What are the guidelines for using Pradaxa (dabigatran) in elderly patients with impaired renal function?

From the Guidelines

Elderly patients with impaired renal function should have their Pradaxa (dabigatran) dose reduced to 110 mg twice daily if they have moderate renal impairment (creatinine clearance 30-50 mL/min), and its use should be cautiously considered in those with severe renal impairment. When considering the use of Pradaxa in elderly patients, it's crucial to assess renal function, as dabigatran is primarily eliminated by the kidneys, with 80% of its clearance being renal 1. Key factors influencing dosing adjustments include:

• Age, particularly for those over 75 years, who may require additional dose reduction due to a higher bleeding risk
• Renal function, with dose reductions recommended for moderate renal impairment and cautious use in severe impairment
• Concomitant use of certain medications, such as P-glycoprotein inhibitors, which may necessitate further dose adjustments According to the most recent guidelines, for patients with moderate renal impairment (creatinine clearance 30-50 mL/min), a dose reduction to 110 mg twice daily is recommended 1. It's also important to note that Pradaxa is contraindicated in patients with creatinine clearance below 15 mL/min, as indicated by earlier recommendations 1, but the most recent and highest quality study 1 provides the dosing guidance for moderate to severe renal impairment. Regular monitoring of renal function, at least annually or more frequently if renal function deteriorates, is essential for elderly patients on Pradaxa, especially given the potential for declining renal function with age.

From the FDA Drug Label

Of the total number of patients in the RE-LY study, 82% were 65 and over, while 40% were 75 and over. The risk of stroke and bleeding increases with age, but the risk-benefit profile is favorable in all age groups [see Warnings and Precautions (5), Adverse Reactions (6. 1), and Clinical Studies (14.1)]. Reduction of Risk of Stroke and Systemic Embolism in Non-valvular Atrial Fibrillation in Adult Patients No dose adjustment of dabigatran etexilate capsules is recommended in patients with mild or moderate renal impairment [see Clinical Pharmacology (12. 3)]. Reduce the dose of dabigatran etexilate capsules in patients with severe renal impairment (CrCl 15 to 30 mL/min) [see Dosage and Administration (2.2.4) and Clinical Pharmacology (12. 3)].

The guidelines for using Pradaxa (dabigatran) in elderly patients with impaired renal function are as follows:

• No dose adjustment is recommended for patients with mild or moderate renal impairment.
• The dose of Pradaxa should be reduced in patients with severe renal impairment (CrCl 15 to 30 mL/min).
• Dosing recommendations cannot be provided for patients with CrCl <15 mL/min or on dialysis. 2

From the Research

Guidelines for Using Pradaxa in Elderly Patients

The use of Pradaxa (dabigatran) in elderly patients with impaired renal function requires careful consideration of the guidelines and recommendations.

• Pradaxa does not require monitoring or dose adjustment, except in cases of moderate renal insufficiency or in elderly patients (>75 years old) 3.
• The European Medicines Agency recommends using the lower dose of 150 mg once daily in elderly patients (aged over 75 years) and those with reduced renal function (creatinine clearance between 30 and 50 ml/min) 4.
• Studies have shown that dabigatran 150 mg once daily is as effective as the standard European enoxaparin regimen, with numerically fewer major bleeding events in elderly patients or those with moderate renal impairment undergoing knee or hip replacement surgery 4.

Renal Function and Dabigatran

Elderly patients with impaired renal function are at a higher risk of bleeding complications when taking dabigatran.

• A study reported two cases of rectal bleeding associated with hemostatic disorders in elderly patients treated with dabigatran etexilate, highlighting the importance of monitoring renal function and coagulation parameters in these patients 5.
• Chronic kidney disease is a common disorder in the geriatric population, and pharmacologic management of diseases in elderly individuals with chronic kidney disease requires caution when prescribing drugs, including dabigatran 6.

Dose Adjustment and Monitoring

Dose adjustment and monitoring of dabigatran are crucial in elderly patients with impaired renal function.

• The recommended dose of 220 mg is administered once-daily, starting with a half-dose 1-4 h after surgery, but the dose may need to be adjusted in elderly patients with moderate renal insufficiency 3.
• Coagulation monitoring, including prothrombin time (PT) and international normalized ratio (INR), is essential in patients taking dabigatran, especially in those with a high risk of overdose, such as elderly patients or those with renal function impairment 5.