Crestor and Levofloxacin Interaction
No clinically significant drug-drug interaction exists between Crestor (rosuvastatin) and levofloxacin, and these medications can be safely co-administered without dose adjustment or special monitoring beyond standard statin safety surveillance.
Pharmacokinetic Rationale
The absence of interaction between these agents is explained by their distinct metabolic pathways:
- Rosuvastatin undergoes minimal hepatic metabolism via CYP450 enzymes (only ~10% metabolized, primarily by CYP2C9), with the majority excreted unchanged in feces 1, 2
- Levofloxacin is predominantly eliminated renally (80% unchanged) without significant CYP450 involvement 3, 4
- Rosuvastatin's hydrophilic nature and lack of CYP3A4 metabolism specifically reduces the potential for drug interactions compared to lipophilic statins 2
Clinical Evidence
While no direct interaction studies between rosuvastatin and levofloxacin appear in major cardiovascular or infectious disease guidelines 5, the pharmacologic profiles indicate no overlapping metabolic pathways that would create clinically meaningful interactions.
Important distinction: The hepatitis C treatment guidelines specifically contraindicate rosuvastatin with certain antiviral regimens (e.g., sofosbuvir/velpatasvir/voxilaprevir causes a 19-fold increase in rosuvastatin exposure via BCRP transporter inhibition) 5, but fluoroquinolones like levofloxacin do not affect these transporters.
Standard Monitoring Recommendations
When using this combination, monitor for:
- Statin-related adverse effects: Myalgia, elevated creatine kinase (>10x ULN), or transaminase elevations (>3x ULN) 1, 6
- Fluoroquinolone-related effects: Tendon pain, neurologic symptoms (dizziness, insomnia), or gastrointestinal disturbances 3, 4
- These adverse effects occur independently and are not potentiated by co-administration
Administration Considerations
Critical timing requirement for levofloxacin:
- Do not administer levofloxacin within 2 hours of antacids or medications containing divalent cations (calcium, magnesium, aluminum, iron), as these markedly decrease fluoroquinolone absorption 3, 7
- Rosuvastatin does not contain these cations and does not interfere with levofloxacin absorption
Renal Function Adjustments
- Levofloxacin requires dose reduction to 750-1000 mg three times weekly when creatinine clearance <50 mL/min 3, 4
- Rosuvastatin requires no renal dose adjustment but should be used cautiously in severe renal impairment 1
- These adjustments are independent of co-administration
Emerging Research Context
One in vitro and animal study demonstrated synergistic antibacterial effects when rosuvastatin was combined with levofloxacin against Staphylococcus aureus, showing enhanced bacterial killing and reduced biofilm formation 8. However, this represents experimental research rather than a clinically relevant drug interaction concern in human therapeutics.