Pharmacokinetics of flecainide acetate in patients with severe renal impairment

We studied the effect of renal disease on the pharmacokinetics of flecainide after single intravenous, single oral, and multiple oral doses to patients with severe renal disease (creatinine clearances less than 12 ml/min/m2). The absorption and volume of distribution of flecainide were not altered by renal impairment. The average plasma half-life was prolonged by about twofold that of healthy subjects but most patients were within the range of values for healthy subjects. Total body clearance was reduced. With multiple oral doses of 50 mg b.i.d. or 50 mg daily, steady-state plasma levels were reached by 6 days and no further accumulation in plasma was observed. In patients with severe renal disease, therapy with flecainide should be initiated at 100 mg daily (or 50 mg b.i.d.). If necessary, dosage increases should be made cautiously at intervals of more than 4 days when plasma levels have plateaued as demonstrated by plasma level monitoring.