Sprycel

Sprycel Adverse Reactions

dasatinib

Manufacturer:

Bristol-Myers Squibb

Distributor:

DKSH
Full Prescribing Info
Adverse Reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling.
Myelosuppression (see Dosage & Administration and Precautions).
Bleeding related events (see Precautions).
Fluid retention (see Precautions).
QT prolongation (see Precautions).
Cardiac Adverse Reactions (see Precautions).
Pulmonary Arterial Hypertension (see Precautions).
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 in the following text reflect exposure to SPRYCEL at all doses studies in clinical studies including 324 patients with newly diagnosed chronic phase CML and in 2388 patients with imatinib resistant or intolerant chronic or advanced phase CML or Ph+ALL. The median duration of therapy in 2712 SPRYCEL treated patients was 19.2 months (range 0-93.2 months).
In the Phase III newly diagnosed chronic phase CML study, the median duration of therapy was approximately 60 months for both SPRYCEL (range 0.03-72.7 months) and imatinib (range 0.3-74.6 months). In these 1618 patients with chronic phase CML the median duration of therapy was 29 months (range 0-92.9 months). In 1094 patients with advanced phase CML or Ph+ ALL, the median duration of treatment for patients was 6.2 months (range 0-93.2 months).
The majority of SPRYCEL-treated patients experienced adverse reactions at some time. In the overall population of 2712 SPRYCEL-treated subjects, 520 (19%) experienced adverse reactions leading to treatment discontinuation.
In the Phase III newly diagnosed chronic phase CML study, drug was discontinued for adverse reactions in 14% of SPRYCEL-treated patients and 7% of imatinib-treated patients with a minimum of 60 months follow up. Among the 1,618 SPRYCEL-treated subjects with chronic phase CML, adverse reactions leading to discontinuation were reported in 329 (20.3%) subjects, and among the 1,094 SPRYCEL-treated subjects with advanced phase disease, adverse reactions leading to discontinuation were reported in 191 (17.5%) subjects.
Adverse reactions reported in ≥ 10 % of patients, and other adverse reactions of interest, in a Phase III trial of newly diagnosed chronic phase CML at a median follow-up of approximately 60 months are presented in Table 2. In this study, pleural effusion was reported in 73 patients (28%) receiving SPRYCEL. The median time to onset for Grade 1 or 2 pleural effusion events was 114 weeks (range 4-299 weeks). Fewer than 3% of pleural effusion events were Grade 3 or 4. With appropriate medical care, 58 patients (80% of those with pleural effusion) were able to continue on SPRYCEL (see Precautions).
Adverse reactions reported in ≥10% of patients treated at the recommended dose of 100 mg once daily (n=165), and other adverse reactions of interest, in a Phase III 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 4. (See Table 4.)
Drug-related serious adverse events (SAEs) were reported for 16.7% of SPRYCEL-treated patients in a Phase III trial of patients with newly diagnosed chronic phase CML. The only serious adverse reaction reported in ≥5% of patients was pleural effusion (5%).
Drug-related SAEs were reported for 26.1% of patients treated at the recommended dose of 100 mg once daily in a Phase III trial of patients with chronic phase CML resistant or intolerant to prior imatinib therapy. The only serious adverse reaction reported in ≥5% of patients was pleural effusion (10%).
Chronic Myeloid Leukemia (CML): Adverse reactions (excluding laboratory abnormalities) that were reported in at least 10% of the patients are shown in Table 2 for newly diagnosed patients with chronic phase CML and Tables 4 and 6 for CML patients with resistance or intolerance to prior imatinib therapy. (See Tables 2, 4 and 6.)

Click on icon to see table/diagram/image

A comparison of cumulative rates of selected adverse reactions in the Phase III study of newly diagnosed patients with chronic phase CML with minimum follow-up of one and five years are shown in Table 3. (See Table 3.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

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 Phase III trial of imatinib-resistant or -intolerant patients with chronic phase CML are shown in Table 5. (See Table 5.)

