Ayvakit

/ Neopharm (Israel) 1996 Ltd.

Patient Selection for GIST Harboring PDGFRA Exon 18 Mutations: Select patients for treatment based on the presence of a PDGFRA exon 18 mutation.
Recommended Dosage for GIST Harboring PDGFRA Exon 18 Mutations: The recommended dosage is 300 mg orally once daily in patients with GIST. Continue treatment until disease progression or unacceptable toxicity.
Recommended Dosage for Advanced Systemic Mastocytosis: The recommended dosage is 200 mg orally once daily in patients with AdvSM. Continue treatment until disease progression or unacceptable toxicity.
Recommended Administration: Administer orally on an empty stomach, at least 1 hour before or 2 hours after a meal. Do not make up for a missed dose within 8 hours of the next scheduled dose. Do not repeat dose if vomiting occurs after avapritinib but continue with the next scheduled dose.
See prescribing information for full details.

Treatment of 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.

Known hypersensitivity to avapritinib or any of the excipients.

Intracranial Hemorrhage: Serious intracranial hemorrhage may occur with avapritinib treatment; fatal events occurred in less than 1% of patients. Monitor patients closely for the risk of intracranial hemorrhage including those with thrombocytopenia, vascular aneurysm or a history of intracranial hemorrhage or cerebrovascular accident within the prior year. Permanently discontinue avapritinib if intracranial hemorrhage of any grade occurs.
In patients with Advanced Systemic Mastocytosis (AdvSM), a platelet count must be performed prior to initiating therapy; avapritinib is not recommended in patients with AdvSM with platelet counts < 50 X 109 /L. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks regardless of baseline platelet count. After 8 weeks of treatment, monitor platelet counts every 2 weeks (or more frequently as clinically indicated) if values are less than 75 X 109 /L, every 4 weeks if values are between 75 and 100 X 109 /L, and as clinically indicated if values are greater than 100 X 109 /L. Manage platelet counts of < 50 X 109 /L by treatment interruption or dose-reduction of avapritinib. Platelet support may be necessary.
Cognitive Effects: Cognitive adverse reactions can occur in patients receiving avapritinib. Depending on the severity, withhold avapritinib and then resume at the same dose or at a reduced dose upon improvement, or permanently discontinue avapritinib.
Photosensitivity: Avapritinib may cause photosensitivity reactions. Advise patients to limit direct ultraviolet exposure during treatment with avapritinib and for one week after discontinuation of treatment.
Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, avapritinib can cause fetal harm when administered to pregnant women. Oral administration of avapritinib during the period of organogenesis was teratogenic and embryotoxic in rats at exposures approximately 6.3 and 2.7 times the human exposure based on area under the curve (AUC) at the 200 mg and 300 mg dose, respectively. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use effective contraception during treatment with avapritinib and for 6 weeks after the final dose.
Effects on ability to drive and use machines: Advise patients not to drive or operate hazardous machinery if they are experiencing cognitive adverse reactions.
See prescribing information for full details.

The most common adverse reactions (≥ 20%) in clinical trials were edema, nausea, fatigue/asthenia, cognitive impairment, vomiting, decreased appetite, diarrhea, hair color changes, increased lacrimation, abdominal pain, constipation, rash, and dizziness.
See prescribing information for full details.

Strong and Moderate CYP3A Inhibitors: Coadministration of avapritinib with a strong or moderate CYP3A inhibitor increases avapritinib plasma concentrations, which may increase the incidence and severity of adverse reactions of avapritinib. Avoid coadministration of avapritinib with strong or moderate CYP3A
inhibitors. If coadministration of avapritinib with a moderate CYP3A inhibitor cannot be avoided, reduce the dose of avapritinib.
Strong and Moderate CYP3A Inducers: Coadministration of avapritinib with a strong or moderate CYP3A inducer decreases avapritinib plasma concentrations, which may decrease efficacy of avapritinib. Avoid coadministration of avapritinib with strong or moderate CYP3A inducers.

Pregnancy: Based on findings from animal studies and its mechanism of action, avapritinib can cause fetal harm when administered to a pregnant woman. There are no available data on avapritinib use in pregnant women. 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. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with avapritinib and for 2 weeks following the final dose.
See prescribing information for full details.       

Store below 25°C. To be used within 60 days after first opening.