4CPS-059 Linezolid dosing in patients with liver cirrhosis: standard dosing risks’ toxicity

Abstract

BackgroundLinezolid is used at a standard dose of 600 mg/12 hours regardless of renal or hepatic function but very little data concerning its pharmacokinetics (PK), efficacy and safety in patients with liver cirrhosis is available.PurposeThe objectives were to describe the PK, efficacy and safety of linezolid in cirrhotic patients.Material and methodsA prospective case-control 1:1 study conducted between January 2015 to June 2017. Cases were all cirrhotic patients treated with linezolid undergoing therapeutic drug monitoring (TDM). Controls were matched by age, actual bodyweight, comorbidities, renal function (glomerular filtration rate (GFR)) and severity. Subtherapeutic linezolid concentrations were defined as a through (Cmin) concentration <2 mg/L and supratherapeutic as a Cmin >10 mg/L. Thrombocytopaenia was defined as a decrease in platelet count to <75% and anaemia as an ≥2 g/dL decrease in haemoglobin, both from baseline. Data are described as the mean± (standard deviation SD). The Student’s t-test or Mann–Whitney U-test for continuous variables and the Chi-square or Fisher’s exact test for dichotomous variables were used.ResultsFifty-two patients were included. Mean age: 62 (±11. 9) years, males 66. 1%, without differences in baseline demographic and clinical characteristics excepting for low baseline platelet count (57.7% vs. 26.9%, p=0.025).Abstract 4CPS-059 Table 1 Cases (n= 26) Controls (n= 26) P value Baseline GFR (CKD-EPI, ml/min/1.73 m2) 75.0 (44.8) 70.1 (48.6) 0.709 Linezolid dose (mg/kg) 16.9 (2.8) 17.5 (3.3) 0.479 Cmin, ss (mg/L) 22.6 (14.7) 7.4 (9.0) < 0.001 Subtherapeutic concentrations 0 (0%) 9 (32.0%) 0.002 Supratherapeutic concentrations 20 (80%) 7 (28%) < 0.001 Clinical cure 19 (73.1%) 12 (46.1%) 0.348 Anaemia 7 (28.4%) 6 (24.2%) 0.747 Thrombocytopaenia 13 (52%) 8 (33.3%) 0.187 Final platelet count<100. 000/mm3 18 (69.2%) 4 (16.7%) < 0.001 Discontinuation due to haematological toxicity 5 (19.2%) 1 (3.8%) 0.083 ConclusionCirrhotic patients were more likely to have supratherapeutic concentrations of linezolid and a lower final platelet count, probably due to reduced non-renal clearance. Linezolid showed a good clinical response rate with no differences between patients with and without cirrhosis. These results question the use of standard doses of linezolid to this population and highlight the need to perform TDM to reduce toxicity.No conflict of interest