Can Augmentin (amoxicillin/clavulanate) be taken with simvastatin in a patient with impaired renal function?

Can Augmentin Be Taken with Simvastatin?

Yes, Augmentin (amoxicillin/clavulanate) can be taken with simvastatin, but this combination requires heightened vigilance for muscle-related adverse effects, particularly in patients with impaired renal function who face compounded risk.

Evidence for Drug Interaction

The primary concern stems from a documented case report showing that amoxicillin/clavulanate can precipitate rhabdomyolysis in patients on statin therapy:

• A 55-year-old woman developed rhabdomyolysis when amoxicillin/clavulanate was added to her existing atorvastatin regimen, highlighting that this antibiotic class can interact with statins to cause severe muscle injury 1
• While this case involved atorvastatin rather than simvastatin, the mechanism of concern applies broadly to all statins, particularly those metabolized via CYP3A4 (which includes simvastatin) 1

Risk Amplification in Renal Impairment

Patients with impaired renal function face substantially elevated risk when combining these medications:

• Chronic renal insufficiency, especially when combined with diabetes, independently increases the risk of statin-associated myopathy 2
• Simvastatin requires dose limitation in severe renal failure (CrCl <30 mL/min), with careful monitoring recommended for doses >10 mg 2
• The FDA specifically warns against simvastatin 80 mg in new patients due to increased myopathy risk, and this highest dose should be avoided entirely in patients with renal impairment 2

Practical Management Algorithm

For patients requiring both medications:

1. Assess baseline risk factors 2:

   • Advanced age (especially >80 years, women > men)
   • Small body frame and frailty
   • Degree of renal impairment (CrCl <30 mL/min represents highest risk)
   • Diabetes combined with chronic renal failure
   • Current simvastatin dose

2. Optimize simvastatin dosing before adding Augmentin 2:

   • If CrCl <30 mL/min: Use simvastatin ≤10 mg daily
   • Consider switching to atorvastatin, which requires no renal dose adjustment regardless of kidney function severity 3
   • Alternatively, consider rosuvastatin, fluvastatin, or pravastatin as they have different metabolic pathways and may pose lower interaction risk 2

3. Obtain baseline measurements before starting Augmentin 2:

   • Creatine kinase (CK) level
   • Thyroid-stimulating hormone (TSH) if not recently checked
   • Baseline assessment of muscle symptoms

4. Implement intensive monitoring during concurrent therapy 2:

   • Educate patient to immediately report muscle soreness, tenderness, pain, or weakness
   • If symptoms develop: obtain CK measurement and compare to baseline
   • If CK >10 times upper limit of normal (ULN) with muscle symptoms: discontinue both medications immediately 2
   • If CK 3-10 times ULN with symptoms: follow weekly until resolution or worsening 2

Alternative Antibiotic Considerations

While the evidence specifically documents amoxicillin/clavulanate interaction with statins, macrolide antibiotics (erythromycin, clarithromycin) are explicitly contraindicated or require extreme caution with simvastatin due to CYP3A4 inhibition 2. If clinically appropriate, consider:

• Using a non-interacting antibiotic class for the infection
• Temporarily holding simvastatin during short-course antibiotic therapy (though this approach should be individualized based on cardiovascular risk) 2

Critical Caveats

• The combination is not absolutely contraindicated, unlike simvastatin with cyclosporine, gemfibrozil, or certain HIV protease inhibitors 2
• Short-term antibiotic courses (typically 7-14 days for Augmentin) may justify accepting the interaction risk with close monitoring rather than disrupting statin therapy 2
• Perioperative periods and acute illness independently increase myopathy risk, so hospitalized patients receiving this combination warrant particularly careful surveillance 2
• Patients with diabetes and CKD represent the highest-risk population and should be monitored most carefully 2