dasatinib Dailymed

Based on limited human data, dasatinib can cause fetal harm when administered to a pregnant woman. Adverse pharmacologic effects of dasatinib including hydrops fetalis, fetal leukopenia and fetal thrombocytopenia have been reported with maternal exposure to dasatinib. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with dasatinib and for 30 days after the last dose  .

Based on limited human data, dasatinib can cause fetal harm when administered to a pregnant woman. Adverse pharmacologic effects of dasatinib including hydrops fetalis, fetal leukopenia and fetal thrombocytopenia have been reported with maternal exposure to dasatinib. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with dasatinib and for 30 days after the last dose [see Use in Specific Populations (8.1, 8.3)].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to dasatinib administered as single-agent therapy at all doses tested in clinical studies (n=2,809), including 324 adult patients with newly diagnosed chronic phase CML, 2,388 adult patients with imatinib-resistant or -intolerant chronic or advanced phase CML or Ph+ ALL. The median duration of therapy in a total of 2,712 adult patients was 19.2 months (range 0 to 93.2 months). In a randomized trial in patients with newly diagnosed chronic phase CML, the median duration of therapy was approximately 60 months. The median duration of therapy in 1,618 adult patients with chronic phase CML was 29 months (range 0 to 92.9 months). The median duration of therapy in 1,094 adult patients with advanced phase CML or Ph+ ALL was 6.2 months (range 0 to 93.2 months). In the overall population of 2,712 adult patients, 88% of patients experienced adverse reactions at some time and 19% experienced adverse reactions leading to treatment discontinuation. In the randomized trial in adult patients with newly diagnosed chronic phase CML, drug was discontinued for adverse reactions in 16% of patients with a minimum of 60 months of follow-up. After a minimum of 60 months of follow-up, the cumulative discontinuation rate was 39%. Among the 1,618 patients with chronic phase CML, drug-related adverse reactions leading to discontinuation were reported in 329 (20.3%) patients; among the 1,094 patients with advanced phase CML or Ph+ ALL, drug-related adverse reactions leading to discontinuation were reported in 191 (17.5%) patients. Adverse reactions reported in ≥ 10% of adult patients and other adverse reactions of interest, in a randomized trial in patients with newly diagnosed chronic phase CML at a median follow-up of approximately 60 months are presented in Table 6. Adverse reactions reported in ≥ 10% of adult patients treated at the recommended dose of 100 mg once daily (n=165) and other adverse reactions of interest, in a randomized dose-optimization trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy at a median follow-up of approximately 84 months are presented in Table 8. Drug-related serious adverse reactions (SARs) were reported for 16.7% of adult patients in the randomized trial of patients with newly diagnosed chronic phase CML. Serious adverse reactions reported in ≥ 5% of patients included pleural effusion (5%). Drug-related SARs were reported for 26.1% of patients treated at the recommended dose of 100 mg once daily in the randomized dose-optimization trial of adult patients with chronic phase CML resistant or intolerant to prior imatinib therapy. Serious adverse reactions reported