Source: European Medicines Agency (EU) Revision Year: 2021 Publisher: Deciphera Pharmaceuticals (Netherlands) B.V., Atrium Building Floor 4th, Strawinskylaan 3051, 1077ZX, Amsterdam, Netherlands
QINLOCK 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.
QINLOCK should be prescribed by physicians experienced in the administration of anticancer agents.
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 QINLOCK 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 QINLOCK administration, the patient should not take a replacement dose and should resume the dosing schedule the next day at the usual time.
Treatment with QINLOCK should continue as long as benefit is observed or until unacceptable toxicity (see section 4.4).
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.
QINLOCK should be permanently discontinued in patients who are unable to tolerate 100 mg orally once daily. The recommended dose modifications for QINLOCK for adverse reactions are provided in Table 1.
Table 1. Recommended dose modifications for adverse reactions:
| Adverse reaction | Severitya | QINLOCK dose modifications |
|---|---|---|
| Palmar-Plantar Erythrodysaesthesia Syndrome (PPES) (see sections 4.4 and 4.8) | 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 (see sections 4.4 and 4.8) | 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 (see sections 4.4 and 4.8) | Grade 3 or 4 | Permanently discontinue. |
| Arthralgia or myalgia (see section 4.8) | 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 (see section 4.8) | 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 (see sections 4.4 and 4.5). If a strong or moderate CYP3A inducer must be co-administered, the QINLOCK 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 QINLOCK 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.
No dose adjustment is recommended in patients with mild and moderate renal impairment (see section 5.2). Only limited clinical data are available in patients with severe renal impairment [creatinine clearance (CLcr) <30 mL/min]. A recommended dose of QINLOCK has not been established in patients with severe renal impairment (see section 5.2).
No dose adjustment is recommended in patients with mild hepatic impairment. A recommended dose of QINLOCK has not been established in patients with moderate or severe hepatic impairment. Close monitoring of overall safety is recommended in these patients (see section 5.2).
In clinical studies, no clinically relevant differences were observed between elderly (aged >65 years) and younger patients (aged ≤65 and ≥18 years) (see section 5.1).
The safety and efficacy of QINLOCK in children below 18 years of age have not been established (see section 5.1). No data are available.
QINLOCK is for oral use.
The tablets should be taken at the same time each day with or without food (see section 5.2).
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.
There is no known specific antidote for overdose with QINLOCK.
In the event of suspected overdose, QINLOCK must be discontinued immediately, best supportive care should be initiated by a medical professional, and the patient must be observed until clinical stabilisation.
3 years.
This medicinal product does not require any special temperature storage conditions.
Store in the original package and keep bottle tightly closed in order to protect from light and moisture.
White high-density polyethylene (HDPE) bottle with an aluminium foil/polyethylene (PE) tamper evident seal and a white polypropylene (PP) child-resistant closure, together with one PE desiccant canister containing silica gel. Each bottle contains 30 or 90 tablets.
Not all pack sizes may be marketed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
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