Posology : מינונים

2           DOSAGE AND ADMINISTRATION

2.1         Patient Selection
Select patients for treatment with TABRECTA based on the presence of a mutation that leads to MET exon 14 skipping in tumor or plasma specimens [see Clinical Studies (14)]. If a mutation that leads to MET exon 14 skipping is not detected in a plasma specimen, test tumor tissue if feasible.
2.2         Recommended Dosage
The recommended dosage of TABRECTA is 400 mg orally twice daily with or without food, adequate hydration is recommended. Swallow TABRECTA tablets whole. Do not break, crush or chew the tablets.
If a patient misses or vomits a dose, instruct the patient not to make up the dose, but to take the next dose at its scheduled time.
2.3         Dosage Modifications for Adverse Reactions
The recommended dose reductions for the management of adverse reactions are listed in Table 1.
Table 1: Recommended TABRECTA Dose Reductions for Adverse Reactions
Dose reduction                            Dose and schedule
First                                             300 mg orally twice daily Second                                            200 mg orally twice daily Permanently discontinue TABRECTA in patients who are unable to tolerate 200 mg orally twice daily.
The recommended dosage modifications of TABRECTA for adverse reactions are provided in Table 2.



TAB API AUG24 V5                                                                                   USPI 03.24 Table 2: Recommended TABRECTA Dosage Modifications for Adverse Reactions 

Adverse reaction                        Severity                 Dosage modification Interstitial Lung Disease              Any grade                      Permanently discontinue (ILD)/Pneumonitis                                                     TABRECTA.
[see Warnings and Precautions (5.1)]
Increased ALT and/or AST without       Grade 3                        Withhold TABRECTA until increased total bilirubin                                             recovery to baseline ALT/AST.
[see Warnings and Precautions (5.2)]                                  If recovered to baseline within 7 days, then resume TABRECTA at the same dose; otherwise resume
TABRECTA at a reduced dose.
Grade 4                        Permanently discontinue
TABRECTA.



TAB API AUG24 V5                                                              USPI 03.24 Adverse reaction                                 Severity                             Dosage modification Increased ALT and/or AST with                   ALT and/or AST greater than 3 times          Permanently discontinue increased total bilirubin in the absence        ULN with total bilirubin greater than        TABRECTA.
of cholestasis or hemolysis                     2 times ULN
[see Warnings and Precautions (5.2)]


Increased total bilirubin without               Grade 2                                      Withhold TABRECTA until concurrent increased ALT and/or AST                                                          recovery to baseline bilirubin.
[see Warnings and Precautions (5.2)]                                                         If recovered to baseline within 7 days, then resume TABRECTA at the same dose; otherwise resume
TABRECTA at a reduced dose.
Grade 3                                      Withhold TABRECTA until recovery to baseline bilirubin.
If recovered to baseline within 7 days, then resume TABRECTA at a reduced dose; otherwise permanently discontinue
TABRECTA.
Grade 4                                      Permanently discontinue
TABRECTA.
Increased lipase or amylase                     Grade 3
[see Warnings and Precautions (5.3)]                                                         Withhold TABRECTA until ≤ Grade 2 or baseline.
If recovered to baseline or ≤
Grade 2 within 14 days,
resume TABRECTA at a reduced dose; otherwise permanently discontinue
TABRECTA.

Grade 4                                     Permanently discontinue
TABRECTA.
Pancreatitis                                    Grade 3 or Grade 4                          Permanently discontinue [see Warnings and Precautions (5.3)]                                                         TABRECTA.
Other Adverse Reactions                         Grade 2                                      Maintain dose level. If intolerable, consider withholding TABRECTA
[see Adverse Reactions (6.1)] until resolved, then resume
TABRECTA at a reduced dose.
Grade 3                                      Withhold TABRECTA until resolved, then resume TABRECTA at a reduced dose.
Grade 4                                      Permanently discontinue
TABRECTA.
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ILD, interstitial lung disease; ULN, upper limit of normal.
Grading according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.


TAB API AUG24 V5                                                                                       USPI 03.24  3          DOSAGE FORMS AND STRENGTHS
Tablets:
•    150 mg: pale orange brown, ovaloid, curved film-coated with beveled edges, unscored, debossed with ‘DU’ on one side and ‘NVR’ on the other side
•    200 mg: yellow, ovaloid, curved film-coated with beveled edges, unscored, debossed with ‘LO’ on one side and ‘NVR’ on the other side