What is the recommended dose and indication for Alirocumab (Praluent) in adults with heterozygous familial hypercholesterolemia or clinical atherosclerotic cardiovascular disease?

Alirocumab Dosing and Indications for HeFH and ASCVD

Alirocumab (Praluent) is indicated for adults with heterozygous familial hypercholesterolemia (HeFH) or clinical atherosclerotic cardiovascular disease (ASCVD) with a recommended starting dose of 75 mg subcutaneously every 2 weeks, which can be increased to 150 mg every 2 weeks if additional LDL-C reduction is needed.

FDA-Approved Indications

Alirocumab is FDA-approved for:

1. Reducing the risk of myocardial infarction, stroke, and unstable angina requiring hospitalization in adults with established cardiovascular disease 1
2. As an adjunct to diet, alone or in combination with other LDL-C-lowering therapies, in adults with primary hyperlipidemia, including HeFH 1
3. As an adjunct to other LDL-C-lowering therapies in adult patients with homozygous familial hypercholesterolemia (HoFH) 1

Dosing Recommendations for Adults with HeFH or ASCVD

Initial Dosing

• Starting dose: 75 mg subcutaneously every 2 weeks 2, 1
• Alternative starting regimen: 300 mg subcutaneously every 4 weeks (administered as two 150 mg injections consecutively at two different injection sites) 2, 1

Dose Adjustment

• If LDL-C reduction is inadequate, the dose may be increased to 150 mg every 2 weeks 2, 1
• For patients receiving the 300 mg every 4 weeks dose, LDL-C should be measured just prior to the next scheduled dose, as LDL-C can vary between doses 1

Special Populations

• For adults with HeFH undergoing LDL apheresis or adults with HoFH: 150 mg subcutaneously every 2 weeks is recommended 2, 1

Administration Guidelines

• Administer subcutaneously in the thigh, abdomen, or upper arm 2, 1
• Allow Praluent to warm to room temperature for 30-40 minutes if refrigerated 1
• Visually inspect the solution before administration - it should be clear, colorless to pale yellow 1
• For the 300 mg dose, administer two 150 mg injections consecutively at two different injection sites 1

Efficacy

• When added to maximally tolerated statin therapy, alirocumab 75 mg and 150 mg every 2 weeks reduces LDL-C by an additional 45% and 58%, respectively 2
• In patients with HeFH and very high baseline LDL-C levels (≥160 mg/dL), alirocumab 150 mg every 2 weeks demonstrated significant LDL-C reductions of approximately 45.7% at week 24 3
• The ODYSSEY HoFH trial showed that alirocumab 150 mg every 2 weeks reduced LDL-C by 26.9% in patients with homozygous familial hypercholesterolemia 4

Monitoring

• LDL-C can be measured as early as 4 weeks after initiation to assess response 1
• No specific laboratory monitoring is required beyond routine lipid profile assessment 2
• Unlike statins, no monitoring for muscle-related side effects, liver function, or glucose levels is required 5

Safety and Adverse Effects

• Common adverse effects include nasopharyngitis, injection site reactions, and influenza-like symptoms 2
• Hypersensitivity reactions may occur; if serious, discontinue therapy and treat according to standard of care 2
• The only contraindication is a history of hypersensitivity to the medication 2
• No evidence of increased cognitive adverse effects was observed in clinical trials 2

Clinical Pearls

• The LDL-lowering effect of alirocumab may be measured as early as 4 weeks after initiation 1
• If a dose is missed within 7 days, instruct the patient to administer the dose and resume the original schedule 1
• If a dose is missed by more than 7 days, instruct the patient to wait until the next scheduled dose for the every 2-week regimen, or to administer the dose and start a new schedule for the every 4-week regimen 1
• Alirocumab has demonstrated cardiovascular benefit in the ODYSSEY Outcomes trial, reducing the primary endpoint of CHD death, MI, ischemic stroke, or hospitalization for unstable angina 2

By following these evidence-based dosing recommendations, clinicians can effectively use alirocumab to reduce cardiovascular risk and lower LDL-C levels in patients with HeFH or established ASCVD.