Click on icon to see table/diagram/image


Click on icon to see table/diagram/image

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 7 and 8). In newly diagnosed chronic phase CML, myelosuppression was less frequently reported than in chronic phase CML patients with resistance or intolerance to prior imatinib therapy (Tables 7 and 8). Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities. (See Tables 7 and 8.)
In patients who experienced severe myelosuppression, recovery generally occurred following dose interruption or reduction; permanent discontinuation of treatment occurred in 2% of patients with newly diagnosed chronic phase CML patients in the Phase III study and 5 % of patients with resistance or intolerance to prior imatinib therapy in the Phase III study (see Precautions).
Grade 3 or 4 elevations of transaminase 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 transaminase or bilirubin were usually managed with dose reduction or interruption. Patients developing Grade 3 or 4 hypocalcemia during the course of SPRYCEL therapy often had recovery with oral calcium supplementation.
Laboratory abnormalities reported in patients with newly diagnosed chronic phase CML are shown in Table 7. There were no discontinuations of SPRYCEL therapy in this patient population due to biochemical laboratory parameters. (See Table 7.)

Click on icon to see table/diagram/image

Laboratory abnormalities received at 24 months of follow-up reported in CML patients with imatinib resistance or intolerance who received the recommended starting doses of SPRYCEL are shown by disease phase in Table 8. (See Table 8.)

