Repatha (Evolocumab) Initial Dosing
The recommended initial dose of Repatha for adults and children ≥10 years with heterozygous familial hypercholesterolemia is either 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly, with no dose adjustments required for renal or hepatic impairment. 1
Standard Dosing Regimens
Adults with Primary Hyperlipidemia or Mixed Dyslipidemia
- 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly 1, 2, 3
- Both regimens provide comparable LDL-C reduction: 64% with the every-2-week regimen and 58% with the monthly regimen 1
- In the FOURIER trial, 86% of participants used the every-2-week regimen 1
- Either dosing schedule may be selected based on patient preference, as lipid-lowering efficacy is equivalent 4, 1
Pediatric Patients (≥10 Years) with Heterozygous Familial Hypercholesterolemia
- 420 mg subcutaneously once monthly 5
- This dosing achieved a 44.5% reduction in LDL-C at 24 weeks in pediatric patients aged 10-17 years 5
- Patients should have an LDL-C ≥130 mg/dL despite stable lipid-lowering therapy for at least 4 weeks 5
Homozygous Familial Hypercholesterolemia
- Initial dose: 420 mg once monthly 1
- If inadequate response after 12 weeks: increase to 420 mg every 2 weeks 1
- Expected LDL-C reduction is approximately 30% in this population, with efficacy dependent on residual LDL receptor activity 4
No Dose Adjustments Required
Renal Impairment
- No dose adjustment necessary for any degree of renal impairment, including end-stage renal disease 6
- Pharmacodynamic effects on LDL-C remain consistent regardless of renal function 6
Hepatic Impairment
- No dose adjustment necessary for mild to moderate hepatic impairment 6
- No clinically meaningful differences in LDL-C reduction were observed 6
Other Patient Factors
- No adjustments needed based on body weight, race, sex, or age 6
- Concomitant statin use does not require dose modification; evolocumab provides additional 50-60% LDL-C reduction when added to maximally tolerated statin therapy 1, 7
Patient Selection Criteria for Initiation
Adults
- LDL-C ≥70 mg/dL (or non-HDL-C ≥100 mg/dL) despite maximally tolerated statin therapy 1
- For heterozygous familial hypercholesterolemia: adults aged 30-75 years with LDL-C ≥100 mg/dL on maximal statin plus ezetimibe 1
- For severe primary hypercholesterolemia: baseline LDL-C ≥220 mg/dL and on-treatment LDL-C ≥130 mg/dL despite maximal therapy 1
Pediatric Patients
- Age 10-17 years with heterozygous familial hypercholesterolemia 5
- LDL-C ≥130 mg/dL and triglycerides ≤400 mg/dL 5
- Stable lipid-lowering treatment for at least 4 weeks before initiation 5
Expected Lipid Effects at Initial Dosing
- LDL-C reduction: 50-65% from baseline, with median achieved LDL-C of 30 mg/dL at 48 weeks 4, 1
- Absolute LDL-C reduction: approximately 62 mg/dL 1
- Non-HDL-C reduction: 51% 1
- Lipoprotein(a) reduction: 25-27% 4, 1
- HDL-C increase: 8% 1
- Triglyceride reduction: 16% 1
Pharmacokinetic Considerations
- Effective half-life: 11-17 days, allowing for biweekly or monthly dosing 6
- Peak LDL-C reduction: approximately 1 week after 140 mg every 2 weeks; 2 weeks after 420 mg monthly 6
- Maximum PCSK9 suppression: within 4 hours of administration 6
- Elimination occurs through saturable binding to PCSK9 at lower concentrations and nonsaturable proteolytic pathways at higher concentrations 6
Common Pitfalls to Avoid
- Do not delay initiation waiting for specific renal or hepatic function tests, as no adjustments are needed 6
- Do not underdose pediatric patients: the 420 mg monthly dose is appropriate for children ≥10 years, not a reduced "pediatric" dose 5
- Do not switch dosing regimens frequently: both schedules are equally effective; choose one based on patient preference and maintain consistency 1
- Ensure adequate background therapy: patients should be on maximally tolerated statin therapy before adding evolocumab, as this population derives the greatest benefit 1, 7