The apparent plasma half-life averages about 20 hours and is quite variable (range, 12 to 27 hours) after multiple oral doses in patients with premature ventricular contractions (PVCs). With multiple dosing, plasma levels increase because of its long half-life with steady-state levels approached in 3 to 5 days; once at steady-state, no additional (or unexpected) accumulation of drug in plasma occurs during chronic therapy. Over the usual therapeutic range, data suggest that plasma levels in an individual are approximately proportional to dose, deviating upwards from linearity only slightly (about 10 to 15% per 100 mg on average).

In healthy subjects, about 30% of a single oral dose (range, 10 to 50%) is excreted in urine as unchanged drug. The two major urinary metabolites are meta-O-dealkylated flecainide (active, but about one-fifth as potent) and the meta-O-dealkylated lactam of flecainide (non-active metabolite). These two metabolites (primarily conjugated) account for most of the remaining portion of the dose. Several minor metabolites (3% of the dose or less) are also found in urine; only 5% of an oral dose is excreted in feces. In patients, free (unconjugated) plasma levels of the two major metabolites are very low (less than 0.05 mcg/mL).

In vitro metabolic studies have confirmed that cytochrome P450IID6 is involved in the metabolism in flecainide.

When urinary pH is very alkaline (8 or higher), as may occur in rare conditions (e.g., renal tubular acidosis, strict vegetarian diet), flecainide elimination from plasma is much slower.

The elimination of flecainide from the body depends on renal function (i.e., 10 to 50% appears in urine as unchanged drug). With increasing renal impairment, the extent of unchanged drug excretion in urine is reduced and the plasma half-life of flecainide is prolonged. Since flecainide is also extensively metabolized, there is no simple relationship between creatinine clearance and the rate of flecainide elimination from plasma. (See DOSAGE AND ADMINISTRATION.)

In patients with NYHA class III congestive heart failure (CHF), the rate of flecainide elimination from plasma (mean half-life, 19 hours) is moderately slower than for healthy subjects (mean half-life, 14 hours), but similar to the rate for patients with PVCs without CHF. The extent of excretion of unchanged drug in urine is also similar. (See DOSAGE AND ADMINISTRATION.)

Under one year of age, currently available data are limited but suggest that the half-life at birth may be as long as 29 hours, decreasing to 11 to 12 hours by three months of age and 6 hours by one year of age. The pharmacokinetics in hydropic infants have not been studied, but case reports suggest prolonged elimination. In children aged 1 year to 12 years the half-life is approximately 8 hours. In adolescents (age 12 to 15) the plasma elimination half-life is approximately 11 to 12 hours. Since milk may inhibit absorption in infants, a reduction in flecainide dosage should be considered when milk is removed from the diet (e.g., gastroenteritis, weaning). Plasma trough flecainide levels should be monitored during major changes in dietary milk intake.

From age 20 to 80, plasma le