Click on icon to see table/diagram/image

Among chronic phase CML patients with resistance or intolerance to prior imatinib therapy, cumulative Grade 3 or 4 cytopenias were similar at 2 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): A total of 135 patients with Ph+ ALL were treated with SPRYCEL in clinical studies. The median duration of treatment was 3 months (range 0.03-31 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 Data From Multiple Clinical Trials: The following additional adverse reactions were reported in SPRYCEL CML and Ph+ ALL clinical studies at a frequency of ≥10%, 1%-<10%, 0.1%-<1%, or <0.1%. These events are included on the basis of clinical relevance.
Gastrointestinal Disorders: ≥10% - diarrhea, nausea, vomiting, abdominal pain; 1%-<10% - gastrointestinal bleeding, mucosal inflammation (including mucositis/stomatitis), dyspepsia, abdominal distension, constipation, gastritis, colitis (including neutropenic colitis), oral soft tissue disorder; 0.1%-<1% - ascites, dysphagia, anal fissure, upper gastrointestinal ulcer, esophagitis, pancreatitis, gastro-esophageal reflux disease; <0.1% - protein-losing gastroenteropathy, ileus, pancreatitis acute, anal fistula.
General Disorders and Administration Site Conditions: ≥10% - peripheral edemaf, fatigue, pyrexia, face edemag; 1%-<10% - asthenia, pain, chest pain, generalized edemah, chills; 0.1%-<1% - malaise, other superficial edemai; <0.1% - gait disturbance.
Skin and Subcutaneous Tissue Disorders: ≥10% - skin rashe; 1%-<10% - pruritus, acne, alopecia, dry skin, hyperhidrosis, urticaria, dermatitis (including eczema); 0.1%-<1% - pigmentation disorder, skin ulcer, bullous conditions, photosensitivity, nail disorder, neutrophilic dermatosis, palmar-plantar erythrodysesthesia syndrome, panniculitis, hair disorder; <0.1% - leukocytoclastic vasculitis, skin fibrosis.
Respiratory, Thoracic, and Mediastinal Disorders: ≥10% - pleural effusion, dyspnea; 1%-<10% -pulmonary edema, lung infiltration, pneumonitis, pulmonary hypertension, cough; 0.1%-<1% -pulmonary arterial hypertension, asthma, bronchospasm, dysphonia; <0.1% - pulmonary embolism, acute respiratory distress syndrome.
Nervous System Disorders: ≥10% - headache; 1%-<10% - neuropathy (including peripheral neuropathy), dizziness, dysgeusia, somnolence; 0.1%-<1% - CNS bleedingb, 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: ≥10% - myelosuppression (including anemia, neutropenia, thrombocytopenia); 1%-<10% - febrile neutropenia; 0.1%-<1% - lymphadenopathy, lymphopenia; <0.1% - aplasia pure red cell.
Musculoskeletal and Connective Tissue Disorders: ≥10% - musculoskeletal pain; 1%-<10% - arthralgia, myalgia, muscular weakness, musculoskeletal stiffness, muscle spasm; 0.1%-<1% - rhabdomyolysis, oteonecrosis, tendonitis, muscle inflammation, arthritis.
Investigations: 1%-<10% - weight decreased, weight increased; 0.1%-<1% - blood creatine phosphokinase increased, Gamma-glutamyltransferase increased.
Infections and Infestations: ≥10% - infection (including bacterial, viral, fungal, non-specified); 1%-<10% - pneumonia (including bacterial, viral, and fungal), upper respiratory tract infection/inflammation, herpes virus infection, enterocolitis infection, sepsis (including uncommon reports of fatal outcomes).
Metabolism and Nutrition Disorders: 1%-<10% - appetite disturbances, hyperuricemia; 0.1%-<1%- tumor lysis syndrome, dehydration, hypoalbuminemia, hypercholesterolemia; <0.1% - diabetes mellitus.
Cardiac Disorders: 1%- <10% - pericardial effusion, arrhythmia (including tachycardia), congestive heart failure/cardiac dysfunctionc, palpitations; 0.1%-<1% - electrocardiogram QT prolonged, angina pectoris, cardiomegaly, pericarditis, ventricular arrhythmia (including ventricular tachycardia), myocardial infarction (including fatal outcomes), electrocardiogram T-wave abnormal, troponin increased; <0.1% - myocarditis, acute coronary syndrome, cor pulmonale, cardiac arrest, electrocardiogram PR prolongation, coronary artery disease, pleuropericarditis.
Eye Disorders: 1%-<10% - visual disorder (including visual disturbance, vision blurred, and visual acuity reduced), dry eye; 0.1% -<1% - visual impairment, conjunctivitis, photophobia, lacrimation increased.
Vascular Disorders: ≥10% - hemorrhaged ; 1%-<10% - flushing, hypertension; 0.1%-<1% - hypotension, thrombophlebitis; <0.1% - deep vein thrombosis, embolism, livedo reticularis.
Psychiatric Disorders: 1%-<10% - insomnia, depression; 0.1%-<1% - anxiety, affect lability, confusional state, libido decreased.
Pregnancy, puerperium and perinatal conditions: <0.1%- Abortion.
Reproductive System and Breast Disorders: 0.1%-<1% - gynecomastia, menstrual disorder.
Injury, Poisoning, and Procedural Complications: 1%-<10% - contusion.
Ear and Labyrinth Disorders: 1%-<10% - tinnitus, 0.1%-<1% - hearing loss, vertigo.
Hepatobiliary Disorders: 0.1%-<1% - cholestasis, cholecystitis, hepatitis.
Renal and Urinary Disorders: 0.1%-<1% - urinary frequency, renal failure, proteinuria; <0.1%-renal impairment.
Immune System Disorders: 0.1%-<1%- hypersensitivity (including erythema nodosum).
Endocrine Disorders: 0.1%-<1%- hypothyroidism; <0.1%- hyperthyroidism, thyroiditis.
a Includes decreased appetite, early satiety, increased appetite.
b Includes central nervous system hemorrhage, cerebral hematoma, cerebral hemorrhage, extradural hematoma, hemorrhage intracranial, hemorrhagic stroke, subarachnoid hemorrhage, subdural hematoma, and subdural hemorrhage.
c Includes brain natriuretic peptide increased, ventricular dysfunction, left ventricular dysfunction, right ventricular dysfunction, cardiac failure, cardiac failure acute, cardiac failure chronic, cardiac failure congestive, cardiomyopathy, congestive cardiomyopathy, diastolic dysfunction, ejection fraction decreased, ventricular failure, left ventricular failure, right ventricular failure, and ventricular hypokinesis.
d Excludes gastrointestinal bleeding and CNS bleeding; these ADRs are reported under the gastrointestinal disorders system organ class and the nervous system disorders system organ class, respectively.
e Includes drug eruption, erythema, erythema multiforme, erythrosis, exfoliative rash, generalized erythema, genital rash, heat rash, milia, miliaria, pustular psoriasis, rash, rash erythematous, rash follicular, rash generalized, rash macular, rash maculopapular, rash papular, rash pruritic, rash pustular, rash vesicular, skin exfoliation, skin irritation, toxic skin eruption, urticaria vesiculosa, and vasculitic rash.
f Includes gravitational edema, localized edema, edema peripheral.
g Includes conjunctival edema, eye edema, eye swelling, eyelid edema, face edema, lip edema, macular edema, edema mouth, orbital edema, periorbital edema, swelling face.
h Includes fluid overload, fluid retention, gastrointestinal edema, generalized edema, edema, edema due to cardiac disease, perinephric effusion, post procedural edema, visceral edema.
Postmarketing Experience: The following additional adverse reactions have been identified during post approval use of SPRYCEL. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. (See Table 9.)

Click on icon to see table/diagram/image
Register or sign in to continue
Asia's one-stop resource for medical news, clinical reference and education
Sign up for free
Already a member? Sign in