What is the risk of rhabdomyolysis with concurrent use of statins and daptomycin?

Risk of Rhabdomyolysis with Concurrent Use of Statins and Daptomycin

Concurrent use of statins and daptomycin significantly increases the risk of myopathy and rhabdomyolysis, and temporary discontinuation of statins should be considered during daptomycin therapy.

Mechanism and Risk Assessment

Daptomycin and statins both independently carry risks for muscle toxicity, but through different mechanisms:

• Daptomycin can cause myopathy, defined as muscle pain or weakness with creatine phosphokinase (CPK) elevations >10 times the upper limit of normal (ULN), which may progress to rhabdomyolysis 1
• Statins alone carry a small but definite risk of myopathy (0.08-0.09%) 2

When used concurrently, the risk increases substantially:

• Recent evidence from a 2022 meta-analysis showed statin use significantly increased the incidence of daptomycin-related rhabdomyolysis (odds ratio: 3.83) 3
• A 2023 disproportionality analysis using FDA data found that the combination of daptomycin with rosuvastatin (ROR: 124.39), atorvastatin (ROR: 68.53), and simvastatin (ROR: 94.83) substantially increased reporting of myopathy 4
• A 2018 case-control study identified statin coadministration as an independent risk factor for both myopathy (odds ratio: 2.60) and rhabdomyolysis (odds ratio: 4.67) during daptomycin therapy 5

Monitoring and Management Recommendations

The FDA label for daptomycin explicitly addresses this risk:

1. CPK Monitoring:

   • Monitor CPK levels weekly in all patients receiving daptomycin
   • More frequent monitoring is recommended in patients receiving concurrent statin therapy 1

2. Statin Management:

   • "Consideration should be given to suspending agents associated with rhabdomyolysis, such as HMG-CoA reductase inhibitors, temporarily in patients receiving daptomycin" 1
   • The 2018 case-control study recommends twice-weekly CPK monitoring during coadministration 5

3. Discontinuation Criteria:

   • Discontinue daptomycin in patients with:
     • Unexplained signs/symptoms of myopathy with CPK >1,000 U/L (~5× ULN)
     • Asymptomatic patients with marked CPK elevations >2,000 U/L (≥10× ULN) 1

Risk Factors for Increased Myopathy Risk

Additional factors that may further increase risk when using daptomycin and statins together:

• Deep abscess treatment (OR: 2.80) 5
• Obesity (OR: 3.28 for rhabdomyolysis) 5
• Complex medical problems and multiple medications 2
• Compromised hepatic or renal function 6
• Hypothyroidism and diabetes 6

Clinical Approach

1. Before starting daptomycin:

   • Assess baseline CPK levels
   • Consider temporarily discontinuing statin therapy if clinically appropriate
   • Document pre-existing muscle symptoms to avoid misattribution

2. During therapy:

   • If statin must be continued, monitor CPK twice weekly 5
   • Educate patients to immediately report muscle pain, tenderness, or weakness
   • Consider lower doses of both medications if concurrent use is necessary

3. If myopathy develops:

   • Discontinue both medications immediately
   • Monitor renal function and urine myoglobin
   • Provide supportive care including IV hydration

Conclusion

While one small retrospective study from 2013 found no increased risk 7, multiple more recent and larger studies have consistently demonstrated a significant increased risk of myopathy and rhabdomyolysis with concurrent use of statins and daptomycin. The FDA label specifically recommends considering temporary suspension of statins during daptomycin therapy. Given the potential for serious adverse outcomes including acute renal failure, caution is warranted when these medications must be used together.