Colorectal and other GI cancers:
Indications for: AYVAKIT
In adults with unresectable or metastatic gastrointestinal stromal tumor (GIST) harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations.
Adult Dosage:
Give on an empty stomach (at least 1hr before or 2hrs after a meal). 300mg once daily; continue until disease progression or unacceptable toxicity. Avoid concomitant use with strong or moderate CYP3A inhibitors; if use with moderate CYP3A inhibitor is unavoidable, initiate dosing at 100mg once daily. Dose modifications: see full labeling.
Children Dosage:
Not established.
AYVAKIT Warnings/Precautions:
Risk of intracranial hemorrhage; monitor closely including those with thrombocytopenia, vascular aneurysm, or history of intracranial hemorrhage or cerebrovascular accident within the prior year. Permanently discontinue if intracranial hemorrhage of any grade occurs. In AdvSM: interrupt or reduce dose if platelet counts <50×109/L; platelet support may be needed. Risk of CNS effects (eg, cognitive impairment, dizziness, sleep disorders, others); if occurs, withhold dose and then resume at reduced (or at same) dose upon resolution, or permanently discontinue based on severity. Advise to limit direct UV exposure during and for 1 week after treatment discontinuation. Severe renal impairment (CrCl 15–29mL/min) or ESRD (CrCl <15mL/min). Severe hepatic impairment. Embryo-fetal toxicity. Advise females and males of reproductive potential to use effective contraception during and for 6 weeks after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 2 weeks after the last dose).
AYVAKIT Classification:
Tyrosine kinase inhibitor.
AYVAKIT Interactions:
See Adults. Potentiated by strong or moderate CYP3A inhibitors (eg, itraconazole, fluconazole). Antagonized by strong or moderate CYP3A inducers (eg, rifampin, efavirenz); avoid. Increased risk for intracranial hemorrhage with anticoagulants.
Adverse Reactions:
Edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, increased lacrimation, abdominal pain, rash, constipation, dizziness, hair color changes; also for ISM: eye edema; photosensitivity, anemia, subdural hematoma, pleural effusion, ascites, pneumonia, sepsis.
Drug Elimination:
Fecal (70%), renal (18%).
Half-life: 32–57 hours for GIST; 20–39 hours for systemic mastocytosis.
Steady state mean apparent oral clearance: 21.8 L/h (12%) at 300 mg for GIST; 40.3 L/h (86%) at 200 mg for systemic mastocytosis.
Generic Drug Availability:
NO
How Supplied:
Tabs—30
Miscellaneous immune disorders:
Indications for: AYVAKIT
In adults with advanced systemic mastocytosis (AdvSM), including those with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SMAHN), and mast cell leukemia (MCL). In adults with indolent systemic mastocytosis (ISM).
Limitations of Use:
Not for use in patients with AdvSM or ISM with platelet counts <50x109/L.
Adult Dosage:
Give on an empty stomach (at least 1hr before or 2hrs after a meal). AdvSM: 200mg once daily; continue until disease progression or unacceptable toxicity. ISM: 25mg once daily. Avoid concomitant use with strong or moderate CYP3A inhibitors; if use with moderate CYP3A inhibitor is unavoidable, initiate dosing at 50mg once daily for AdvSM. Severe hepatic impairment (Child-Pugh Class C): AdvSM: initially 100mg once daily; ISM: initially 25mg every other day. Dose modifications: see full labeling.
Children Dosage:
Not established.
AYVAKIT Warnings/Precautions:
Risk of intracranial hemorrhage; monitor closely including those with thrombocytopenia, vascular aneurysm, or history of intracranial hemorrhage or cerebrovascular accident within the prior year. Permanently discontinue if intracranial hemorrhage of any grade occurs. In AdvSM: interrupt or reduce dose if platelet counts <50×109/L; platelet support may be needed. Risk of CNS effects (eg, cognitive impairment, dizziness, sleep disorders, others); if occurs, withhold dose and then resume at reduced (or at same) dose upon resolution, or permanently discontinue based on severity. Advise to limit direct UV exposure during and for 1 week after treatment discontinuation. Severe renal impairment (CrCl 15–29mL/min) or ESRD (CrCl <15mL/min). Severe hepatic impairment. Embryo-fetal toxicity. Advise females and males of reproductive potential to use effective contraception during and for 6 weeks after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 2 weeks after the last dose).
AYVAKIT Classification:
Tyrosine kinase inhibitor.
AYVAKIT Interactions:
See Adults. Potentiated by strong or moderate CYP3A inhibitors (eg, itraconazole, fluconazole). Antagonized by strong or moderate CYP3A inducers (eg, rifampin, efavirenz); avoid. Increased risk for intracranial hemorrhage with anticoagulants.
Adverse Reactions:
Edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, increased lacrimation, abdominal pain, rash, constipation, dizziness, hair color changes; also for ISM: eye edema; photosensitivity, anemia, subdural hematoma, pleural effusion, ascites, pneumonia, sepsis.
Drug Elimination:
Fecal (70%), renal (18%).
Half-life: 32–57 hours for GIST; 20–39 hours for systemic mastocytosis.
Steady state mean apparent oral clearance: 21.8 L/h (12%) at 300 mg for GIST; 40.3 L/h (86%) at 200 mg for systemic mastocytosis.
Generic Drug Availability:
NO
How Supplied:
Tabs—30
