In this episode I’ll:
1. Discuss a review article about musculoskeletal toxicities in patients receiving concomitant statin and daptomycin therapy
2. Answer the drug information question “Is there any benefit in de-escalating ceftriaxone to cefazolin?”
Article
Musculoskeletal toxicities in patients receiving concomitant statin and daptomycin therapy
Lead author: Kazuhiko Kido
Published in American Journal of Health-System Pharmacy February 2019
This article is a narrative review of the safety of concomitant therapy with daptomycin and statins.
The authors identified 5 retrospective cohort studies that look at creatine phosphokinase (CPK) elevation in patients receiving daptomycin monotherapy versus daptomycin and statin concomitant therapy. Four of these five studies also looked at myalgia or myopathy incidence between groups.
Daptomycin and statins each have different mechanisms for causing myopathy. This explains the concern that the use of the two medications together could possibly have a synergistic effect on the development of musculoskeletal toxicities.
The current prescribing information recommendations regarding daptomycin and statin use is as follows:
In patients who receive CUBICIN, CPK levels should be monitored weekly, and more frequently in patients who received recent prior or concomitant therapy with an HMG-CoA reductase inhibitor or in whom elevations in CPK occur during treatment with CUBICIN.
Experience with the coadministration of HMG-CoA reductase inhibitors and CUBICIN in patients is limited; therefore, consideration should be given to suspending use of HMG-CoA reductase inhibitors temporarily in patients receiving CUBICIN.
There has been a significant amount of new information published since the development of these recommendations in the prescribing information.
Study 1 included 500 patients receiving daptomycin alone, daptomycin plus statin, and daptomycin with recent statin use placed on hold. There was no difference between groups of CPK levels or myalgia.
Study 2 included 220 patients receiving daptomycin alone or daptomycin plus statin. There was no significant difference in CPK elevation between groups.
Study 3 included 233 patients receiving daptomycin alone or daptomycin plus statin. There was no significant difference in CPK elevation between groups.
Study 4 included over 4000 patients, with more than 900 receiving both daptomycin and statin therapy together. Patients with an elevated CPK at initiation of daptomycin were excluded. The authors found the incidence of CPK elevation was actually significantly higher in the daptomycin monotherapy group at 4.4% compared to the concurrent statin cohort at 2.9%.
Study 5 included 100 patients receiving daptomycin alone or daptomycin plus statin. The authors found that numerically more patients on daptomycin monotherapy had grade 2 CPK elevations, however this was not statistically significant.
The data represented in these retrospective studies is not perfect. Some studies had patients using daptomycin for only 7 days, while others had much higher median durations of daptomycin use.
There is also the potential that withholding a statin in a patient with cardiovascular disease could lead to higher rates of adverse cardiovascular outcomes.
Conclusion
The authors of this review propose a method of dealing with daptomycin and statin use that differs from the prescribing infomation and is supported by the available evidence. The authors state:
Published cohort studies do not demonstrate a statistically significant difference in the rate of CPK elevations or musculoskeletal toxicities between patients receiving daptomycin monotherapy and daptomycin plus a statin. Patients receiving statins who start daptomycin therapy should continue statin but with weekly monitoring of CPK levels. Continuation of statins is especially important in high-risk patients receiving statins for secondary prevention for atherosclerotic cardiovascular diseases. If myalgia develops, it is reasonable to evaluate the degree of CPK elevation and reassess the need for statin use during daptomycin treatment.
Drug information question
Q: Is there any benefit in de-escalating ceftriaxone to cefazolin?
A: My answer to this question is “maybe.” There is not any direct evidence to suggest a benefit to cefazolin over ceftriaxone. However, this article suggests that the cephalosporins are not equal to each other in terms of C. diff infection risk, and that cefazolin has a lower CDI risk than ceftriaxone.
Cefazolin is primarily renally excreted, and agents that are primarily excreted via the kidneys result in relatively low levels of intestinal exposure, and only minor disruption of intestinal microbiota, especially anaerobes.
Ceftriaxone is excreted in the bile, and has at least an order of magnitude higher concentration in the bile than cefazolin. This, in theory, could result in less disruption of the gut flora and therefore less C diff.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.
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