inclisiran (Rx)

Brand and Other Names:Leqvio
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

injectable SC solution

  • 284mg/1.5mL (prefilled syringe)

Hypercholesterolemia

Indicated as an adjunct to diet and maximally tolerated statin therapy for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) who require additional lowering of low-density lipoprotein cholesterol (LDL-C)

284 mg SC x 1 dose initially

Repeat in 3 months and then every 6 months thereafter

Dosage Modifications

Renal impairment

  • Mild, moderate, or severe: No dosage adjustment necessary

Hepatic impairment

  • Mild or moderate: No dosage adjustment necessary
  • Severe: Not studied

Dosing Considerations

Monitor parameters: Assess LDL-C when clinically indicated; may be measured as early as 30 days after initiation

Limitation of use: Effect on cardiovascular morbidity and mortality has not been determined

Safety and efficacy not established

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Adverse Effects

1-10%

Injection site reaction (8.2%)

Arthralgia (5%)

Urinary tract infection (4.4%)

Bronchitis (4.3%)

Diarrhea (3.9%)

Pain in extremity (3.3%)

Dyspnea (3.2%)

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Warnings

Contraindications

None

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Pregnancy & Lactation

Pregnancy

No data are available on use in pregnant females for drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

Discontinue therapy when pregnancy is recognized

Based on mechanism of action, therapy may cause fetal harm when administered to pregnant females

Animal data

  • No evidence of embryo-fetal toxicity or teratogenicity was observed in rats with SC administration during organogenesis at doses up to 5-10x the maximum recommended human dose (MRHD)
  • No effects on the development of the F1 generation (eg, survival, growth, physical and reflexological development, behavior, and reproductive performance) were observed at doses up to 5x the MRHD, based on body surface area comparison/dose

Lactation

There is no information on drug presence in human milk, effects on breastfed infants, or effects on milk production

Inclisiran was present in the milk of lactating rats in all dosing groups

When a drug is present in animal milk, it is likely that the drug will be present in human milk

Oligonucleotide-based products usually have poor bioavailability; consider it unlikely that low levels of inclisiran present in milk will adversely impact an infant’s development during lactation

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

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Pharmacology

Mechanism of Action

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 RNA interference mechanism and directs catalytic breakdown of mRNA for proprotein convertase subtilisin kexin type 9 (PCSK9); this increases LDL-C receptor recycling and expression on the hepatocyte cell surface, which increases LDL-C uptake andlowers LDL-C levels in the circulation

Absorption

Peak plasma time: 4 hr

Peak plasma concentration: 509 ng/mL

AUC: 7980 ng⋅hr/mL

Distribution

Protein bound: 87%

Vd: 500 L (healthy adults)

Metabolism

Primarily metabolized by nucleases to shorter nucleotides of varying length

Not a substrate for CYP450 or transporters

Elimination

Half-life: 9 hr

Renally cleared: ~16% of drug

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Administration

SC Administration

Injection should be administered by healthcare provider

Administer SC into abdomen, upper arm, or thigh; do NOT inject in areas of active skin disease or injury (eg, sunburns, skin rashes, inflammation, or skin infections)

Visually inspect before use; solution appears clear and colorless to pale yellow; discard if particulate matter or discoloration is seen

Missed dose

  • <3 months: administer inclisiran and maintain dosing according to original schedule
  • >3 months: Restart with new dosing schedule; administer inclisiran initially, again at 3 months, and then q6months

Storage

Store at 20-25ºC (68-77ºF); excursions allowed to 15-30ºC (59-86ºF)

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Images

No images available for this drug.
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Patient Handout

A Patient Handout is not currently available for this monograph.
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Formulary

FormularyPatient Discounts

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The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

Tier Description
1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
NC NOT COVERED – Drugs that are not covered by the plan.
Code Definition
PA Prior Authorization
Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
QL Quantity Limits
Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
ST Step Therapy
Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
OR Other Restrictions
Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.