Antithrombotic Prophylaxis and Therapy in Renal Failure

Drug Therapy in Patients With Chronic Renal Failure by Dr. med. Bertram Hartmann, PD Dr. med. David Czock, Prof. Dr. med. Frieder Keller in volume 37/2010

The authors postulate a “deep compartment” for enoxaparin. This is surprising in view of a distribution volume of some 5 liters and monophasic elimination (compare product information). Because of the structural differences of low molecular weight heparins, the pharmacokinetics of each low molecular weight heparin should be examined individually (1). Such substance specific studies in renal failure have been published for enoxaparin for a long time and have resulted in different dosage recommendations (1, 2, product information). Unfortunately, all this was ignored in the review article. For this reason, the article’s conclusions directly contradict the national and international licensing status of enoxaparin (for example, the US Food and Drug Administration [FDA]’s or the German Federal Institute for Drugs and Medical Devices [BfArM]’s).

After repeated subcutaneous administration of the prophylactic dose (40 mg) in patients with a creatinine clearance <30 mL/min enoxaparin, the area under the plasma concentration time curve (AUC) is increased by an average of 65%. Because of this, the prophylactic dose in patients with severely restricted renal function, according to the existing risk of thromboembolism should not be higher than 20 mg or 30 mg. After administration of the therapeutic dose (1 mg/mg KG b.d.) in severely impaired renal function, the AUC has been shown to double. In the product information it is therefore recommended to reduce the dose by 50%. Registry data from 4687 patients with acute coronary syndrome without ST-segment elevation and moderately to severely impaired renal function imply that low molecular weight heparins (more than 80% of patients were treated with enoxaparin) result in less severe hemorrhages than treatment with unfractionated heparins (3). Especially in the situation of medication treatment in chronic renal failure, which poses particular difficulties for the treating physicians, all existing studies and the licensing status should be given enough attention when evaluating therapeutic options.

DOI: 10.3238/arztebl.2011.0112b

Dr. med. Carsten Kienitz

Dr. med. Ludger Rosin

Prof. Dr. med. W. Dieter Paar

Sanofi-Aventis Deutschland GmbH

Potsdamer Str. 8

10785 Berlin, Germany

Conflict of interest statement
Dr Carsten Kienitz, Ludger Rosin MD, and Professor W Dieter Paar MD work in the medical department of Sanofi-Aventis Germany. Enoxaparin is marketed by Sanofi-Aventis Germany, P O Box 800860, 65908 Frankfurt/Main.

References

1. Schmid P, Fischer AG, Wuillemin WA: Low-molecular-weight heparin in patients with renal insufficiency. Swiss Med Wkly 2009; 139: 438–52.

2. Darius H, Hester K, Paar WD, Sanderink GJ: Antithrombotische Therapie mit niedermolekularen Heparinen bei Niereninsuffizienz. J Kardiol 2004; 11(7–8): 313–6.

3. Collet JP, Montalescot G, Agnelli G, et al. : Non-ST-segment elevation acute coronary syndrome in patients with renal dysfunction: benefit of low-molecular-weight heparin alone or with glycoprotein IIb/IIIa inhibitors on outcomes. The Global Registry of Acute Coronary Events. Eur Heart J 2005; 26: 2285–93.

4. Hartmann B, Czock D, Keller F: Drug therapy in patients with chronic renal failure. Dtsch Arztebl Int 2010; 107(37): 647–56.