AYVAKIT- avapritinib tablet, film coated

Valsts: Amerikas Savienotās Valstis

Valoda: angļu

Klimata pārmaiņas: NLM (National Library of Medicine)

Aktīvā sastāvdaļa:

avapritinib (UNII: 513P80B4YJ) (avapritinib - UNII:513P80B4YJ)

Pieejams no:

Blueprint Medicines Corporation

Ievadīšanas:

ORAL

Receptes veids:

PRESCRIPTION DRUG

Ārstēšanas norādes:

AYVAKIT® is indicated for the treatment of adults with unresectable or metastatic GIST harboring a platelet-derived growth factor receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V mutations [see Dosage and Administration (2.2)] . AYVAKIT is indicated for the treatment of adult patients with advanced systemic mastocytosis (AdvSM). AdvSM includes patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL). Limitations of Use : AYVAKIT is not recommended for the treatment of patients with AdvSM with platelet counts of less than 50 × 109 /L [see Warnings and Precautions (5.1)] . AYVAKIT is indicated for the treatment of adult patients with indolent systemic mastocytosis (ISM). Limitations of Use : AYVAKIT is not recommended for the treatment of patients with ISM with platelet counts of less than 50 × 109 /L [see Warnings and Precautions (5.1)] . None. Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)] , AYVAKIT can cause fetal harm when administered to a pregnant woman. There are no available data on AYVAKIT use in pregnant women. Oral administration of avapritinib to pregnant rats during the period of organogenesis was teratogenic and embryotoxic at exposure levels approximately 31.4, 6.3 and 2.7 times the human exposure based on AUC at the 25 mg, 200 mg and 300 mg dose, respectively (see Data) . Advise pregnant women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Data Animal Data In a reproductive toxicity study, administration of avapritinib to rats during the period of organogenesis resulted in decreased fetal body weights, post-implantation loss, and increases in visceral (hydrocephaly, septal defect, and stenosis of the pulmonary trunk) and skeletal (sternum) malformations at doses greater than or equal to 10 mg/kg/day (approximately 31.4, 6.3 and 2.7 times the human exposure based on AUC at the 25 mg, 200 mg and 300 mg dose, respectively). Risk Summary 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 AYVAKIT and for 2 weeks following the final dose. Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating AYVAKIT [see Use in Specific Populations (8.1)] . Contraception AYVAKIT can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]. Females Advise females of reproductive potential to use effective contraception during treatment with AYVAKIT and for 6 weeks after the final dose. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with AYVAKIT and for 6 weeks after the final dose. Infertility Females Based on findings from animal studies, AYVAKIT may impair female fertility. These findings were not reversible within a two month recovery period [see Nonclinical Toxicology (13.1)]. Males Based on findings from animal studies, AYVAKIT may impair male fertility. These findings were not reversible within a two month recovery period [see Nonclinical Toxicology (13.1)] . The safety and effectiveness of AYVAKIT in pediatric patients have not been established. Of the 204 patients with unresectable or metastatic GIST who received AYVAKIT in NAVIGATOR, 40% were 65 years or older, while 6% were 75 years and older. Of the 131 patients with AdvSM who received AYVAKIT in EXPLORER and in PATHFINDER, 62% were 65 years or older, while 21% were 75 years and older. Of the 141 patients with ISM who received AYVAKIT in PIONEER, 6% were 65 years or older, while <1% were 75 years and older. No overall differences in safety or efficacy were observed between these patients and younger adult patients. No dose adjustment is recommended for patients with mild or moderate renal impairment [creatinine clearance (CLcr) 30 to 89 mL/min estimated by Cockcroft-Gault]. The recommended dose of AYVAKIT has not been established for patients with severe renal impairment (CLcr 15 to 29 mL/min) or end-stage renal disease (CLcr <15 mL/min) [see Clinical Pharmacology (12.3)] . No dose adjustment is recommended for patients with mild [total bilirubin ≤ upper limit of normal (ULN) and aspartate aminotransferase (AST) > ULN or total bilirubin > 1 to 1.5 times ULN and any AST], or moderate [total bilirubin >1.5 to 3 times ULN and any AST] hepatic impairment. Unbound AUC0-INF was 61% higher in subjects with severe hepatic impairment (Child-Pugh Class C) as compared to matched healthy subjects with normal hepatic function. A lower starting dose is recommended in patients with severe hepatic impairment [see Dosage and Administration (2.7)] .

