PCSK9 Inhibitor Dosing Frequency
For evolocumab, administer 140 mg subcutaneously every 2 weeks OR 420 mg once monthly; for alirocumab, use 75-150 mg every 2 weeks OR 300 mg once monthly; for inclisiran, give 284 mg at baseline, repeat at 3 months, then every 6 months thereafter. 1
Evolocumab Dosing
- Standard regimen: 140 mg subcutaneously every 2 weeks 2, 3
- Alternative regimen: 420 mg subcutaneously once monthly 2, 3
- Both regimens provide equivalent LDL-C lowering efficacy (~60% reduction) 4
- Patient preference determines which schedule to use; 86% of patients in the FOURIER trial chose the every-2-week regimen 4
Alirocumab Dosing
- Starting dose: 75 mg subcutaneously every 2 weeks 1, 3
- Higher dose: 150 mg every 2 weeks (if additional LDL-C lowering needed) 1, 3
- Monthly alternative: 300 mg once monthly 3
- Dose can be titrated based on LDL-C response; in ODYSSEY OUTCOMES, dosing was adjusted between 75-150 mg to maintain LDL-C between 25-50 mg/dL 1
Inclisiran Dosing
- Initial dose: 284 mg subcutaneously at baseline 5
- Second dose: 284 mg at 3 months 5
- Maintenance: 284 mg every 6 months thereafter 6, 7
- This twice-yearly dosing represents a major practical advantage over monoclonal antibodies, though cardiovascular outcomes data are still pending 6
Key Practical Considerations
Storage requirements differ: Evolocumab and alirocumab require refrigeration at 2-8°C 8, while inclisiran has similar storage needs 5. This matters for patient adherence and travel.
Self-administration: Both evolocumab and alirocumab are self-injected at home 7, whereas inclisiran is typically administered in the clinic due to its infrequent dosing schedule 6.
Dose equivalence: The every-2-week and monthly regimens for evolocumab and alirocumab provide comparable LDL-C reductions 9. Modeling suggests alirocumab 75 mg every 2 weeks approximates 150 mg every 3 weeks, and evolocumab 140 mg every 2 weeks approximates 420 mg every 5 weeks 9.
Common Pitfall
Do not combine PCSK9 inhibitors: There is no evidence for additional benefit from combining a monoclonal antibody with inclisiran 6. If switching from evolocumab or alirocumab to inclisiran, discontinue the monoclonal antibody. Be aware that LDL-C may temporarily rise during the transition, as inclisiran takes longer to achieve its full effect compared to the immediate action of monoclonal antibodies 10.
Monitor during switches: When changing between PCSK9 inhibitors, expect different magnitudes of LDL-C reduction. Alirocumab typically reduces LDL-C by 50-60% 3, evolocumab by approximately 60% 4, and inclisiran by 30-50% 10. Regular LDL-C monitoring is essential after any switch 10.