Safety analysis of high dose (>6 mg/kg/day) daptomycin in patients with concomitant statin therapy

Abstract

There is a paucity of data regarding efficacy and safety of concomitant therapy of daptomycin and statins, so we reviewed patients that concomitantly received daptomycin and statins to identify any potential increase in toxicity in our cohort. This retrospective study included all patients that received >6 mg/kg/day of daptomycin along with statins and had efficacy and safety data. Patients on high dose (>6 mg/kg/day) daptomycin therapy that did not received statins served as controls. One hundred four patients were included. Median daptomycin dose was 7.8 mg/kg/day (range 6.5-10.8 mg/kg/day), for a mean duration of therapy of 17 days (range 10-51 days). Thirty-six patients received daptomycin and statins and 68 received only daptomycin. Muscular toxicity defined as CPK levels>1000 UI/L (2.5 times upper normal limit, range of determination 200-400 UI/L) was equally distributed between both groups (3/36, 8% vs 7/68, 10%; p=0.746). Despite biochemical toxicity, we did not find clinical toxicity and daptomycin treatment was completed in all cases. We did not find predictors of increased CPK during daptomycin therapy. Based on our data, concomitant administration of daptomycin and statins is safe and is not associated with an increased risk of rhabdomyolysis.

The safety and efficacy of high-dose daptomycin combined with rifampicin for the treatment of Gram-positive osteoarticular infections

“…Recent studies indicate a growing interest in the design of novel therapeutic protocols for deep-seated multi-resistant Gram-positive infections, as alternatives to the standard glycopeptide therapy [2][3][4][5][6][7][8]. Daptomycin has attractive properties for treating osteoarticular infections, because of its rapid bactericidal activity against susceptible as well as multi-resistant, Gram-positive isolates.…”

“…Very few antimicrobial agents remain available for therapy of osteoarticular infections that are due to multi-resistant Gram-positive pathogens, in particular methicillin-resistant S. aureus (MRSA). Besides glycopeptides that remain the mainstay for therapy of MRSA deep-seated infections, some recently developed agents that are active against both susceptible and multi-resistant, gram-positive pathogens including MRSA, in particular daptomycin [2][3][4][5][6] and linezolid [7,8], have been recently evaluated for therapy of osteoarticular infections.…”

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

“…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].…”

“…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].…”