Inclisiran

FDA Drug Information • Also known as: Leqvio

Brand Names: Leqvio
Dosage Form: LIQUID
Product Type: BULK INGREDIENT

Description

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. With one exception, the 2'ribose moieties of the inclisiran sodium are present as 2'-F or 2'-OMe ribonucleotide. In addition, six of the terminal phosphodiester backbones are present as phosphorothioate linkages as indicated below. The molecular formula of inclisiran sodium is C 529 H 664 F 12 N 176 Na 43 O 316 P 43 S 6 and its molecular weight is 17,284.72 g/mol. It has the following structural formula: Abbreviations: Af = adenine 2'-F ribonucleotide; Cf = cytosine 2'-F ribonucleotide; Gf = guanine 2'-F ribonucleotide; Am = adenine 2'-OMe ribonucleotide; Cm = cytosine 2'-OMe ribonucleotide; Gm = guanine 2'-OMe ribonucleotide; Um = uracil 2'-OMe ribonucleotide; L96 = triantennary GalNAc (N-acetyl-galactosamine) LEQVIO is a sterile, preservative-free, clear, and colorless to pale yellow solution for subcutaneous use in a prefilled syringe. Each syringe contains 1.5 mL of solution containing the equivalent of 284 mg inclisiran (present as 300 mg inclisiran sodium salt). LEQVIO is formulated in Water for Injection and may also contain sodium hydroxide and/or phosphoric acid for pH adjustment to a target pH of 7.0. molecular formula of inclisiran sodium

What Is Inclisiran Used For?

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: adults with hypercholesterolemia. ( 1 ) adults and pediatric patients aged 12 years and older with heterozygous familial hypercholesterolemia (HeFH). ( 1 ) pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH). ( 1 )

Dosage and Administration

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 every 6 months. If a planned dose is missed by less than 3 months, administer LEQVIO and maintain dosing according to the patient’s original schedule. If a planned dose is missed by more than 3 months, restart with a new dosing schedule - administer LEQVIO initially, again at 3 months, and then every 6 months. Assess LDL-C when clinically indicated. The LDL-lowering effect of LEQVIO may be measured as early as 30 days after initiation and anytime thereafter without regard to timing of the dose. 2.2 Important Administration Instructions LEQVIO should be administered by a healthcare professional. Inject LEQVIO subcutaneously into the abdomen, upper arm, or thigh. Do not inject in areas of active skin disease or injury, such as sunburns, skin rashes, inflammation, or skin infections. Inspect LEQVIO visually before use. It should appear clear and colorless to pale yellow. Do not use if particulate matter or discoloration is seen. For more detailed instruction on administration of the prefilled syringe, see Instructions for Use.

Side Effects (Adverse Reactions)

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. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Reactions in Adults with Hypercholesterolemia The data in Table 1 are derived from 3 placebo-controlled trials that included 1,833 adults with hypercholesterolemia treated with LEQVIO, including 1,682 exposed for 18 months (median treatment duration of 77 weeks) [see Clinical Studies (14)] . The mean age of the population was 64 years, 32% of the population were female, 92% were White, 6% were Black or African American, 1% were Asian, and < 1% were other races; 6% identified as Hispanic or Latino ethnicity. At baseline, 12% of patients had a diagnosis of HeFH and 85% had clinical atherosclerotic cardiovascular disease (ASCVD). Adverse reactions reported in at least 3% of LEQVIO-treated patients, and more frequently than in placebo-treated patients, are shown in Table 1. Table 1: Adverse Reactions Occurring in Greater Than or Equal to 3% of LEQVIO-treated Adults with Hypercholesterolemia and More Frequently than with Placebo (Trials 1, 2, and 3) Adverse Reactions Placebo (N = 1,822) % LEQVIO (N = 1,833) % †includes related terms such as: injection site pain, erythema and rash Injection site reaction† 2 8 Arthralgia 4 5 Bronchitis 3 4 Adverse reactions led to discontinuation of treatment in 2.5% of patients treated with LEQVIO and 1.9% of patients treated with placebo. The most common adverse reactions leading to treatment discontinuation in patients treated with LEQVIO were injection site reactions (0.2% versus 0% for LEQVIO and placebo, respectively). Adverse Reactions in Pediatric Patients with HeFH In a 24-month, two-part trial of 141 pediatric patients aged 12 years and older with HeFH (Trial 4), consisting of a 12-month randomized, double-blind, placebo-controlled part (Part 1/Year 1), followed by a 12-month open-label part (Part 2/Year 2), 93 patients received 284 mg of LEQVIO subcutaneously during Part 1 and 139 patients were treated with LEQVIO during Part 2 [see Clinical Studies (14)] . During Part 2, 91 patients continued LEQVIO treatment for a second year and 48 patients switched from placebo to LEQVIO for 1 year of treatment. The safety profile reported in pediatric patients with HeFH was consistent with the description above for adult patients with hypercholesterolemia, with the exception of headache. In pediatric patients with HeFH, the incidence of headache was 6% among patients who received placebo versus 13% of LEQVIO-treated patients during the double-blind study period. Adverse Reactions in Pediatric Patients with HoFH In a 24-month, two-part trial of 13 pediatric patients aged 12 years and older with HoFH (Trial 5), consisting of a 12-month randomized, double-blind, placebo-controlled part (Part 1/Year 1), followed by a 12-month open-label part (Part 2/Year 2), 9 patients received 284 mg of LEQVIO administered subcutaneously during Part 1 and 13 patients were treated with LEQVIO during Part 2 [see Clinical Studies (14)] . During Part 2, 9 patients continued LEQVIO treatment for a second year and 4 patients switched from placebo to LEQVIO for 1 year of treatment. The safety profile reported in pediatric patients was consistent with adult patients with hypercholesterolemia. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of LEQVIO....

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.

Pregnancy and Breastfeeding

8.1 Pregnancy 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 hypercholesterolemia 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 hypercholesterolemia 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...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING 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)].

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.