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

Recommended Use and Dosage of Repatha (Evolocumab) for Patients with High Cholesterol

Repatha (evolocumab) should be used as a third-line therapy for patients with high cholesterol who have not achieved target LDL-C levels despite maximally tolerated statin therapy plus ezetimibe, with dosing of 140 mg subcutaneously every 2 weeks or 420 mg once monthly.

Patient Selection Criteria

Repatha is indicated for specific patient populations:

• Established ASCVD with inadequate LDL-C control:

  • Patients with LDL-C ≥70 mg/dL despite maximally tolerated statin plus ezetimibe 1, 2

• Familial Hypercholesterolemia:

  • Heterozygous FH (HeFH): LDL-C ≥100 mg/dL despite maximally tolerated statin plus ezetimibe 2
  • Homozygous FH (HoFH): As an adjunct to other LDL-C-lowering therapies 3

• Statin Intolerance:

  • Documented intolerance to at least 2 different statins, including one at lowest approved dose 2

Dosage Recommendations

The FDA-approved dosing regimens for Repatha are 3:

• Standard dosing options:

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

• Special populations:

  • Adults and pediatric patients (≥10 years) with HoFH: Initial dose of 420 mg monthly, with option to increase to 420 mg every 2 weeks if clinically meaningful response not achieved after 12 weeks
  • Patients on lipid apheresis: 420 mg every 2 weeks, administered after apheresis session

Treatment Algorithm

1. First-line therapy: High-intensity statin (atorvastatin ≥40 mg or rosuvastatin ≥20 mg daily) 2

2. Second-line therapy: Add ezetimibe if LDL-C reduction is <50% from baseline or target LDL-C not achieved 2

3. Third-line therapy: Add Repatha if LDL-C remains elevated despite maximally tolerated statin plus ezetimibe 1, 2:

   • For ASCVD patients: Consider if LDL-C ≥70 mg/dL
   • For HeFH without ASCVD: Consider if LDL-C >4.5 mmol/L (>180 mg/dL) or >3.6 mmol/L (>140 mg/dL) with additional risk factors 1

Administration Guidelines

• Allow Repatha to warm to room temperature for at least 30 minutes before administration 3
• Administer subcutaneously into abdomen, thigh, or upper arm, rotating injection sites 2, 3
• If a dose is missed 3:
  • Within 7 days: Administer and resume original schedule
  • After 7 days: For every-2-week dosing, wait until next scheduled dose; for monthly dosing, administer and start new schedule

Efficacy and Monitoring

• Repatha reduces LDL-C by 50-65% when added to statins 2, 4, 5
• The FOURIER trial demonstrated a 15% relative risk reduction in composite cardiovascular endpoints (HR 0.85,95% CI 0.79-0.92) 2, 6
• LDL-C lowering effect may be measured as early as 4 weeks after initiation 3
• For patients on monthly dosing, measure LDL-C just prior to the next scheduled dose 3
• Long-term efficacy has been demonstrated with consistent LDL-C reduction of approximately 56% maintained for up to 5 years 7

Safety Considerations

• Common side effects include injection site reactions, nasopharyngitis, and upper respiratory tract infections 2
• Patients with latex sensitivity should be advised that some needle covers contain dry natural rubber 2, 3
• No significant differences in serious adverse events compared to placebo in clinical trials 2, 6
• No neutralizing antibodies detected in long-term follow-up studies 7

Practical Considerations

• Prior authorization processes may be burdensome and high cost may restrict use despite excellent efficacy 2
• Ensure patient adherence to maximally tolerated statin plus ezetimibe before considering Repatha 1
• Verify that inadequate LDL-C control is not due to poor adherence to existing therapy 1

By following this structured approach, Repatha can be effectively incorporated into lipid management for appropriate patients with high cholesterol who have not achieved adequate control with standard therapies.