What is the recommended dosage for PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibitor therapy, such as Repatha (evolocumab) or Praluent (alirocumab)?

Recommended Dosage for PCSK9 Inhibitor Therapy

For PCSK9 inhibitor therapy, evolocumab (Repatha) is recommended at 140 mg subcutaneously every 2 weeks OR 420 mg once monthly, while alirocumab (Praluent) is recommended at 75 mg subcutaneously every 2 weeks (can be increased to 150 mg every 2 weeks if additional LDL-C lowering is needed) OR 300 mg every 4 weeks. 1, 2

Dosing Guidelines for Evolocumab (Repatha)

• For adults with established cardiovascular disease or primary hyperlipidemia: 140 mg subcutaneously every 2 weeks OR 420 mg once monthly 2
• For pediatric patients aged 10 years and older with heterozygous familial hypercholesterolemia (HeFH): 140 mg subcutaneously every 2 weeks OR 420 mg once monthly 2, 3
• For adults and pediatric patients aged 10 years and older with homozygous familial hypercholesterolemia (HoFH): 420 mg once monthly initially, which can be increased to 420 mg every 2 weeks if clinically meaningful response is not achieved in 12 weeks 2
• For patients on lipid apheresis: 420 mg every 2 weeks to correspond with apheresis schedule (administer after apheresis session is complete) 2

Dosing Guidelines for Alirocumab (Praluent)

• Initial dose: 75 mg subcutaneously every 2 weeks 1
• If additional LDL-C reduction is needed, dose may be increased to 150 mg every 2 weeks 1
• Alternative starting dose: 300 mg subcutaneously every 4 weeks 1

Administration Considerations

• Allow PCSK9 inhibitors to warm to room temperature before administration (at least 30 minutes for prefilled syringes/autoinjectors) 2
• Administer in the abdomen, thigh, or upper arm 1, 2
• For the 420 mg dose of evolocumab, give 3 consecutive injections of 140 mg within 30 minutes 1
• LDL-C lowering effect may be measured as early as 4 weeks after initiation 2
• For patients receiving monthly dosing, LDL-C can vary during the dosing interval; measure LDL-C just prior to the next scheduled dose 2

Clinical Efficacy

• Evolocumab reduces LDL-C by 58-64% when added to maximally tolerated statin therapy 1, 4
• Alirocumab reduces LDL-C by 45-58% when added to maximally tolerated statin therapy 1, 4
• Both agents have demonstrated cardiovascular outcomes benefits in large clinical trials (FOURIER for evolocumab and ODYSSEY Outcomes for alirocumab) 1, 4

Indications for PCSK9 Inhibitor Therapy

• Adjunct to diet and maximally tolerated statin therapy in adults with heterozygous familial hypercholesterolemia (HeFH) or clinical ASCVD who require additional LDL-C lowering 1
• For patients with clinical ASCVD at very high risk who are on maximally tolerated LDL-C lowering therapy with LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL 1
• For patients with HoFH who need additional LDL-C reduction despite maximally tolerated statin therapy and ezetimibe 1

Common Adverse Effects

• Nasopharyngitis, injection site reactions, influenza, upper respiratory tract infection 1, 5
• No evidence of increased cognitive adverse effects 1
• Generally well-tolerated with safety profiles comparable to placebo in clinical trials 5, 4

Alternative Dosing Considerations

• For patients who miss a dose within 7 days: administer as soon as possible and resume original schedule 2
• For patients who miss a dose by more than 7 days: for every 2-week dosing, wait until next scheduled dose; for monthly dosing, administer and start a new schedule based on this date 2
• Alternative dosing regimens such as alirocumab 150 mg every 3 weeks or evolocumab 420 mg every 5 weeks may provide comparable LDL-C lowering to standard regimens 6

Special Populations

• In pediatric patients with FH, both evolocumab and alirocumab have demonstrated significant LDL-C reduction (approximately 38%) 3
• Patients with HoFH may have variable responses depending on LDL receptor activity; those with null/null variants (LDL receptor activity <2%) may not respond adequately 1, 3

PCSK9 inhibitors represent an important therapeutic option for patients who cannot achieve target LDL-C levels with maximally tolerated statin therapy with or without ezetimibe, particularly those at very high cardiovascular risk 1, 4.