What is the dosing regimen for Evolocumab (Repatha) 140 MG/ML solution auto-injector in patients with hypercholesterolemia (high cholesterol)?

Evolocumab (Repatha) 140 MG/ML Dosing for Hypercholesterolemia

For adults with hypercholesterolemia, administer evolocumab 140 mg subcutaneously every 2 weeks OR 420 mg subcutaneously once monthly—both regimens provide equivalent LDL-C reduction and cardiovascular benefit. 1

Standard Dosing Regimens

The FDA-approved dosing for evolocumab in patients with established cardiovascular disease or primary hyperlipidemia offers two equivalent options 1:

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

Both regimens reduce LDL-C by approximately 59-64% when added to maximally tolerated statin therapy, with the every-2-week regimen achieving 64% reduction and the monthly regimen achieving 58% reduction 2, 3. These differences are not clinically meaningful, and the choice between regimens should be based on patient preference for injection frequency 4.

Administration Details

Injection technique and sites 1:

• Administer subcutaneously into the abdomen, thigh, or upper arm
• Rotate injection sites with each administration
• Allow the autoinjector to warm to room temperature for at least 30 minutes before injection if refrigerated 1

For the 420 mg monthly dose 2, 4:

• Use the prefilled single-dose on-body infuser, OR
• Give three consecutive 140 mg injections within 30 minutes at different injection sites

Switching Between Regimens

If switching from every-2-week to monthly dosing (or vice versa), administer the first dose of the new regimen on the next scheduled date of the prior regimen 1. This ensures continuous LDL-C control without gaps in therapy.

Special Populations

Pediatric patients (≥10 years) with heterozygous familial hypercholesterolemia 2, 4:

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

Homozygous familial hypercholesterolemia (HoFH) 2, 4, 1:

• Initial dose: 420 mg once monthly
• If inadequate LDL-C reduction after 12 weeks, increase to 420 mg every 2 weeks
• Patients on lipid apheresis may initiate at 420 mg every 2 weeks to correspond with apheresis schedule; administer after apheresis is complete 1

Monitoring and Expected Response

LDL-C assessment 1:

• The LDL-lowering effect can be measured as early as 4 weeks after initiation
• For patients receiving 420 mg monthly, LDL-C can vary during the dosing interval; measure LDL-C just prior to the next scheduled dose for most accurate assessment

Expected LDL-C levels 3, 5:

• In patients with baseline median LDL-C of 92 mg/dL, evolocumab reduces LDL-C by 59% to a median value of 30 mg/dL at 48 weeks
• Peak reduction occurs approximately 1 week after the 140 mg every-2-week dose and 2 weeks after the 420 mg monthly dose 6

Cardiovascular Outcomes

Evolocumab demonstrated significant cardiovascular benefit in the FOURIER trial, reducing the composite endpoint of CV death, MI, stroke, revascularization, or hospitalization for unstable angina (HR 0.85; 95% CI 0.79-0.92; P<0.001) 2, 4, 5. This benefit was consistent across all baseline LDL-C levels, including patients in the lowest quartile with median baseline LDL-C of 74 mg/dL 5.

Safety Considerations

Contraindications 2, 4:

• History of hypersensitivity to evolocumab

Common adverse effects 2, 4:

• Nasopharyngitis, upper respiratory tract infection, influenza, back pain, and injection site reactions
• No evidence of increased cognitive adverse effects in FOURIER or EBBINGHAUS trials

Latex sensitivity 2, 4:

• Some presentations contain dry natural rubber (latex derivative) in the needle cover
• Consider prescribing a latex-free presentation for latex-sensitive patients

Missed Dose Management

If a dose is missed 1:

• Within 7 days: Administer immediately and resume the original schedule
• More than 7 days for every-2-week dosing: Wait until the next scheduled dose
• More than 7 days for monthly dosing: Administer the dose and start a new schedule based on this date

Clinical Pitfalls to Avoid

The American College of Cardiology guidelines emphasize that both dosing regimens provide comparable efficacy 2, so avoid the misconception that one regimen is superior. The choice should be driven by patient preference for injection frequency rather than efficacy concerns. Additionally, when monitoring patients on monthly dosing, avoid measuring LDL-C at random times during the dosing interval, as levels fluctuate; instead, measure just before the next dose 1.