Relationship between myalgias/arthralgias occurring in patients receiving quinupristin/dalfopristin and biliary dysfunction.
OBJECTIVE
To determine whether myalgias/arthralgias occurring in cancer patients who receive quinupristin/dalfopristin are associated with biliary tract dysfunction.


METHODS
We studied 56 patients with vancomycin-resistant enterococcal infections who were treated with quinupristin/dalfopristin 7.5 mg/kg every 8 h for a mean duration of 12 days (range 2-52 days). Liver function tests, including a test for alkaline phosphatase, were performed before, during and after the end of therapy. All patients were followed for 1 month after completion of therapy.


RESULTS
Thirty-eight (68%) of the 56 patients responded. Myalgias/arthralgias were the leading adverse events occurring in 20 (36%) of the patients. Patients with myalgias/arthralgias had significantly higher levels of alkaline phosphatase (mean 318.7 IU/L) during the mid-term therapy cycle compared with patients without any joint or muscular pain (mean 216.3 IU/L, P = 0.05). In addition, 3/18 (16.6%) patients with myalgias/arthralgias had more than five-fold the normal levels of alkaline phosphatase, which did not occur in any of the other patients who did not develop myalgias/arthralgias (P = 0.04). All myalgias/arthralgias resolved after the discontinuation of quinupristin/dalfopristin. By univariate analysis, other factors associated with myalgias/arthralgias were relapse of haematological malignancy (P = 0.01), receiving tacrolimus within 1 month prior to treatment (P = 0.04) and receiving methotrexate during antimicrobial therapy (P = 0.05).


CONCLUSIONS
Myalgias/arthralgias occur frequently in cancer patients receiving quinupristin/dalfopristin and may be associated with biliary tract dysfunction, as measured by alkaline phosphatase or other factors that could lead to intra-hepatic cholestasis, such as relapse of haematological malignancy or treatment with tacrolimus or methotrexate.
Raad
Issam
I
M.D. Anderson Cancer Center, Department of Infectious Diseases, 1515 Holcombe Blvd, Unit 402, Houston, TX 77030, USA. iraad@mdanderson.org
Hachem
Ray
R
Hanna
Hend
H
D000368:Aged; D000469:Alkaline Phosphatase / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects; D018771:Arthralgia / Q000139:chemically induced*; D001660:Biliary Tract Diseases / Q000150:complications*; D016983:Enterococcus; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000150:complications / Q000188:drug therapy; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008111:Liver Function Tests; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D009135:Muscular Diseases / Q000139:chemically induced*; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000139:chemically induced*; D012008:Recurrence; D012307:Risk Factors; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use; D014769:Virginiamycin / Q000009:adverse effects* / Q000031:analogs & derivatives*
D000900:Anti-Bacterial Agents; D000964:Antimetabolites, Antineoplastic; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D014769:Virginiamycin; C113825:quinupristin; D000469:Alkaline Phosphatase; D016559:Tacrolimus; D008727:Methotrexate