Ayvakit Avapritinib Tablets

1. Indications and Usage
Gastrointestinal Stromal Tumors (GIST): Indicated for adult patients with unresectable or metastatic GIST who have a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including the D842V mutation.
2. Dosage and Administration
Recommended Dose: The recommended oral dose is 300 mg once daily.
Administration: Take on an empty stomach, at least 1 hour before or 2 hours after a meal. Continue therapy until disease progression or unacceptable toxicity.
Missed Dose: Do not take a missed dose if it is within 8 hours of the next scheduled dose. Take the next dose at the regularly scheduled time. Do not double the dose.
Dose Modification: For intolerable adverse reactions, withhold or permanently discontinue based on severity. If co-administered with moderate CYP3A inhibitors, reduce the starting dose to 100 mg once daily.
3. Mechanism of Action
Kinase Inhibition: Avapritinib is a selective tyrosine kinase inhibitor that specifically targets mutant PDGFRA and wild-type KIT.
Pathway Blockade: By binding to the ATP-binding pocket of these receptors, it inhibits downstream signaling pathways, thereby blocking tumor cell proliferation and survival.
4. Safety and Warnings
Intracranial Hemorrhage: Serious and fatal intracranial hemorrhage has been reported. Monitor platelet counts and coagulation parameters regularly.
CNS Effects: Cognitive impairment, including memory impairment, cognitive disorder, confusion, and encephalopathy, is a common adverse reaction.
Fluid Retention: Peripheral edema, facial edema, orbital edema, and ascites may occur.
Embryo-Fetal Toxicity: Can cause fetal harm. Effective contraception is required during treatment and for 6 weeks after the final dose.
5. Adverse Reactions and Clinical Research
Adverse Reactions: The most common adverse reactions (≥20%) include nausea, fatigue, anemia, periorbital edema, facial edema, hyperbilirubinemia, diarrhea, vomiting, peripheral edema, increased lacrimation, and decreased appetite.
Clinical Research: Clinical trials have demonstrated significant objective response rates and durable disease control in patients with PDGFRA exon 18-mutated GIST, particularly those with limited treatment options.
6. Drug Interactions
CYP3A Inhibitors: Concomitant use with strong or moderate CYP3A inhibitors (e.g., ketoconazole, clarithromycin) increases avapritinib exposure.
CYP3A Inducers: Concomitant use with strong or moderate CYP3A inducers (e.g., rifampin, phenytoin) decreases avapritinib exposure and should be avoided.
Anticoagulants: Concomitant use with anticoagulants may increase the risk of bleeding.
7. Pharmaceutical Information
Composition: The active ingredient is avapritinib.
Appearance: Round (100 mg) or oval (200 mg, 300 mg) film-coated tablets, white to off-white.
Storage: Store at room temperature in the original container to protect from moisture and light.