in ≥ 5% of patients included pleural effusion (10%). Chronic Myeloid Leukemia (CML) Adverse reactions (excluding laboratory abnormalities) that were reported in at least 10% of adult patients are shown in Table 6 for newly diagnosed patients with chronic phase CML and Tables 8 and 10 for CML patients with resistance or intolerance to prior imatinib therapy. Table 6 Adverse Reactions Reported in ≥ 10% of Adult Patients with Newly Diagnosed Chronic Phase CML (minimum of 60 months follow-up) a Includes cardiac failure acute, cardiac failure congestive, cardiomyopathy, diastolic dysfunction, ejection fraction decreased and left ventricular dysfunction. b Includes erythema, erythema multiforme, rash, rash generalized, rash macular, rash papular, rash pustular, skin exfoliation and rash vesicular. c Adverse reaction of special interest with < 10% frequency. d Includes conjunctival hemorrhage, ear hemorrhage, ecchymosis, epistaxis, eye hemorrhage, gingival bleeding, hematoma, hematuria, hemoptysis, intra-abdominal hematoma, petechiae, scleral hemorrhage, uterine hemorrhage and vaginal hemorrhage. All Grades Grade 3/4 Dasatinib (n=258) Imatinib (n=258) Dasatinib (n=258) Imatinib (n=258) Adverse Reaction Percent (%) of Patients Fluid retention 38 45 5 1 Pleural effusion 28 1 3 0 Superficial localized edema 14 38 0 < 1 Pulmonary hypertension 5 < 1 1 0 Generalized edema 4 7 0 0 Pericardial effusion 4 1 1 0 Congestive heart failure/ cardiac dysfunctiona 2 1 < 1 < 1 Pulmonary edema 1 0 0 0 Diarrhea 22 23 1 1 Musculoskeletal pain 14 17 0 < 1 Rashb 14 18 0 2 Headache 14 11 0 0 Abdominal pain 11 8 0 1 Fatigue 11 12 < 1 0 Nausea 10 25 0 0 Myalgia 7 12 0 0 Arthralgia 7 10 0 <1 Hemorrhagec 8 8 1 1 Gastrointestinal bleeding 2 2 1 0 Other bleedingd 6 6 0 < 1 CNS bleeding < 1 < 1 0 < 1 Vomiting 5 12 0 0 Muscle spasms 5 21 0 < 1 A comparison of cumulative rates of adverse reactions reported in ≥ 10% of patients with minimum follow-up of 1 year and 5 years in a randomized trial of newly diagnosed patients with chronic phase CML treated with dasatinib are shown in Table 7. Table 7 Adverse Reactions Reported in ≥ 10% of Adult Patients with Newly Diagnosed Chronic Phase CML in the Dasatinib-Treated Arm (n=258) a Includes cardiac failure acute, cardiac failure congestive, cardiomyopathy, diastolic dysfunction, ejection fraction decreased and left ventricular dysfunction. b Includes erythema, erythema multiforme, rash, rash generalized, rash macular, rash papular, rash pustular, skin exfoliation and rash vesicular. Minimum of 1 Year Follow-up Minimum of 5 Years Follow-up All Grades Grade 3/4 All Grades Grade 3/4 Adverse Reaction Percent (%) of Patients Fluid retention 19 1 38 5 Pleural effusion 10 0 28 3 Superficial localized edema 9 0 14 0 Pulmonary hypertension 1 0 5 1 Generalized edema 2 0 4 0 Pericardial effusion 1 < 1 4 1 Congestive heart failure/cardiac dysfunctiona 2 < 1 2 < 1 Pulmonary edema < 1 0 1 0 Diarrhea 17 < 1 22 1 Musculoskeletal pain 11 0 14 0 Rashb 11 0 14 0 Headache 12 0 14 0 Abdominal pain 7 0 11 0 Fatigue 8 < 1 11 < 1 Nausea 8 0 10 0 At 60 months, there were 26 deaths in dasatinib-treated patients (10.1%) and 26 deaths in imatinib-treated patients (10.1%); 1 death in each group was assessed by the investigator as related to study therapy. Table 8 Adverse Reactions Reported in ≥ 10% of Adult Patients with Chronic Phase CML Resistant or Intolerant to Prior Imatinib Therapy (minimum of 84 months follow-up) a Includes drug eruption, erythema, erythema multiforme, erythrosis, exfoliative rash, generalized erythema, genital rash, heat rash, milia, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, skin exfoliation, skin irritation, urticaria vesiculosa and rash vesicular. 