Quentin Minson1, Chris A Gentry. 1. Pharmacy Service, Oklahoma City Department of Veterans Affairs Medical Center, Oklahoma City, Oklahoma 73104, USA.
Abstract
STUDY OBJECTIVES: 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. DESIGN: Retrospective medical record review. SETTING: Academic Veterans Affairs medical center. PATIENTS: Four hundred forty-four patients (mean age 63.7 yrs) who received 544 courses of linezolid from 2004-2007. MEASUREMENTS AND MAIN 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%). CONCLUSION: 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.
STUDY OBJECTIVES: 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. DESIGN: Retrospective medical record review. SETTING: Academic Veterans Affairs medical center. PATIENTS: Four hundred forty-four patients (mean age 63.7 yrs) who received 544 courses of linezolid from 2004-2007. MEASUREMENTS AND MAIN 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%). CONCLUSION: 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.