Do I need to stop statin (HMG-CoA reductase inhibitor) therapy before starting daptomycin (antibiotic) treatment?

Statin Therapy During Daptomycin Treatment

You should temporarily suspend statin therapy while a patient is receiving daptomycin due to the increased risk of muscle injury, including rhabdomyolysis. 1

Drug Interaction Between Statins and Daptomycin

• Daptomycin's FDA label explicitly states: "consideration should be given to suspending use of HMG-CoA reductase inhibitors temporarily in patients receiving daptomycin" 1
• Both medications independently can cause muscle symptoms and elevated creatine phosphokinase (CPK) levels 1, 2
• Post-marketing reports have identified cases of rhabdomyolysis in patients treated concurrently with daptomycin and HMG-CoA reductase inhibitors 1

Evidence Supporting Statin Discontinuation

• In a 2018 matched case-control study, statin coadministration with daptomycin was independently associated with myopathy (OR 2.60, p=.03) and rhabdomyolysis (OR 4.67, p=.03) 3
• This is the strongest and most recent evidence supporting the recommendation to withhold statins during daptomycin therapy 3
• Patients with both statin therapy and daptomycin had approximately 2-fold risk of CPK elevation compared to those who had their statin therapy held 4

Conflicting Evidence

• Some retrospective studies have found no statistically significant difference in CPK elevation between patients receiving daptomycin alone versus daptomycin with statins 5, 6
• A 2019 multisite retrospective study found concomitant use of daptomycin and statins did not show an increased risk of CPK elevation (HR 1.05, p=.85) 5
• However, these studies have methodological limitations and the FDA recommendation still stands 1

Management Algorithm

1. Before starting daptomycin:

   • Obtain baseline CPK levels 1
   • Temporarily discontinue statin therapy 1

2. During daptomycin therapy:

   • Monitor CPK levels at least weekly 1, 3
   • Watch for symptoms of muscle injury (pain, tenderness, weakness, fatigue) 7

3. If muscle symptoms develop during therapy:

   • For severe symptoms: Promptly discontinue daptomycin and evaluate for rhabdomyolysis (CPK, creatinine, urinalysis for myoglobinuria) 7
   • For mild to moderate symptoms: Consider discontinuing daptomycin until symptoms can be evaluated 7

4. After completing daptomycin therapy:

   • Resume statin therapy as indicated for cardiovascular risk reduction 7
   • Statins should not be permanently discontinued in patients with established atherosclerotic cardiovascular disease 7

Special Considerations

• The risk of statin discontinuation should be weighed against the risk of muscle injury, especially in patients with recent acute coronary syndrome 7
• For patients at very high cardiovascular risk where statin discontinuation poses significant concern, consider alternative antibiotics if clinically appropriate 7
• If concomitant use is absolutely necessary, twice-weekly CPK monitoring is recommended 3

Remember that the temporary discontinuation of statins during a short course of daptomycin is unlikely to significantly impact long-term cardiovascular outcomes, while preventing potential serious muscle injury is a priority 1, 3.