GAVRETO- pralsetinib capsule

Valsts: Amerikas Savienotās Valstis

Valoda: angļu

Klimata pārmaiņas: NLM (National Library of Medicine)

Aktīvā sastāvdaļa:

PRALSETINIB (UNII: 1WPE73O1WV) (PRALSETINIB - UNII:1WPE73O1WV)

Pieejams no:

Genentech, Inc.

Ievadīšanas:

ORAL

Receptes veids:

PRESCRIPTION DRUG

Ārstēšanas norādes:

GAVRETO is indicated for the treatment of adult patients with metastatic RET fusion-positive non-small cell lung cancer (NSCLC) as detected by an FDA approved test. GAVRETO is indicated for the treatment of adult and pediatric patients 12 years of age and older with advanced or metastatic RET fusion-positive thyroid cancer who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate). This indication is approved under accelerated approval based on overall response rate and duration of response [see Clinical Studies (14.2)] . Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). None. Risk Summary Based on findings from animal studies and its mechanism of action, GAVRETO can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on GAVRETO use in pregnant women to inform drug-associated risk. Oral administration of pralsetinib to pregnant rats during the period of organogenesis resulted in malformations and embryolethality at maternal exposures below the human exposure at the clinical dose of 400 mg once daily (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 an embryo-fetal development study, once daily oral administration of pralsetinib to pregnant rats during the period of organogenesis resulted in 100% post-implantation loss at dose levels ≥ 20 mg/kg (approximately 1.8 times the human exposure based on area under the curve [AUC] at the clinical dose of 400 mg). Post-implantation loss also occurred at the 10 mg/kg dose level (approximately 0.6 times the human exposure based on AUC at the clinical dose of 400 mg). Once daily oral administration of pralsetinib at dose levels ≥ 5 mg/kg (approximately 0.2 times the human AUC at the clinical dose of 400 mg) resulted in an increase in visceral malformations and variations (absent or small kidney and ureter, absent uterine horn, malpositioned kidney or testis, retroesophageal aortic arch) and skeletal malformations and variations (vertebral and rib anomalies and reduced ossification). Risk Summary There are no data on the presence of pralsetinib or its metabolites in human milk or their effects on either the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with GAVRETO and for 1 week after the last dose. Based on animal data, GAVRETO can cause embryolethality and malformations at doses resulting in exposures below the human exposure at the clinical dose of 400 mg daily [see Use in Specific Populations (8.1)]. Pregnancy Testing Verify pregnancy status of females of reproductive potential prior to initiating GAVRETO [see Use in Specific Populations (8.1)]. Contraception GAVRETO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)]. Females Advise females of reproductive potential to use effective non-hormonal contraception during treatment with GAVRETO and for 2 weeks after the last dose. GAVRETO may render hormonal contraceptives ineffective. Males Advise males with female partners of reproductive potential to use effective contraception during treatment with GAVRETO and for 1 week after the last dose. Infertility Based on histopathological findings in the reproductive tissues of male and female rats and a dedicated fertility study in which animals of both sexes were treated and mated to each other, GAVRETO may impair fertility [see Nonclinical Toxicology (13.1)]. The safety and effectiveness of GAVRETO have been established in pediatric patients aged 12 years and older for RET fusion-positive thyroid cancer. Use of GAVRETO in this age group is supported by evidence from an adequate and well-controlled study of GAVRETO in adults with additional population pharmacokinetic data demonstrating that age and body weight had no clinically meaningful effect on the pharmacokinetics of pralsetinib, that the exposure of pralsetinib is expected to be similar between adults and pediatric patients age 12 years and older, and that the course of RET fusion-positive thyroid cancer is sufficiently similar in adults and pediatric patients to allow extrapolation of data in adults to pediatric patients [see Adverse Reactions (6.1), Clinical Pharmacology (12.3), and Clinical Studies (14.2)]. The safety and effectiveness of GAVRETO have not been established in pediatric patients with RET fusion-positive NSCLC or in pediatric patients younger than 12 years old with RET fusion-positive thyroid cancer. Animal Toxicity Data In a 4-week repeat-dose toxicology study in non-human primates, physeal dysplasia in the femur occurred at doses resulting in exposures similar to the human exposure (AUC) at the clinical dose of 400 mg. In rats there were findings of increased physeal thickness in the femur and sternum as well as tooth (incisor) abnormalities (fractures, dentin matrix alteration, ameloblast/odontoblast degeneration, necrosis) in both 4- and 13-week studies at doses resulting in exposures similar to the human exposure (AUC) at the clinical dose of 400 mg. Recovery was not assessed in the 13-week toxicology study, but increased physeal thickness in the femur and incisor degeneration did not show evidence of complete recovery in the 28-day rat study. Monitor growth plates in adolescent patients with open growth plates. Consider interrupting or discontinuing therapy based on the severity of any growth plate abnormalities and based on an individual risk-benefit assessment. Of the 540 patients in ARROW who received the recommended dose of GAVRETO at 400 mg once daily, 31% were 65 years or and over, while 7% were 75 years and over. No overall differences in pharmacokinetics (PK), safety or effectiveness were observed between patients aged 65 years or older and younger patients. No dose adjustment is required for patients with mild (total bilirubin ≤ ULN and AST > ULN or total bilirubin > 1 to 1.5 × ULN and any AST), moderate (total bilirubin > 1.5 to 3 × ULN and any AST) or severe (total bilirubin > 3 × ULN and any AST) hepatic impairment.

