Recommended Dose of Inclisiran
The recommended dose of inclisiran is 284 mg administered as a single subcutaneous injection initially, again at 3 months, and then every 6 months thereafter. 1, 2
Dosing Schedule
The dosing regimen follows a specific pattern designed to achieve sustained LDL-C reduction:
- Initial dose: 284 mg subcutaneous injection on Day 1 1, 2
- Second dose: 284 mg at 3 months (Day 90) 1, 2
- Maintenance doses: 284 mg every 6 months thereafter 1, 2
This twice-yearly maintenance schedule after the loading phase provides a significant adherence advantage compared to other non-statin lipid-lowering therapies. 1
Formulation Details
Each prefilled syringe contains 1.5 mL of solution with the equivalent of 284 mg inclisiran (present as 300 mg inclisiran sodium salt). 2 The medication is administered subcutaneously and is formulated as a sterile, preservative-free, clear, colorless to pale yellow solution. 2
Special Populations
No dose adjustments are required for the following patient populations:
- Renal impairment: No adjustment needed for mild, moderate, or severe renal impairment, though inclisiran has not been studied in end-stage renal disease 2
- Hepatic impairment: No adjustment needed for mild to moderate hepatic impairment, though not studied in severe hepatic impairment 2
- Geriatric patients: No dose adjustment required for patients 65 years or older 2
- Gender, race, or body weight: Population pharmacodynamic analysis showed these factors do not significantly influence inclisiran pharmacokinetics 2
Clinical Efficacy with Standard Dosing
The 284 mg dose administered on this schedule achieves robust LDL-C reductions:
- Mean placebo-corrected LDL-C reduction of 50.7% at day 510 in phase 3 trials (ORION-9, ORION-10, ORION-11) 1
- Time-adjusted mean reduction of 50.5% demonstrating sustained efficacy 1
- LDL-C reduction becomes apparent within 14 days post-dose, with mean reductions of 38-51% observed 30-180 days after a single dose 2
Important Clinical Considerations
Common pitfall to avoid: The medication requires refrigeration and specific handling per FDA labeling. 2 The most common adverse effect is injection site reactions (5.0% vs 0.7% for placebo), which are predominantly mild and not persistent. 1
The pharmacokinetic profile shows plasma concentrations peak approximately 4 hours post-dose with a terminal elimination half-life of approximately 9 hours, and no accumulation occurs with multiple dosing. 2 Despite higher plasma exposures in patients with renal impairment (2.3 to 3.3-fold increase in Cmax), LDL-C reductions remain similar across all renal function groups. 2