Overview
11 DESCRIPTION LEQVIO contains inclisiran sodium, a small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA. Inclisiran contains a covalently linked ligand containing three N-acetylgalactosamine (GalNAc) residues to facilitate delivery to hepatocytes.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Inclisiran is a double-stranded small interfering ribonucleic acid (siRNA), conjugated on the sense strand with triantennary N-Acetylgalactosamine (GalNAc) to facilitate uptake by hepatocytes. In hepatocytes, inclisiran utilizes the RNA interference mechanism and directs catalytic breakdown of mRNA for PCSK9. This increases LDL-C receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake and lowers LDL-C levels in the circulation. 12.2 Pharmacodynamics Following a single subcutaneous administration of 284 mg of inclisiran, LDL-C reduction was apparent within 14 days post dose. Mean reductions of 38% to 51% for LDL-C were observed 30 to 180 days post dose.
Indications
- 1 INDICATIONS AND USAGE LEQVIO ® is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in: adults with hypercholesterolemia. adults and pediatric patients aged 12 years and older with heterozygous familial hypercholesterolemia (HeFH). pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH). LEQVIO is a small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 (PCSK9) mRNA indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in:...
Common Doses
- 284 mg
Dosage
2 DOSAGE AND ADMINISTRATION The recommended dosage of LEQVIO for adults and pediatric patients aged 12 years and older 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 ) 2.1 Recommended Dosage The recommended dosage of LEQVIO for adults and pediatric patients aged 12 years and older is 284 mg administered as a single subcutaneous injection initially, again at 3 months, and then...
Contraindications
- 4 CONTRAINDICATIONS LEQVIO is contraindicated in patients with a prior serious hypersensitivity reaction to inclisiran or any of the excipients in LEQVIO. Serious hypersensitivity reactions have included anaphylaxis and angioedema [see Adverse Reactions (6.2)] . Prior serious hypersensitivity to inclisiran or any of the excipients in LEQVIO.
Side Effects
- 6 ADVERSE REACTIONS The following adverse reactions are also discussed in other sections of the label: Hypersensitivity Reactions [see Warnings and Precautions (5.1)] 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. 6.
Interactions
- No major interactions listed on the FDA label. Always consult a healthcare professional.