Should statin (HMG-CoA reductase inhibitor) therapy be held while a patient is on daptomycin?

Statin Therapy During Daptomycin Treatment

Consideration should be given to suspending statin therapy temporarily in patients receiving daptomycin due to the potential increased risk of myopathy and rhabdomyolysis. 1

Risk Assessment and Evidence

Daptomycin carries a known risk of muscle toxicity, and this risk may be amplified when combined with statins. The FDA drug label for daptomycin specifically states that "consideration should be given to suspending use of HMG-CoA reductase inhibitors temporarily in patients receiving daptomycin" 1. This recommendation is based on observations from clinical trials where some patients receiving both medications developed elevated creatine phosphokinase (CPK) levels.

Mechanism of Concern

Both medications can independently cause muscle toxicity:

• Daptomycin can cause myopathy and rhabdomyolysis
• Statins inhibit HMG-CoA reductase and may cause muscle pain or weakness with elevated CPK levels

Evidence for Risk

The Infectious Diseases Society of America (IDSA) guidelines for prosthetic joint infections note that "it is recommended that statins be stopped, if possible, while administering daptomycin" 2. This recommendation stems from case reports of rhabdomyolysis in patients receiving both medications.

A case-control study by Britt et al. (2018) found that statin coadministration was independently associated with daptomycin-associated myopathy (odds ratio 2.60, P=.03) and rhabdomyolysis (odds ratio 4.67, P=.03) 3. This study provides the strongest evidence supporting the association between concomitant therapy and increased risk.

Conflicting Evidence

More recent research suggests the risk may be lower than initially thought:

• Berg et al. (2019) found no statistically significant difference in CPK elevations between patients receiving daptomycin alone versus daptomycin with statins 4
• Nguyen et al. (2019) concluded that concomitant therapy was not significantly associated with CPK elevation compared to daptomycin monotherapy 5
• Parra-Ruiz et al. (2012) reported that high-dose daptomycin with statins did not show increased toxicity compared to daptomycin alone 6

Practical Approach

Despite the conflicting evidence, the FDA recommendation and IDSA guidelines carry significant weight. The approach should be:

1. For short-term daptomycin therapy (≤7 days):

   • Consider holding statin therapy if cardiovascular risk allows
   • Restart statin after completion of daptomycin course

2. For longer daptomycin courses:

   • Assess cardiovascular risk from statin discontinuation
   • If statin must be continued, implement enhanced monitoring:
     • Baseline CPK before starting therapy
     • Monitor CPK twice weekly
     • Educate patient about muscle pain symptoms
     • Discontinue both medications if CPK >10x upper limit of normal or if patient develops muscle symptoms with CPK >5x upper limit of normal

3. Risk factors requiring extra caution:

   • Renal impairment
   • Advanced age (especially >80 years)
   • Small body frame/frailty
   • Multiple medications
   • Higher daptomycin doses

Conclusion

While recent studies suggest the risk may be lower than initially thought, the FDA recommendation and IDSA guidelines still advise temporary suspension of statin therapy during daptomycin treatment when possible. If statins must be continued, close monitoring for muscle symptoms and CPK elevations is essential.