LEQVIO- inclisiran injection, solution

Χώρα: Ηνωμένες Πολιτείες

Γλώσσα: Αγγλικά

Πηγή: NLM (National Library of Medicine)

Δραστική ουσία:

INCLISIRAN SODIUM (UNII: UPC6BTX7PY) (INCLISIRAN - UNII:UOW2C71PG5)

Διαθέσιμο από:

Novartis Pharmaceuticals Corporation

Οδός χορήγησης:

SUBCUTANEOUS

Τρόπος διάθεσης:

PRESCRIPTION DRUG

Θεραπευτικές ενδείξεις:

LEQVIO® is indicated as an adjunct to diet and statin therapy for the treatment of adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH), to reduce low-density lipoprotein cholesterol (LDL-C). None. Risk Summary Discontinue LEQVIO when pregnancy is recognized. Alternatively, consider the ongoing therapeutic needs of the individual patient. Inclisiran increases LDL-C uptake and lowers LDL-C levels in the circulation, thus decreasing cholesterol and possibly other biologically active substances derived from cholesterol; therefore, LEQVIO may cause fetal harm when administered to pregnant patients based on the mechanism of action [see Clinical Pharmacology (12.1)] . In addition, treatment of hyperlipidemia is not generally necessary during pregnancy. Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hyperlipidemia for most patients. There are no available data on the use of LEQVIO in pregnant patients to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In animal reproduction studies, no adverse developmental effects were observed in rats and rabbits with subcutaneous administration of inclisiran during organogenesis at doses up to 5 to 10 times the maximum recommended human dose (MRHD) based on body surface area (BSA) comparison (see Data ). No adverse developmental outcomes were observed in offspring of rats administered inclisiran from organogenesis through lactation at 5 times the MRHD based on BSA comparison (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. 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 embryo-fetal development studies conducted in Sprague-Dawley rats and New Zealand White rabbits, inclisiran was administered by subcutaneous injection at dose levels of 50, 100, and 150 mg/kg once daily during organogenesis (rats: Gestation Days 6 to 17; rabbits: Gestation Days 7 to 19). There was no evidence of embryo-fetal toxicity or teratogenicity at doses up to 5 and 10 times, respectively, the MRHD based on BSA comparison/dose. Inclisiran crosses the placenta and was detected in rat fetal plasma at concentrations that were 65 to 154 times lower than maternal levels. In a pre- and postnatal development study conducted in Sprague-Dawley rats, inclisiran was administered once daily by subcutaneous injection at levels of 50, 100, and 150 mg/kg from Gestation Day 6 through Lactation Day 20. Inclisiran was well-tolerated in maternal rats, with no evidence of maternal toxicity and no effects on maternal performance. There were no effects on the development of the F1 generation, including survival, growth, physical and reflexological development, behavior, and reproductive performance at doses up to 5 times the MRHD, based on BSA comparison/dose. Risk Summary There is no information on the presence of inclisiran in human milk, the effects on the breastfed infant, or the effects on milk production. Inclisiran was present in the milk of lactating rats in all dose groups. When a drug is present in animal milk, it is likely that the drug will be present in human milk (see Data ). Oligonucleotide-based products typically have poor oral bioavailability; therefore, it is considered unlikely that low levels of inclisiran present in milk will adversely impact an infant’s development during lactation. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LEQVIO and any potential adverse effects on the breastfed infant from LEQVIO or from the underlying maternal condition. Data In lactating rats, inclisiran was detected in milk at mean maternal plasma:milk ratios that ranged between 0.361 and 1.79. However, there is no evidence of systemic absorption in the suckling rat neonates. The safety and effectiveness of LEQVIO have not been established in pediatric patients. Of the 1,833 patients treated with LEQVIO in clinical studies, 981 (54%) patients were 65 years of age and older, while 239 (13%) patients were 75 years of age and older. No overall differences in safety or effectiveness were observed between patients 65 years of age and older and younger adult patients. No dose adjustments are necessary for patients with mild, moderate, or severe renal impairment [see Clinical Pharmacology (12.3)] . LEQVIO has not been studied in patients with end stage renal disease [see Clinical Pharmacology (12.3)] . No dose adjustment is necessary in patients with mild to moderate hepatic impairment. LEQVIO has not been studied in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)] .

Περίληψη προϊόντος:

LEQVIO injection is a clear, colorless to pale yellow solution, 284 mg/1.5 mL (189 mg/mL) of inclisiran supplied as: Carton containing 1 single-dose prefilled syringe: NDC 0078-1000-60 Store LEQVIO at controlled room temperature 20°C to 25°C (68°F to 77°F) with allowable excursions between 15°C and 30°C (59°F and 86°F) [see USP, Controlled Room Temperature (CRT)].

Καθεστώς αδειοδότησης:

New Drug Application

Αρχείο Π.Χ.Π.

LEQVIO- INCLISIRAN INJECTION, SOLUTION
NOVARTIS PHARMACEUTICALS CORPORATION
----------
HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
LEQVIO SAFELY AND
EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR LEQVIO.
LEQVIO (INCLISIRAN) INJECTION, FOR SUBCUTANEOUS USE
INITIAL U.S. APPROVAL: 2021
RECENT MAJOR CHANGES
Indications and Usage (1)
7/2023
INDICATIONS AND USAGE
LEQVIO is a small interfering RNA (siRNA) directed to proprotein
convertase subtilisin kexin type 9 (PCSK9)
mRNA indicated as an adjunct to diet and statin therapy for the
treatment of adults with primary
hyperlipidemia, including heterozygous familial hypercholesterolemia
(HeFH), to reduce low-density
lipoprotein cholesterol (LDL-C). (1)
DOSAGE AND ADMINISTRATION
The recommended dosage of LEQVIO, in combination with statin therapy,
is 284 mg administered as a
single subcutaneous injection initially, again at 3 months, and then
every 6 months. (2.1)
LEQVIO should be administered by a healthcare professional. (2.2)
Inject LEQVIO subcutaneously into the abdomen, upper arm, or thigh.
(2.2)
DOSAGE FORMS AND STRENGTHS
Injection: 284 mg/1.5 mL (189 mg/mL) in a single-dose prefilled
syringe. (3)
CONTRAINDICATIONS
None. (4)
ADVERSE REACTIONS
Common adverse reactions in clinical trials (≥ 3%): injection site
reaction, arthralgia, and bronchitis. (6)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT NOVARTIS
PHARMACEUTICALS CORPORATION
AT 1-888-669-6682 OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
SEE 17 FOR PATIENT COUNSELING INFORMATION.
REVISED: 7/2023
FULL PRESCRIBING INFORMATION: CONTENTS*
1 INDICATIONS AND USAGE
2 DOSAGE AND ADMINISTRATION
2.1 Recommended Dosage
2.2 Important Administration Instructions
3 DOSAGE FORMS AND STRENGTHS
4 CONTRAINDICATIONS
6 ADVERSE REACTIONS
6.1 Clinical Trials Experience
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
®
8.2 Lactation
8.4 Pediatric Use
8.5 Geriatric Use
8.6 Renal Impairment
8.7 Hepatic Impairment
11 DESCRIPTION
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of A