SKYCLARYS- omaveloxolone capsule

Country: Amerika Syarikat

Bahasa: Inggeris

Sumber: NLM (National Library of Medicine)

Bahan aktif:

omaveloxolone (UNII: G69Z98951Q) (omaveloxolone - UNII:G69Z98951Q)

Boleh didapati daripada:

Reata Pharmaceuticals, Inc.

Laluan pentadbiran:

ORAL

Jenis preskripsi:

PRESCRIPTION DRUG

Tanda-tanda terapeutik:

SKYCLARYS is indicated for the treatment of Friedreich's ataxia in adults and adolescents aged 16 years and older. None. Risk Summary There are no adequate data on the developmental risks associated with the use of SKYCLARYS in pregnant women. In animal studies, administration of omaveloxolone during pregnancy or throughout pregnancy and lactation produced evidence of developmental toxicity (embryofetal mortality and growth impairment, and mortality, growth impairment, and neurobehavioral deficits in offspring) at plasma exposures similar to or less than exposures in humans (see Animal Data). In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The background risk of major birth defects and miscarriage for the indicated population is unknown. Data Animal Data Oral administration of omaveloxolone (0, 1, 3, or 10 mg/kg/day) to pregnant rats throughout organogenesis resulted in no adverse effects on embryofetal development; however, in a dose range-finding study, oral administration of omaveloxolone at doses up to 30 mg/kg/day to pregnant rats throughout organogenesis produced increases in post-implantation loss and resorptions, resulting in a decrease in viable fetuses, and reduced fetal weight at the highest dose tested. At the highest dose tested in the pivotal study (10 mg/kg/day), plasma exposure (AUC) was approximately 5 times that in humans at the recommended human dose (RHD) of 150 mg/day. Oral administration of omaveloxolone (0, 3, 10, or 30 mg/kg/day) to pregnant rabbits throughout organogenesis resulted in increased embryofetal mortality and skeletal variations and reduced fetal weight at the highest dose tested, which was associated with maternal toxicity. At the no-effect dose for adverse effects on embryofetal development (10 mg/kg/day), plasma exposure was less than that in humans at the RHD. Oral administration of omaveloxolone (0, 1, 3, or 10 mg/kg/day) to rats throughout pregnancy and lactation resulted in an increase in stillbirths and impaired neurobehavioral function (increased locomotor activity and learning and memory deficits) in offspring at all doses, reduced body weight in offspring at all but the lowest dose tested, and delayed sexual maturation (males), increased postnatal mortality, and impaired reproductive performance in offspring at the highest dose tested. A no-effect dose for adverse effects on pre- and postnatal development was not identified. Plasma exposure (AUC) at the lowest dose tested was less than that in humans at the RHD. Risk Summary There are no data on the presence of omaveloxolone or its metabolites in human milk. The effects on milk production and the breastfed infant are unknown. Omaveloxolone was excreted in the milk of lactating rats following oral administration. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for SKYCLARYS and any potential adverse effects on the breastfed infant from SKYCLARYS or from the underlying maternal condition. SKYCLARYS may decrease the efficacy of hormonal contraceptives [see Drug Interactions (7.2) and Clinical Pharmacology (12.3)] . Advise patients to avoid concomitant use with combined hormonal contraceptives (e.g., pill, patch, ring), implants, and progestin only pills. Counsel females using hormonal contraceptives to use an alternative contraceptive method (e.g., non-hormonal intrauterine system) or additional non-hormonal contraceptive (e.g., condoms) during concomitant use and for 28 days after discontinuation of SKYCLARYS. The safety and effectiveness of SKYCLARYS for the treatment of Friedreich's ataxia have been established in pediatric patients aged 16 years and older. Use of SKYCLARYS for this indication is supported by evidence from one adequate and well-controlled study (Study 1) in adults and in pediatric patients aged 16 years and older [see Clinical Studies (14)] . Safety and effectiveness of SKYCLARYS have not been established in pediatric patients less than 16 years of age. Clinical studies of SKYCLARYS in Friedreich's ataxia did not include patients aged 65 and over. No data are available to determine whether they respond differently than younger adult patients. Omaveloxolone plasma exposure is increased in patients with moderate or severe hepatic impairment (Child-Pugh Class B and C) [see Clinical Pharmacology (12.3)] . Avoid treatment with SKYCLARYS in patients with severe hepatic impairment, including those who develop severe hepatic impairment. If hepatic function improves to moderate impairment, mild impairment, or normal function, initiation of SKYCLARYS treatment at the approved recommended dosage may be considered. For patients with moderate hepatic impairment, a reduced dosage is recommended with close monitoring for adverse reactions [see Dosage and Administration (2.5)] . For patients with mild hepatic impairment (Child-Pugh Class A), no dose adjustments are recommended.

Ringkasan produk:

SKYCLARYS (omaveloxolone) capsules, 50 mg, are supplied as opaque, hard capsules having a light green body and blue cap imprinted with “RTA 408” in white ink on the body and “50” in white ink on the cap. SKYCLARYS is supplied in high density polyethylene bottles that contain 90 capsules, with a foil induction seal and child-resistant closure (NDC 73179-250-90). Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C and 30°C (59°F to 86°F) [see USP Controlled Room Temperature].

Status kebenaran:

New Drug Application

Ciri produk

SKYCLARYS- OMAVELOXOLONE CAPSULE
REATA PHARMACEUTICALS, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
SKYCLARYS SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR SKYCLARYS.
SKYCLARYS (OMAVELOXOLONE) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2023
RECENT MAJOR CHANGES
Dosage and Administration (2.2)
1/2024
INDICATIONS AND USAGE
SKYCLARYS is indicated for the treatment of Friedreich's ataxia in
adults and adolescents aged 16 years
and older. (1)
DOSAGE AND ADMINISTRATION
Obtain alanine aminotransferase (ALT), aspartate aminotransferase
(AST), bilirubin, B-type natriuretic
peptide (BNP), and lipid parameters prior to initiating SKYCLARYS and
during treatment. (2.1, 5.1, 5.2,
5.3)
Recommended dosage is 150 mg (3 capsules) taken orally once daily.
(2.2)
Administer SKYCLARYS on an empty stomach at least 1 hour before
eating. (2.2)
Swallow SKYCLARYS capsules whole or open and sprinkle the entire
contents of both halves of the
capsule onto applesauce and mix. Do not crush or chew capsules. (2.2)
Moderate and Severe Hepatic Impairment: The recommended dosage of
SKYCLARYS is 100 mg once
daily for patients with moderate hepatic impairment. If adverse
reactions emerge, further reduce the
dosage to 50 mg once daily. Avoid use in patients with severe hepatic
impairment. (2.5, 8.6, 12.3)
DOSAGE FORMS AND STRENGTHS
Capsules: 50 mg (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
Elevation of Aminotransferases: Monitor ALT, AST, and total bilirubin
prior to initiation, every month for
the first 3 months of treatment, and periodically thereafter. (2.1,
5.1)
Elevation of B-type Natriuretic Peptide (BNP): Advise patients of
signs and symptoms of fluid overload.
(2.1, 5.2)
Lipid Abnormalities: Monitor cholesterol periodically during
treatment. (2.1, 5.3)
ADVERSE REACTIONS
Most common adverse reactions (incidence ≥20% and greater than
placebo) are elevated liver enzymes
(AST/ALT), headache, nausea, abdominal pain, fatigue, diarrhea, and
m