• Unresectable or metastatic gastrointestinal stromal tumor (GIST) that possesses a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.
• Advanced systemic mastocytosis (including aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia).

Contraindicated in:

• Platelet count <50 x 10⁹/L (patients with advanced systemic mastocytosis only) (↑ risk of intracranial hemorrhage)
• Concurrent use of strong or moderate CYP3A inhibitors
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Severe renal impairment or end-stage renal disease
• Severe hepatic impairment
• Women of reproductive potential and men with female partners of reproductive potential
• Pedi: Safety and effectiveness not established in children.

CV: edema, hypertension.

Derm: alopecia, hair color changes, rash.

EENT: ↑tear production.

Endo: hyperthyroidism, hypothyroidism.

F and E: hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.

GI: abdominal pain, constipation, diarrhea, dyspepsia, hyperbilirubinemia, hypoalbuminemia, ↑liver enzymes, nausea, vomiting, GI BLEEDING.

GU: acute kidney injury, ↓ fertility.

Hemat: anemia, leukopenia, neutropenia, thrombocytopenia.

Metab: ↓appetite, ↓weight.

Neuro: cognitive impairment, dizziness, headache, mood disorders, sleep disorders, taste disturbances, hallucinations, INTRACRANIAL HEMORRHAGE, speech disorders.

Resp: dyspnea, pleural effusion.
Misc: fatigue, fever.

Drug-Drug:

• Strong CYP3A inhibitors, including ketoconazole, or moderate CYP3A inhibitors, including fluconazole, may ↑ levels and risk of toxicity; avoid concurrent use. If concurrent use with moderate CYP3A4 inhibitor cannot be avoided, ↓ avapritinib dose.
• Strong CYP3A inducers, including rifampin, or moderate CYP3A inducers, including efavirenz, may ↓ levels and effectiveness; avoid concurrent use.

• Tablets: 25 mg; 50 mg; 100 mg; 200 mg; 300 mg;

Gastrointestinal Stromal Tumor Harboring PDGFRA Exon 18 Mutations

• PO (Adults): 300 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A inhibitor — 100 mg once daily until disease progression or unacceptable toxicity.

Advanced Systemic Mastocytosis

• PO (Adults): 200 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A inhibitor — 50 mg once daily until disease progression or unacceptable toxicity.

Ayvakit

• Tyrosine kinase inhibitor that binds to and inhibits PDGFRA which contributes to its antitumor activity. It specifically targets tumors that contain PDGFRA and PDGFRA D842 mutants as well as multiple KIT exon 11, 11/17 and 17 mutants.

• Decreased progression of GIST.
• Reduced number of mast cells for patients with advanced systemic mastocytosis.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: kinase inhibitors, platelet-derived growth factor receptor alpha blockers

Absorption: Extent of absorption increased with high-fat meals.

Distribution: Extensively distributed to tissues.

Metabolism/Excretion: Primarily metabolized by the liver via CYP3A4 isoenzyme (and CYP2C9 to a lesser extent). Primarily excreted in feces (70%; 11% as unchanged drug); 18% excreted in urine (primarily as metabolites).

Half-life: 32–57 hr.

(plasma concentrations)

• Instruct patient to take avapritinib as directed. Take missed doses as soon as possible, but not within 8 hrs of next dose. Do not take an additional dose if vomiting occurs after dose; continue with next scheduled dose.
• May cause cognitive impairment and dizziness. Instruct patient to avoid driving and other activities requiring alertness until response to medication is known.
• Advise patient to notify health care professional if signs and symptoms of intracranial hemorrhage or central nervous system side effects (forgetfulness, confusion, getting lost, trouble thinking, drowsiness, dizziness, trouble sleeping, word finding problems, seeing objects or hearing things that are not there, change in mood or behavior) occur.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
• Discuss the possibility of hair loss with patient. Explore methods of coping.
• May cause fetal harm. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during and for at least 6 wks after last dose. Advise women to avoid breastfeeding during and for 2 wks following last dose. May impair male and female fertility.

A-va-PRI-ti-nib