Leqvio Inclisiran Sodium Injection

1. Indications and Usage
Primary Hypercholesterolemia or Mixed Dyslipidemia: For adult patients who have not achieved their LDL-C goals on maximum tolerated statin therapy, used in combination with statins or other lipid-lowering therapies; or for those who are intolerant or have contraindications to statins, used alone or in combination with other lipid-lowering therapies.
2. Dosage and Administration
Route of Administration: For Subcutaneous (SC) Injection ONLY.
Recommended Dosage: 284 mg administered as a single dose.
Critical Administration Instructions:
Dosing Schedule: Initial dosing on Day 0 and Day 90 (Month 3), followed by maintenance dosing every 6 months thereafter.
Administration Site: Primarily administered in the abdomen. Alternative sites include the upper arm or thigh.
Missed Dose: If the next dose is delayed by less than 3 months, administer immediately and continue the original schedule. If delayed by more than 3 months, restart the initial regimen (Day 0 and Day 90).
Transition from PCSK9 mAbs: Can be administered immediately after the last dose of a PCSK9 inhibitor monoclonal antibody (ideally within 2 weeks to maintain LDL-C lowering effects).
3. Mechanism of Action
RNA Interference: Inclisiran is a double-stranded siRNA conjugated with N-acetyl-galactosamine (GalNAc) for targeted hepatocyte uptake.
PCSK9 Inhibition: It specifically binds to and degrades PCSK9 messenger RNA (mRNA) in the liver, blocking PCSK9 protein synthesis.
LDL-C Reduction: By reducing PCSK9 levels, it increases the recycling and expression of LDL receptors on hepatocyte surfaces, thereby enhancing hepatic uptake of LDL-C and lowering circulating LDL-C levels.
4. Safety and Warnings
Hypersensitivity: Hypersensitivity to the active substance or excipients is a contraindication. Serious allergic reactions (e.g., urticaria, angioedema) have been reported.
Hepatic Impairment: No dose adjustment is required for mild-to-moderate hepatic impairment. However, use with caution in severe hepatic impairment (Child-Pugh C).
Renal Impairment: No dose adjustment is required for mild-to-severe renal impairment or end-stage renal disease. However, experience is limited in these populations.
5. Adverse Reactions and Clinical Research
Most Common Adverse Reactions: The most common adverse reaction is injection site reactions, including injection site pain, erythema, and rash.
Clinical Research Highlights: Key Phase 3 clinical trials (ORION-9, ORION-10, ORION-11) demonstrated that Inclisiran significantly reduced LDL-C levels with a favorable safety profile and a low discontinuation rate.
6. Drug Interactions
Statins and Other Lipid-Lowering Therapies: No clinically significant pharmacokinetic interactions have been observed. It is safe to use in combination with statins (e.g., atorvastatin, rosuvastatin).
Hemodialysis: For patients undergoing hemodialysis, dialysis should be avoided for at least 72 hours after administration of the drug.
7. Pharmaceutical Information
Chemical Composition: Active Ingredient: Inclisiran Sodium. Excipients: Water for Injection, Sodium Hydroxide, Phosphoric Acid.
Appearance: Clear, colorless to pale yellow solution.
Packaging: 284 mg/1.5 mL pre-filled syringe (single-use).
Storage: Store at room temperature (up to 30°C) and protect from light. Do not freeze.