Introduction

Antilipemic agent; small interfering RNA (siRNA) directed to proprotein convertase subtilisin kexin type 9 PCSK9 mRNA.

Uses for Inclisiran (Systemic)

Primary Hyperlipidemia

Used 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).

AHA/ACC cholesterol management guideline states that lifestyle modification is the foundation of atherosclerotic cardiovascular disease (ASCVD) risk reduction.

If pharmacologic therapy is needed, statins are the first-line drugs of choice.

Certain patient groups may benefit from the addition of a nonstatin drug such as inclisiran if maximally tolerated statin therapy is insufficient to achieve goal reductions in LDL cholesterol concentrations.

Guidelines support the use of inclisiran in patients receiving maximal statin therapy who require additional LDL-lowering therapy despite treatment with ezetimibe and/or a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor.

Inclisiran (Systemic) Dosage and Administration

General

Patient Monitoring

• Monitor LDL-C) when clinically indicated during treatment; the LDL-lowering effect of inclisiran may be measured as early as 30 days after initiation and anytime thereafter without regard to timing of the dose.

Administration

Sub-Q Administration

Administer by sub-Q injection.

Available as single-dose prefilled syringes containing 284 mg/1.5 mL (189 mg/mL).

Administer by a healthcare professional. Administer sub-Q injections into the abdomen, upper arm, or thigh; do not inject in areas of active skin disease or injury (e.g., sunburns, skin rashes, inflammation, skin infections).

Dosage

Available as inclisiran sodium; dosage expressed in terms of inclisiran. Each 1.5-mL syringe contains the equivalent of 284 mg inclisiran.

Adults

Primary Hyperlipidemia

Sub-Q

284 mg as a single injection, again at 3 months, and then every 6 months; used in combination with statin therapy.

If a planned dose is missed by <3 months, administer inclisiran and maintain dosing according to the patient’s original schedule.

If a planned dose is missed by >3 months, restart with a new dosing schedule by administering inclisiran initially, again at 3 months, and then every 6 months.

Prescribing Limits

Special Populations

Hepatic Impairment

No dose adjustments necessary in mild or moderate hepatic impairment. Not evaluated in patients with severe hepatic impairment.

Renal Impairment

No dose adjustments necessary in mild, moderate, or severe renal impairment. Not evaluated in patients with end stage renal disease.

Geriatric Use

No specific dosage recommendations at this time.

Contraindications

None.

Warnings/Precautions

Warnings

Immunogenicity

Potential for immunogenicity with all oligonucleotides, including inclisiran. In clinical studies, anti-inclisiran antibodies detected. No evidence that presence of anti-drug binding antibodies impacted efficacy, safety, or pharmacodynamics; however, long-term consequences of continued inclisiran treatment in presence of anti-drug binding antibodies unknown.

Specific Populations

Pregnancy

No available data on use in pregnant women to assess for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Based on mechanism of action, may cause fetal harm when administered during pregnancy. Discontinue inclisiran when pregnancy is recognized or, alternatively, consider ongoing therapeutic needs of the individual patient. Treatment of hyperlipidemia is not generally necessary during pregnancy.

Lactation

Not known whether inclisiran is distributed into human milk; effects of the drug on breast-fed infants or on milk production also unknown. Inclisiran was detected in milk of lactating rats; therefore, likely that the drug will be present in human milk. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for inclisiran and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

In clinical studies, no overall differences in safety or efficacy observed between patients ≥65 years of age and younger patients; however, greater sensitivity to adverse reactions in some older individuals cannot be ruled out.

Hepatic Impairment

No dose adjustment necessary for patients with mild to moderate hepatic impairment. Not studied in patients with severe hepatic impairment.

Renal Impairment

No dose adjustment necessary for patients with mild, moderate, or severe renal impairment. Not studied in patients with end stage renal disease.

Common Adverse Effects

Common adverse reactions (≥3%): injection site reaction, arthralgia, bronchitis.

General

Patient Monitoring

• Monitor LDL-C) when clinically indicated during treatment; the LDL-lowering effect of inclisiran may be measured as early as 30 days after initiation and anytime thereafter without regard to timing of the dose.

Administration

Sub-Q Administration

Administer by sub-Q injection.

Available as single-dose prefilled syringes containing 284 mg/1.5 mL (189 mg/mL).

Administer by a healthcare professional. Administer sub-Q injections into the abdomen, upper arm, or thigh; do not inject in areas of active skin disease or injury (e.g., sunburns, skin rashes, inflammation, skin infections).

Dosage

Available as inclisiran sodium; dosage expressed in terms of inclisiran. Each 1.5-mL syringe contains the equivalent of 284 mg inclisiran.

Adults

Primary Hyperlipidemia

Sub-Q

284 mg as a single injection, again at 3 months, and then every 6 months; used in combination with statin therapy.

If a planned dose is missed by <3 months, administer inclisiran and maintain dosing according to the patient’s original schedule.

If a planned dose is missed by >3 months, restart with a new dosing schedule by administering inclisiran initially, again at 3 months, and then every 6 months.

Prescribing Limits

Special Populations

Hepatic Impairment

No dose adjustments necessary in mild or moderate hepatic impairment. Not evaluated in patients with severe hepatic impairment.

Renal Impairment

No dose adjustments necessary in mild, moderate, or severe renal impairment. Not evaluated in patients with end stage renal disease.

Geriatric Use

No specific dosage recommendations at this time.