100 mg Once Daily Chronic (n=165) All Grades Grade 3/4 Adverse Reaction Percent (%) of Patients Fluid retention 48 7 Superficial localized edema 22 0 Pleural effusion 28 5 Generalized edema 4 0 Pericardial effusion 3 1 Pulmonary hypertension 2 1 Headache 33 1 Diarrhea 28 2 Fatigue 26 4 Dyspnea 24 2 Musculoskeletal pain 22 2 Nausea 18 1 Skin rasha 18 2 Myalgia 13 0 Arthralgia 13 1 Infection (including bacterial, viral, fungal and non-specified) 13 1 Abdominal pain 12 1 Hemorrhage 12 1 Gastrointestinal bleeding 2 1 Pruritus 12 1 Pain 11 1 Constipation 10 1 Cumulative rates of selected adverse reactions that were reported over time in patients treated with the 100 mg once daily recommended starting dose in a randomized dose-optimization trial of imatinib-resistant or -intolerant patients with chronic phase CML are shown in Table 9. Table 9 Selected Adverse Reactions Reported in Adult Dose Optimization Trial (Imatinib-Intolerant or -Resistant Chronic Phase CML)a a Randomized dose-optimization trial results reported in the recommended starting dose of 100 mg once daily (n=165) population. Minimum of 2 Years Follow-up Minimum of 5 Years Follow-up Minimum of 7 Years Follow-up All Grades Grade 3/4 All Grades Grade 3/4 All Grades Grade 3/4 Adverse Reaction Percent (%) of Patients Diarrhea 27 2 28 2 28 2 Fluid retention 34 4 42 6 48 7 Superficial edema 18 0 21 0 22 0 Pleural effusion 18 2 24 4 28 5 Generalized edema 3 0 4 0 4 0 Pericardial effusion 2 1 2 1 3 1 Pulmonary hypertension 0 0 0 0 2 1 Hemorrhage 11 1 11 1 12 1 Gastrointestinal bleeding 2 1 2 1 2 1 Table 10 Adverse Reactions Reported in ≥ 10% of Adult Patients with Advanced Phase CML Resistant or Intolerant to Prior Imatinib Therapy a Includes ventricular dysfunction, cardiac failure, cardiac failure congestive, cardiomyopathy, congestive cardiomyopathy, diastolic dysfunction, ejection fraction decreased and ventricular failure. b Includes drug eruption, erythema, erythema multiforme, erythrosis, exfoliative rash, generalized erythema, genital rash, heat rash, milia, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, skin exfoliation, skin irritation, urticaria vesiculosa and rash vesicular. 140 mg Once Daily Accelerated  (n=157) Myeloid Blast  (n=74) Lymphoid Blast (n=33) All Grades Grade 3/4 All Grades Grade 3/4 All Grades Grade 3/4 Adverse Reaction Percent (%) of Patients Fluid retention 35 8 34 7 21 6 Superficial localized edema 18 1 14 0 3 0 Pleural effusion 21 7 20 7 21 6 Generalized edema 1 0 3 0 0 0 Pericardial effusion 3 1 0 0 0 0 Congestive heart failure/cardiac dysfunctiona 0 0 4 0 0 0 Pulmonary edema 1 0 4 3 0 0 Headache 27 1 18 1 15 3 Diarrhea 31 3 20 5 18 0 Fatigue 19 2 20 1 9 3 Dyspnea 20 3 15 3 3 3 Musculoskeletal pain 11 0 8 1 0 0 Nausea 19 1 23 1 21 3 Skin rashb 15 0 16 1 21 0 Arthralgia 10 0 5 1 0 0 Infection (including bacterial, viral, fungal and non-specified) 10 6 14 7 9 0 Hemorrhage 26 8 19 9 24 9 Gastrointestinal bleeding 8 6 9 7 9 3 CNS bleeding 1 1 0 0 3 3 Vomiting 11 1 12 0 15 0 Pyrexia 11 2 18 3 6 0 Febrile neutropenia 4 4 12 12 12 12 Adverse reactions associated with bone growth and development were reported in 5 (5.2%) of pediatric patients with chronic phase CML [see Warnings and Precautions (5.10)]. Laboratory Abnormalities Myelosuppression was commonly reported in all patient populations. The frequency of Grade 3 or 4 neutropenia, thrombocytopenia and anemia was higher in patients with advanced phase CML than in chronic phase CML (Tables 12 and 13). Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities. In patients who experienced severe myelosuppression, recovery generally occurred following dose interruption or reduction; permanent discontinuation of treatment occurred in 2% of adult patients with newly diagnosed chronic phase CML and 5% of adult patients with resistance or intolerance to prior imatinib therapy [see Warnings and Precautions (5.1)]. Grade 3 or 4 elevations of transaminases or bilirubin and Grade 3 or 4 hypocalcemia, hypokalemia and hypophosphatemia were reported in patients with all phases of CML but were reported with an increased frequency in patients with myeloid or lymphoid blast phase CML. Elevations in transaminases or bilirubin were usually managed with dose reduction or interruption. Patients developing Grade 3 or 4 hypocalcemia during dasatinib therapy often had recovery with oral calcium supplementation. Laboratory abnormalities reported in adult patients with newly diagnosed chronic phase CML are shown in Table 12. There were no discontinuations of dasatinib therapy in this patient population due to biochemical laboratory parameters. Table 12 CTC Grade 3/4 Laboratory Abnormalities in Adult Patients with Newly Diagnosed Chronic Phase CML (minimum of 60 months follow-up) CTC grades: neutropenia (Grade 3 ≥ 0.5 to < 1 × 109/L, Grade 4 < 0.5 × 109/L); thrombocytopenia (Grade 3 ≥ 25 to < 50 × 109/L, Grade 4 < 25 × 109/L); anemia (hemoglobin Grade 3 ≥ 65 to < 80 g/L, Grade 4 < 65 g/L); elevated creatinine (Grade 3 > 3 to 6 × upper limit of normal range (ULN), Grade 4 > 6 × ULN); elevated bilirubin (Grade 3 > 3 to 10 × ULN, Grade 4 > 10 × ULN); elevated SGOT or SGPT (Grade 3 > 5 to 20 × ULN, Grade 4 > 20 × ULN); hypocalcemia (Grade 3 < 7 mg/dL to 6 mg/dL, Grade 4 < 6  mg/dL); hypophosphatemia (Grade 3 < 2 mg/dL to 1 mg/dL, Grade 4 < 1 mg/dL); hypokalemia (Grade 3 < 3 to 2.5 mmol/L, Grade 4 < 2.5 mmol/L). Dasatinib  (n=258) Imatinib (n=258) Percent (%) of Patients Hematology Parameters Neutropenia 29 24 Thrombocytopenia 22 14 Anemia 13 9 Biochemistry Parameters Hypophosphatemia 7 31 Hypokalemia 0 3 Hypocalcemia 4 3 Elevated SGPT (ALT) < 1 2 Elevated SGOT (AST) < 1 1 Elevated Bilirubin 1 0 Elevated Creatinine 1 1 Laboratory abnormalities reported in patients with CML resistant or intolerant to imatinib who received the recommended starting doses of dasatinib are shown by disease phase in Table 13. Table 13 CTC Grade 3/4 Laboratory Abnormalities in Clinical Studies of CML in Adults: Resistance or Intolerance to Prior Imatinib Therapy CTC grades: neutropenia (Grade 3 ≥ 0.5 to < 1 × 109/L, Grade 4 < 0.5 × 109/L); thrombocytopenia (Grade 3 ≥ 25 to < 50 × 109/L, Grade 4 < 25 × 109/L); anemia (hemoglobin Grade 3 ≥ 65 to < 80 g/L, Grade 4 < 65 g/L); elevated creatinine (Grade 3 > 3 to 6 × upper limit of normal range (ULN), Grade 4 > 6 × ULN); elevated bilirubin (Grade 3 > 3 to 10 × ULN, Grade 4 > 10 × ULN); elevated SGOT or SGPT (Grade 3 > 5 to 20 × ULN, Grade 4 > 20 × ULN); hypocalcemia (Grade 3 < 7 to 6 mg/dL, Grade 4 < 6 mg/dL); hypophosphatemia (Grade 3 < 2 to 1 mg/dL, Grade 4 < 1 mg/dL); hypokalemia (Grade 3 < 3 to 2.5 mmol/L, Grade 4 < 2.5 mmol/L). * Hematology parameters for 