DASATINIB-TEVA FC TABLET 50MG [SIN16730P]

Product Info

DASATINIB-TEVA FC TABLET 50MG

[SIN16730P]

4 INDICATIONS AND USAGE

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.

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.

5 DOSAGE AND ADMINISTRATION

5.1 Dosage of Dasatinib in Adult Patients
The recommended starting dosage of Dasatinib for chronic phase CML in adults is 100 mg administered orally once daily. The recommended starting dosage of Dasatinib for accelerated phase CML, myeloid or lymphoid blast phase CML, or Ph+ ALL in adults is 140mg, administered orally once daily. Tablets should not be crushed or cut; they should be swallowed whole. Dasatinib can be taken with or without a meal, either in the morning or in the evening.

5.2 Dosage of Dasatinib 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 (10.3) and Clinical Pharmacology (13) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

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

Refer to Section 5.4 for recommendations on dose escalation in adults with CML and Ph+ ALL, and pediatric patients with CML.

5.3 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 Dasatinib dose increase. If the dose of Dasatinib is increased, monitor the patient carefully for toxicity [see Drug Interactions (9.2) – 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 Dasatinib must be administered with a strong CYP3A4 inhibitor, consider a dose decrease to:

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

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

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

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

These reduced doses of Dasatinib 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 Dasatinib is not tolerated after dose reduction, either discontinue the strong CYP3A4 inhibitor or interrupt Dasatinib until the inhibitor is discontinued. Allow a washout period of approximately 1 week after the inhibitor is stopped before the Dasatinib dose is increased. [See Drug Interactions (9.1) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.]

5.4 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 140mg once daily (chronic phase CML) or 180mg 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 120mg once daily (see Table 2 below). Dose escalation is not recommended for pediatric patients with Ph+ ALL, where Dasatinib is administered in combination with chemotherapy.

Escalate the Dasatinib 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.

5.5 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 Dasatinib 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 Dasatinib 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 Dasatinib 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 Dasatinib may be considered.

Non-hematological adverse reactions
If a moderate (Grade 2) non-hematologic adverse reaction develops with Dasatinib,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 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 severity and recurrence of the event [See Warnings and Precautions (7) – 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 100mg once daily, dose reduction to 80mg once daily with further reduction from 80mg once daily to 50mg once daily, if needed, is recommended. For adult patients with advanced phase CML or Ph+ ALL who received 140mg once daily, dose reduction to 100mg once daily with further reduction from 100mg once daily to 50mg 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 Dasatinib. Dose reduction recommendations are described in Table 5.

5.6 Duration of Treatment
In clinical studies, treatment with Dasatinib 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 Dasatinib in pediatric patients with Ph+ ALL was administered for a maximum duration of 2 years [see Dosage and Administration (5.2) and Clinical Studies (15) – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information].

6 CONTRAINDICATIONS

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