What is the indication and dosing for Rapatha (evolocumab) in patients with high cholesterol?

Repatha (Evolocumab): Indications and Dosing

Repatha (evolocumab) is FDA-approved to reduce cardiovascular events in adults with established cardiovascular disease and to lower LDL-cholesterol in patients with primary hyperlipidemia (including familial hypercholesterolemia), with standard dosing of 140 mg subcutaneously every 2 weeks or 420 mg once monthly. 1

FDA-Approved Indications

Evolocumab is indicated for: 2, 1

• Cardiovascular risk reduction: To reduce the risk of MI, stroke, and coronary revascularization in adults with established atherosclerotic cardiovascular disease 1
• Primary hyperlipidemia: As adjunct to diet, alone or with other LDL-lowering therapies, in adults with primary hyperlipidemia including heterozygous familial hypercholesterolemia (HeFH) 1
• Pediatric HeFH: In patients aged ≥10 years with HeFH, as adjunct to diet and other LDL-lowering therapies 1
• Homozygous familial hypercholesterolemia (HoFH): In adults and pediatric patients aged ≥10 years, as adjunct to other LDL-lowering therapies 1

Standard Dosing Regimens

Adults with ASCVD or Primary Hyperlipidemia

Administer either 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly 2, 3, 1

• Both regimens provide comparable LDL-C reduction (approximately 60% when added to statin therapy) 3, 4
• When switching between regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen 1
• Injection sites include thigh, abdomen, or upper arm; rotate sites with each administration 2, 3, 1

Pediatric Patients (≥10 years) with HeFH

Use the same dosing as adults: 140 mg every 2 weeks OR 420 mg once monthly 2, 3, 1

Homozygous Familial Hypercholesterolemia (HoFH)

Initial dose: 420 mg subcutaneously once monthly 2, 3, 1

• If inadequate LDL-C reduction after 12 weeks, increase to 420 mg every 2 weeks 2, 3, 1
• For patients on LDL apheresis, may initiate at 420 mg every 2 weeks to correspond with apheresis schedule 2, 1
• Administer evolocumab after the apheresis session is complete 2, 1

Administration Details

For the 420 mg dose, use either the prefilled single-dose on-body infuser OR give 3 consecutive 140 mg injections within 30 minutes at different injection sites 2, 3

• Allow refrigerated product to warm to room temperature for at least 30 minutes before injection 1
• Visually inspect prior to administration; solution should be clear to opalescent, colorless to pale yellow 1
• Some presentations contain dry natural rubber (latex derivative) in the needle cover; consider latex-free presentations for sensitive patients 3, 1

Monitoring and Response Assessment

LDL-C lowering effect can be measured as early as 4 weeks after initiation 1

• For patients receiving 420 mg monthly, LDL-C can vary during the dosing interval; measure just prior to the next scheduled dose 1
• In the FOURIER trial, evolocumab reduced LDL-C from a median baseline of 92 mg/dL to 30 mg/dL (59% reduction) 4

Clinical Efficacy Evidence

Evolocumab reduces major adverse cardiovascular events by 15% (HR 0.85; 95% CI 0.79-0.92; P<0.001) in patients with established ASCVD 3, 4

• The composite endpoint included CV death, MI, stroke, revascularization, or hospitalization for unstable angina 3, 4
• The key secondary endpoint of CV death, MI, or stroke was reduced by 20% (HR 0.80; 95% CI 0.73-0.88) 4
• Benefits were consistent across subgroups, including patients with baseline LDL-C as low as 74 mg/dL 4

Guideline-Based Treatment Algorithm

When to Add Evolocumab

For very high-risk ASCVD patients: 2

• If LDL-C remains ≥100 mg/dL (2.6 mmol/L) despite maximally tolerated statin and ezetimibe, adding a PCSK9 inhibitor is reasonable 2
• European guidelines recommend PCSK9 inhibitors for very high-risk patients not achieving LDL-C goals <55 mg/dL (1.4 mmol/L) on maximal statin plus ezetimibe 2

For severe primary hypercholesterolemia: 2

• Consider evolocumab in patients with baseline LDL-C ≥220 mg/dL who have LDL-C ≥130 mg/dL on maximal statin and ezetimibe 2
• For HeFH patients aged 30-75 years with LDL-C ≥100 mg/dL on maximal statin and ezetimibe, adding evolocumab may be reasonable 2

Safety Profile

Common adverse effects include nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions 3, 5

• Contraindicated in patients with hypersensitivity to evolocumab 3, 1
• No evidence of increased cognitive adverse effects in FOURIER or EBBINGHAUS trials 3
• Long-term safety data over median 4.1 years in familial hypercholesterolemia patients showed good tolerability 5

Special Considerations for Apheresis Patients

Evolocumab can reduce or eliminate the need for lipoprotein apheresis 6

• In the DE LAVAL study, 84% of patients avoided apheresis at 6 weeks when switched to evolocumab 6
• At 24 weeks, 77% of patients did not require apheresis 6
• For patients continuing apheresis, administer evolocumab after the apheresis session 1

Missed Dose Management

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

If missed >7 days: 1

• For every-2-week dosing: Wait until next scheduled dose
• For monthly dosing: Administer immediately and start new schedule based on this date