Recommended Dose of Evolocumab
For adults with atherosclerotic cardiovascular disease (ASCVD) or primary hypercholesterolemia including heterozygous familial hypercholesterolemia (HeFH), administer evolocumab 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly. 1
Dosing by Clinical Indication
Standard Dosing (ASCVD, Primary Hypercholesterolemia, HeFH)
- 140 mg subcutaneously every 2 weeks (most commonly used regimen—86% of patients in FOURIER trial) 2
- OR 420 mg subcutaneously once monthly as an alternative 1, 2
- Administer in the thigh, abdomen, or upper arm 1
Homozygous Familial Hypercholesterolemia (HoFH)
- Start with 420 mg subcutaneously once monthly 1, 2
- If inadequate LDL-C reduction after 12 weeks, increase to 420 mg every 2 weeks 1
- For patients on LDL apheresis: may initiate at 420 mg every 2 weeks to align with apheresis schedule; administer after apheresis is complete 1
Pediatric Patients (≥10 years old)
- HeFH: 140 mg every 2 weeks OR 420 mg once monthly 1
- HoFH: Same dosing as adults (420 mg monthly, escalate to every 2 weeks if needed) 1
Administration Details
For the 420 mg dose, you must give either:
- Three consecutive 140 mg injections within 30 minutes at different injection sites 1, 3, OR
- Use the prefilled single-dose on-body infuser 1
Expected LDL-C Reduction
The magnitude of LDL-C lowering varies by regimen:
- 140 mg every 2 weeks: 64% additional reduction when added to maximally tolerated statin 1
- 420 mg monthly: 58% additional reduction when added to maximally tolerated statin 1
Both regimens achieve median LDL-C levels around 30 mg/dL (0.78 mmol/L) in clinical trials 4, with 95% of patients reaching LDL-C <70 mg/dL (1.8 mmol/L) 5.
Clinical Context
The every-2-week regimen provides slightly greater LDL-C reduction (64% vs 58%), which may be relevant for patients requiring maximal lipid lowering 1. However, both dosing schedules demonstrated cardiovascular benefit in outcomes trials 4. The FOURIER trial, which established cardiovascular risk reduction with evolocumab, predominantly used the 140 mg every 2 weeks regimen 2, 4.
No dose adjustment is needed for renal impairment (including end-stage renal disease on hemodialysis) or mild-to-moderate hepatic impairment 2. No data exist for severe hepatic impairment 2.
Common Pitfalls
- Don't underdose HoFH patients: Start at 420 mg monthly but be prepared to escalate to every 2 weeks if LDL-C goals aren't met after 12 weeks 1
- For 420 mg dosing: Remember this requires either three separate injections or the on-body infuser device—ensure patients understand the administration method 1
- Latex sensitivity: The needle covers contain latex; advise latex-sensitive patients accordingly 1