How should Praluent (alirocumab) 75 mg be administered and dosed in adults with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease, including storage, injection site rotation, dose escalation, and contraindications?

Praluent 75 mg Dosing Instructions

Start Praluent at 75 mg subcutaneously every 2 weeks for adults with established cardiovascular disease or primary hypercholesterolemia including heterozygous familial hypercholesterolemia, and escalate to 150 mg every 2 weeks if LDL-C response is inadequate. 1

Initial Dosing

• Adults with established cardiovascular disease or primary hypercholesterolemia (including HeFH): Begin with 75 mg subcutaneously every 2 weeks OR 300 mg every 4 weeks 1
• Adults with HeFH undergoing LDL apheresis or HoFH: Start directly at 150 mg every 2 weeks 1
• Pediatric patients (8+ years) with HeFH:
  • Body weight <50 kg: 150 mg every 4 weeks (escalate to 75 mg every 2 weeks if inadequate response) 1
  • Body weight ≥50 kg: 300 mg every 4 weeks (escalate to 150 mg every 2 weeks if inadequate response) 1

Dose Escalation Strategy

• Measure LDL-C at 4 weeks to assess initial response, as the LDL-lowering effect can be measured this early 1
• If LDL-C response is inadequate on 75 mg every 2 weeks: Increase to 150 mg every 2 weeks 1
• For patients on the 300 mg monthly regimen, measure LDL-C just prior to the next scheduled dose, as LDL-C can vary between doses in some patients 1
• In the ODYSSEY OUTCOMES trial, alirocumab was titrated between 75-150 mg to achieve target LDL-C levels of 25-50 mg/dL, demonstrating the clinical rationale for dose adjustment 2

Administration Technique

• Allow to warm: Remove from refrigerator and let sit at room temperature for 30-40 minutes before injection 1
• Inspect visually: Solution should be clear, colorless to pale yellow; do not use if cloudy, discolored, or contains particles 1
• Injection sites: Administer into thigh, abdomen, or upper arm areas that are not tender, bruised, red, or indurated 1
• Rotate sites: Use different injection sites for each administration 1
• For 300 mg dose: Give two consecutive 150 mg injections at two different injection sites 1

Supervision Requirements for Pediatric Patients

• Ages 12-17 years: Recommended to be given by or under adult supervision 1
• Ages 8-11 years: Must be given by a caregiver 1

Missed Dose Management

• If missed within 7 days: Administer immediately and resume original schedule 1
• If missed >7 days:
  • Every 2-week dosing: Wait until next scheduled dose 1
  • Every 4-week dosing: Administer immediately and start new schedule based on this date 1

Special Considerations

• Timing with LDL apheresis: Can be administered without regard to apheresis timing 1
• Concomitant therapy: Use as adjunct to maximally tolerated statin therapy; in ODYSSEY OUTCOMES, 88.6% of patients were on high-intensity statins 2
• Monitoring: Assess LDL-C when clinically appropriate, with particular attention at 4 weeks and when considering dose escalation 1

Contraindications

• Only contraindication: History of hypersensitivity to alirocumab 1

Common Adverse Effects

• Injection-site reactions: Occur in 3.8% vs 2.1% with placebo (HR 1.82) 2
• Injection-site reactions decline in frequency with increasing age 3
• No unexpected long-term safety concerns observed over 3 years of treatment 4

Clinical Efficacy Context

• Alirocumab reduces LDL-C by 50-60% when added to statin therapy 5, 6
• In ODYSSEY OUTCOMES, alirocumab reduced major adverse cardiovascular events by 15% (HR 0.85,95% CI 0.78-0.93, NNT=63) over 2.8 years in patients with recent acute coronary syndrome 2
• Greater absolute benefit observed in patients with diabetes (2.3% absolute risk reduction) compared to prediabetes or normoglycemia 2

Storage

• Refrigerate until use; allow to reach room temperature before administration 1