Evaluation of Impact of Statin Use on Development of CPK Elevation During Daptomycin Therapy

Berg, Melody L.; Estes, Lynn L.; Dierkhising, Ross A.; Curran, Brian; Enzler, Mark J.

doi:10.1177/1060028013514377

Cited by 22 publications

(45 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Daptomycin product labeling recommends that consideration be given to discontinuing statin therapy while administering daptomycin due to potential for additive toxicity, primarily myopathic toxicities. Limited data exist regarding safety of coadministration of daptomycin with statin therapy (4,7,8,9). The objective of our study was to report on the safety of concomitant statin and daptomycin therapy among hospitalized patients.…”

mentioning

confidence: 99%

Musculoskeletal Safety Outcomes of Patients Receiving Daptomycin with HMG-CoA Reductase Inhibitors

Bland

Bookstaver

Zhiqiang

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

dDaptomycin, a cyclic lipopeptide antibiotic, and 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) are commonly administered in the inpatient setting and are associated with creatine phosphokinase (CPK) elevations, myalgias, and muscle weakness. Safety data for coadministration of daptomycin with statins are limited. To determine the safety of coadministration of daptomycin with statin therapy, a multicenter, retrospective, observational study was performed at 13 institutions in the Southeastern United States. Forty-nine adult patients receiving statins concurrently with daptomycin were compared with 171 patients receiving daptomycin without statin therapy. Detailed information, including treatment indication and duration, infecting pathogen, baseline and subsequent CPK levels, and presence of myalgias or muscle complaints, was collected. Myalgias were noted in 3/49 (6.1%) patients receiving combination therapy compared with 5/171 (2.9%) of patients receiving daptomycin alone (P ‫؍‬ 0.38). CPK elevations of >1,000 U/liter occurred in 5/49 (10.2%) patients receiving combination therapy compared to 9/171 (5.3%) patients receiving daptomycin alone (P ‫؍‬ 0.32). Two of five patients experiencing CPK elevations of >1,000 U/liter in the combination group had symptoms of myopathy. Three patients (6.1%) discontinued therapy due to CPK elevations with concurrent myalgias in the combination group versus 6 patients (3.5%) in the daptomycin-alone group (P ‫؍‬ 0.42). CPK levels and myalgias reversed upon discontinuation of daptomycin therapy. Overall musculoskeletal toxicity was numerically higher in the combination group but this result was not statistically significant. Further prospective study is warranted in a larger population.

show abstract

mentioning

confidence: 99%

Musculoskeletal Safety Outcomes of Patients Receiving Daptomycin with HMG-CoA Reductase Inhibitors

Bland

Bookstaver

Zhiqiang

et al. 2014

Antimicrob Agents Chemother

View full text Add to dashboard Cite

show abstract

“…22 The manufacturer of atorvastatin recommends against a dosage exceeding 20 mg/day when co-administered with clarithromycin [16,17].Clarithromycin and erythromycin should be avoided with simvastatin because they increase the AUC of simvastatin acid by 11 times and 4 times their original values, respectively [7,16,18,42]. A similar effect is expected with lovastatin given that it is a major CYP3A4 substrate [46].…”

Section: Statins Interactions With Macrolidesmentioning

confidence: 87%

“…[21]. Berg et al's study compared 498 patients receiving daptomycin (63 with statins and 384 without statins) and did not find a statistically significant difference in frequency of CK elevation (Hazard Ratio, 0.44; 95% Confidence Interval, 0.14-1.40; p = 0.17) [22]. Golightly et al's study compared 157 patients receiving statins (52 with daptomycin and 105 without daptomycin) and did not find a statistically significant difference in frequency of CK elevation (9% vs 21%, respectively; p = 0.135) [23].Parra-Ruiz et al's study compared 104 patients receiving daptomycin (52 with statins and 105 without statins) and did not find a statistically significant difference in frequency of CK levels>1000 U/L (8% vs 10%, respectively; p = 0.746) [24].…”

