Category: Toxicology
Keywords: Dabigatran, Hemodialysis, Renal Replacement Therapy (PubMed Search)
Posted: 5/14/2015 by Kishan Kapadia, DO
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Dabigatran is an orally administered, potent, direct thrombin inhibitor approved for the prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation, and for the treatment and secondary prevention of venous thromboembolism.
Several pharmacokinectic studies have suggested that dabigatran possesses a number of ideal properties for expedited removal via extracorporeal methods. Dabigatran has low oral bioavailability (3-7%) and is predominantly cleared (80%) by the kidneys. It is not significantly protein bound, low-to-moderate steady state volume of distribution, and has a low molecular weight. All of these attributes make it a candidate for extracorporeal removal. Low protein binding may suggest redistribution into the plasma post extracorporeal removal.
Dabigatran is a substrate for the multidrug efflux transporter P-glycoprotein. Administration of the drug with potent P-glycoprotein inhibitors (ketoconazole, verapamil, amiodarone, quinidine) may significantly increase risk of toxicity, i.e. bleeding.
Most of the current evidence is based on case reports/case series where HD was the primary mode of removal.
Caution: Redistribution effect in plasma dabigatran concentration was also observed in several cases within 20 min to 12 hours post cessation of renal replacement therapy. Other limitations include:
1) Hemodynamic instability such as hypotension that may make initiation of extracoporeal removal difficult
2) Availability of indicators demonstrating effectiveness of extracorporeal removal
3) Amount of time needed to prepare patient to receive extracorporeal therapy
4) Use of extracorporeal removal as a treatment modality has not been prospectively evaluated
Bottom line: Extracorporeal removal may be an option for patients in the setting of life-threatening bleeding but with consideration of several limitations and should not preclude or delay use of other supplemental hemostatic therapies.
Awad NI, Brunetti L, Juurlink DN. Enhanced Elimination of Dabigatran Through Extracorporeal Methods. J Med Toxicol 2015;11:85-95.
