SPRYCEL TABLETS 70MG [SIN13352P]

Product Info

SPRYCEL TABLETS 70MG

[SIN13352P]

1 INDICATIONS AND USAGE

SPRYCEL® (dasatinib) is indicated for the treatment of adult patients with

• newly diagnosed Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase.

• chronic, accelerated, or myeloid or lymphoid blast phase 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.

SPRYCEL® (dasatinib) is indicated for the treatment of pediatric patients with

• newly diagnosed Ph+ CML in chronic phase or Ph+ CML-CP resistant or intolerant to prior therapy including imatinib.

• newly diagnosed Ph+ ALL in combination with chemotherapy.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage of SPRYCEL in Adult Patients

The recommended starting dosage of SPRYCEL (dasatinib) for chronic phase CML in adults 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 in adults 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.

2.2 Dosage of SPRYCEL in Pediatric Patients with CML or Ph+ ALL

The recommended starting dosage for pediatrics is based on body weight as shown in Table 1. The recommended dose should be administered orally once daily with or without food. Recalculate the dose every 3 months based on changes in body weight, or more often if necessary.

Do not crush, cut or chew tablets. Swallow tablets whole. There are additional administration considerations for pediatric patients who have difficulty swallowing tablets whole. Dispersal of tablets shows a reduction in exposure of dasatinib based on limited clinical data [see Use in Specific Populations (8.3) and Clinical Pharmacology (11) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

There is no experience with SPRYCEL treatment in children under 1 year of age.

Refer to Section 2.4 for recommendations on dose escalation in adults with CML and Ph+ ALL, and pediatric patients with CML.

2.3 Dose Modification

Strong CYP3A4 inducers: Avoid the use of concomitant strong CYP3A4 inducers and St. John’s wort. If patients must be coadministered a strong CYP3A4 inducer, consider a SPRYCEL dose increase. If the dose of SPRYCEL is increased, monitor the patient carefully for toxicity [see Drug Interactions (7.2) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

Strong CYP3A4 inhibitors: Avoid the use of concomitant strong CYP3A4 inhibitors and grapefruit juice. Recommend selecting an alternate concomitant medication with no or minimal enzyme inhibition potential, if possible. If SPRYCEL must be administered with a strong CYP3A4 inhibitor, consider a dose decrease to:

• 40 mg daily for patients taking SPRYCEL 140 mg daily.

• 20 mg daily for patients taking SPRYCEL 100 mg daily.

• 20 mg daily for patients taking SPRYCEL 70 mg daily.

For patients taking SPRYCEL 60 mg or 40 mg daily, consider interrupting SPRYCEL until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before reinitiating SPRYCEL.

These reduced doses of SPRYCEL are predicted to adjust the area under the curve (AUC) to the range observed without CYP3A4 inhibitors; however, clinical data are not available with these dose adjustments in patients receiving strong CYP3A4 inhibitors. If SPRYCEL is not tolerated after dose reduction, either discontinue the strong CYP3A4 inhibitor or interrupt SPRYCEL until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before the SPRYCEL dose is increased. [See Drug Interactions (7.1) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

2.4 Dose Escalation in Adults with CML and Ph+ ALL, and Pediatric Patients with CML

For adult patients with CML and Ph+ ALL, consider dose escalation to 140 mg once daily (chronic phase CML) or 180 mg once daily (advanced phase CML and Ph+ ALL) in patients who do not achieve a hematologic or cytogenetic response at the recommended starting dosage.

For pediatric patients with CML, consider dose escalation to 120 mg once daily (see Table 2 below). Dose escalation is not recommended for pediatric patients with Ph+ ALL, where SPRYCEL is administered in combination with chemotherapy.

Escalate the SPRYCEL dose as shown in Table 2 in pediatric patients with chronic phase CML who do not achieve a hematologic or cytogenetic response at the recommended starting dosage at the recommended time points, per current treatment guidelines, and who tolerate the treatment.

2.5 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 for adults and pediatric patients are summarized in Tables 3 and 4, respectively.

For pediatric patients with chronic phase CML, if Grade ≥ 3 neutropenia or thrombocytopenia recurs during complete hematologic response (CHR), interrupt SPRYCEL and resume at a reduced dose. Implement temporary dose reductions for intermediate degrees of cytopenia and disease response as needed.

For pediatric patients with Ph+ ALL, if neutropenia and/or thrombocytopenia result in a delay of the next block of treatment by more than 14 days, interrupt SPRYCEL and resume at the same dose level once the next block of treatment is started. If neutropenia and/or thrombocytopenia persist and the next block of treatment is delayed another 7 days, perform a bone marrow assessment to assess cellularity and percentage of blasts. If marrow cellularity is <10%, interrupt treatment with SPRYCEL until ANC >500/microlitre (0.5 x 10⁹/L), at which time treatment may be resumed at full dose. If marrow cellularity is >10%, resumption of treatment with SPRYCEL may be considered.

Non-hematological adverse reactions

If a moderate (Grade 2) non-hematologic adverse reaction develops with SPRYCEL, treatment should be interrupted until the adverse reaction has resolved or returned to baseline. The same dose should be resumed if this is the first occurrence and the dose should be reduced if this is a recurrent adverse reaction. If a severe (Grade 3 or 4) non-hematologic 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 severity and recurrence of the event [See Warnings and Precautions (5) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

For adult patients with chronic phase CML who received 100 mg once daily, dose reduction to 80 mg once daily with further reduction from 80 mg once daily to 50 mg once daily, if needed, is recommended. For adult patients with advanced phase CML or Ph+ ALL who received 140 mg once daily, dose reduction to 100 mg once daily with further reduction from 100 mg once daily to 50 mg once daily, if needed, is recommended.

For pediatric patients with chronic phase CML who develop non-hematologic adverse reactions, the dose reduction recommendations for hematologic adverse reactions that are described above should be followed.

For pediatric patients with Ph+ ALL, interrupt treatment for cases of grade ≥ 3 non-hematologic adverse reactions with the exception of liver function test abnormalities, and resume at a reduced dose when resolved to grade ≤1. For elevated direct bilirubin over 5 times the institutional upper limit of normal (ULN), interrupt treatment until improvement to baseline or grade ≤1. For elevated AST/ALT over 15 times the institutional ULN, interrupt treatment until improvement to baseline or grade <1. For recurrent liver function test abnormalities as above, reduce the dose if this adverse reaction recurs after reinitiation of SPRYCEL. Dose reduction recommendations are described in Table 5.

2.6 Duration of Treatment

In clinical studies, treatment with SPRYCEL in adults and in pediatric patients with chronic phase CML was continued until disease progression or until no longer tolerated by the patient. The effect of stopping treatment on long-term disease outcome after the achievement of a cytogenetic response (including complete cytogenetic response [CCyR]) or major molecular response (MMR and MR4.5) has not been established.

In clinical studies, treatment with SPRYCEL in pediatric patients with Ph+ ALL was administered for a maximum duration of 2 years [see Dosage and Administration (2.2) and Clinical Studies (13) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

4 CONTRAINDICATIONS

Hypersensitivity to the active substance or to any of the excipients.