Retrospective evaluation of a pharmacokinetic program for adjusting enoxaparin in renal impairment

Background Although clinical trials have found that enoxaparin clearance is prolonged in renal impairment, only one letter describes experience with adjusting doses. Only pharmacokinetic studies exist to guide dose adjustment in response to anti-Xa levels. Unfractionated heparin has comparable major bleeding in renal impairment compared with unadjusted enoxaparin. This necessitates a pharmacokinetic program to adjust enoxaparin with anti-Xa monitoring. Methods A pharmacokinetic program was created in response to adverse events and physician interest in a service. A program was designed providing all patients a loading dose of 1 mg/kg enoxaparin. Subsequent doses were 0.50 mg/kg per dose subcutaneously (SC) every 12 hours (q12h) for patients with a creatinine clearance (CrCl) less than or equal to 30 mL/min (severe group) and 0.75 mg/kg per dose SC q12h for patients with CrCl of 30 to 60 mL/min (moderate group). A 1-year review of 170 hospitalized patients is reported. Results The mean +/- SD [95% Cl] anti-Xa level 4 hours after the third dose was 0.65 +/- 0.19 [0.59 to 0.70] IU/mL for the severe group and 0.82 +/- 0.18 [0.79 to 0.85] IU/mL for the moderate group (P <.001). Eighty percent of patients with moderate renal failure and 60% of the patients with severe renal failure were in the therapeutic anti-Xa range after the third dose. A dose-adjustment ratio was used to adjust doses in patients whose levels were outside the therapeutic range: New dose = [(Current dose) X (Goal anti-Xa level)] /(Current anti-Xa level). An incidence of bleeding comparable to that found in normal patients was found. Conclusions In high-risk patients, it is reasonable to limit the exposure of patients to low molecular weight heparins by using anti-Xa levels as a marker. The enoxaparin protocol for renally impaired patients successfully placed patients in the therapeutic range established by consensus guidelines. The dose-adjustment ratio adds significant understanding to the pharmacokinetics of dose adjustment.