Avapritinib
Indications
Avapritinib is used for:
Gastrointestinal Stromal Tumors
Adult Dose
Gastrointestinal Stromal Tumors
Indicated for adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutation
300 mg PO qDay
Continue until disease progression or unacceptable toxicity
Hepatic impairment
Mild-to-moderate (total bilirubin ?3x ULN and any AST): No dosage adjustment necessary
Severe (total bilirubin >3x ULN and any AST): Recommended dose has not been established
Child Dose
Renal Dose
Renal impairment
Mild-to-moderate (CrCl 30 to 90 mL/mL): No dosage adjustment necessary
Severe or end-stage renal disease (CrCl <30 mL/min): Recommended dose has not been established
Administration
Administer on an empty stomach, at least 1 hr before and 2 hr after a meal
Contra Indications
Precautions
A broad spectrum of CNS adverse reactions were reported; these include cognitive impairment, dizziness, sleep disorders, mood disorders, speech disorders, and hallucinations
Based on findings from animal studies and its mechanism of action, fetal harm can occur when administered to pregnant women
Intracranial hemorrhage (eg, subdural hematoma, intracranial hemorrhage, cerebral hemorrhage) occurred
Pregnancy-Lactation
Pregnancy
Based on findings from animal studies and its mechanism of action, fetal harm may occur when administered to a pregnant woman
No data available on use in pregnant women
Verify pregnancy status of females of reproductive potential before initiation
Contraception
Females of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose
Males with female partners of reproductive potential: Use effective contraception during treatment and for 6 weeks after the final dose
Infertility
Based on findings from animal studies, may impair fertility for both males and females
Animal studies H4
Oral administration of avapritinib to pregnant animals during organogenesis was teratogenic and embryotoxic in rats at exposure levels ~2.7 times the human exposure based on AUC at the 300-mg dose
Advise pregnant women of the potential risk to a fetus
Lactation
There are no data on the presence of avapritinib or its metabolites in human milk or the effects of avapritinib on the breastfed child or milk production
Advise women not to breastfeed during treatment and for 2 weeks following the final dose
Interactions
Adverse Effects
Side effects of Avapritinib :
>10%
All grades
Decreased hemoglobin (81%)
Edema (72%)
Increased bilirubin (69%)
Nausea (64%)
Decreased leukocytes (62%)
Fatigue (61%)
Increased AST (51%)
Decreased phosphate (49%)
Cognitive impairment (48%)
Decreased neutrophils (43%)
Vomiting (38%)
Decreased appetite (38%)
Diarrhea (37%)
Decreased potassium (34%)
Increased lacrimation (33%)
Abdominal pain (31%)
Decreased albumin (31%)
Decreased magnesium (29%)
Increased creatinine (29%)
Decreased sodium (28%)
Decreased platelets (27%)
Increased INR (24%)
Constipation (23%)
Rash (23%)
Dizziness (22%)
Hair color changes (21%)
Increased ALT (19%)
Headache (17%)
Dyspnea (17%)
Sleep disorders (16%)
Taste effects (15%)
Pyrexia (14%)
Increased alkaline phosphatase (14%)
Mood disorders (13%)
Alopecia (13%)
Decreased weight (13%)
Increased activated partial thromboplastin time (13%)
Pleural effusion (12%)
Grade >3
Decreased hemoglobin (28%)
Decreased phosphate (13%)
1-10%
All grades
Hypertension (8%)
Thyroid disorders (hyperthyroid, hypothyroid) (3%)
Palmar-plantar erythrodysesthesia (1%)
Grade>3
Fatigue (9%)
Increased bilirubin (9%)
Abdominal pain (6%)
Decreased neutrophils (6%)
Decreased potassium (6%)
Decreased sodium (7%)
Decreased leukocytes (5%)
Diarrhea (4.9%)
Cognitive impairment (4.9%)
Decreased appetite (2.9%)
Nausea (2.5%)
Dyspnea (2.5%)
Rash (2.1%)
Vomiting (2%)
Edema (2%)
Pleural effusion (2%)
Decreased albumin (2%)
Constipation (1.5%)
Increased AST (1.5%)
Mood disorders (1%)
Decreased weight (1%)
Decreased magnesium (1%)
Increased alkaline phosphatase (1%)
<1%
Grade >3
Increased INR (0.6%)
Pyrexia (0.5%)
Dizziness (0.5%)
Headache (0.5%)
Hair color changes (0.5%)
Decreased platelets (0.5%)
Increased ALT (0.5%)
Mechanism of Action
Tyrosine kinase inhibitor binds to and inhibits specific mutant forms of PDGFRα and c-Kit, including the PDGFRα D842V mutant and various KIT exon 17 mutants
This results in the inhibition of PDGFRa- and c-Kit-mediated signal transduction pathways and the inhibition of proliferation in tumor cells that express these PDGFRa and c-Kit mutants