100 mg once-daily dosing in chronic phase CML reflects 60-month minimum follow-up. Chronic Phase CML 100 mg Once Daily Advanced Phase CML 140 mg Once Daily (n=165) Accelerated Phase (n=157) Myeloid Blast Phase (n=74) Lymphoid Blast Phase (n=33) Percent (%) of Patients Hematology Parameters* Neutropenia 36 58 77 79 Thrombocytopenia 24 63 78 85 Anemia 13 47 74 52 Biochemistry Parameters Hypophosphatemia 10 13 12 18 Hypokalemia 2 7 11 15 Hypocalcemia < 1 4 9 12 Elevated SGPT (ALT) 0 2 5 3 Elevated SGOT (AST) < 1 0 4 3 Elevated Bilirubin < 1 1 3 6 Elevated Creatinine 0 2 8 0 Among adult patients with chronic phase CML with resistance or intolerance to prior imatinib therapy, cumulative Grade 3 or 4 cytopenias were similar at 2 years and 5 years including: neutropenia (36% vs. 36%), thrombocytopenia (23% vs. 24%) and anemia (13% vs. 13%). Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia (Ph+ ALL) in Adults A total of 135 adult patients with Ph+ ALL were treated with dasatinib in clinical studies. The median duration of treatment was 3 months (range 0.03 to 31 months). The safety profile of patients with Ph+ ALL was similar to those with lymphoid blast phase CML. The most frequently reported adverse reactions included fluid retention events, such as pleural effusion (24%) and superficial edema (19%) and gastrointestinal disorders, such as diarrhea (31%), nausea (24%) and vomiting (16%). Hemorrhage (19%), pyrexia (17%), rash (16%) and dyspnea (16%) were also frequently reported. Serious adverse reactions reported in ≥ 5% of patients included pleural effusion (11%), gastrointestinal bleeding (7%), febrile neutropenia (6%) and infection (5%). Additional Pooled Data from Clinical Trials The following additional adverse reactions were reported in adult patients in dasatinib CML clinical studies and adult patients in Ph+ ALL clinical studies at a frequency of ≥ 10%, 1% to < 10%, 0.1% to < 1%, or < 0.1%. These adverse reactions are included based on clinical relevance. Gastrointestinal Disorders: 1% to < 10% – mucosal inflammation (including mucositis/stomatitis), dyspepsia, abdominal distension, constipation, gastritis, colitis (including neutropenic colitis), oral soft tissue disorder; 0.1% to < 1% – ascites, dysphagia, anal fissure, upper gastrointestinal ulcer, esophagitis, pancreatitis, gastroesophageal reflux disease; < 0.1% – protein losing gastroenteropathy, ileus, acute pancreatitis, anal fistula. General Disorders and Administration-Site Conditions: ≥ 10% – peripheral edema, face edema; 1% to < 10% – asthenia, chest pain, chills; 0.1% to < 1% – malaise, other superficial edema, peripheral swelling; < 0.1% – gait disturbance. Skin and Subcutaneous Tissue Disorders: 1% to < 10% – alopecia, acne, dry skin, hyperhidrosis, urticaria, dermatitis (including eczema); 0.1% to < 1% – pigmentation disorder, skin ulcer, bullous conditions, photosensitivity, nail disorder, neutrophilic dermatosis, panniculitis, palmar-plantar erythrodysesthesia syndrome, hair disorder; < 0.1% – leukocytoclastic vasculitis, skin fibrosis. Respiratory, Thoracic and Mediastinal Disorders: 1% to < 10% – lung infiltration, pneumonitis, cough; 0.1% to < 1% – asthma, bronchospasm, dysphonia, pulmonary arterial hypertension; < 0.1% – acute respiratory distress syndrome, pulmonary embolism. Nervous System Disorders: 1% to < 10% – neuropathy (including peripheral neuropathy), dizziness, dysgeusia, somnolence; 0.1% to < 1% – amnesia, tremor, syncope, balance