Product Description.:
BMS 100, 852
tablet , film-coated , off-white white , oval oblong
DebossedBiconvex
SPRYCEL? (dasatinib) is indicated for the treatment of adults with chronic, accelerated, or myeloid or lymphoid blast phase chronic myeloid leukemia (CML) with resistance or intolerance to prior therapy including imatinib.
SPRYCEL is also indicated for the treatment of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) with resistance or intolerance to prior therapy.
Myelosuppression:
* Treatment with SPRYCEL? (dasatinib) is associated with severe (NCI CTC Grade 3/4) thrombocytopenia, neutropenia, and anemia. Their occurrence is more frequent in advanced phase CML or Ph+ ALL than in chronic phase CML. Myelosuppression was reported in patients with normal baseline laboratory values as well as in patients with pre-existing laboratory abnormalities
o ? Complete blood counts (CBCs) should be performed weekly for the first 2 months and then monthly thereafter, or as clinically indicated
o ? In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study therapy
o ? Hematopoietic growth factor has been used in patients with resistant myelosuppression
Bleeding Related Events:
* SPRYCEL caused platelet dysfunction in vitro and thrombocytopenia in humans. Severe central nervous system (CNS) hemorrhage, including fatalities, occurred in 1% of patients
* Severe gastrointestinal (GI) hemorrhage occurred in 4% of patients and generally required treatment interruptions and transfusions
* Other cases of severe hemorrhage occurred in 2% of patients
* Most bleeding events were associated with severe thrombocytopenia
o ? Caution is advised in patients required to take medications that inhibit platelet function or anticoagulants
Fluid Retention:
* Fluid retention was severe in 10% of patients, including pleural and pericardial effusions reported in 7% and 1%, respectively. Severe ascites and generalized edema were each reported in <1% of patients. Severe pulmonary edema was reported in 1% of patients
o ? Patients who develop symptoms suggestive of pleural effusion such as dyspnea or dry cough should be evaluated by chest X-ray
o ? Severe pleural effusion may require thoracentesis and oxygen therapy
o ? Fluid retention was typically managed by supportive care measures that included diuretics or short courses of steroids
o ? Patients aged 65 years and older are more likely to experience fluid retention events and dyspnea
QT Prolongation:
* In vitro data suggest that SPRYCEL has the potential to prolong cardiac ventricular repolarization (QT interval)
* In 865 patients with leukemia from five single-arm studies, the mean changes in QTcF from baseline were 4?6 msec the upper 95% confidence intervals (CIs) for all mean changes from baseline were <7 msec
* Of the 2182 patients treated with SPRYCEL in clinical studies, 14 (<1%) patients had QTc prolongation as an adverse reaction. Twenty-one patients (1%) experienced a QTcF >500 msec
* SPRYCEL should be administered with caution to patients who have or may develop prolongation of QTc, including patients with hypokalemia, hypomagnesemia, or congenital long QT syndrome and patients taking anti-arrhythmic drugs, other medicinal products that lead to QT prolongation, and cumulative high-dose anthracycline therapy
o ? Hypokalemia or hypomagnesemia should be corrected prior to SPRYCEL administration
Pregnancy:
SPRYCEL may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of SPRYCEL in pregnant women. Women of childbearing potential should be advised of the potential hazard to the fetus and to avoid becoming pregnant. If SPRYCEL is used during pregnancy, or if the patient becomes pregnant while taking SPRYCEL, the patient should be apprised of the potential hazard to the fetus.
Drug Interactions:
SPRYCEL is a CYP3A4 substrate.
* Drugs that may increase SPRYCEL plasma concentrations are:
o ? Strong CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole)
o ? Concomitant use of SPRYCEL and drugs that inhibit CYP3A4 should be avoided
o ? If systemic administration of a potent CYP3A4 inhibitor cannot be avoided, close monitoring for toxicity and a SPRYCEL dose reduction or temporary discontinuation should be considered
o ? Grapefruit juice may also increase plasma concentrations of SPRYCEL and should be avoided
* Drugs that may decrease SPRYCEL plasma concentrations are:
o ? Strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rif
