Class / MOA
- Selective tyrosine kinase inhibitor (TKI).
- Potently inhibits PDGFRA exon 18 mutations (esp. D842V) and KIT mutations.
- Designed for mutations resistant to imatinib and other TKIs.
Indications
- FDA-approved for:
- GIST with PDGFRA exon 18 mutation, including D842V (unresectable or metastatic).
- Systemic mastocytosis (SM) (aggressive, advanced SM, ASM, SM-AHN, MCL) — not BCOP exam’s primary focus but worth knowing.
Dosing
- GIST: 300 mg PO once daily.
- Systemic mastocytosis: Higher dose (200 mg PO daily, sometimes titrated).
- Administer on empty stomach (≥1 hr before or ≥2 hrs after food).
Toxicities / Monitoring
- CNS effects: Cognitive impairment, memory issues, confusion (unique exam pearl).
- GI: Nausea, vomiting, diarrhea.
- Hematologic: Anemia, thrombocytopenia.
- Other: Fluid retention, periorbital edema.
- DDIs: CYP3A4 substrate → avoid strong inducers/inhibitors.
- Monitoring: Baseline and periodic CBC, cognitive assessment, hepatic function.
BCOP Exam Pearls
- Key niche fact: Only approved drug for PDGFRA exon 18 mutations, especially D842V.
- Different from imatinib (which is ineffective in this mutation).
- Sequencing in non-D842V GIST usually goes: Imatinib → Sunitinib → Regorafenib → Ripretinib. Avapritinib is mutation-driven, not sequence-driven.
- Side effect cognitive toxicity is unique and testable.