Section: Statins Interactions With Daptomycinmentioning

confidence: 99%

“…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].…”

Section: Statins Interactions With Daptomycinmentioning

confidence: 99%

“…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.…”

Section: Literature Reviewmentioning

confidence: 99%

See 2 more Smart Citations

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

Eljaaly¹,

Alshehri²

2017

J Transl Sci

View full text Add to dashboard Cite

Numerous antimicrobial agents interact with statins. It is important to prevent these drug interactions and resulting statin toxicity and/or reduced efficacy. We review and highlight major drug-drug interactions between statins and antibacterial and antifungal agents; interactions with antiviral agents were not considered. Daptomycin interacts with statins via additive skeletal muscle toxicity. One possibility is to discontinue statins during daptomycin therapy, though no retrospective studies to date have shown a statistically significant elevation of adverse outcome risk. Multiple doses of rifampin induce cytochrome P450 (CYP), particularly 3A4 and 2C9, resulting in reduced systemic exposures to all statins, except rosuvastatin, for which the response was variable. Macrolide antibiotics are inhibitors of CYP3A4 and organic anion-transporting polypeptide-1B1. Azithromycin has the fewest drug interactions, while clarithromycin and erythromycin increase systemic exposure to all statins except rosuvastatin and fluvastatin. Azole antifungals are CYP450 inhibitors. Itraconazole and posaconazole are strong CYP3A4 inhibitors and mainly affect simvastatin, lovastatin, and atorvastatin, while fluconazole is an inhibitor of CYP2C9 and potentially CYP2C19 and mainly affects fluvastatin; however, risk cannot be ruled out with rosuvastatin.

show abstract

Clinical Guidance for Managing Statin and Antimicrobial Drug-Drug Interactions

Gravatt

Flurie

Lajthia

2017

Curr Atheroscler Rep

View full text Add to dashboard Cite

In addition to statin utilization increasing in recent years, there is greater emphasis on using moderate to high-intensity statin doses. Statin-related adverse effects are often dose-dependent; therefore, patients may be at increased risk. Antimicrobial use has also increased in recent years, and various efforts have been implemented to ensure appropriate use of antimicrobials. Commonly used antimicrobials, such as macrolide antibiotics and azole antifungals, interact significantly with the CYP3A4 enzyme pathway similarly to lovastatin, simvastatin, and atorvastatin. Consequently, the potential for significant drug-drug interactions is increasing. In 2012, the US Food and Drug Administration strengthened warning labels for statins and dose adjustments related to drug-drug interactions. As such, it is imperative that clinicians are comfortable identifying drug-drug interactions between statins and antimicrobials and making appropriate therapy modifications as clinically warranted. Statins and antimicrobials are frequently coprescribed, and the available pharmacokinetic data supports the potential for clinically significant drug-drug interactions. Macrolides and selected antifungals can significantly increase drug levels of select statins, particularly those metabolized by the CYP3A4 pathway. Contrarily, rifampin can significantly reduce drug levels of statins, limiting their efficacy. Future research efforts should identify interventions to improve clinician recognition of these drug-drug interactions and the prevention of unwarranted statin-related adverse effects.

show abstract

Evaluation of Impact of Statin Use on Development of CPK Elevation During Daptomycin Therapy

Abstract: Our findings suggest that holding statin during daptomycin therapy may not be necessary, but may indicate need for increased frequency of CPK monitoring when these medications are used concurrently.

Cited by 22 publications

References 21 publications

Musculoskeletal Safety Outcomes of Patients Receiving Daptomycin with HMG-CoA Reductase Inhibitors

Musculoskeletal Safety Outcomes of Patients Receiving Daptomycin with HMG-CoA Reductase Inhibitors

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

Clinical Guidance for Managing Statin and Antimicrobial Drug-Drug Interactions

Contact Info

Product

Resources

About