What are the potential drug interactions with rosuvastatin (Crestor)?

Significant Drug Interactions with Rosuvastatin

Rosuvastatin has fewer drug interactions compared to other statins due to its minimal metabolism through the CYP450 system, but several important drug interactions still require careful management to prevent serious adverse effects like myopathy and rhabdomyolysis. 1, 2

Major Drug Interactions Requiring Dose Adjustments or Avoidance

Cyclosporine

• Cyclosporine increases rosuvastatin exposure 7-fold
• Maximum dose: Do not exceed 5 mg rosuvastatin daily 2
• Mechanism: Inhibition of OATP1B1-mediated hepatic uptake 1

Gemfibrozil

• Avoid concomitant use if possible
• If combination necessary: Initiate rosuvastatin at 5 mg daily and do not exceed 10 mg daily 2
• Increases rosuvastatin plasma concentrations approximately 1.88-fold 3
• Mechanism: Inhibition of OATP2-mediated rosuvastatin hepatic uptake 3
• Note: Fenofibrate is preferred over gemfibrozil when fibrate therapy is needed with statins 1

Other Medications Requiring Dose Limitations

• Teriflunomide, Enasidenib, Capmatinib: Do not exceed rosuvastatin 10 mg daily 2
• Fostamatinib, Febuxostat: Do not exceed rosuvastatin 20 mg daily 2
• Tafamidis: Avoid concomitant use 2

Immunosuppressive Agents

• Avoid lovastatin, simvastatin, or pitavastatin with immunosuppressants 1
• Rosuvastatin can be used with immunosuppressants but limit to 5 mg daily with cyclosporine, tacrolimus, everolimus, or sirolimus 1

Antiretroviral Agents

• Caution needed with protease inhibitors (e.g., atazanavir)
• Mechanism: Inhibition of OATP1B1 and CYP enzymes 4
• Consider pravastatin, fluvastatin, or rosuvastatin (with dose adjustment) as safer alternatives to simvastatin or lovastatin 5

Calcium Channel Blockers

• Minor increases in statin exposure with amlodipine and other calcium channel blockers
• Generally considered safe for concomitant use 1

Colchicine

• Risk of myopathy may be increased when used with statins
• Mechanism: Competition for P-gp-mediated efflux 1
• Monitor for muscle symptoms when used together

Practical Management Approach

1. Before starting rosuvastatin:

   • Review complete medication list for potential interactions
   • Consider alternative statins if multiple interacting drugs are present

2. When adding new medications to a patient on rosuvastatin:

   • Check for interactions and adjust rosuvastatin dose accordingly
   • Consider drug levels monitoring when appropriate

3. Monitoring recommendations:

   • Baseline liver function tests and creatine kinase
   • Follow-up testing based on risk profile
   • Educate patients about muscle pain symptoms

4. Safer alternatives when interactions are unavoidable:

   • Pravastatin and fluvastatin have fewer CYP-mediated interactions 5
   • Consider non-statin lipid-lowering therapies when appropriate

Key Advantages of Rosuvastatin

• Hydrophilic nature and hepatoselectivity
• Low systemic bioavailability
• Minimal metabolism via CYP3A4 (unlike simvastatin, lovastatin) 6
• These properties contribute to a favorable drug interaction profile compared to some other statins 4

Remember that rosuvastatin's interaction potential, while lower than some other statins, still requires vigilance, particularly with drugs that inhibit OATP1B1/1B3 transporters or when used in patients with multiple medications.