Advanced gastrointestinal stromal tumour (GIST)

Active Ingredient: Ripretinib

Indication for Ripretinib

Population group: only adults (18 years old or older)
Therapeutic intent: Curative procedure

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:

150 mg once daily

For:

Route of admnistration

Oral

Defined daily dose

150 - 150 mg

Dosage regimen

From 150 To 150 mg once every day

Detailed description

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.

Posology adjustments

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

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.

Dosage considerations

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.

Active ingredient

Ripretinib

Ripretinib is a novel tyrosine kinase inhibitor that inhibits KIT proto-oncogene receptor tyrosine kinase and PDGFRA kinase, including wild type, primary, and secondary mutations. Ripretinib also inhibits other kinases in vitro, such as PDGFRB, TIE2, VEGFR2, and BRAF.

Read more about Ripretinib

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