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

Repatha (Evolocumab) Dosage and Recommendations for High Cholesterol

Repatha (evolocumab) is recommended at a dose of 140 mg subcutaneously every 2 weeks OR 420 mg once monthly for patients with high cholesterol who have not achieved target LDL-C levels despite maximally tolerated statin therapy plus ezetimibe. 1, 2

Indications for Repatha

Repatha is indicated for:

1. Primary hyperlipidemia (including heterozygous familial hypercholesterolemia)

   • For adults with LDL-C ≥100 mg/dL despite maximally tolerated statin plus ezetimibe 2
   • As an adjunct to diet, alone or in combination with other LDL-C-lowering therapies 1

2. Homozygous familial hypercholesterolemia (HoFH)

   • Initial dose: 420 mg once monthly
   • Can be increased to 420 mg every 2 weeks if clinically meaningful response is not achieved in 12 weeks 1
   • For patients on apheresis: 420 mg every 2 weeks, administered after the apheresis session 2, 1

3. Established cardiovascular disease

   • For secondary prevention to reduce the risk of major adverse cardiovascular events 1
   • Priority for patients with ASCVD and LDL-C ≥70 mg/dL despite maximally tolerated statin plus ezetimibe 2

4. Pediatric patients (≥10 years) with heterozygous familial hypercholesterolemia

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

Treatment Algorithm

1. First-line therapy: High-intensity statin therapy (atorvastatin 40-80 mg or rosuvastatin 20-40 mg) 3

2. Second-line therapy: Add ezetimibe when LDL-C goals are not met with maximally tolerated statin therapy 3

3. Third-line therapy: Add Repatha when LDL-C remains elevated despite maximally tolerated statin plus ezetimibe:

   • For patients with ASCVD: Add when LDL-C ≥70 mg/dL 2
   • For patients with HeFH: Add when LDL-C ≥100 mg/dL 2
   • For patients with severe primary hypercholesterolemia without HeFH: Consider when baseline LDL-C ≥220 mg/dL and current LDL-C ≥130 mg/dL despite maximally tolerated statin plus ezetimibe 3

Administration Guidelines

• The 140 mg dose is administered using a prefilled single-dose SureClick autoinjector or prefilled syringe 1
• The 420 mg dose can be administered using the on-body infusor or by giving three 140 mg injections consecutively within 30 minutes 2, 1
• Allow Repatha to warm to room temperature for at least 30 minutes (prefilled autoinjector/syringe) or 45 minutes (on-body infusor) 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 and Monitoring

• Repatha reduces LDL-C by approximately 50-60% when added to statin therapy 2, 4, 5
• LDL-C reduction can be measured as early as 4 weeks after initiation 1
• For patients receiving the monthly 420 mg dose, LDL-C should be measured just prior to the next scheduled dose due to potential variations during the dosing interval 1
• No specific laboratory monitoring beyond routine lipid profile assessment is required 2

Safety Considerations

• Most common adverse effects include nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions 2
• Some presentations contain dry natural rubber (latex derivative) in the needle cover; consider latex-free options for sensitive individuals 1
• Long-term safety data from a study of patients with familial hypercholesterolemia showed good tolerability over a median of 4.1 years 6

Clinical Pearls

• Repatha has demonstrated a 15% relative risk reduction in composite cardiovascular endpoints and a 20% reduction in the combined endpoint of cardiovascular death, MI, or stroke 2
• Unlike combination therapy with statins plus fibrates or niacin (which are generally not recommended due to lack of proven cardiovascular benefit), PCSK9 inhibitors have shown cardiovascular outcome benefits 3
• Cost considerations and prior authorization requirements may limit access despite proven efficacy 2

Repatha represents an important advancement in lipid management for patients unable to achieve target LDL-C levels with conventional therapies, particularly those with familial hypercholesterolemia or established cardiovascular disease.