Risk Factors for Arthralgias or Myalgias Associated With Quinupristin-Dalfopristin Therapy

Peggy L. Carver, Pharm.D., Emily Whang, Pharm.D., Heather L. VandenBussche, Pharm.D., Carol A. Kauffman, M.D., Preeti N. Malani, M.D.

Disclosures

Pharmacotherapy. 2003;23(2) 

In This Article

Abstract and Introduction

Study Objective: To evaluate risk factors for the development of arthralgias or myalgias associated with quinupristin-dalfopristin.
Design: Retrospective chart review and case-control analysis.
Setting: An 850-bed tertiary care medical center.
Patients: All adult and pediatric patients who had received quinupristin-dalfopristin through either a compassionate-use protocol (February 1996-October 1999) or in the year after quinupristin-dalfopristin was added to the hospital formulary (November 1999-October 2000) were included in this study. Case patients were those who developed arthralgias or myalgias while receiving quinupristin-dalfopristin therapy; control patients were those who received quinupristin-dalfopristin but did not develop arthralgias or myalgias.
Intervention: Medical records, pharmacy dispensing information, and microbiology data were reviewed by a physician and a pharmacist, both of whom specialized in infectious diseases. Presence or absence of arthralgias or myalgias was the primary outcome assessed.
Measurements and Main Results: Quinupristin-dalfopristin was administered to 68 patients during the period defined by the study. Arthralgias and myalgias could not be assessed in 18 of the 68 patients because they were sedated and paralyzed, or they were young children who could not communicate the presence of pain. Univariate analysis demonstrated that significant risk factors for arthralgias or myalgias associated with quinupristin-dalfopristin were female sex, chronic liver disease, receipt of liver transplant, elevated bilirubin level at baseline, major surgery, and receipt of either mycophenolate or cyclosporine. Multivariate analysis demonstrated a strong association with chronic liver disease, receipt of liver transplant, elevated bilirubin level at baseline, and receipt of either cyclosporine or mycophenolate. Of 50 evaluable patients receiving quinupristin-dalfopristin, 25 had pain that may have been associated with this antimicrobial agent.
Conclusion: The mechanism for development of arthralgias or myalgias associated with quinupristin-dalfopristin remains unknown, but these adverse events are more likely to occur in patients with chronic liver disease and those who have received a liver transplant or are receiving cyclosporine or mycophenolate.

Quinupristin-dalfopristin is a streptogramin agent with a broad spectrum of activity against many resistant gram-positive organisms, such as vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus.[1,2,3] During initial treatment trials with quinupristin-dalfopristin, arthralgias or myalgias were not reported in some studies[4,5] and were reported in approximately 10% of patients in others.[6,7,8] However, several subsequent reports demon-strated a rate of occurrence of these adverse effects of 33-47%.[9,10,11]

In our medical center it appeared that a significant proportion of patients receiving quinupristin-dalfopristin experienced arthralgias or myalgias, and often required therapy with intravenous analgesics or discontinuation of quinupristin-dalfopristin. We reviewed our experience to assess the proportion of patients who developed these adverse effects and to determine if specific underlying illnesses or concurrent drugs contributed to their occurrence.

processing....