Contraception
Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with SPRYCEL and for 30 days after the last dose.
Infertility
Based on animal data, dasatinib may result in damage to female and male reproductive tissues [see Nonclinical Toxicology (13.1)].
Pediatric Use
Ph+ CML in Chronic Phase
The safety and effectiveness of SPRYCEL monotherapy have been demonstrated in pediatric patients with newly diagnosed chronic phase CML [see Clinical Studies (14.3)]. There are no data in children under 1 year of age. Adverse reactions associated with bone growth and development were reported in 5 (5.2%) of patients [see Warnings and Precautions (5.10)].
Ph+ ALL
The safety and effectiveness of SPRYCEL in combination with chemotherapy have been demonstrated in pediatric patients one year and over with newly diagnosed Ph+ ALL. Use of SPRYCEL in pediatric patients is supported by evidence from one pediatric study. There are no data in children under 1 year of age. One case of grade 1 osteopenia was reported.
The safety profile of SPRYCEL in pediatric subjects was comparable to that reported in studies in adult subjects [see Adverse Reactions (6.1) and Clinical Studies (14.3, 14.4)].
Monitor bone growth and development in pediatric patients [see Warnings and Precautions (5.10)].
Pediatric Patients with Difficulty Swallowing Tablets
Five patients with Ph+ ALL 2 to 10 years of age received at least one dose of SPRYCEL tablet dispersed in juice on Study CA180372. The exposure for dispersed tablets was 36% lower as compared to intact tablets in pediatric patients [see Clinical Pharmacology (12.3)]. Due to the limited available clinical data, it is unclear whether dispersing SPRYCEL tablets significantly alters the safety and/or efficacy of SPRYCEL.
Geriatric Use
Of the 2712 patients in clinical studies of SPRYCEL, 617 (23%) were 65 years of age and older, and 123 (5%) were 75 years of age and older. No differences in confirmed Complete Cytogenetic Response (cCCyR) and MMR were observed between older and younger patients. While the safety profile of SPRYCEL in the geriatric population was similar to that in the younger population, patients aged 65 years and older 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.
None.
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 [see Adverse Reactions (6.1) and Use in Specific Populations (8.4)]. Of these 5 cases, 1 case of osteopenia and 1 case of gynecomastia resolved during treatment.
Monitor bone growth and development in pediatric patients.