Flecainide excretion in human breast milk

Healthy human volunteers who intended not to breast feed were placed on a regimen of 100 mg oral flecainide every 12 hours for 5½ days beginning 1 day after parturition. Milk and blood samples were collected during the dosing period and for 2 days after the last dose. Concentrations of flecainide in milk and plasma were assayed by HPLC. Apparent steady‐state levels of flecainide in both milk and plasma were achieved in most cases by day 4 of the study. Highest daily average concentration of flecainide in milk ranged from 270 to 1529 ng/ml for the 11 subjects. Mean ± SD milk to plasma flecainide ratios were 3.7 ± 3.5, 3.2 ± 2.3, 3.5 ± 2.1, and 2.6 ± 0.7 on study days 2, 3, 4, and 5, respectively. After the last dose of flecainide, peak milk levels of the drug occurred at 3 to 6 hours and then declined monoexponentially. The half‐life for elimination of flecainide from milk was 14.7 ± 3.5 hours and is very similar to the plasma elimination half‐life of flecainide in healthy human subjects. The mean milk to plasma ratios for flecainide after the last dose were 2.3 ±1.0 and 2.9 ± 1.1 at 24 and 48 hours after the dose, respectively. Based on the pharmacokinetics of flecainide in infants, the expected average steady‐state plasma concentration of flecainide in a newborn infant consuming all of the milk production of its mother (~700 ml/day) would not be expected to exceed about 62 ng/ml. Because previous studies in infants and children has indicated very few toxic side effects attributed to flecainide at plasma levels ranging from 100 to 990 ng/ml, it appears that the risk to a suckling infant of ingesting toxic amounts of flecainide in human breast milk is very low. