**2.3.3.1 Dabigatran etexilate**

Dabigatran etexilate is a direct thrombin inhibitor, currently approved for the prevention of venous thromboembolism in orthopedic surgery patients. After oral administration peak plasma concentrations are achieved within 2 hours of administration. Elimination of dabigatran is predominantly via the renal pathway, 80% of the administered dose is excreted unchanged in the urine within the first 24 hours after an intravenous dose and is contraindicated in patients with severe renal impairment (Stangier, 2008)

Limited data are avalaible on dabigatran pharmacokinetics in patients with renal impairment for venous thromboembolism treatment.(Dahl, 2009)

Venous Thromboembolism in Neonates, Children and

Table 1. Clasification of Renal impairment

minimal

RES minimal

cleavage 80% Renal 20%

100%(CYP3A4)

Hepatic 100% (CYP2C9)

hepatic 50%

**Fondaparinux** Renal>80% 17 -21 h after SC

CrCl: creatinine clearance

**UFH** RES,renal

**LMWH** Mainly renal

**Bivalirudin** Proteolytic

**Argatroban** Hepatic

**Rivaroxaban** Renal 50%

**Vitamin K agonists** 

serum creatinine [Reference: Harder, 2011]

1 Normal o Increased GFR ≥90 2 Mild decrease in GFR 60 to 80 3 Moderate decrease in GFR 30 to 59 4 Severe decrease in GFR 15 to 29

5 Kidney failure (End stage renal disease) <15(or dialysis)

a Clasification by National Kidney Foundation. Chronic kidney disease is defined as either kidney damage or GFR of <60 mL/min/1.73m2 for ≥ 3 months. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.GFR reported by the National Kidney Foundation, using the modification of Diet in Renal Disease Study equation based on age, gender, race, and

**Anticoagulant Elimination Half life\* Monitoring Antidote Dose** 

30-150 min after IV administration

2-8 h after SC administration

~25 min after IV administration

40-50 min after IV administration

administration

**Dabigatran** Renal 80% 8 -10 h ECT None Not

ACT =Activated clotting time; aPTT=activated partial thromboplastin time; CYP= cytochrome p450 ECT = ecarin clotting time; INR= International normalized ratio; IV =Intravenous; LMWH= low molecular weight heparin; RES= reticuloendothelial system; SC= subcutaneous; UFH= unfractionated heparin.

Table 2. Anticoagulants characteristics and dose adjustment in severe renal impairment

**Apixaban** Renal 50% 8 – 15 h INR, aPTT,

{Reference: Grand'Maison A, Charest A,Geerts W, 2005 ; Harder S,2011]

aPTT, anti Xa ACT

aPTT,ACT, ECT

7 -11 h Anti Xa None Not

Anti Xa

~36-42 h INR Vitamin K Careful dose

Anti Xa Protamine

partially effective

Anti Xa None Drug no

None No

None Yes

ACT None Yes

Patients with Chronic Renal Disease – Special Considerations 49

**mL/min/1.73m2** 

**adjustment in severe renal impairment** 

adjustment Monitoring high doses

recommended

recommended

recommended

titration

Yes

Protamine No dose

**Stage Kidney damage Glomerular filtration rate CrCl,** 

#### **2.3.3.2 Rivaroxaban**

Rivaroxaban inhibits both free and clot-bound Factor Xa, this oral anticoagulant has been approved for the prevention of venous thromboembolism after elective hip or knee replacement surgery in adults (Bauer, 2008)

Rivaroxaban has a dual mode of elimination hepatic and renal and the inhibition of factor Xa activityalso increased with the reduce renal function. Rivaroxaban is not recommended for patients with a Creatine clearance of less than 15 mil/min. (Kubitza, 2010). To the date there are not reported studies for rivaroxaban in patients with renal impairment for venous thromboembolism.
