Pharmacodynamics
Dosed as a twice daily oral tablet, dabigatran reaches a peak plasma concentration after 1–2 h with a half-life of 12–17 h. Renal clearance accounts for 80–85% elimination of dabigatran. Doses should be reduced in patients with moderate renal impairment (defined as CrCl 30–50 ml/min) and should be avoided in patients with severe renal impairment (defined as CrCl 15–30 ml/min) and concomitant use of medications requiring use of P-glycoprotein (see Table 2). Current manufacturer recommendations state that dosing modifications are not necessary in patients with hepatic impairment.
Reversal Agents To date, there are no available antidotes for dabigatran. Blood products, such as fresh frozen plasma, are the principal agents of reversal. Hemodialysis may be effective in removing as much as 60% of circulating drug, as the majority of dabigtran is unbound to protein; however, there is insufficient data to support this as a means of a reversal.
Recommended Withholding Period Before Endoscopic Procedures
For patients with normal renal function and high risk of bleeding or major surgery, it is recommended to withhold for 2 days, and for otherwise average risks, for 24 h.Table 3 illustrates manufacturer recommendations for the discontinuation of dabigatran before elective surgery, as stratified by renal function.