What is the recommended dose of Pradaxa (dabigatran) for patients with severe impaired renal function?

Dabigatran 75 mg Dosing in Severe Renal Impairment

For patients with severe renal impairment (creatinine clearance 15-30 mL/min), dabigatran should be dosed at 75 mg twice daily. 1

Dosing Recommendations Based on Renal Function

Dabigatran dosing is highly dependent on renal function due to its significant renal clearance (80% of the drug is eliminated through the kidneys). The FDA-approved dosing recommendations for dabigatran in patients with non-valvular atrial fibrillation are:

• Normal to moderate renal function (CrCl >30 mL/min): 150 mg twice daily
• Severe renal impairment (CrCl 15-30 mL/min): 75 mg twice daily
• End-stage renal disease (CrCl <15 mL/min) or dialysis: Not recommended 1

Evidence Supporting the 75 mg Dose

The 75 mg twice daily dose for severe renal impairment was FDA-approved based on pharmacokinetic modeling data, not from clinical trials. The pivotal RE-LY trial that established dabigatran's efficacy did not evaluate this lower dose 2.

It's important to note that the American College of Cardiology/American Heart Association guidelines confirm this dosing recommendation, stating that for patients with severe renal impairment (CrCl 15-30 mL/min), dabigatran should be dosed at 75 mg twice daily 2.

Cautions with Very Low Dosing

Some clinicians might consider further reducing the dose below 75 mg twice daily in patients with very poor renal function, but this approach is not supported by evidence. A retrospective study found that patients receiving the very low dose of 75 mg twice daily had a significantly higher risk of thromboembolic events compared to those receiving the standard doses (odds ratio 5.73,95% CI 1.55-21.2) 3.

Special Considerations

• P-glycoprotein inhibitors: In patients with moderate renal impairment (CrCl 30-50 mL/min) who are also taking P-glycoprotein inhibitors like dronedarone or ketoconazole, the dose should be reduced to 75 mg twice daily 1
• Avoid in very severe renal impairment: Dabigatran is not recommended for patients with CrCl <15 mL/min or those on dialysis 1
• Monitoring: Regular assessment of renal function is essential as changes may necessitate dose adjustments 1

Alternatives for Very Severe Renal Disease

For patients with end-stage renal disease or CrCl <15 mL/min, alternative anticoagulants should be considered:

• Warfarin with dose adjusted to achieve INR 2.0-3.0 may be appropriate if good time in therapeutic range (>65-70%) can be maintained 2
• Apixaban may be considered in some dialysis patients according to some guidelines, though evidence is limited 2

Perioperative Management

For patients on dabigatran with severe renal impairment (CrCl 15-30 mL/min) who require surgery:

• For low bleeding risk procedures: Stop dabigatran 3 days before surgery (skip 4 doses)
• For high bleeding risk procedures: Stop dabigatran 4-5 days before surgery (skip 6-8 doses) 2

Bleeding Management

In case of bleeding complications in patients on dabigatran:

• There is a specific reversal agent (idarucizumab) available for emergency situations
• Hemodialysis can remove approximately 49-57% of dabigatran in 4 hours and may be considered in severe bleeding when other measures fail 1

Remember that while the 75 mg twice daily dose is appropriate for patients with severe renal impairment, using doses below the FDA-approved recommendation may lead to inadequate anticoagulation and increased risk of thromboembolic events.