Produktu pārskats:

GAVRETO (pralsetinib) 100 mg, light blue, opaque, immediate release, hydroxypropyl methylcellulose (HPMC) hard capsule printed with "BLU-667" on the capsule shell body and "100 mg" on the capsule shell cap are supplied as follows: 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] . Protect from moisture.

Autorizācija statuss:

New Drug Application

Produkta apraksts

GAVRETO- PRALSETINIB CAPSULE
GENENTECH, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
GAVRETO SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR GAVRETO.
GAVRETO (PRALSETINIB) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2020
RECENT MAJOR CHANGES
Indications and Usage, Metastatic _RET_ Fusion-Positive Non-Small Cell
Lung Cancer –
Accelerated Approval text removed (1.1)
(8/2023)
Indications and Usage, _RET_-Mutant Medullary Thyroid Cancer
–Indication Removed
(1.2)
(7/2023)
Dosage and Administration (2.1)
(7/2023)
Dosage and Administration, Dose Modification for Use with CYP3A and/or
P-
glycoprotein (P-gp) Inhibitors (2.4)
(6/2023)
Dosage and Administration, Dose Modification for Use with CYP3A
Inducers (2.5)
(6/2023)
INDICATIONS AND USAGE
GAVRETO is a kinase inhibitor indicated for treatment of:
Adult patients with metastatic rearranged during transfection _(RET_)
fusion-positive non-small cell lung
cancer as detected by an FDA approved test (NSCLC). (1.1)
Adult and pediatric patients 12 years of age and older with advanced
or metastatic _RET_ fusion-positive
thyroid cancer who require systemic therapy and who are radioactive
iodine-refractory (if radioactive
iodine is appropriate).
This indication is approved under accelerated approval based on
overall response rate and duration of
response. Continued approval for this indication may be contingent
upon verification and description of
clinical benefit in confirmatory trial(s). (1.2)
DOSAGE AND ADMINISTRATION
Select patients for treatment with GAVRETO based on the presence of a
_RET_ gene fusion. (2.1, 14)
The recommended dosage in adults and pediatric patients 12 years and
older is 400 mg orally once
daily on an empty stomach (no food intake for at least 2 hours before
and at least 1 hour after taking
GAVRETO). (2.2)
DOSAGE FORMS AND STRENGTHS
Capsules: 100 mg. (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
Interstitial Lung Disease (ILD)/Pneumonitis: Withhold GAVRET