Can Zetia (ezetimibe) and Crestor (rosuvastatin) be given together?

Combination Therapy with Zetia (Ezetimibe) and Crestor (Rosuvastatin)

Yes, Zetia (ezetimibe) and Crestor (rosuvastatin) can be safely and effectively given together as a combination therapy for enhanced LDL-C reduction. 1, 2

Rationale for Combination Therapy

• Complementary mechanisms of action:

  • Rosuvastatin: Inhibits HMG-CoA reductase, reducing hepatic cholesterol synthesis
  • Ezetimibe: Inhibits intestinal absorption of cholesterol
  • This dual approach provides synergistic LDL-C lowering effects 1

• Enhanced efficacy:

  • Combination therapy reduces LDL-C by 50-75%, significantly more than rosuvastatin monotherapy 3
  • Fixed-dose combinations of ezetimibe/rosuvastatin achieve >50% reduction in LDL-C levels 3
  • More patients achieve target LDL-C goals with combination therapy (92.3%) compared to rosuvastatin monotherapy (79.9%) 3

Clinical Indications for Combination Therapy

1. Insufficient response to maximally tolerated statin therapy:

   • When patients fail to achieve ≥50% reduction in LDL-C or LDL-C remains ≥100 mg/dL on maximally tolerated statin 1
   • When additional LDL-C lowering beyond 25% is desired 1

2. Severe hypercholesterolemia:

   • Patients with LDL-C ≥190 mg/dL who require greater LDL-C reduction than statin monotherapy can achieve 1
   • When LDL-C remains ≥100 mg/dL despite maximally tolerated statin therapy 1

3. Very high-risk ASCVD patients:

   • When LDL-C levels remain ≥70 mg/dL despite maximally tolerated statin therapy 1
   • Particularly beneficial in patients with diabetes or multiple ASCVD risk factors 1

4. Statin intolerance:

   • To allow lower doses of rosuvastatin while maintaining efficacy 1
   • Combination therapy may reduce statin-related adverse effects while providing similar LDL-C reduction 1

Safety Considerations

• Similar safety profile to monotherapy:

  • The combination of ezetimibe and rosuvastatin is generally well-tolerated 3
  • No significant differences in overall adverse events, adverse drug reactions, or serious adverse events compared to rosuvastatin monotherapy 3
  • Laboratory findings, including liver function tests and creatinine kinase levels, are comparable between combination therapy and monotherapy 3

• Potential concerns:

  • Monitor for myopathy and rhabdomyolysis, though risk is not significantly increased with combination therapy 2
  • Perform liver enzyme testing as clinically indicated 2
  • Consider withdrawal of ezetimibe if ALT or AST ≥3 times upper limit of normal persist 2

Administration Guidelines

• Ezetimibe: 10 mg once daily, with or without food 2
• Rosuvastatin: Typically 5-40 mg once daily
• Fixed-dose combinations are available and may improve adherence 1, 4
• Important: If also using bile acid sequestrants (e.g., cholestyramine), administer ezetimibe either ≥2 hours before or ≥4 hours after the bile acid sequestrant to prevent reduced ezetimibe effectiveness 5, 2

Clinical Pearls

• Assess LDL-C levels when clinically appropriate, as early as 4 weeks after initiating combination therapy 2
• Consider patient-specific factors such as cardiovascular risk, baseline LDL-C, and treatment goals when deciding on combination therapy
• The 2022 ACC guidelines recommend ezetimibe as the initial non-statin agent when <25% additional LDL-C lowering is desired 1
• Fixed-dose combinations may improve adherence compared to separate pills 1
• Combination therapy may be particularly beneficial for high-risk patients requiring LDL-C levels <70 mg/dL 1

In conclusion, the combination of Zetia (ezetimibe) and Crestor (rosuvastatin) provides a potent, synergistic approach to LDL-C reduction with a safety profile comparable to statin monotherapy, making it an excellent option for patients requiring additional lipid-lowering beyond statin therapy alone.