Flecainide Pharmacokinetics After Multiple Dosing in Patients with Impaired Renal Function
Authors: Forland Steven C. , Cutler Ralph E. , McQuinn Roy L. , Kvam Don C. , Miller A. M. , Conard Gordon J. , Parish S. 
Published: March 2013

Study objective: To determine the pharmacokinetics of oral flecainide acetate after single and multiple doses in patients with impaired renal function. Design: Paired study of single followed by multiple oral doses. Setting: Patients enrolled in a Veterans Administration Hospital renal subspecialty clinic and dialysis unit. Patients: Twenty men and one woman between the ages of 33 and 74 years with impaired renal function including ten patients with end‐stage renal disease receiving maintenance hemodialysis. Interventions: All patients received a single, oral, 200‐mg dose of flecainide acetate followed by sequential venous blood sampling. Seven to 14 days after the single‐dose study, each patient received 100 mg of flecainide acetate by mouth every 12 hours or every 24 hours for 10 days. Venous blood samples were drawn periodically during multiple dosing and sequentially after the last dose. Measurements and primary results: Peak flecainide acetate concentrations (μgA*) were 330 ±104 μg/L (mean ± SD) after the single dose and 687 ± 505 μg/L after multiple doses. Time to peak occurred at 3.3 ± 2.3 hours and 2.7 ± 1.2 hours after single and multiple doses, respectively. The apparent volume of distribution was 8.2 ± 2.9 L/kg and 9.2 ± 5 L/kg after single and multiple dose studies, respectively. Plasma elimination half‐life after the single dose (20.4 ± 9.0 hours) was significantly shorter (P <.001) than after multiple doses (37.8 ± 39.7 hours), as was total body clearance: 391 ±154 mL/min versus 302 ±194 mL/min. There were no statistically significant differences between pharmacokinetic measurements determined for patients on chronic hemodialysis when compared with nondialysis patients during the multiple‐dose study. No meaningful correlation was found between either plasma elimination half‐life or total body clearance and creatinine clearance. Renal clearance of flecainide correlated reasonably well (r2 = .785) with creatinine clearance after multiple doses. Conclusion: The pharmacokinetics of orally administered flecainide acetate are significantly different after multiple doses compared with single doses in patients with impaired renal junction. Single‐dose studies should not be used to determine dose requirements for patients with renal impairment. Creatinine clearance is not an accurate guide for flecainide acetate dosing. For patients with normal renal function or those with impairment but not requiring hemodialysis, a dose of 100 mg every 12 hours should be safe and effective. Patients requiring chronic hemodialysis should be started on a lower dose, for example 100 mg daily (or 50 mg bid). Plasma flecainide concentrations should be carefully monitored in patients with impaired renal function during dose optimization and until steady‐state concentrations are reached. Dosage increases should be made very cautiously when plasma concentrations have plateaued because it may take longer than 7 days before a new steady state is achieved after a dosage change.