disorder; < 0.1% – convulsion, cerebrovascular accident, transient ischemic attack, optic neuritis, VIIth nerve paralysis, dementia, ataxia. Blood and Lymphatic System Disorders: 0.1% to < 1% – lymphadenopathy, lymphopenia; < 0.1% – aplasia pure red cell. Musculoskeletal and Connective Tissue Disorders: 1% to < 10% – muscular weakness, musculoskeletal stiffness; 0.1% to < 1% – rhabdomyolysis, tendonitis, muscle inflammation, osteonecrosis, arthritis; < 0.1% – epiphyses delayed fusion (reported at 1% to < 10% in the pediatric studies), growth retardation (reported at 1% to < 10% in the pediatric studies). Investigations: 1% to < 10% – weight increased, weight decreased; 0.1% to < 1% – blood creatine phosphokinase increased, gamma-glutamyltransferase increased. Infections and Infestations: 1% to < 10% – pneumonia (including bacterial, viral and fungal), upper respiratory tract infection/inflammation, herpes virus infection, enterocolitis infection, sepsis (including fatal outcomes [0.2%]). Metabolism and Nutrition Disorders: 1% to < 10% – appetite disturbances, hyperuricemia; 0.1% to < 1% – hypoalbuminemia, tumor lysis syndrome, dehydration, hypercholesterolemia; < 0.1% – diabetes mellitus. Cardiac Disorders: 1% to < 10% – arrhythmia (including tachycardia), palpitations; 0.1% to < 1% – angina pectoris, cardiomegaly, pericarditis, ventricular arrhythmia (including ventricular tachycardia), electrocardiogram T-wave abnormal, troponin increased; < 0.1% – cor pulmonale, myocarditis, acute coronary syndrome, cardiac arrest, electrocardiogram PR prolongation, coronary artery disease, pleuropericarditis. Eye Disorders: 1% to < 10% – visual disorder (including visual disturbance, vision blurred and visual acuity reduced), dry eye; 0.1% to < 1% – conjunctivitis, visual impairment, lacrimation increased, < 0.1% – photophobia. Vascular Disorders: 1% to < 10% – flushing, hypertension; 0.1% to < 1% – hypotension, thrombophlebitis, thrombosis; < 0.1% – livedo reticularis, deep vein thrombosis, embolism. Psychiatric Disorders: 1% to < 10% – insomnia, depression; 0.1% to < 1% – anxiety, affect lability, confusional state, libido decreased. Pregnancy, Puerperium and Perinatal Conditions: < 0.1% – abortion. Reproductive System and Breast Disorders: 0.1% to < 1% – gynecomastia, menstrual disorder. Injury, Poisoning and Procedural Complications: 1% to < 10% – contusion. Ear and Labyrinth Disorders: 1% to < 10% – tinnitus; 0.1% to < 1% – vertigo, hearing loss. Hepatobiliary Disorders: 0.1% to < 1% – cholestasis, cholecystitis, hepatitis. Renal and Urinary Disorders: 0.1% to < 1% – urinary frequency, renal failure, proteinuria; < 0.1% – renal impairment. Immune System Disorders: 0.1% to < 1% – hypersensitivity (including erythema nodosum). Endocrine Disorders: 0.1% to < 1% – hypothyroidism; < 0.1% – hyperthyroidism, thyroiditis. Pediatric use information is approved for Bristol-Myers Squibb Company's Sprycel (dasatinib) tablets. However, due to Bristol-Myers Squibb Company's marketing exclusivity rights, this drug product is not labeled with that pediatric information.



Risk Summary Based on limited human data, dasatinib 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 dasatinib. 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.

Dasatinib can cause fetal harm when administered to a pregnant woman .

Dasatinib 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 dasatinib 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)].