"The U.S. Food and Drug Administration today approved Iclusig (ponatinib) to treat adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases."...
SPRYCEL® (dasatinib) is indicated for the treatment of adults with
- newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase. The effectiveness of SPRYCEL is based on cytogenetic response and major molecular response rates [see Clinical Studies]. The trial is ongoing and further data will be required to determine long-term outcome.
- chronic, accelerated, or myeloid or lymphoid blast phase Ph+ CML with resistance or intolerance to prior therapy including imatinib.
- Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ALL) with resistance or intolerance to prior therapy.
DOSAGE AND ADMINISTRATION
The recommended starting dosage of SPRYCEL for chronic phase CML is 100 mg administered orally once daily. The recommended starting dosage of SPRYCEL for accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL is 140 mg administered orally once daily. Tablets should not be crushed or cut; they should be swallowed whole. SPRYCEL can be taken with or without a meal, either in the morning or in the evening.
In clinical studies, treatment with SPRYCEL was continued until disease progression or until no longer tolerated by the patient. The effect of stopping treatment after the achievement of a complete cytogenetic response (CCyR) has not been investigated.
Concomitant Strong CYP3A4 inducers: The use of concomitant strong CYP3A4 inducers may decrease dasatinib plasma concentrations and should be avoided (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, phenobarbital). St. John's Wort may decrease dasatinib plasma concentrations unpredictably and should be avoided. If patients must be coadministered a strong CYP3 A4 inducer, based on pharmacokinetic studies, a SPRYCEL dose increase should be considered. If the dose of SPRYCEL is increased, the patient should be monitored carefully for toxicity [see DRUG INTERACTIONS].
Concomitant Strong CYP3A4 inhibitors: CYP3A4 inhibitors (eg, ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole) may increase dasatinib plasma concentrations. Grapefruit juice may also increase plasma concentrations of dasatinib and should be avoided.
Selection of an alternate concomitant medication with no or minimal enzyme inhibition potential, if possible, is recommended. If SPRYCEL must be administered with a strong CYP3A4 inhibitor, a dose decrease should be considered. Based on pharmacokinetic studies, a dose decrease to 20 mg daily should be considered for patients taking SPRYCEL 100 mg daily. For patients taking SPRYCEL 140 mg daily, a dose decrease to 40 mg daily should be considered. These reduced doses of SPRYCEL are predicted to adjust the area under the curve (AUC) to the range observed without CYP3A4 inhibitors. However, there are no clinical data with these dose adjustments in patients receiving strong CYP3A4 inhibitors. If SPRYCEL is not tolerated after dose reduction, either the strong CYP3A4 inhibitor must be discontinued, or SPRYCEL should be stopped until treatment with the inhibitor has ceased. When the strong inhibitor is discontinued, a washout period of approximately 1 week should be allowed before the SPRYCEL dose is increased. [See DRUG INTERACTIONS.]
In clinical studies of adult CML and Ph+ ALL patients, dose escalation to 140 mg once daily (chronic phase CML) or 180 mg once daily (advanced phase CML and Ph+ ALL) was allowed in patients who did not achieve a hematologic or cytogenetic response at the recommended starting dosage.
Dose Adjustment for Adverse Reactions
In clinical studies, myelosuppression was managed by dose interruption, dose reduction, or discontinuation of study therapy. Hematopoietic growth factor has been used in patients with resistant myelosuppression. Guidelines for dose modifications are summarized in Table 1.
Table 1: Dose Adjustments for Neutropenia and Thrombocytopenia
|Chronic Phase CML
(starting dose 100 mg
|ANC* < 0.5 × 109/L
Platelets < 50 × 109/L
|Accelerated Phase CML, Blast Phase CML and Ph+ ALL (starting dose 140 mg once daily)||ANC* < 0.5 × 109/L or Platelets < 10 × 109/L||
|*ANC: absolute neutrophil count|
Non-hematological adverse reactions
If a severe non-hematological adverse reaction develops with SPRYCEL use, treatment must be withheld until the event has resolved or improved. Thereafter, treatment can be resumed as appropriate at a reduced dose depending on the initial severity of the event.
Dosage Forms and Strengths
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.
SPRYCEL® (dasatinib) tablets are available as described in Table 9.
Table 9: SPRYCEL Trade Presentations
|NDC Number||Strength||Description||Tablets per Bottle|
|0003-0527-11||20 mg||white to off-white, biconvex, round, film-coated tablet with "BMS" debossed on one side and "527" on the other side||60|
|0003-0528-11||50 mg||white to off-white, biconvex, oval, film-coated tablet with "BMS" debossed on one side and "528" on the other side||60|
|0003-0524-11||70 mg||white to off-white, biconvex, round, film-coated tablet with "BMS" debossed on one side and "524" on the other side||60|
|0003-0855-22||80 mg||white to off-white, biconvex, triangle, film-coated tablet with "BMS" and "80" (BMS over 80) debossed on one side and "855" on the other side||30|
|0003-0852-22||100 mg||white to off-white, biconvex, oval, film-coated tablet with "BMS 100" debossed on one side and "852" on the other side||30|
|0003-0857-22||140 mg||white to off-white, biconvex, round, film-coated tablet with "BMS" and "140" (BMS over 140) debossed on one side and "857" on the other side||30|
SPRYCEL® tablets should be stored at 20° to 25°C (68° to 77°F); excursions permitted between 15°-30°C (59°-86°F) [see USP Controlled Room Temperature].
Handling and Disposal
Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published [see References].
SPRYCEL (dasatinib) tablets consist of a core tablet (containing the active drug substance), surrounded by a film coating to prevent exposure of pharmacy and clinical personnel to the active drug substance. However, if tablets are inadvertently crushed or broken, pharmacy and clinical personnel should wear disposable chemotherapy gloves. Personnel who are pregnant should avoid exposure to crushed or broken tablets.
Manufactured by: Bristol-Myers Squibb Company Princeton, NJ 08543 USA.
Last reviewed on RxList: 10/21/2011
This monograph has been modified to include the generic and brand name in many instances.
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