Produktu pārskats:

AYVAKIT (avapritinib) tablets are supplied as follows: 25 mg, round, white film-coated tablet with debossed text. One side reads "BLU" and the other side reads "25"; available in bottles of 30 tablets (NDC 72064-125-30). 50 mg, round, white film-coated tablet with debossed text. One side reads "BLU" and the other side reads "50"; available in bottles of 30 tablets (NDC 72064-150-30). 100 mg, round, white film-coated tablet, printed with blue ink "BLU" on one side and "100" on the other side; available in bottles of 30 tablets (NDC 72064-110-30). 200 mg, capsule shaped, white film-coated tablet, printed with blue ink "BLU" on one side and "200" on the other side; available in bottles of 30 tablets (NDC 72064-120-30). 300 mg, capsule shaped, white film-coated tablet, printed with blue ink "BLU" on one side and "300" on the other side; available in bottles of 30 tablets (NDC 72064-130-30). Store at 20°C to 25°C (68°F to 77°F); excursions are permitted from 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Autorizācija statuss:

New Drug Application

Produkta apraksts

AYVAKIT- AVAPRITINIB TABLET, FILM COATED
BLUEPRINT MEDICINES CORPORATION
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
AYVAKIT SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR AYVAKIT.
AYVAKIT (AVAPRITINIB) TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2020
RECENT MAJOR CHANGES
Indications and Usage (1)
5/2023
Dosage and Administration (2)
5/2023
Warnings and Precautions (5)
5/2023
INDICATIONS AND USAGE
AYVAKIT is a kinase inhibitor indicated for:
Gastrointestinal Stromal Tumor (GIST)
the treatment of adults with unresectable or metastatic GIST harboring
a platelet-derived growth factor
receptor alpha (PDGFRA) exon 18 mutation, including PDGFRA D842V
mutations. (1.1, 2.2)
Advanced Systemic Mastocytosis (AdvSM)
the treatment of adult patients with AdvSM. AdvSM includes patients
with aggressive systemic
mastocytosis (ASM), systemic mastocytosis with an associated
hematological neoplasm (SM-AHN),
and mast cell leukemia (MCL). (1.2)
Limitations of Use: AYVAKIT is not recommended for the treatment of
patients with AdvSM with platelet
counts of less than 50 × 10 /L (1.2)
Indolent Systemic Mastocytosis (ISM)
the treatment of adult patients with ISM. (1.3)
Limitations of Use: AYVAKIT is not recommended for the treatment of
patients with ISM with platelet
counts of less than 50 × 10 /L (1.2)
DOSAGE AND ADMINISTRATION
GIST: Select patients for treatment with AYVAKIT based on the presence
of a PDGFRA exon 18
mutation. (2.2)
GIST: The recommended dosage is 300 mg orally once daily. (2.2)
AdvSM: The recommended dosage is 200 mg orally once daily. (2.3)
ISM: The recommended dosage is 25 mg orally once daily. (2.4)
Patients with severe hepatic impairment (Child-Pugh Class C): reduce
dose of AYVAKIT. (2.7)
DOSAGE FORMS AND STRENGTHS
Tablets: 25 mg, 50 mg, 100 mg, 200 mg and 300 mg. (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
Intracranial Hemorrhage: Permanently discontinue for any occurrence of
any grade. (2.5, 5.1)
Cognitive Effects: