LEQVIOR is indicated as an adjunct to diet and exercise to reduce low-density lipoprotein cholesterol (LDL-C) in:1. adults with hypercholesterolemia.2. adults and pediatric patients aged 12 years and older with heterozygous familial hypercholesterolemia (HeFH).3. pediatric patients aged 12 years and older with homozygous familial hypercholesterolemia (HoFH).

Cholesterol Absorption Inhibitors

Absorption:Following a single subcutaneous administration, systemic exposure to inclisiran increased in a linear and dose proportional manner over a range from 25 mg to 800 mg of inclisiran sodium. At the recommended dosing regimen of 284 mg of LEQVIO, plasma concentrations reached peak in approximately 4 hours post dose with a mean Cmax of 509 ng/mL. Concentrations reached undetectable levels after 24 to 48 hours post dosing. The mean area under the plasma concentration-time curve from dosing extrapolated to infinity was 7,980 ng*h/mL. Pharmacokinetic findings following multiple subcutaneous administrations of LEQVIO were similar to single-dose administration.Distribution:Inclisiran is 87% protein bound in vitro at the relevant clinical plasma concentrations. Following a single subcutaneous 284 mg dose of LEQVIO to healthy adults, the apparent volume of distribution is approximately 500 L. Inclisiran has been shown to have high uptake into, and selectively for the liver, the target organ for cholesterol lowering.Elimination:The terminal elimination half-life of LEQVIO is approximately 9 hours, and no accumulation occurs with multiple dosing.Metabolism:Inclisiran is primarily metabolized by nucleases to shorter nucleotides of varying length. Inclisiran is not a substrate for CYP450 or transporters.Excretion:Approximately 16% of LEQVIO is cleared through the kidney.

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

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.

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.

副作用：Hypersensitivity: anaphylaxis, angioedema, rash, pruritus, and urticaria.

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.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.

The safety and effectiveness of LEQVIO as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HeFH have been established in pediatric patients aged 12 years and older. Use of LEQVIO for this indication is based on data from a 12-month, randomized, placebo-controlled, double-blind study in 141 pediatric patients with HeFH. This indication is also supported by evidence from an adequate and well-controlled study in adults with HeFH. The safety profile reported in pediatric patients aged 12 years and older with HeFH was consistent with adult patients with hypercholesterolemia, with the exception of headache [see Adverse Reactions (6.1), Clinical Studies (14)].The safety and effectiveness of LEQVIO as an adjunct to diet and other LDL-C-lowering therapies for the treatment of HoFH have been established in pediatric patients aged 12 years and older. Use of LEQVIO for this indication is based on data from a 12-month, randomized, placebo-controlled, double-blind study in 13 pediatric patients with HoFH [see Adverse Reactions (6.1), Clinical Studies (14)].The safety and effectiveness of LEQVIO have not been established in pediatric patients with HeFH or HoFH younger than 12 years of age. The safety and effectiveness of LEQVIO has not been established in pediatric patients with other types of hypercholesterolemia.

No dose adjustments are necessary for patients with mild, moderate, or severe renal impairment. LEQVIO has not been studied in patients with end stage renal disease.

No dose adjustment is necessary in patients with mild to moderate hepatic impairment. LEQVIO has not been studied in patients with severe hepatic impairment.

Store LEQVIO at controlled room temperature 20°C to 25°C with allowable excursions between 15°C and 30°C