Dosing strategy to allow continued therapy with daptomycin after asymptomatic increases in creatine kinase levels

• Published in: American journal of health-system pharmacy Vol. 71; no. 13; pp. 1101 - 1107
• Main Authors: BURDETTE, STEVEN D, OLESON, FREDERICK, McDANELD, PATRICK M, BENZIGER, DAVID, PATEL, HINA N
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Copyright American Society of Health-System Pharmacists, Inc. All rights reserved 01.07.2014; American Society of Health Pharmacists; Oxford University Press
• Subjects: Adult; Aged; Anti-Bacterial Agents - administration & dosage; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Biomarkers - blood; Case studies; Creatine kinase; Creatine Kinase - blood; Daptomycin - administration & dosage; Dose-Response Relationship, Drug; Drug therapy; Female; Health aspects; Humans; Infectious skin diseases; Male; Medical sciences; Methicillin-Resistant Staphylococcus aureus - drug effects; Middle Aged; Pharmacology. Drug treatments; Staphylococcal Infections - blood; Staphylococcal Infections - drug therapy; Staphylococcus aureus infections; Young Adult; United States; Human; Peptides; Enzyme; Creatine kinase; Transferases; Daptomycin; Asymptomatic; Posology; Antibiotic; Treatment; Application method; Antibacterial agent; Lipopeptide
• ISSN: 1079-2082; 1535-2900
• DOI: 10.2146/ajhp130527

PURPOSEA case series in which a novel dosing strategy for managing mild, asymptomatic creatine kinase (CK) increases associated with daptomycin therapy is presented. SUMMARYEight patients received a mean daptomycin dosage of 7.75 mg/kg/day for a median duration of 42 days. Seven of the eight patients were being treated for a bone and joint infection, and all but one had methicillin-resistant Staphylococcus aureus. All patients had asymptomatic increases in CK concentrations during daptomycin therapy (peak range, 400–1200 IU/L). A single daptomycin dose was withheld from each patient, and therapy was resumed 24 hours later, most often at the same dosage. The elevated CK values in these patients resolved, and all patients were able to complete daptomycin therapy without further increases in CK elevations. These findings indicate that withholding one dose of daptomycin during treatment may allow patients with asymptomatic, elevated CK concentrations to continue therapy with CK level normalization. Although the mechanism of daptomycin-mediated muscle injury is not fully understood, a reduction in daptomycin exposure via a one-dose cessation of therapy may allow for physiological restoration of sarcolemma membrane integrity that may be disrupted by daptomycin in individuals exhibiting CK elevation. CONCLUSIONA single daptomycin dose was withheld from eight patients with asymptomatic increases in serum CK concentrations, then daptomycin therapy was resumed 24 hours later, most often at the previous dosage. The CK concentrations returned to normal, and all patients were able to complete daptomycin therapy without further increases in CK concentrations.