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

Evolocumab (Repatha) 140 MG/ML Solution Auto-Injector Dosing

For adults with established cardiovascular disease or primary hypercholesterolemia, administer evolocumab 140 mg subcutaneously every 2 weeks OR 420 mg once monthly, with both regimens providing equivalent LDL-C reduction of approximately 58-64%. 1

Standard Dosing Regimens

Adults with ASCVD or Primary Hyperlipidemia

• 140 mg subcutaneously every 2 weeks (using the 140 mg/mL auto-injector) 2, 1
• Alternative: 420 mg once monthly (requires three 140-mg injections consecutively within 30 minutes) 2, 1
• Both regimens reduce LDL-C by an additional 58-64% when added to maximally tolerated statin therapy 2

Pediatric Patients (≥10 years) with HeFH

• Same dosing as adults: 140 mg every 2 weeks OR 420 mg once monthly 2, 1
• If switching between regimens, administer the first dose of the new regimen on the next scheduled date of the prior regimen 1

Homozygous Familial Hypercholesterolemia (HoFH)

• Initial dose: 420 mg once monthly 2, 1
• Escalation: If clinically meaningful response not achieved after 12 weeks, increase to 420 mg every 2 weeks 2, 1
• Patients on LDL apheresis: May initiate at 420 mg every 2 weeks to correspond with apheresis schedule; administer after apheresis session is complete 2, 1

Administration Details

Injection Technique

• Sites: Administer subcutaneously in the thigh, abdomen, or upper arm 2, 1
• Rotation: Rotate injection sites with each administration 1
• Preparation: Allow to warm to room temperature for at least 30 minutes if refrigerated before using the auto-injector 1

Monitoring

• LDL-C assessment: Can be measured as early as 4 weeks after initiation 1
• For monthly dosing: LDL-C can vary during the dosing interval; measure just prior to the next scheduled dose for most accurate assessment 1
• Peak reduction timing: Occurs approximately 1 week after the every-2-week dose and 2 weeks after the monthly dose 3

Missed Dose Management

Within 7 days of missed dose: Administer immediately and resume original schedule 1

More than 7 days after missed dose: 1

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

Clinical Efficacy Context

The FOURIER trial demonstrated that evolocumab reduced LDL-C from a median baseline of 92 mg/dL to 30 mg/dL (59% reduction) and significantly reduced cardiovascular events (hazard ratio 0.85 for primary composite endpoint of CV death, MI, stroke, hospitalization for unstable angina, or coronary revascularization) 2, 4. This cardiovascular benefit was consistent across patients, including those with baseline LDL-C as low as 74 mg/dL 4.

Important Safety Considerations

• Contraindication: History of hypersensitivity to evolocumab 2
• Latex sensitivity: Some presentations contain dry natural rubber (latex derivative) in the needle cover; prescribe latex-free presentations for sensitive individuals 1
• Common adverse effects: Nasopharyngitis, upper respiratory tract infection, influenza, back pain, injection site reactions (all <2%) 2
• No cognitive effects: No evidence of increased cognitive adverse effects observed in FOURIER or EBBINGHAUS trials 2

Practical Prescribing Notes

• No dose adjustment needed based on hepatic impairment (mild/moderate), renal impairment, body weight, race, sex, or age 3
• No drug-drug interactions of clinical significance identified 2
• Combination with statins: Provides additional LDL-C lowering without pharmacokinetic interaction 3
• Prior authorization: May be required; cost considerations apply 2