KOSELUGO- selumetinib capsule

Země: Spojené státy

Jazyk: angličtina

Zdroj: NLM (National Library of Medicine)

Aktivní složka:

SELUMETINIB (UNII: 6UH91I579U) (SELUMETINIB - UNII:6UH91I579U)

Dostupné s:

AstraZeneca Pharmaceuticals LP

Podání:

ORAL

Druh předpisu:

PRESCRIPTION DRUG

Terapeutické indikace:

KOSELUGO is indicated for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable plexiform neurofibromas (PN). None. Risk Summary Based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1)] , KOSELUGO can cause fetal harm when administered to a pregnant woman. There are no available data on the use of KOSELUGO in pregnant women to evaluate drug-associated risk. In animal reproduction studies, administration of selumetinib to mice during organogenesis caused reduced fetal weight, adverse structural defects, and effects on embryofetal survival at exposures approximately > 5 times the human exposure at the clinical dose of 25 mg/m2 twice daily (see Data ). Advise pregnant women of the potential risk to the fetus. 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. Data Animal Data In embryo-fetal development studies in mice at doses > 2.5 mg/kg twice daily (~5-times the human exposure based on area under the curve [AUC] at the clinical dose of 25 mg/m2 twice daily), selumetinib caused increases in post-implantation loss, a reduction in mean fetal and litter weights, and an increased occurrence of open eye and cleft palate, but did not induce significant maternal toxicity. Administration of selumetinib to pregnant mice from gestation Day 6 through lactation Day 20 resulted in reduced pup body weights and fewer pups met the pupil constriction criterion on day 21 post-partum. The incidence of malformations (e.g., prematurely open eye(s) and cleft palate) was increased even at the lowest dose of 0.5 mg/kg twice daily (maternal maximal concentration [Cmax ] of ~0.6 times the human Cmax at the clinical dose of 25 mg/m2 twice daily). Risk Summary There are no data on the presence of selumetinib or its active metabolite in human milk or their effects on the breastfed child or milk production. Selumetinib and its active metabolite were present in the milk of lactating mice (see Data ). Due to the potential for adverse reactions in a breastfed child, advise women not to breastfeed during treatment with KOSELUGO and for 1 week after the last dose. Data Animal Data Selumetinib and its active metabolite were present in milk from mice dosed with selumetinib throughout gestation and lactation, with a mean plasma/milk ratio of 1.5 in lactating dams dosed at 5 mg/kg twice daily. Administration of selumetinib to dams during gestation and early lactation was associated with adverse events in pups, including reduced growth rates and incidence of malformations [see Use in Specific Populations (8.1)]. KOSELUGO can cause fetal harm when administered to a pregnant woman [see Use in Specific Populations (8.1)] . Pregnancy Testing Verify the pregnancy status of females of reproductive potential prior to initiating KOSELUGO [see Use in Specific Populations (8.1)] . Contraception Females Advise females of reproductive potential to use effective contraception during treatment and for 1 week after the last dose. Males Advise male patients with female partners of reproductive potential to use effective contraception during treatment with KOSELUGO and for 1 week after the last dose. The safety and effectiveness have been established in pediatric patients 2 years of age and older with NF1 who have inoperable PN and the information on this use is discussed throughout the labeling. The safety and effectiveness of KOSELUGO have not been established in pediatric patients younger than 2 years of age. Animal Toxicity Data In 3-month general toxicology studies, male rats receiving selumetinib at doses ≥ 10 mg/kg daily (~60-times the human exposure based on AUC at the clinical dose of 25 mg/m2 twice daily) showed growth plate dysplasia. Clinical studies did not include patients 65 years of age and older. No dose adjustment is recommended in patients with renal impairment or those with End Stage Renal Disease [see Clinical Pharmacology (12.3)]. Selumetinib exposures increased in patients with moderate or severe hepatic impairment [see Clinical Pharmacology (12.3)] . Reduce the dose of KOSELUGO for patients with moderate hepatic impairment (Child-Pugh B). A recommended dosage of KOSELUGO for use in patients with severe hepatic impairment (Child-Pugh C) has not been established [see Dosage and Administration (2.3)] .

Přehled produktů:

How Supplied Strength Description Capsules per Bottle NDC Number 10 mg White to off-white, opaque, hard capsule sealed with a clear band and marked with “SEL 10” in black ink. 60 0310-0610-60 28 0310-0610-28 25 mg Blue, opaque, hard capsule sealed with a clear band and marked with “SEL 25” in black ink. 60 0310-0625-60 28 0310-0625-28 Storage Store at 20°C to 25°C (68°F to 77°F) with excursions permitted to 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature]. Dispense in original bottle. Keep the bottle tightly closed. Do not remove desiccant. Protect from moisture.

Stav Autorizace:

New Drug Application

Charakteristika produktu

KOSELUGO- SELUMETINIB CAPSULE
ASTRAZENECA PHARMACEUTICALS LP
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
KOSELUGO SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR KOSELUGO.
KOSELUGO (SELUMETINIB) CAPSULES, FOR ORAL USE
INITIAL U.S. APPROVAL: 2020
RECENT MAJOR CHANGES
INDICATIONS AND USAGE
KOSELUGO is a kinase inhibitor indicated for the treatment of
pediatric patients 2 years of age and older
with neurofibromatosis type 1 (NF1) who have symptomatic, inoperable
plexiform neurofibromas (PN). (1)
DOSAGE AND ADMINISTRATION
•
•
DOSAGE FORMS AND STRENGTHS
Capsules: 10 mg and 25 mg. (3)
CONTRAINDICATIONS
None. (4)
WARNINGS AND PRECAUTIONS
•
•
•
•
•
•
ADVERSE REACTIONS
Most common adverse reactions (≥ 40%) are: vomiting, rash (all),
abdominal pain, diarrhea, nausea, dry
skin, fatigue, musculoskeletal pain, pyrexia, acneiform rash,
stomatitis, headache, paronychia, and
pruritus. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT ASTRAZENECA AT
1-800-236-9933 OR FDA
AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
DRUG INTERACTIONS
®
Dosage and Administration (2.1) 01/2024
The recommended dosage is 25 mg/m2 taken orally twice daily. KOSELUGO
can be taken with or
without food. (2.1)
Reduce the recommended dosage to 20 mg/m orally twice daily for
patients with moderate hepatic
impairment (Child-Pugh B). The recommended dosage for use in patients
with severe hepatic
impairment (Child-Pugh C) has not been established. (2.2, 8.7)
2
Cardiomyopathy: Assess ejection fraction prior to initiating
treatment, every 3 months during the first
year, then every 6 months thereafter and as clinically indicated.
Withhold, reduce dose, or
permanently discontinue KOSELUGO based on severity of adverse
reaction. (2.2, 5.1)
Ocular Toxicity: Conduct ophthalmic assessments prior to initiating
KOSELUGO, at regular intervals
during treatment and for new or worsening visual changes. Permanently
discontinue KOSELUGO for
retinal vein occlusion (RVO). Withho