Anti-factor Xa activity of enoxaparin administered at prophylactic dosage to patients over 75 years old

What is already known about this subject Major bleeds with low-molecular-weight heparin have been reported at curative and prophylactic dosages. Enoxaparin clearance depends on body weight, and therefore weight-adjusted dosing is recommended to minimize interindividual variability in drug exposure and the risk of haemorrhage in patients treated at curative doses. Monitoring of this treatment is recommended in curative indications in patients at risk. The need for monitoring of patients at risk receiving prophylactic doses of enoxaparin, in this case the elderly, remains unclear. What this study adds Clearance of enoxaparin at prophylactic doses is predictably related to body weight and creatinine clearance in the elderly. The simplified Modification of Diet in Renal Disease formula seems to be most discriminating and powerful in detecting any influence of glomerular filtration rate in the elderly. The influence of these covariates does not seem to be sufficiently clinically relevant to support routine assessment in the elderly. Major bleeding complications with low-molecular-weight heparin (LMWH) treatment have been reported both in clinical studies and during postmarketing surveillance. Monitoring of antifactor Xa (anti-Xa) activities is therefore recommended in special populations often predisposed to renal impairment. The PROPHRE.75 study was conducted to estimate the distribution parameters of anti-Xa activity in the elderly. PROPHRE.75 was a prospective study of a cohort of consecutive patients aged > 75 years and treated with 4000 IU of enoxaparin once daily for venous thromboembolism prophylaxis. Dosing history and measurements of anti-Xa activity in sparse samples were recorded throughout treatment. The covariates included weight, gender, age, renal function, medical history and concomitant medication. Population parameters and interindividual variability were estimated using NONMEM (R) V software. Anti-Xa activity was studied in 189 patients (mean age 82 +/- 5 years, 22% weighing < 50 kg, 50% presenting renal impairment according to the Cockcroft and Gault formula). A first-order input two-compartment model best fitted the data. Clearance was significantly related to body weight and creatinine clearance based on the simplified Modification of Diet in Renal Disease formula, central volume being related to body weight. According to individual Bayesian estimations, 4% of patients presented with a peak anti-Xa activity > 1.0 IU ml(-1), but this group did not include the sole patient experiencing a major bleed (0.53%). Systematic monitoring of anti-Xa activity in elderly patients treated with enoxaparin at prophylactic doses does not seem to be necessary to prevent the occurrence of major bleeding.