PCSK9 Inhibitor Dosing
For PCSK9 inhibitors, start alirocumab at 75 mg subcutaneously every 2 weeks (or 300 mg monthly) and evolocumab at 140 mg every 2 weeks (or 420 mg monthly), administered in the thigh, abdomen, or upper arm. 1
Alirocumab (Praluent) Dosing
Standard dosing regimens:
- Initial dose: 75 mg subcutaneously every 2 weeks
- Uptitration: Increase to 150 mg every 2 weeks if additional LDL-C reduction is needed
- Alternative regimen: 300 mg subcutaneously every 4 weeks (given as two consecutive 150 mg injections at different sites) 1
Special populations:
- HeFH on apheresis or HoFH: 150 mg every 2 weeks 1
- Post-ACS patients: Start at 75 mg every 2 weeks, uptitrate to 150 mg if targets not met 2
The 75 mg starting dose allows for dose optimization based on individual response, with approximately 45% LDL-C reduction at this dose and 58% reduction at 150 mg when added to maximally tolerated statin therapy 3.
Evolocumab (Repatha) Dosing
Standard dosing regimens:
- Primary option: 140 mg subcutaneously every 2 weeks
- Alternative option: 420 mg subcutaneously once monthly 1
Administration of 420 mg dose:
- Use prefilled single-dose on-body infuser (Pushtronex system), OR
- Give three consecutive 140 mg injections within 30 minutes at different sites 1, 4
Special populations:
- HoFH: Start 420 mg monthly; if inadequate LDL-C reduction after 12 weeks, increase to 420 mg every 2 weeks 1
- HoFH on apheresis: May initiate 420 mg every 2 weeks to correspond with apheresis schedule; administer after apheresis is complete 1
- Pediatric patients (≥10 years) with HeFH or HoFH: Same adult dosing (140 mg every 2 weeks or 420 mg monthly) 1, 4
Both dosing intervals (every 2 weeks vs monthly) achieve similar LDL-C reductions of approximately 60-64% when added to maximally tolerated statin therapy 3, 5.
Practical Administration Details
Injection sites: Rotate between thigh, abdomen, or upper arm 1
Timing considerations:
- Maximum LDL-C reduction occurs by 2 weeks after 140 mg evolocumab and by 3 weeks after 420 mg evolocumab 4
- Steady-state concentrations achieved by 12 weeks of dosing 4
- For patients on apheresis, inject PCSK9 inhibitors soon after (not immediately before) the apheresis procedure 6
Common pitfall: The monthly dosing regimens (300 mg alirocumab or 420 mg evolocumab) require multiple injections or specialized delivery devices, which may affect patient preference and adherence. The every-2-week regimens use single prefilled syringes or autoinjectors, potentially improving ease of use 1.
Clinical Context
These agents reduce LDL-C by approximately 50-60% across diverse populations and have demonstrated cardiovascular outcome benefits in major trials (FOURIER for evolocumab: 15% relative risk reduction; ODYSSEY OUTCOMES for alirocumab: 15% relative risk reduction) 2, 5, 2, 7. Both are well-tolerated with primarily injection-site reactions as adverse effects 3, 2.
The choice between alirocumab and evolocumab, or between dosing intervals, should be based on patient preference for injection frequency, ease of administration, and formulary considerations, as efficacy and safety profiles are comparable 5, 8.