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Ayvakit Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Manufacturer
Generic Availability
Mechanism of Action
Ayvakit Indications
Indications
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.
Ayvakit Dosage and Administration
Adult
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
Ayvakit Contraindications
Not Applicable
Ayvakit Boxed Warnings
Not Applicable
Ayvakit Warnings/Precautions
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 Pharmacokinetics
Absorption
Steady state concentration was reached by day 15 following daily dosing.
Median time to peak concentration (Tmax) ranged from 2–4 hours.
Cmax was increased by 59% and the AUC0-INF was increased by 29% when Ayvakit was taken with a high-calorie, high-fat meal compared with the fasted state.
Distribution
Mean apparent volume of distribution: 1200 L (43%) at 300 mg for GIST; 1900 L (43%) at 200 mg for systemic mastocytosis.
In vitro protein binding: 98.8%.
Blood-to-plasma ratio: 0.95.
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.
Ayvakit Interactions
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.
Ayvakit Adverse Reactions
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.
Ayvakit Clinical Trials
See Literature
Ayvakit Note
Not Applicable
Ayvakit Patient Counseling
See Literature
Ayvakit Generic Name & Formulations
Legal Class
General Description
Pharmacological Class
How Supplied
Manufacturer
Generic Availability
Mechanism of Action
Ayvakit Indications
Indications
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.
Ayvakit Dosage and Administration
Adult
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
Ayvakit Contraindications
Not Applicable
Ayvakit Boxed Warnings
Not Applicable
Ayvakit Warnings/Precautions
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 Pharmacokinetics
Absorption
Steady state concentration was reached by day 15 following daily dosing.
Median time to peak concentration (Tmax) ranged from 2–4 hours.
Cmax was increased by 59% and the AUC0-INF was increased by 29% when Ayvakit was taken with a high-calorie, high-fat meal compared with the fasted state.
Distribution
Mean apparent volume of distribution: 1200 L (43%) at 300 mg for GIST; 1900 L (43%) at 200 mg for systemic mastocytosis.
In vitro protein binding: 98.8%.
Blood-to-plasma ratio: 0.95.
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.
Ayvakit Interactions
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.
Ayvakit Adverse Reactions
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.
Ayvakit Clinical Trials
See Literature
Ayvakit Note
Not Applicable
Ayvakit Patient Counseling
See Literature
