Posology : מינונים

2           DOSAGE AND ADMINISTRATION
2.1         Patient Selection for GIST Harboring PDGFRA Exon 18 Mutations
Select patients for treatment with AYVAKIT based on the presence of a PDGFRA exon 18 mutation [see Clinical Studies (12.1)].
2.2         Recommended Dosage for GIST Harboring PDGFRA Exon 18 Mutations
The recommended dosage of AYVAKIT is 300 mg orally once daily in patients with GIST. Continue treatment until disease progression or unacceptable toxicity.
2.3         Recommended Dosage for Advanced Systemic Mastocytosis
The recommended dosage of AYVAKIT is 200 mg orally once daily in patients with AdvSM. Continue treatment until disease progression or unacceptable toxicity.
Modify dosage for adverse reactions as outlined in Table 2 [see Dosage and Administration (2.5)].
2.4         Recommended Administration
Administer AYVAKIT orally on an empty stomach, at least 1 hour before or 2 hours after a meal [see Clinical Pharmacology (10.3)].
Do not make up for a missed dose within 8 hours of the next scheduled dose.
Do not repeat dose if vomiting occurs after AYVAKIT but continue with the next scheduled dose.
2.5         Dosage Modifications for Adverse Reactions
The recommended dose reductions and dosage modifications for adverse reactions are provided in Tables 1 and 2.
Table 1. Recommended Dose Reductions for AYVAKIT for Adverse Reactions Dose Reduction      GIST (starting dose 300 mg)*          AdvSM (starting dose 200 mg)** First               200 mg once daily                     100 mg once daily Second              100 mg once daily                     50 mg once daily Third               -                                     25 mg once daily *
Permanently discontinue AYVAKIT in patients with GIST who are unable to tolerate a dose of 100 mg once daily.
**
Permanently discontinue AYVAKIT in patients with AdvSM who are unable to tolerate a dose of 25 mg once daily.

Table 2. Recommended Dosage Modifications for AYVAKIT for Adverse Reactions Adverse Reaction                  Severity*               Dosage Modification Patients with GIST or AdvSM
Intracranial Hemorrhage [see      Any grade               Permanently discontinue AYVAKIT.
Warnings and Precautions
(5.1)]
Cognitive Effects [see Warnings   Grade 1                 Continue AYVAKIT at same dose or and Precautions (5.2)]                                    reduced dose or withhold until improvement to baseline or resolution. Resume at same dose or reduced dose.


Grade 2 or Grade 3        Withhold AYVAKIT until improvement to baseline, Grade 1, or resolution. Resume at same dose or reduced dose.
Grade 4                   Permanently discontinue AYVAKIT.
Other [see Adverse Reactions      Grade 3 or Grade 4        Withhold AYVAKIT until improvement to (6.1)]                                                      less than or equal to Grade 2. Resume at same dose or reduced dose, as clinically appropriate.
Patients with AdvSM
Thrombocytopenia [see             <50 X 109/L               Interrupt AYVAKIT until platelet count is Warnings and Precautions                                     ≥ 50 X 109/L, then resume at reduced dose (5.1)]                                                      (per Table 1). If platelet counts do not recover above 50 X 109/L, consider platelet support.
*Severity as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 
2.6       Concomitant Use of Strong or Moderate CYP3A Inhibitors
Avoid concomitant use of AYVAKIT with strong or moderate CYP3A inhibitors. If concomitant use with a moderate CYP3A inhibitor cannot be avoided, the starting dosage of AYVAKIT is as follows [see Drug Interactions (7.1)]:
• GIST: 100 mg orally once daily
• AdvSM: 50 mg orally once daily