Qinlock Ripretinib Tablets

1. Indications and Usage
Gastrointestinal Stromal Tumor (GIST):
Indicated for the treatment of adult patients with advanced gastrointestinal stromal tumor (GIST) who have received prior treatment with three or more kinase inhibitors, including imatinib.
Note: This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
2. Dosage and Administration
Route of Administration:
For Oral Use ONLY.
Recommended Dosage:
Standard Dose: 150 mg once daily.
Administration Instructions:
Take with or without food.
Swallow tablets whole; do not crush or chew.
If a dose is missed, take it as soon as possible within 6 hours of the scheduled time. If more than 6 hours have passed, skip the missed dose and resume at the next scheduled time.
If vomiting occurs, do not take an extra dose; resume at the next scheduled time.
3. Mechanism of Action
Switch-Control Master Switch Inhibitor:
Ripretinib is a novel, broad-spectrum, small-molecule kinase inhibitor that functions as a “switch-control” inhibitor of KIT and PDGFRA.
Action:
It inhibits both the activation and switch control modes of these kinases, thereby suppressing downstream signaling pathways (such as MAPK and PI3K/AKT) that drive tumor cell proliferation. It is particularly effective against a broad spectrum of primary and secondary resistance mutations.
4. Safety and Warnings
Hypertension:
Can cause hypertension, which may be severe. Monitor blood pressure regularly and manage with antihypertensive therapy as needed.
Cardiac Failure:
Can cause cardiac failure (e.g., decreased left ventricular ejection fraction). Monitor cardiac function (e.g., echocardiogram) at baseline and periodically during treatment.
Hemorrhage:
Can cause severe and fatal hemorrhagic events, including gastrointestinal bleeding.
Fetal Toxicity:
Can cause fetal harm. Effective contraception is required during treatment and for at least 3 weeks after the final dose.
5. Adverse Reactions
Most Common:
General: Fatigue (41%), Musculoskeletal pain (37%).
Dermatologic: Hair color changes (36%), Alopecia (35%), Palmar-plantar erythrodysesthesia syndrome (PPES) (24%).
Gastrointestinal: Nausea (33%), Diarrhea (25%), Vomiting (24%), Constipation (22%), Abdominal pain (21%).
6. Drug Interactions
Metabolic Pathway:
Ripretinib is primarily metabolized by CYP3A4.
Strong CYP3A4 Inhibitors (e.g., Itraconazole, Clarithromycin): Avoid co-administration. If unavoidable, reduce the ripretinib dose.
Strong CYP3A4 Inducers (e.g., Rifampin): Avoid co-administration as they significantly decrease ripretinib exposure.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Ripretinib (as phosphate).
Appearance: White to off-white, oval-shaped, film-coated tablets.
Storage: Store at 20°C–25°C (68°F–77°F).