Instructions for Ripretinib

1. Generic name: Ripetinib

Product name:Qinlock

All names: Ripretinib, Ripretinib, Ripretinib, Ripretinib, Qingle

2. Indications:

Ripretinib is suitable for the treatment of adult patients with advanced gastrointestinal stromal tumors (GIST) who have been treated with three or more kinase inhibitors (including imatinib).

3. Usage and dosage:

1. Recommended dose: The recommended dose of repetinib is 150 mg once a day until disease progression or unacceptable toxicity occurs. If less than 8 hours have passed since the missed scheduled dose, patients are advised to take the missed dose. If a patient experiences vomiting after taking repetinib, do not take additional doses but continue with the next scheduled dose.

2. Dose adjustment: If the patient experiences adverse reactions during treatment with repetinib, the dose can be reduced to 100 mg orally once daily. Patients who cannot tolerate 100 mg orally once daily should permanently discontinue repetinib.

For example: If symptoms of grade 3 hypertension occur, repetinib should be discontinued until symptoms resolve and blood pressure is controlled. If blood pressure is controlled at ≤1 level or baseline, resume the same dose of repetitinib; otherwise, reduce the dose and resume. If grade 3 hypertension recurs, discontinue repetinib until symptoms resolve and blood pressure is controlled, then resume repetinib at a reduced dose.

3. Combined medication:

Avoid concomitant use of moderate CYP3A inducers during repetinib treatment. If this cannot be avoided, increase the dosing frequency from the recommended dose of 150 mg once daily to 150 mg twice daily during coadministration. If the concomitant moderate CYP3A inducer is discontinued, resume the dose of repectinib to 150 mg once daily 14 days after discontinuation of the moderate CYP3A inducer.

4. Adverse reactions:

The most common adverse reactions of repetinib (≥20%) are alopecia, fatigue, nausea, abdominal pain, constipation, myalgia, diarrhea, decreased appetite, palmar-plantar erythrodysesthesia syndrome (PPFS) and vomiting. The most common grade 3 or 4 laboratory abnormalities (≥4%) were elevated lipase and decreased phosphate. Clinically relevant adverse reactions occurring in <10% of patients include cardiac ischemic events (including acute coronary syndrome and fatal cardiac arrest or myocardial infarction), photosensitivity.

5. Storage:

Repetinib is stored20°C to 25°C (68°F to 77°F); excursions allowed between 15°C and 30°C (59°F to 86°F) Store in the original container with desiccant to protect it from moisture and light.

6. Special groups:

1. Women: Taking rapitinib may cause harm to the fetus. Women of reproductive potential should use effective contraceptive measures during treatment and within 1 week after the last dose. Do not breastfeed during treatment with ripatinib and within 1 week after the last dose.

2. Men: Men who are female partners of potential reproductive potential should use effective contraceptive measures during treatment and within 1 week after the last dose.

3. Hepatic impairment: Dosage adjustment is not recommended for patients with hepatic impairment (Child-Pugh Class A, B or C).

7. Mechanism of action:

Repetinib is a tyrosine kinase inhibitor that inhibitsKIT proto-oncogene receptor tyrosine kinase (KIT) and platelet-derived growth factor receptor A (PDGFRA) kinase, including wild-type, primary and secondary mutations. Ripetinib also inhibits other kinases in vitro, such as PDGFRB, TIE2, VEGFR2 and BRAF

8. Notes:

Patients should be aware of the occurrence of palmar-plantar dysesthesia syndrome, new primary cutaneous malignancies, hypertension, cardiac dysfunction, impaired wound healing, photosensitivity and other events during treatment with repetinib.

The original drug of Ripetinib has been marketed in China and has been approved by the National Medical Insurance Bureau to enter the scope of Class B medical insurance, but it is limited to patients who meet the indications. The price of each box of 50mg*30 tablets may be around 30,000 yuan. The expensive price may increase the pressure on families with heavy financial burdens. U.S. versionRepetinibSpecifications launched overseasThe price of each box of 50mg*90 tablets may be around RMB 77,000 (the price may fluctuate due to exchange rates). The ingredients of foreign original drugs are basically the same as those of domestic original drugs. Currently, there is no generic drug of Ripetinib produced and marketed overseas. For specific prices and drug information, please consult Yaode’s medical consultant.