October 10, 2017
Pharmacokinetic Considerations for Apixaban Use in End-Stage Renal Disease: There is little data about use of the direct-acting oral anticoagulant (DOAC) apixaban in patients with nonvalvular atrial fibrillation and end-stage renal disease (ESRD). Recommended apixaban dosing in patients with normal kidney function is 5 mg twice daily; 2.5 mg twice daily is recommended in patients with at least two of these characteristics: age ≥80 years old, weight ≤60 kg, and serum creatinine ≥1.5 mg/dL. A recent cohort study of apixaban steady-state pharmacokinetic data in ESRD patients receiving hemodialysis found that apixaban 2.5 mg twice daily leads to systemic drug exposure comparable to the standard dose (5 mg twice daily) in patients with normal kidney function. In addition, apixaban 5 mg twice daily resulted in supratherapeutic concentrations in ESRD patients and should be avoided.
CHAPTER SUMMARY FROM THE PHARMACOTHERAPY HANDBOOK
For the chapter in the Wells Handbook, please go to Chapter 6. Arrhythmias.
The use of antiarrhythmic drugs (AADs) in the United States has declined because of major trials that show increased mortality with their use in several clinical situations, the realization of proarrhythmia as a significant side effect, and the advancing technology of nonpharmacologic therapies such as ablation and the implantable cardioverter-defibrillator (ICD).
AADs frequently cause side effects and are complex in their pharmacokinetic characteristics. Close monitoring is required of all of these drugs to assess for adverse effects as well as potential drug interactions.
The most commonly prescribed AAD is now amiodarone. This drug is effective in terminating and preventing a wide variety of symptomatic supraventricular and ventricular arrhythmias. However, because this AAD is plagued by frequent side effects, it requires close monitoring. The most concerning toxicity is pulmonary fibrosis; side effect profiles of the intravenous (IV) (acute, short-term) and oral (chronic, long-term) forms of amiodarone differ substantially.
In patients with atrial fibrillation (AF), therapy is traditionally aimed at controlling ventricular rate (digoxin, nondihydropyridine (non-DHP) calcium channel blockers (CCBs), β-blockers), preventing thromboembolic (TE) complications (warfarin, aspirin), and restoring and maintaining sinus rhythm (SR) (AADs, direct current cardioversion). Studies show there is no need to aggressively pursue strategies to maintain SR (ie, long-term AAD therapy); rate control alone (leaving the patient in AF) is often sufficient in patients who can tolerate it. Nonetheless, chronic AAD therapy may still be needed in patients who continue to have symptoms despite adequate ventricular rate control.
Paroxysmal supraventricular tachycardia (PSVT) is usually a result of reentry in or proximal to the atrioventricular (AV) node or AV reentry incorporating an extranodal pathway; common tachycardias can be terminated acutely with AV nodal blocking drugs such as adenosine, and recurrences can be prevented by ablation with radiofrequency current.
Patients with Wolff-Parkinson-White (WPW) syndrome may have several different tachycardias that are acutely treated by different strategies: orthodromic reentry (adenosine), antidromic reentry (adenosine or procainamide), and AF (procainamide or amiodarone). AV ...