platelet-derived growth factor receptor alpha blockers
Unresectable or metastatic gastrointestinal stromal tumor (GIST) that possesses a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.
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.
Absorption: Extent of absorption increased with high-fat meals.
Distribution: Extensively distributed to tissues.
Metabolism and 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.
TIME/ACTION PROFILE (plasma concentrations)
|PO||unknown||2–4 hr||24 hr|
- OB: Pregnancy (may cause fetal harm);
- Lactation: Lactation.
Use Cautiously in:
- Severe renal impairment or end-stage renal disease
- Severe hepatic impairment
- Rep: Women of reproductive potential and men with female partners of reproductive potential
- Pedi: Safety and effectiveness in children not established.
Adverse Reactions/Side Effects
CV: edema, hypertension
Derm: alopecia, hair color changes, rash
EENT: ↑ tear production
Endo: hyperthyroidism, hypothyroidism
F and E: hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia
GI: GI BLEEDING, abdominal pain, constipation, diarrhea, dyspepsia, hyperbilirubinemia, hypoalbuminemia, ↑ liver enzymes, nausea, vomiting
GU: acute kidney injury, ↓ fertility
Hemat: NEUTROPENIA, anemia, leukopenia, thrombocytopenia
Metabolic: ↓ appetite, ↓ weight
Neuro: INTRACRANIAL HEMORRHAGE, cognitive impairment, dizziness, headache, mood disorders, sleep disorders, taste disturbances, hallucinations, speech disorders
Resp: dyspnea, pleural effusion
Misc: fatigue, fever
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong CYP3A4 inhibitors, including ketoconazole, or moderate CYP3A4 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 CYP3A4 inducers, including rifampin, or moderate CYP3A4 inducers, including efavirenz , may ↓ levels and effectiveness; avoid concurrent use.
PO (Adults): 300 mg once daily until disease progression or unacceptable toxicity. Concurrent use of moderate CYP3A4 inhibitor– 100 mg once daily until disease progression or unacceptable toxicity.
Tablets: 100 mg, 200 mg, 300 mg
- Monitor for signs and symptoms of intracranial hemorrhage (severe headache, vision problems, severe sleepiness, severe weakness on one side of body) periodically during therapy. If Grade 1 or Grade 2 signs occur, hold dose and resume with 100 mg dose. If Grade 1 or 2 recurs or Grade 3 or Grade 4 occurs, permanently discontinue avapritinib.
- Monitor for signs and symptoms of central nervous system adverse reactions (cognitive impairment, dizziness, sleep disorders, mood disorders, speech disorders, hallucinations) periodically during therapy. If Grade 1 symptoms occur, continue at same dose or hold dose until return to baseline or resolution. Resume at same or reduced dose. If Grade 2 or Grade 3 symptoms occur, hold until return to baseline, Grade 1, or resolution. Resume at same or reduced dose. If Grade 4 symptoms occur, discontinue permanently.
Lab Test Considerations:
Obtain a negative pregnancy test before starting avapritinib.
- May cause ↓ hemoglobin, leukocytes, neutrophils, platelets and ↑ INR and activated partial thromboplastin time.
- May cause ↑ bilirubin, AST, ALT, alkaline phosphatase, creatinine and ↓ phosphate, potassium, albumin, magnesium, and sodium.
- PO Administer once daily on an empty stomach, at least 1 hr before and 2 hrs after a meal.
- 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.
- Rep: May be teratogenic. 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.
Decreased progression of GIST.
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