What dose of ezetimibe, bile acid sequestrant, or PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) inhibitor, such as evolocumab (Repatha) or alirocumab (Praluent), is recommended for patients with elevated Low-Density Lipoprotein (LDL) levels who experience side effects from statin medication?

Recommended Dosages for Non-Statin Lipid-Lowering Medications in Patients with Statin Side Effects

For patients with elevated LDL levels who experience side effects from statin medication, ezetimibe 10 mg daily is the recommended first-line non-statin therapy, followed by bile acid sequestrants or PCSK9 inhibitors at specific doses based on patient characteristics and LDL response.

Ezetimibe Dosing

• Ezetimibe is recommended at a standard dose of 10 mg orally once daily, with or without food 1
• Take ezetimibe at least 2 hours before or at least 4 hours after bile acid sequestrants if used in combination 1
• Ezetimibe typically provides an 18% reduction in LDL-C as monotherapy and approximately 25% additional reduction when combined with statins 1
• Ezetimibe is generally well tolerated with minimal side effects and is available as a generic medication 1

Bile Acid Sequestrant Dosing

• Bile acid sequestrants may be considered in patients with baseline LDL-C ≥190 mg/dL who achieve <50% reduction in LDL-C while taking maximally tolerated statin and ezetimibe therapy, and have fasting triglycerides ≤300 mg/dL 1
• The specific dosing for bile acid sequestrants varies by agent:
  • Cholestyramine: 4-24 g daily in divided doses
  • Colestipol: 5-30 g daily in divided doses
  • Colesevelam: 3.75 g daily (6 tablets) or 1.875 g twice daily 1

PCSK9 Inhibitor Dosing

Alirocumab (Praluent)

• Initial dose: 75 mg subcutaneously every 2 weeks 1
• If additional LDL reduction is needed, dose may be increased to 150 mg every 2 weeks 1
• Alternative dosing: 300 mg subcutaneously every 4 weeks 1
• Typically provides 45-58% additional LDL-C reduction when added to maximally tolerated statin therapy 1

Evolocumab (Repatha)

• For primary hypercholesterolemia with established ASCVD or heterozygous FH: 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly 1
• For homozygous FH: 420 mg subcutaneously once monthly 1
• To administer the 420 mg dose, give three 140 mg injections consecutively within 30 minutes 1
• Typically provides 58-64% additional LDL-C reduction when added to maximally tolerated statin therapy 1

Treatment Algorithm for Patients with Statin Side Effects

Step 1: Ezetimibe

• Start with ezetimibe 10 mg daily as the first non-statin agent 2
• Ezetimibe provides 15-25% LDL-C reduction and has a favorable safety profile 2

Step 2: Consider Adding Bile Acid Sequestrant

• If LDL-C remains elevated despite ezetimibe therapy and triglycerides are ≤300 mg/dL 1
• Most appropriate for patients with baseline LDL-C ≥190 mg/dL who achieve <50% reduction with ezetimibe 1

Step 3: Consider PCSK9 Inhibitor

• For patients with established ASCVD: Add PCSK9 inhibitor if LDL-C remains ≥70 mg/dL despite maximally tolerated statin and ezetimibe therapy 1
• For patients with heterozygous FH (age 30-75): Add PCSK9 inhibitor if LDL-C remains ≥100 mg/dL despite maximally tolerated statin and ezetimibe therapy 1
• For patients with severe hypercholesterolemia (baseline LDL-C ≥220 mg/dL): Add PCSK9 inhibitor if on-treatment LDL-C remains ≥130 mg/dL despite maximally tolerated statin and ezetimibe therapy 1

Special Considerations

• PCSK9 inhibitors provide substantial LDL-C reduction (45-64%) but at a significantly higher cost compared to ezetimibe 1, 3
• Ezetimibe is generally well-tolerated with common side effects including upper respiratory tract infection, diarrhea, arthralgia, and sinusitis 1
• PCSK9 inhibitors' common side effects include nasopharyngitis, injection site reactions, and influenza-like symptoms 1
• Bile acid sequestrants should be avoided in patients with triglycerides >300 mg/dL due to potential triglyceride elevation 1
• When using combination therapy, monitor for potential drug interactions, especially between statins and bile acid sequestrants 1

Common Pitfalls to Avoid

• Skipping the step-wise approach and moving directly to PCSK9 inhibitors without first trying ezetimibe 2
• Using bile acid sequestrants in patients with elevated triglycerides (>300 mg/dL) 1
• Failing to separate administration times between bile acid sequestrants and other medications (including ezetimibe) 1
• Not considering cost-effectiveness in treatment selection, as PCSK9 inhibitors represent a significant cost burden compared to generic ezetimibe 2
• Overlooking the potential for drug interactions when combining multiple lipid-lowering therapies 4