Analysis of linezolid-associated hematologic toxicities in a large veterans affairs medical center.
OBJECTIVE
To characterize linezolid-associated hematologic toxicities in a large clinical practice setting and to examine the variables associated with development of hematologic toxicities; a secondary objective was to characterize other linezolid-associated toxicities in this population.


METHODS
Retrospective medical record review.


METHODS
Academic Veterans Affairs medical center.


METHODS
Four hundred forty-four patients (mean age 63.7 yrs) who received 544 courses of linezolid from 2004-2007.


RESULTS
Pertinent laboratory data were collected at baseline, periodically throughout each linezolid course, and up to 31 days after discontinuation. The frequencies of grade 1-2 and grade 3-4 thrombocytopenia were 7.6% and 5.2%, respectively. Grade 3-4 anemia developed in 18.8% of courses; each of the patients had baseline grade 1-2 anemia. Linezolid was discontinued because of toxicity in 35 (6.4%) of the 544 courses. Independent variables associated with grade 3-4 thrombocytopenia included a baseline hemoglobin level of less than 10.5 g/dl, presence of immunosuppression, and a baseline platelet count of 50-99.9 x 10(3)/mm(3). Independent variables associated with development of grade 3-4 anemia included presence of a cardiovascular condition, urologic condition, immunosuppression, and a baseline platelet count of 50-99.9 x 10(3)/mm(3). Other toxicities reported with linezolid included diarrhea (6.6% of courses), followed by nausea (4.4%) and vomiting (4.0%).


CONCLUSIONS
The overall rates of thrombocytopenia and anemia for patients receiving linezolid were found to be higher than those in phase III clinical trials. This may be attributable in part to the inclusion of patients with comorbidities that were exclusion criteria in the phase III clinical trials. Clinicians should be aware of variables associated with the development of severe thrombocytopenia and anemia in patients receiving linezolid so that they may predict which patients are likely to develop these toxicities and consider potential alternative therapies in those patients.
Minson
Quentin
Q
Pharmacy Service, Oklahoma City Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104, USA.
Gentry
Chris A
CA
D000081:Acetamides / Q000009:adverse effects*; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000890:Anti-Infective Agents / Q000009:adverse effects*; D001792:Blood Platelets / Q000187:drug effects; D005260:Female; D006402:Hematologic Diseases / Q000139:chemically induced*; D006787:Hospitals, Veterans; D006801:Humans; D007297:Inpatients; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D010045:Outpatients; D023303:Oxazolidinones / Q000009:adverse effects*; D010976:Platelet Count; D012189:Retrospective Studies; D013921:Thrombocytopenia / Q000139:chemically induced
D000081:Acetamides; D000890:Anti-Infective Agents; D023303:Oxazolidinones; D000069349:Linezolid