A Retrospective Multisite Case-Control Series of Concomitant Use of Daptomycin and Statins and the Effect on Creatine Phosphokinase

Abstract

ObjectiveDaptomycin has been associated with increased creatine phosphokinase (CPK) due to muscle injury leading to myalgias and muscle weakness. Statins have been proven to cause the same effects and it is recommended to discontinue the use of statins while on daptomycin. Evidence regarding this drug interaction is mixed. This study evaluated the risk of CPK elevation in concomitant use of daptomycin and statins compared to daptomycin alone.MethodThis is a multisite retrospective case-control study of patients who received daptomycin therapy with monitoring of CPK. Rates of CPK elevations were compared in patients receiving daptomycin with a statin versus daptomycin alone. To estimate the association between CPK elevation and daptomycin therapy controlling for other risk factors, logistic regression was used to analyze data. Statistical significance was determined at ɑ of 0.05.ResultsA total of 3658 patients were included in the study, with 2787 on daptomycin therapy alone and 871 with concurrent statin use. The incidence of CPK elevation was 90 events (3.2%) in the daptomycin group and 26 events (3.0%) in the concurrent statin group. Patients who received daptomycin therapy in addition to statins had no statistically significant difference from patients on daptomycin alone (hazard ratio, 1.05; P = .85; 95% confidence interval, 0.61–1.84). After adjusting for potential risk factors, the hazards ratio remained almost the same.ConclusionsConcomitant use of daptomycin and statin did not show an increase risk of CPK elevation. Clinicians may consider concomitant use of daptomycin and statin therapy with weekly CPK monitoring.

Identification of Risk Factors for Daptomycin-Associated Creatine Phosphokinase Elevation and Development of a Risk Prediction Model for Incidence Probability

“…The incidence of daptomycin-associated CPK elevation ranged from 5% to 30% in studies defining CPK elevation as a CPK level >1–3-fold the upper limit of normal (ULN) [ 2 , 3 , 5 , 18–25 ] and 3%–10% in studies defining CPK elevation as a CPK level >5-fold ULN or 1000 IU/L [ 4 , 7 , 8 , 19 , 21 , 26 , 27 ], in line with the current study. Several trials comprising higher daptomycin doses ≥8mg or greater proportion of patients with renal impairment reported higher rates of patients with CPK elevation [ 3 , 20 , 22 , 23 ].…”

“…Risk factors for myopathy associated with statins include elderly age, female sex, Asian and African American ethnicity, and cytochrome P450 inhibitor use [ 30 ]. In studies examining the risk factors for CPK elevation during combined daptomycin and statin treatment, African American ethnicity was cited as a risk factor, similar to other findings that African Americans have a higher risk of CPK elevation during statin treatment [ 7 , 8 ]. Similar results were reported by Imai et al, who investigated Japanese patients [ 28 ].…”

“…The Kaplan-Meier analysis revealed that the incidence of CPK elevation was approximately 5–10 days after daptomycin administration. Lehman et al evaluated the incidence of CPK elevation, defined as a CPK level of >1000 IU/L, using the Kaplan-Meier method and reported that approximately 80% of CPK elevations occurred within 1 week [ 7 ]. In our study, 70.6% patients in the CPK elevation group developed peak CPK levels within 10 days, suggesting that CPK elevation occurred within 10 days of daptomycin administration.…”

“…Case–control studies by Dare et al and Imai et al confirmed the relationship between daptomycin and CPK elevation based on the CPK levels of >ULN and >1000 IU/L or >2000 IU/L, respectively [ 6 , 28 ]. In several studies, statins were not associated with daptomycin-associated CPK elevation [ 7 , 8 , 25 , 27 , 29 ]. However, Bland et al [ 8 ], McConnell et al [ 25 ], and Berg et al [ 29 ] reported that the combination of daptomycin and statin treatment tended to increase the incidence of CPK elevation, defined as CPK levels >ULN, >3× ULN, and >1000 IU/L, respectively, by 2- to 5-fold compared with daptomycin alone, although the difference was not significant.…”

Factors affecting creatine phosphokinase elevation during daptomycin therapy using a combination of machine learning and conventional methods

“…In addition, previous studies were mainly conducted in the USA or European countries, but not in Asia. 4,5,[9][10][11]13,14,22,23 Moreover, the difference in the risk of musculoskeletal toxicities between each statin and DAP is unclear. For example, the strength of the effect of statins, such as low-to high-intensity effects, may be relevant to this drug-drug interaction.…”