Safety outcomes with high‐dose daptomycin in patients with acute kidney injury and/or end‐stage renal disease

• Published in: Journal of clinical pharmacy and therapeutics Vol. 46; no. 2; pp. 363 - 368
• Main Authors: Vlashyn, Olga O., Lorenz, Ashley M., Sobhanie, Mohammad M., Smith, Jessica M., Bond, Megan, Wardlow, Lynn
• Format: Journal Article
• Language: English
• Published: England Hindawi Limited 01.04.2021
• Subjects: Acute Kidney Injury - epidemiology; Age Factors; Aged; Anti-Bacterial Agents - administration & dosage; Anti-Bacterial Agents - adverse effects; Anti-Bacterial Agents - therapeutic use; Bacteremia; Body weight; Creatine; Creatine kinase; Creatine Kinase - blood; Creatinine; Daptomycin; Daptomycin - administration & dosage; Daptomycin - adverse effects; Daptomycin - therapeutic use; Dosage; Dose-Response Relationship, Drug; Female; Gram-Positive Bacterial Infections - drug therapy; Gram-Positive Bacterial Infections - epidemiology; Humans; Hypersensitivity; Kidney diseases; Kidney Failure, Chronic - epidemiology; Leukocytes (eosinophilic); Male; Middle Aged; Myopathy; Patients; Population studies; renal dysfunction; Renal function; Retrospective Studies; Rhabdomyolysis; safety; Severity of Illness Index; Sex Factors; Side effects; daptomycin; rhabdomyolysis; renal dysfunction; safety
• ISSN: 0269-4727; 1365-2710
• DOI: 10.1111/jcpt.13289

What is known Daptomycin is associated with a number of adverse effects including eosinophilic pneumonia, hypersensitivity reaction, myopathy, rhabdomyolysis, headache and transaminitis. The adverse effects of high‐dose daptomycin have not been fully evaluated in patients with end‐stage renal disease (ESRD). Objective To determine the incidence and characteristics of significant adverse effects in patients receiving high‐dose daptomycin with severe renal dysfunction. Methods A single‐centre, retrospective study was conducted to assess safety outcomes of high‐dose daptomycin in patients with an estimated creatinine clearance less than 30 mL/min. Adult patients aged 18 to 89 years admitted between 1 July 2015 and 1 July 2019 were eligible for inclusion. Patients must have received definitive daptomycin therapy with doses greater than or equal to 7.5 mg/kg based on actual body weight. The primary outcome was overall incidence of creatine phosphokinase (CK) elevation, myopathy and rhabdomyolysis. Results and discussion A total of 74 patients who received daptomycin therapy were screened with 50 included in the study. The population was well distributed in terms of gender (48% male, n = 24) with a median age of 61 (IQR, 48‐67) years. The primary indication for daptomycin use was Gram‐positive bacteremia. The median daptomycin dose was 750 (IQR, 600‐875) mg, or 8.46 (IQR, 7.92‐9.96) mg/kg based on actual body weight, with a median patient weight of 81 (IQR, 65‐113) kg. The median duration of therapy was 27 (IQR, 14‐42) days. One patient experienced significant CK elevation while on daptomycin therapy with rhabdomyolysis; however, daptomycin was continued as there was an alternative explanation for an elevated CK. One patient experienced daptomycin discontinuation due to CK elevation without meeting the definition for significant CK elevation. What is new and conclusion In a cohort of patients with severe renal dysfunction treated with daptomycin 7.5 mg/kg or greater, significant CK elevation on daptomycin therapy was infrequently observed. Future research should confirm these findings, with special consideration for higher mg/kg dosages and/or obese populations. In a cohort of patients with severe renal dysfunction treated with daptomycin 7.5 mg/kg or greater, significant CK elevation on daptomycin therapy was infrequently observed.