Leqvio (Inclisiran) Indication and Dosing Regimen
Leqvio (inclisiran) is indicated 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). 1
Dosing Regimen
Recommended dosage: 284 mg administered as a subcutaneous injection
- Initially on day 1
- Again at 3 months
- Then every 6 months thereafter 1
Missed dose management:
- If missed by less than 3 months: Administer and maintain original schedule
- If missed by more than 3 months: Restart with a new dosing schedule (day 1,3 months, then every 6 months) 1
Administration Details
- Must be administered by a healthcare professional
- Injection sites: abdomen, upper arm, or thigh
- Avoid injecting in areas with active skin disease or injury
- Solution should appear clear and colorless to pale yellow 1
Clinical Efficacy
- Reduces LDL-C by approximately 44-54% 2
- LDL-lowering effect may be measured as early as 30 days after initiation 1
- Provides consistent LDL-C reduction with twice-yearly maintenance dosing 3
Patient Selection
Leqvio is appropriate for:
- Adults with primary hyperlipidemia (including HeFH) or mixed dyslipidemia
- Patients unable to reach LDL-C goals on maximally tolerated statin therapy 3
- According to the 2022 ACC Expert Consensus, inclisiran is an option for non-statin therapy in addition to maximally tolerated statin therapy for:
- Patients at very high risk of atherosclerotic cardiovascular disease (ASCVD)
- Patients with LDL-C >190 mg/dL 2
Contraindications
- Prior serious hypersensitivity reaction to inclisiran or any excipients
- Serious hypersensitivity reactions have included angioedema 1
Common Adverse Reactions
- Injection site reactions (8% vs. 2% with placebo)
- Arthralgia (5% vs. 4% with placebo)
- Bronchitis (4% vs. 3% with placebo) 1
Monitoring
- Assess LDL-C when clinically indicated
- The LDL-lowering effect can be measured as early as 30 days after initiation and anytime thereafter 1
Mechanism of Action
Inclisiran is a small interfering RNA (siRNA) that prevents hepatic synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9), thereby:
- Decreasing PCSK9 synthesis
- Reducing degradation of LDL receptors
- Increasing available LDL receptors to clear LDL-C from circulation 2
Clinical Considerations
- Leqvio offers a significant advantage over other non-statin therapies due to its infrequent maintenance dosing regimen (twice yearly) 3
- Cardiovascular outcomes trials (ORION-4, VICTORION-1 PREVENT, and VICTORION-2 PREVENT) are ongoing to evaluate the ability of inclisiran to reduce major cardiovascular events 2
Practical Considerations
- Leqvio should be stored in the refrigerator
- Allow to warm to room temperature for at least 15 minutes before administration
- Inspect visually before use and do not use if particulate matter or discoloration is seen 1