Bristol-Myers Squibb's Sprycel

Bristol-Myers Squibb's Sprycel (dasatinib) tablets were approved by the FDA for the treatment of adults with newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in the chronic phase.

Bristol-Myers Squibb’s Sprycel (dasatinib) tablets are approved by the FDA for the treatment of adults with newly diagnosed Philadelphia chromosome—positive (Ph+) chronic myeloid leukemia (CML) in the chronic phase; adults with chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib; and adults with Ph+ acute lymphoblastic leukemia (ALL) with resistance or intolerance to prior therapy.¹

CML occurs when segments of 2 different chromosomes break apart and become attached to each other, resulting in an uncontrolled amount of abnormal white blood cells.² In 2012, an estimated 5430 new cases of CML will be diagnosed, and approximately 610 deaths will be attributed to CML.³ The cause for the genetic change that results in CML is still unknown.²

Pharmacology and Pharmacokinetics

Sprycel is an oral kinase inhibitor. It exerts its effect by inhibiting the growth of certain CML and ALL cell lines, thus allowing bone marrow to begin reproducing healthy red and white blood cells.^1,4

Sprycel is extensively metabolized by cytochrome P450 (CYP) 3A4. Neither age nor gender affected the pharmacokinetics of Sprycel.¹

Dosage and Administration

Patients with chronic phase CML should receive Sprycel 100 mg orally once daily. Patients with accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL should receive 140 mg orally once daily. Sprycel can be given without regard to food. The tablets should not be crushed or cut.¹

Clinical Trials

Sprycel received its approval based on an open-label, randomized clinical trial of 519 patients with newly diagnosed CML who used either Sprycel 100 mg once daily or imatinib 400 mg once daily. A significant difference was found between the 2 groups: 76.8% of the Sprycel arm achieved the primary end point of confirmed complete cytogenetic response within 12 months compared with 66.2% of the imatinib arm.¹

Contraindications, Warnings, and Precautions

There are no contraindications to treatment with Sprycel.

Complete blood counts should be monitored regularly as severe thrombocytopenia, neutropenia, and anemia may occur during treatment with Sprycel, requiring dose interruption or reduction. Central nervous system and gastrointestinal hemorrhages, including fatalities, have occurred during treatment with Sprycel. Most of these cases have been associated with severe thrombocytopenia; Sprycel should be used cautiously in patients taking anticoagulants or medications that inhibit platelet function. Sprycel has been associated with fluid retention, which in some cases has been severe, and should be monitored and managed with appropriate supportive care.

Sprycel should be used cautiously in patients with or who may develop QT prolongation. Cardiac adverse reactions have been reported during treatment with Sprycel, including cardiomyopathy, congestive heart failure, diastolic dysfunction, fatal myocardial infarction, and left ventricular dysfunction. Monitor patients for signs and symptoms of cardiac dysfunction and treat appropriately. Sprycel may increase the risk for pulmonary arterial hypertension, which may reverse upon discontinuation of treatment. Patients should be evaluated for underlying cardiopulmonary disease prior to beginning Sprycel and throughout treatment.

Sprycel should be used cautiously in patients with hepatic impairment. Sprycel is Pregnancy Category D and should not be used in women who are pregnant. Sprycel should not be used during breast-feeding. Sprycel is not approved for use in patients younger than 18 years.

Coadministration of Sprycel with CYP 3A4 inhibitors should be avoided, as this combination may increase the levels of Sprycel. If concomitant use cannot be avoided, consider a lower dose of Sprycel and monitor closely. Concomitant use of Sprycel with CYP3A4 inducers may decrease the levels of Sprycel. If coadministration cannot be avoided, consider a higher dose of Sprycel. Antacids may decrease Sprycel drug levels and should be spaced at least 2 hours before and/or after the Sprycel dose. Concomitant use of H2 antagonists or proton pump inhibitors should be avoided, as this combination may decrease the levels of Sprycel.

The most common adverse reactions (≥10%) in patients with newly diagnosed chronic phase CML were myelosuppression, fluid retention, diarrhea, headache, musculoskeletal pain, and rash. The most common adverse reactions (≥20%) in patients with resistance or intolerance to prior imatinib therapy included myelosuppression, fluid retention events, diarrhea, headache, dyspnea, skin rash, fatigue, nausea, and hemorrhage.¹

SPT

References

1. Sprycel complete prescribing information. Available at http://packageinserts.bms.com/pi/pi_sprycel.pdf Accessed April 2012.

2. FDA Approves SPRYCEL (dasatinib) as Treatment for Adult Patients with Newly Diagnosed Ph+ Chronic Myeloid Leukemia in Chronic Phase. Available at http://www.bms.com/news/press_releases/pages/default.aspx Accessed April 2012.

3. Leukemia --Chronic Myeloid (Myelogenous). Available at http://www.cancer.org/Cancer/Leukemia-ChronicMyeloidCML/DetailedGuide/index Accessed April 2012.

4. FDA approves additional medical indication for Sprycel. Available at http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm231409.htm Accessed April 2012.

About the Author

Monica Holmberg, PharmD, BCPS, earned her PharmD from the University of Connecticut and completed an ambulatory care residency at the Phoenix VA Healthcare System. Her practice has also included pediatrics and inpatient mental health. She resides in Phoenix, Arizona.