Active Ingredient: Ripretinib
Ripretinib is indicated for the treatment of adult patients with advanced gastrointestinal stromal tumour (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Oral
150 - 150 mg
From 150 To 150 mg once every day
The recommended dose is 150 mg ripretinib (three 50 mg tablets) taken once daily at the same time each day with or without food.
If the patient misses a dose of ripretinib within 8 hours of the time it is usually taken, the patient should be instructed to take it as soon as possible and then take the next dose at the regularly scheduled time. If a patient misses a dose by more than 8 hours of the time it is usually taken, the patient should be instructed not to take the missed dose and simply resume the usual dosing schedule on the following day.
In case of vomiting after ripretinib administration, the patient should not take a replacement dose and should resume the dosing schedule the next day at the usual time.
Treatment with ripretinib should continue as long as benefit is observed or until unacceptable toxicity.
Dose interruptions or dose reductions may be required based on individual safety and tolerability. The recommended dose reduction for adverse reactions is 100 mg orally, once daily.
Ripretinib should be permanently discontinued in patients who are unable to tolerate 100 mg orally once daily. The recommended dose modifications for ripretinib for adverse reactions are provided in Table 1.
Table 1. Recommended dose modifications for adverse reactions:
| Adverse reaction | Severitya | Ripretinib dose modifications |
|---|---|---|
| Palmar-Plantar Erythrodysaesthesia Syndrome (PPES) | Grade 2 | • Withhold until Grade ≤1 or baseline. If recovered within 7 days, resume at same dose; otherwise resume at reduced dose. • Consider re-escalating if maintained at Grade ≤1 or baseline for at least 28 days. • If PPES recurs, withhold until Grade ≤1 or baseline and then resume at a reduced dose regardless of time to improvement. |
| Grade 3 | • Withhold for at least 7 days or until Grade ≤1 or baseline (maximum 28 days). Resume at a reduced dose. • Consider re-escalating if maintained at Grade ≤1 or baseline for at least 28 days. | |
| Hypertension | Grade 3 | • If symptomatic, withhold until symptoms have resolved and blood pressure is controlled. • If blood pressure is controlled to Grade ≤1 or baseline, resume at the same dose; otherwise, resume at reduced dose. • If Grade 3 hypertension recurs, withhold until symptoms have resolved and blood pressure is controlled. Resume at a reduced dose. |
| Grade 4 | Permanently discontinue. | |
| Left ventricular systolic dysfunction | Grade 3 or 4 | Permanently discontinue. |
| Arthralgia or myalgia | Grade 2 | • Withhold until Grade ≤1 or baseline. If recovered within 7 days, resume at same dose; otherwise resume at reduced dose. • Consider re-escalating if maintained at Grade ≤1 or baseline for at least 28 days. • If arthralgia or myalgia recurs, withhold until Grade ≤1 or baseline and then resume at a reduced dose regardless of time to improvement. |
| Grade 3 | • Withhold for at least 7 days or until Grade ≤1 or baseline (maximum of 28 days). Resume at a reduced dose. • Consider re-escalating if maintained at Grade ≤1 or baseline for at least 28 days. | |
| Other adverse reactions | Grade 3 or 4 | • Withhold until Grade ≤1 or baseline (maximum 28 days), and then resume at a reduced dose; otherwise permanently discontinue. • Consider re-escalating if no recurrence of the adverse reaction for at least 28 days. • If Grade 3 or 4 recurs, permanently discontinue. |
a Graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03 (NCI CTCAE v4.03).
Concomitant medicinal products that are strong or moderate inducers of CYP3A should be avoided. If a strong or moderate CYP3A inducer must be co-administered, the ripretinib dosing frequency may be increased during the co-administration period. For strong inducers, the dose may be increased from 150 mg once daily to 150 mg twice daily. For patients taking ripretinib twice daily, if the patient misses a dose within 4 hours of the time it is usually taken, the patient should be instructed to take the missed dose as soon as possible and then take the next dose at the regularly scheduled time. If a patient misses a dose by more than 4 hours of the time it is usually taken, the patient should be instructed not to take the missed dose and simply resume the usual dosing schedule. Close monitoring of overall efficacy and safety is recommended in these patients.
The tablets should be taken at the same time each day with or without food.
Prescribers should instruct patients to swallow the tablets whole and not to chew, split, or crush them. Patients should not ingest the tablets if they are broken, cracked, or otherwise not intact as the potential effects of these alterations have not been evaluated.
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