From the Guidelines
Bivalirudin is filtered by the kidneys, but to a limited extent, with approximately 20% of the drug being cleared by renal elimination. The primary mechanism of elimination for bivalirudin is proteolytic cleavage, which accounts for about 80% of its clearance 1. According to the guidelines for the diagnosis and treatment of non-st-segment elevation acute coronary syndromes, if the creatinine clearance (CrCl) is less than 30 mL/min, a reduction of the infusion rate to 1.0 mg/kg/h should be considered, and if a patient is on haemodialysis, the infusion should be reduced to 0.25 mg/kg/h 1. This suggests that while renal elimination plays a role in the clearance of bivalirudin, it is not the primary mechanism, and dose adjustments are necessary in patients with severe renal impairment.
Some key points to consider when using bivalirudin in patients with renal impairment include:
- Reduction of the infusion rate in patients with CrCl less than 30 mL/min
- Reduction of the infusion rate to 0.25 mg/kg/h in patients on haemodialysis
- No reduction in the bolus dose is needed
- Regular monitoring of renal function and electrolyte balance is recommended
It is essential to consult with a healthcare provider to determine the appropriate dosage and treatment plan for patients with renal impairment who require anticoagulation therapy with bivalirudin 1.
From the FDA Drug Label
Bivalirudin undergoes glomerular filtration. Tubular secretion and tubular reabsorption are also implicated in the excretion of bivalirudin, although the extent is unknown Total body clearance was similar for PTCA patients with normal renal function and with mild renal impairment. Clearance was reduced by 21% in patients with moderate and severe renal impairment with a half-life of 34 and 57 minutes, respectively. In dialysis patients, clearance was reduced by 70%, with a half-life of 3. 5 hours. Approximately 25% bivalirudin is cleared by hemodialysis.
Bivalirudin is filtered by the kidneys through glomerular filtration, with additional mechanisms of tubular secretion and reabsorption also playing a role in its excretion 2.
From the Research
Bivalirudin and Renal Function
- Bivalirudin is a direct thrombin inhibitor that is cleared by both proteolytic cleavage and renal mechanisms, predominantly glomerular filtration 3.
- Approximately 20% of unchanged bivalirudin is cleared via the kidney, and the remainder undergoes proteolysis intracellularly 4.
- The clearance of bivalirudin is dependent on renal function, with patients with moderate and severe renal impairment having reductions in plasma clearance of 21% and 24%, respectively 4.
Renal Impairment and Bivalirudin Dosage
- Patients with renal dysfunction require a reduced dose of bivalirudin to reach a therapeutic activated partial thromboplastin time (aPTT) goal 5.
- The incidence of major bleeding is directly correlated with renal function, and bivalirudin has been shown to have significantly less in-hospital major bleeding than heparin alone or heparin in combination with a GpIIb/IIIa inhibitor 6, 7, 3.
- Bivalirudin dosing adjustments are necessary for patients with reduced renal function, with or without hemodialysis, to minimize the risk of bleeding complications 5.
Bivalirudin Pharmacokinetics and Pharmacodynamics
- The pharmacokinetics of bivalirudin are dose-proportional and characterized by rapid plasma clearance, a small volume of distribution, and an elimination half-life of about 30 minutes 7.
- Bivalirudin inhibits both circulating thrombin and fibrin-bound thrombin directly, and its anticoagulant effect is predictable and reversible 3.
- The pharmacodynamics of bivalirudin are dose-dependent and gender-independent, with a strong positive correlation between plasma bivalirudin concentrations and activated partial thromboplastin time (aPTT) or activated clotting time (ACT) 4, 7.