Posology : מינונים

2          DOSAGE AND ADMINISTRATION

2.1        Recommended Dosage in Patients with Ph+ CML-CP, Previously Treated with Two or More TKIs
The recommended dose of SCEMBLIX is 80 mg taken orally once daily at approximately the same time each day or 40 mg orally twice daily at approximately 12-hour intervals. The recommended dose of SCEMBLIX is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after taking SCEMBLIX [see Clinical Pharmacology (12.2)].
Continue treatment with SCEMBLIX as long as clinical benefit is observed or until unacceptable toxicity occurs.
2.2        Recommended Dosage in Patients with Ph+ CML-CP with the T315I Mutation
The recommended dose of SCEMBLIX is 200 mg taken orally twice daily at approximately 12-hour intervals. The recommended dose of SCEMBLIX is taken orally without food. Avoid food consumption for at least 2 hours before and 1 hour after taking SCEMBLIX [see Clinical Pharmacology (12.2)].
2.3        Missed Dose
Once Daily Dosage Regimen: If a SCEMBLIX dose is missed by more than approximately 12 hours, skip the dose and take the next dose as scheduled.
Twice Daily Dosage Regimens: If a SCEMBLIX dose is missed by more than approximately 6 hours, skip the dose and take the next dose as scheduled.
2.4      Dosage Modifications
Dosage Modifications for Patients with Ph+ CML-CP, Previously Treated with Two or More TKIs For the management of adverse reactions, reduce the SCEMBLIX dose as described in Table 1.
Dosage Modifications for Patients with Ph+ CML-CP with the T315I Mutation For the management of adverse reactions, reduce the SCEMBLIX dose as described in Table 1.

Table 1: Recommended Dosage Reductions for SCEMBLIX for Adverse Reactions Dosage for Patients with CP-CML,                  Dosage for Patients with Ph+ CML-CP Dosage Reduction               Previously Treated with Two or More               with the T315I Mutation TKIs
First                              •   40 mg once daily                          160 mg twice daily OR
•   20 mg twice daily
Subsequent Reduction           Permanently discontinue SCEMBLIX in               Permanently discontinue SCEMBLIX in patients unable to tolerate 40 mg once daily      patients unable to tolerate 160 mg twice OR 20 mg twice daily.                             daily.
The recommended dosage modifications for the management of selected adverse reactions are shown in Table 2.


Table 2: SCEMBLIX Dosage Modification for the Management of Adverse Reactions Adverse Reaction                                             Dosage Modification Thrombocytopenia and/or neutropenia [see Warnings and Precautions (5.1)] ANC less than 1.0 x 109/L and/or PLT less than 50 x          Withhold SCEMBLIX until resolved to ANC greater than 109/L                                                        or equal to 1 x 109/L and/or PLT greater than or equal to 50 x 109/L.
If resolved:
•   Within 2 weeks: resume SCEMBLIX at starting dose.
•   After more than 2 weeks: resume SCEMBLIX at reduced dose.
For recurrent severe thrombocytopenia and/or neutropenia, withhold SCEMBLIX until resolved to ANC greater than or equal to 1 x 109/L and PLT greater than or equal to 50 x 109/L, then resume at reduced dose.
Asymptomatic amylase and/or lipase elevation [see Warnings and Precautions (5.2)] Elevation greater than 2.0 x ULN                             Withhold SCEMBLIX until resolved to less than 1.5 x ULN.
If resolved:
•   Resume SCEMBLIX at reduced dose. If events reoccur at reduced dose, permanently discontinue
SCEMBLIX.
If not resolved:
•   Permanently discontinue SCEMBLIX. Perform diagnostic tests to exclude pancreatitis.
Non-hematologic adverse reactions [see Warnings and Precautions (5.3, 5.4, 5.5)] Grade 31 or higher                                           Withhold SCEMBLIX until recovery to Grade 1 or less.
If resolved:
•    Resume SCEMBLIX at reduced dose.
If not resolved:
• Permanently discontinue SCEMBLIX.
Abbreviations: ANC, absolute neutrophil count; PLT, platelets; ULN, upper limit of normal.
1
Based on Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
2.5       Administration
Advise patients to swallow SCEMBLIX tablets whole. Do not break, crush, or chew the tablets.