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. The effectiveness of SPRYCEL is based on hematologic and cytogenetic response rates [see Clinical Studies]. There are no controlled trials demonstrating a clinical benefit, such as improvement in disease-related symptoms or increased survival.

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 [see Clinical Studies].

The recommended starting dosage of SPRYCEL (dasatinib) for chronic phase CML is 100 mg administered orally once daily (QD), either in the morning or in the evening. The recommended starting dosage of SPRYCEL for accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL is 140 mg/day administered orally in two divided doses (70 mg twice daily [BID]), one in the morning and one in the evening. Tablets should not be crushed or cut; they should be swallowed whole. SPRYCEL can be taken with or without a meal.

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.

Dose Modification

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 CYP3A4 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 concen- trations. 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 is recommended. If SPRYCEL must be administered with a strong CYP3A4 inhibitor, a dose decrease to 20 mg daily should be considered. If 20 mg/day is not tolerated, 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.]

Dose Escalation

In clinical studies of adult CML and Ph+ ALL patients, dose escalation to 140 mg once daily (chronic phase CML) or 100 mg twice 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

Myelosuppression

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

Non-hematological adverse reactions

If a severe non-hematological adverse reaction develops with SPRYCEL (dasatinib) 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 Tablets are available as 20-mg, 50-mg, or 70-mg white to off-white, biconvex, film-coated tablets. [See HOW SUPPLIED.]

SPRYCEL® (dasatinib) tablets are available as described in Table 11.

Table 11: SPRYCEL Trade Presentations

Storage

SPRYCEL tablets should be stored at 25° C (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 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 crushed or broken, pharmacy and clinical personnel should wear disposable chemotherapy gloves. Personnel who are pregnant should avoid exposure to crushed or broken tablets.

REFERENCES

1. Preventing Occupational Exposures to Antineoplastic and Other Hazardous Drugs in Health Care Settings. NIOSH Alert 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999, http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html.

3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. (2006) 63:1172-1193.

4. Polovich M, White JM, Kelleher LO (eds). 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd ed). Pittsburgh, PA: Oncology Nursing Society.

Manufactured by: Bristol-Myers Squibb Company, Princeton, NJ 08543 USA. Rev November 2007. FDA Rev date: 11/8/2007

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