Does rosuvastatin have unique drug interactions not associated with atorvastatin?

Rosuvastatin's Unique Drug Interactions Compared to Atorvastatin

Yes, rosuvastatin has several unique drug interactions that atorvastatin does not have due to differences in their metabolic pathways and transport mechanisms. 1

Key Metabolic Differences

Rosuvastatin and atorvastatin have fundamentally different metabolic pathways:

• Rosuvastatin: Primarily metabolized by CYP2C9 (and minor CYP2C19) 1
• Atorvastatin: Primarily metabolized by CYP3A4 1, 2

This difference creates distinct drug interaction profiles for each medication.

Unique Rosuvastatin Drug Interactions

CYP2C9 Inhibitor Interactions

Rosuvastatin levels can be significantly increased when co-administered with CYP2C9 inhibitors, including:

• Amiodarone
• Fluconazole
• Fluvoxamine
• Ketoconazole
• Metronidazole
• Miconazole
• Sulfamethoxazole/trimethoprim
• Voriconazole 1

Specific Medications with Unique Rosuvastatin Interactions

The FDA specifically identifies several medications that interact uniquely with rosuvastatin:

• Teriflunomide: Increases rosuvastatin exposure >2.5-fold (limit rosuvastatin to 10mg daily) 3
• Enasidenib: Increases rosuvastatin exposure >2.4-fold (limit rosuvastatin to 10mg daily) 3
• Capmatinib: Increases rosuvastatin exposure >2.1-fold (limit rosuvastatin to 10mg daily) 3
• Fostamatinib: Increases rosuvastatin exposure >2.0-fold (limit rosuvastatin to 20mg daily) 3
• Febuxostat: Increases rosuvastatin exposure >1.9-fold (limit rosuvastatin to 20mg daily) 3
• Tafamidis: Significantly increases rosuvastatin exposure (avoid concomitant use) 3

OATP1B3 Transporter Interactions

Rosuvastatin is a substrate for OATP1B3 transporter, while atorvastatin is not. This creates unique interactions with OATP1B3 inhibitors:

• Clarithromycin
• Cyclosporine
• Erythromycin
• Rifampin
• Roxithromycin
• Sacubitril
• Telithromycin 1

Clinical Implications

1. Higher Risk with Certain Medications: Patients taking CYP2C9 inhibitors are at higher risk for rosuvastatin-related adverse effects than with atorvastatin.

2. Renal Considerations: Rosuvastatin has higher renal excretion compared to atorvastatin (<2%), making drug interactions potentially more problematic in patients with impaired renal function 1, 4.

3. Dose Limitations: When specific interacting medications must be used with rosuvastatin, dose limitations are often required to prevent toxicity 3.

Practical Management Approach

When considering statin therapy for patients on multiple medications:

1. Medication Review: Screen for medications that inhibit CYP2C9 or OATP1B3 transporters.

2. Risk Assessment: For patients on CYP2C9 inhibitors, atorvastatin may be preferred over rosuvastatin.

3. Dose Adjustment: If rosuvastatin must be used with interacting medications, follow FDA-recommended dose limitations 3.

4. Monitoring: Monitor for muscle symptoms, which may indicate statin toxicity due to drug interactions 5.

Common Pitfalls to Avoid

• Assuming all statins have similar interaction profiles: The different metabolic pathways create distinct interaction profiles.
• Overlooking renal function: Rosuvastatin's higher renal excretion makes interactions potentially more problematic in renal impairment.
• Missing non-CYP interactions: Remember that transporter-mediated interactions (OATP1B3) are also important for rosuvastatin.

While both statins share some common interactions (like cyclosporine), rosuvastatin's unique metabolic pathway through CYP2C9 and its interaction with OATP1B3 transporters create a distinct interaction profile that requires specific attention when prescribing.