What are the dosing, administration, storage, and monitoring instructions for evolocumab (Repatha) in a patient with hypercholesterolemia requiring additional LDL‑cholesterol reduction beyond statins?

Repatha (Evolocumab) Administration Instructions

Administer Repatha 140 mg subcutaneously every 2 weeks OR 420 mg once monthly, with both regimens providing comparable LDL-C reductions of approximately 59-64%. 1

Dosing Regimens

Standard Dosing for Adults with ASCVD or Primary Hyperlipidemia

• 140 mg subcutaneously every 2 weeks (reduces LDL-C by ~64%) 2
• 420 mg subcutaneously once monthly (reduces LDL-C by ~58%) 2
• Either regimen is acceptable based on patient preference 1
• When switching between regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen 1

Homozygous Familial Hypercholesterolemia (HoFH)

• Initial dose: 420 mg once monthly 1
• If inadequate response after 12 weeks: Increase to 420 mg every 2 weeks 3, 1
• 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) with HeFH

• Same dosing as adults: 140 mg every 2 weeks OR 420 mg once monthly 1

Administration Technique

Preparation Steps

• Allow warming to room temperature: 30 minutes for prefilled autoinjector or syringe; 45 minutes for on-body infusor 1
• Visual inspection: Solution should be clear to opalescent, colorless to pale yellow; do not use if cloudy, discolored, or contains particles 1
• Injection sites: Thigh, abdomen, or upper arm 2, 1

For 420 mg Dose Administration

• Use the prefilled single-dose on-body infuser, OR 1
• Give 3 consecutive 140 mg injections within 30 minutes at different injection sites 2, 1
• For the 300 mg dose (alternative regimen), administer 2 consecutive 150 mg injections at different sites 2

Latex Considerations

• Some presentations contain dry natural rubber (latex derivative) in the needle cover 1
• Prescribe latex-free presentations for latex-sensitive individuals 1

Missed Dose Management

If missed within 7 days: Administer immediately and resume original schedule 1

If missed >7 days:

• Every 2-week regimen: Wait until next scheduled dose 1
• Monthly regimen: Administer dose and start new schedule based on this date 1

Monitoring

LDL-C Assessment Timing

• Earliest measurement: 4 weeks after initiation 1
• For monthly dosing: Measure LDL-C just prior to next scheduled dose, as levels can vary during the dosing interval 1
• Assess LDL-C when clinically appropriate 1

Expected Outcomes

• Median LDL-C reduction from 92 mg/dL to 30 mg/dL (59% reduction) at 48 weeks 3
• Additional 50-60% LDL-C reduction when added to maximally tolerated statin therapy 2, 4
• Also reduces total cholesterol, non-HDL cholesterol, apolipoprotein B, and lipoprotein(a) 5

Storage

• Refrigerate until use 1
• Do not use if refrigeration has been interrupted beyond manufacturer specifications 1

Safety Monitoring

Common Adverse Effects

• Nasopharyngitis, upper respiratory tract infection, influenza 2
• Injection site reactions (<5% of patients, typically very mild) 2
• Back pain 2
• No evidence of increased cognitive adverse effects (FOURIER, EBBINGHAUS trials) 2

Contraindications and Warnings

• Absolute contraindication: History of hypersensitivity to evolocumab 2
• If serious hypersensitivity occurs: Discontinue immediately, treat per standard of care, monitor until resolution 2
• No evidence of increased hemorrhagic stroke risk when added to statin therapy 2
• No detrimental impact on steroid hormone production, bile acid circulation, or neuronal function even at very low LDL-C levels (<20 mg/dL) 2

Clinical Context

Cardiovascular Outcomes

• Reduces major adverse cardiovascular events by 15% (composite endpoint) and cardiovascular death/MI/stroke by 20% in patients with ASCVD 2
• Reduces all strokes by 21% and ischemic stroke by 25% 2
• Benefits maintained with up to 4 years of treatment data available 2

Patient Selection

• Indicated when LDL-C remains ≥70 mg/dL (or non-HDL-C ≥100 mg/dL) despite maximally tolerated statin therapy 2
• Consider in heterozygous FH patients ≥30-75 years with LDL-C ≥100 mg/dL on maximal statin plus ezetimibe 2
• May be considered in severe primary hypercholesterolemia (baseline LDL-C ≥220 mg/dL) with LDL-C ≥130 mg/dL on maximal therapy 2