What is the recommended use and dosage of Repatha (evolocumab) for patients with high cholesterol?

Repatha (Evolocumab) Dosage and Use for High Cholesterol

Repatha (evolocumab) is recommended at a dosage of 140 mg every 2 weeks OR 420 mg once monthly administered subcutaneously for adults with high cholesterol, including those with established cardiovascular disease or primary hyperlipidemia. 1

FDA-Approved Indications

• Reduction of cardiovascular event risk (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, coronary revascularization) in adults with established cardiovascular disease 1
• Treatment of adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) as adjunct to diet, alone or with other LDL-C-lowering therapies 2, 1
• Treatment of pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH) as adjunct to diet and other LDL-C-lowering therapies 2, 1
• Treatment of adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH) as adjunct to diet and other LDL-C-lowering therapies 2, 1

Dosage Recommendations

For Adults with Primary Hyperlipidemia or Established CVD:

• 140 mg subcutaneously every 2 weeks OR
• 420 mg subcutaneously once monthly 2, 1

For Pediatric Patients (≥10 years) with HeFH:

• 140 mg subcutaneously every 2 weeks OR
• 420 mg subcutaneously once monthly 2, 1

For Adults and Pediatric Patients (≥10 years) with HoFH:

• Initial dose: 420 mg subcutaneously once monthly
• May increase to 420 mg every 2 weeks if clinically meaningful response not achieved after 12 weeks
• For patients on lipid apheresis: 420 mg every 2 weeks (administer after apheresis session) 2, 1

Administration Instructions

• Administer subcutaneously in the abdomen, thigh, or upper arm 2
• For 420 mg dose: Use prefilled single-dose on-body infuser or give 3 (140-mg) injections consecutively within 30 minutes 2
• Allow Repatha to warm to room temperature for at least 30 minutes (prefilled autoinjector/syringe) or 45 minutes (on-body infuser) before administration 1
• If a dose is missed within 7 days, administer and resume original schedule; if more than 7 days, follow specific instructions based on dosing regimen 1

Efficacy

• Reduces LDL-C by approximately 60% when added to maximally tolerated statin therapy 2, 3
• Can achieve mean LDL-C levels of approximately 30 mg/dL (0.78 mmol/L) 4
• Also reduces other lipid parameters, including Lp(a) by up to 25% 2
• FOURIER trial demonstrated significant reduction in cardiovascular events (hazard ratio 0.85,95% CI 0.79-0.92) compared to placebo over median 2.2 years of follow-up 4

Safety and Tolerability

• Generally well-tolerated with adverse effects including: 2, 4
  • Injection site reactions (more common with evolocumab than placebo: 2.1% vs 1.6%)
  • Nasopharyngitis
  • Upper respiratory tract infections
  • Influenza-like symptoms
  • Myalgia
• No significant increase in neurocognitive events or new-onset diabetes compared to placebo 4
• Contraindicated in patients with history of hypersensitivity to evolocumab 2
• Consider prescribing a presentation that does not contain dry natural rubber for individuals sensitive to latex 1

Monitoring

• LDL-C lowering effect may be measured as early as 4 weeks after initiation 1
• For patients receiving the monthly 420 mg dose, LDL-C can vary during the dosing interval; recommend measuring LDL-C just prior to the next scheduled dose 1

Clinical Considerations

• Particularly valuable for patients unable to reach LDL-C goals despite treatment with statins or other lipid-lowering therapies 3
• Appropriate for statin-intolerant patients 3
• High cost may restrict use in some clinical settings 5
• Consider as add-on therapy for high-risk patients with inadequate LDL-C reduction on maximally tolerated statin therapy 2

Comparison to Alternatives

• Alirocumab (Praluent) is a similar PCSK9 inhibitor with comparable efficacy and safety profile 6, 7
• Non-PCSK9 inhibitor alternatives include ezetimibe (18-25% LDL-C reduction) and bile acid sequestrants (15-30% LDL-C reduction) 6

Remember that the LDL-lowering effect of Repatha is substantial and can help patients achieve previously unattainable LDL-C levels, which has been shown to reduce cardiovascular events in high-risk populations 4.