Effect of Concomitant 3-Hydroxy-3-Methyl-Glutaryl-CoA Reductase Inhibitor Therapy on Creatine Phosphokinase Levels and Mortality Among Patients Receiving Daptomycin: Retrospective Cohort Study

Abstract

IntroductionThe prescribing information for daptomycin recommends discontinuing statin therapy during receipt of daptomycin. The literature supporting this recommendation is sparse. The objectives of this study were to examine the impact of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase inhibitors (statins) on creatine phosphokinase (CPK) elevations and mortality among patients receiving daptomycin therapy.MethodsA retrospective cohort study was performed among daptomycin recipients in the Upstate New York Veterans’ Healthcare Administration from September 15, 2003 to July 1, 2013. Inclusion criteria were: (1) daptomycin for ≥48 h, (2) availability of baseline CPK value and (3) >1 CPK level measurement taken while on therapy. The following were extracted from medical records: demographics, comorbidities, laboratory data, medication history (daptomycin, statins and concomitant drugs known to increase CPK), Acute Physiology and Chronic Health Evaluation (APACHE)-II score and vital status at 30 days. The exposure of interest was use of statins. The primary outcome was CPK elevation defined as a CPK value ≥3 times the upper limit of normal (ULN) if baseline CPK was normal, and ≥5 times ULN if baseline CPK was elevated. The secondary outcome was death within 30 days of commencing daptomycin.ResultsA total of 233 patients were included in this analysis. Among these patients, 53 received concomitant statin therapy. Most baseline clinical characteristics were similar between statin recipients and non-recipients. Five (2.1%) patients experienced a CPK elevation; 3/53 (5.7%) were statin recipients and 2/180 (1.1%) received daptomycin alone (p = 0.08). All patients with CPK elevations had normal baseline CPK values. No effect modification was observed by use of other concomitant medications known to increase CPK values. Death was observed more frequently among statin non-recipients (17.2%) than recipients (9.4%).ConclusionsAmong patients receiving daptomycin, no significant difference was observed in frequency of CPK elevation between statin recipients and non-recipients.Electronic supplementary materialThe online version of this article (doi:10.1007/s40121-014-0041-y) contains supplementary material, which is available to authorized users.

Observational retrospective single‐centre study in Japan to assess the clinical significance of serum daptomycin levels in creatinine phosphokinase elevation

“…In this study, statins were concomitantly used in six cases; however, none of them induced abnormal CPK elevation, which suggests the safety of the concomitant use of statins. Other previous reports also suggested the safety or insignificance of the concomitant use of statins . On the contrary, a recent clinical study reported that the coadministration of statins was a significant independent risk factor for myopathy and rhabdomyolysis .…”

“…Other previous reports also suggested the safety or insignificance of the concomitant use of statins. [22][23][24][25][26] On the contrary, a recent clinical study reported that the coadministration of statins was a significant independent risk factor for myopathy and rhabdomyolysis. 27 Thus, the safety of the concomitant use of statins may be currently controversial, and frequent CPK monitoring or suspending of statins (if needed) should be conducted to protect patients from severe muscle injuries.…”

An updated review of interactions of statins with antibacterial and antifungal agents

“…McConnell et al's study compared 233 patients receiving daptomycin (53 with statins and 180 without statins) and did not find a statistically significant difference in frequency of CK elevation (5.7% vs 1.1%, respectively; p = 0.08) [25]. Bland et al's study compared 220 patients receiving daptomycin (49 with statins vs 171 without statins) and did not find statistically significant differences in frequencies of myalgia (6.1% vs 2.9%, respectively; p = 0.38), CK levels of >1,000 U/ liter (10.2% vs 5.3%, respectively; p = 0.32), or therapy discontinuation due to CK elevations with concurrent myalgia (6.1% vs 3.5%, respectively; p = 0.42).…”

“…For daptomycin, systematic and manual searches identified four PK studies [21][22][23][24] and one [25] observational study, respectively. For rifampin, a systematic search identified three PK studies [26][27][28] assessing the impact of single dose and four PK studies [29][30][31][32] assessing the impact of multiple doses.…”

“…The prescribing information for daptomycin recommends considering suspending statin during treatment with daptomycin [49]. To date, studies have not found a higher risk of adverse outcomes with concomitant administration; however, these studies are retrospective and could be underpowered [21][22][23][24][25].…”