Ripretinib is a kinase inhibitor specifically indicated for adult patients with advanced gastrointestinal stromal tumors who have previously received three or more kinase inhibitors.

I. Indications and Target Population

1. Core Indication

(1) Ripretinib is indicated for adult patients with advanced gastrointestinal stromal tumors (GIST).

(2) Patients must have received at least three prior kinase inhibitors including imatinib, and have experienced disease progression or intolerance.

2. Therapeutic Positioning

(1) It serves as a later-line treatment option for refractory GIST after failure of multi-line targeted therapy.

(2) It is not indicated for newly diagnosed or early-stage GIST patients who have not undergone the above treatment pathway.

3. Non‑eligible Populations

(1) Safety and efficacy in children and adolescents have not been established; use is not recommended.

(2) Patients with a baseline ejection fraction below 50% have not been evaluated for safety; caution is advised.

II. Standard Dosage and Administration Guidelines

1. Recommended Dose

(1) 150 mg (i.e., three 50‑mg tablets) orally once daily.

(2) Continue until disease progression or unacceptable toxicity occurs, at which point discontinuation may be considered.

2. Administration Instructions

(1) May be taken with or without food, unaffected by meals.

(2) Swallow tablets whole; do not chew, crush, or split.

(3) It is recommended to take at the same time each day to maintain stable plasma concentrations.

3. Missed Dose and Vomiting

(1) If a dose is missed within 8 hours, take it as soon as possible; if more than 8 hours have passed, skip the missed dose and resume the next scheduled dose.

(2) If vomiting occurs after dosing, do not take an extra dose; continue with the next scheduled administration.

III. Dose Modifications in Special Situations

1. Dose Reduction for Adverse Reactions

(1) For moderate to severe adverse reactions, the first dose reduction is to 100 mg (2 tablets) daily.

(2) If 100 mg daily is still not tolerated, permanently discontinue treatment; do not attempt lower doses.

2. Dose Frequency Increase with Concomitant Moderate CYP3A4 Inducers

(1) Concomitant use with moderate CYP3A4 inducers (e.g., certain anticonvulsants, antivirals) should be avoided.

(2) If unavoidable, increase the dosing frequency from once daily to twice daily (150 mg each time) until 14 days after the inducer is discontinued, then resume once‑daily dosing.

3. Use in Special Populations

(1) No dose adjustment is required for patients with hepatic impairment (Child‑Pugh A, B, or C).

(2) Elderly patients (≥65 years) do not require dose adjustment based on age alone, but tolerability should be closely monitored.

(3) Data in patients with severe renal impairment are limited; use with greater caution.