Posology : מינונים

2         DOSAGE AND ADMINISTRATION
2.1       Recommended Dosage
The recommended dosage of QINLOCK is 150 mg orally once daily with or without food until disease progression or unacceptable toxicity.
Instruct patients to swallow tablets whole.
Advise patients to take QINLOCK at the same time each day.
Advise patients to take a missed dose if less than 8 hours have passed since the missed scheduled dose.
Advise patients not to take an additional dose if vomiting occurs after taking QINLOCK and to continue with their next scheduled dose.
2.2       Dosage Modifications for Adverse Reactions
The recommended dose reduction for adverse reactions is:
•   QINLOCK 100 mg orally once daily.
Permanently discontinue QINLOCK in patients who are unable to tolerate 100 mg orally once daily.
The recommended dosage modifications of QINLOCK for adverse reactions are provided in Table 1.



Table 1:          Recommended Dosage Modifications for QINLOCK for Adverse Reactions Adverse Reaction                  Severitya                 QINLOCK Dosage Modifications Palmar-Plantar                    Grade 2                   •   Withhold QINLOCK until Grade ≤1 or baseline. If recovered within Erythrodysesthesia Syndrome                                     7 days, resume QINLOCK at same dose; otherwise resume at reduced (PPES) [see Warnings and                                        dose.
Precautions (5.1)]                                          • Consider re-escalating QINLOCK if maintained at Grade ≤1 or baseline for at least 28 days.
• If PPES recurs, withhold QINLOCK until Grade ≤1 or baseline and then resume QINLOCK at a reduced dose regardless of time to improvement.
Grade 3                   • Withhold QINLOCK for at least 7 days or until Grade ≤1 or baseline (maximum 28 days). Resume QINLOCK at a reduced dose.
• Consider re-escalating QINLOCK if maintained at Grade ≤1 or baseline for at least 28 days.
Hypertension [see Warnings and    Grade 3                   • If symptomatic, withhold QINLOCK until symptoms have resolved Precautions (5.3)]                                              and blood pressure is controlled.
• If blood pressure is controlled to Grade ≤1 or baseline, resume QINLOCK at the same dose; otherwise, resume QINLOCK at reduced dose.
• If Grade 3 hypertension recurs, withhold QINLOCK until symptoms have resolved and blood pressure is controlled. Resume QINLOCK at a reduced dose.
Grade 4                   Permanently discontinue QINLOCK.


Left Ventricular Systolic         Grade 3 or 4              Permanently discontinue QINLOCK.
Dysfunction [see Warnings and
Precautions (5.4)]
Arthralgia or Myalgia [see        Grade 2                   •    Withhold QINLOCK until Grade ≤1 or baseline. If recovered within Adverse Reactions (6.1)]                                         7 days, resume QINLOCK at same dose; otherwise resume QINLOCK at reduced dose.
• Consider re-escalating QINLOCK if maintained at Grade ≤1 or baseline for at least 28 days.
• If arthralgia or myalgia recurs, withhold QINLOCK until Grade ≤1 or baseline and then resume QINLOCK at a reduced dose regardless of time to improvement.
Grade 3               •     Withhold QINLOCK for at least 7 days or until Grade ≤1 or baseline (maximum of 28 days). Resume QINLOCK at a reduced dose.
• Consider re-escalating QINLOCK if maintained at Grade ≤1 or baseline for at least 28 days.
Other Adverse Reactions [see         Grade 3 or 4          •     Withhold QINLOCK until Grade ≤1 or baseline (maximum 28 days), Adverse Reactions (6.1)]                                         and then resume QINLOCK at a reduced dose; otherwise permanently discontinue.
• Consider re-escalating QINLOCK if no recurrence of the adverse reaction for at least 28 days.
• If Grade 3 or 4 recurs, permanently discontinue QINLOCK.
a
Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03).

2.3     Dose Modifications for Moderate CYP3A Inducers
Avoid concomitant use of moderate CYP3A inducers during QINLOCK treatment.
If a moderate CYP3A inducer cannot be avoided, increase the QINLOCK dosing frequency from the recommended dose of 150 mg once daily to 150 mg twice daily during the co-administration period. Monitor for clinical response and tolerability. If the concomitant moderate CYP3A inducer is discontinued, resume QINLOCK dosage back to 150 mg once daily 14 days after the discontinuation of the moderate CYP3A inducer. [see Drug Interactions (7.1) and Clinical Pharmacology (12.3)].