Statin Coadministration Increases the Risk of Daptomycin-Associated Myopathy.
Clin Infect Dis. 2018 Apr 16;:
Authors: Dare RK, Tewell C, Harris B, Wright PW, Van Driest SL, Farber-Eger E, Nelson GE, Talbot TR
Background: Daptomycin-associated myopathy has been identified in 2-14% of patients, and rhabdomyolysis is a known adverse effect. Although risk factors for daptomycin-associated myopathy are poorly defined, creatine phosphokinase (CPK) monitoring and temporary discontinuation of HMG-CoA reductase inhibitors, or "statins", has been recommended.
Methods: We conducted a single-center, retrospective, matched case-control risk factor analysis in adult and pediatric patients from 2004-2015. Patients who developed myopathy, defined as CPK > upper limit of normal (ULN) while on daptomycin, were matched 1:1 to no-myopathy controls with at least the same number of days of therapy (DOT). Risk factors independently associated with myopathy were determined using multivariable conditional logistic regression. Secondary analysis was performed on cases with rhabdomyolysis, defined as CPK ≥10x ULN.
Results: 128 (4.2%) of 3,042 patients reviewed were identified as cases of daptomycin-associated myopathy, 25 (0.8%) of which had rhabdomyolysis. 121 (95%) cases were found in adults, and mean DOT prior to CPK elevation was 16.7 days (range 1-58). In multivariate analysis, deep abscess treatment (OR 2.80, p=0.03), anti-histamine coadministration (OR 3.50, p=0.03), and statin coadministration (OR 2.60, p=0.03) were independent risk factors for myopathy. Obesity (OR 3.28, p=0.03) and statin coadministration (OR 4.67, p=0.03) were found to be independent risk factors for rhabdomyolysis, and older age was associated with reduced risk (OR 0.97, p=0.05).
Conclusions: Statin coadministration with daptomycin was independently associated with myopathy and rhabdomyolysis. This is the first study to provide strong evidence supporting this association. During coadministration, we recommend twice-weekly CPK monitoring and consideration of withholding statins.
PMID: 29668884 [PubMed - as supplied by publisher]