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

Repatha (Evolocumab) Indications and Dosing for High Cholesterol

Repatha (evolocumab) is indicated for adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) as an adjunct to diet, either alone or in combination with other lipid-lowering therapies, to reduce LDL-C; for reducing cardiovascular risk in adults with established cardiovascular disease; and for patients with homozygous familial hypercholesterolemia. 1, 2

FDA-Approved Indications

Repatha is FDA-approved for:

1. Adults with established cardiovascular disease: To reduce the risk of major adverse cardiovascular events (CV death, myocardial infarction, stroke, unstable angina requiring hospitalization, or coronary revascularization) 2

2. Primary hyperlipidemia: As an adjunct to diet, alone or in combination with other LDL-C-lowering therapies in adults with primary hyperlipidemia, including heterozygous familial hypercholesterolemia (HeFH) 2

3. Heterozygous familial hypercholesterolemia (HeFH): For pediatric patients aged 10 years and older with HeFH, as an adjunct to diet and other LDL-C-lowering therapies 2

4. Homozygous familial hypercholesterolemia (HoFH): As an adjunct to other LDL-C-lowering therapies in adults and pediatric patients aged 10 years and older 2

Dosing Recommendations

For Adults with Established CVD or Primary Hyperlipidemia:

• 140 mg every 2 weeks OR
• 420 mg once monthly
• Administered subcutaneously in the abdomen, thigh, or upper arm 1, 2

For Pediatric Patients (≥10 years) with HeFH:

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

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

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

Efficacy

Evolocumab is highly effective at lowering LDL-C:

• Reduces LDL-C by 50-65% from baseline when added to statins 3
• As monotherapy or in combination with other lipid-lowering therapies, evolocumab reduces LDL-C by 54.8-76.3% compared to placebo 4
• When compared to ezetimibe, evolocumab demonstrates 36.9-47.2% greater LDL-C reduction 4

Clinical Outcomes

The FOURIER trial demonstrated that evolocumab:

• Reduced the composite primary endpoint of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization by 15% (HR 0.85; 95% CI 0.79-0.92) 5
• Reduced the key secondary endpoint of cardiovascular death, MI, or stroke by 20% (HR 0.80; 95% CI 0.73-0.88) 5
• Lowered median LDL-C from 92 mg/dL to 30 mg/dL (59% reduction) 5

When to Consider Repatha

According to guidelines, consider Repatha in:

1. Very high-risk patients not achieving LDL-C goals despite maximally tolerated statin therapy and ezetimibe 1

2. Patients with familial hypercholesterolemia who cannot achieve target LDL-C levels with statins and ezetimibe 1, 3

3. Statin-intolerant patients who cannot achieve adequate LDL-C reduction with other therapies 3

Administration Instructions

• Allow Repatha to warm to room temperature for at least 30 minutes (prefilled syringe/autoinjector) or 45 minutes (on-body infusor) if refrigerated
• Administer subcutaneously into abdomen, thigh, or upper arm
• Rotate injection sites
• For the 420 mg dose: Use either the prefilled single-dose on-body infuser or give 3 consecutive 140-mg injections within 30 minutes 2

Monitoring

• LDL-C can be measured as early as 4 weeks after initiation
• For patients receiving the monthly 420 mg dose, measure LDL-C just prior to the next scheduled dose as levels may vary during the dosing interval 2

Adverse Effects

Evolocumab is generally well-tolerated with the most common adverse effects being:

• Nasopharyngitis
• Injection site reactions
• Arthralgia
• Back pain 6, 7

Important Considerations

• Hypersensitivity reactions may occur; discontinue therapy if serious reactions develop
• Some presentations contain dry natural rubber (latex derivative) in the needle cover; consider latex-free options for sensitive individuals 2
• Missed doses: If within 7 days, administer and resume original schedule; if more than 7 days, follow specific instructions based on dosing regimen 2

Evolocumab represents an important therapeutic option for patients with high cholesterol who cannot achieve target LDL-C levels with conventional therapies or who are at high cardiovascular risk requiring additional LDL-C reduction.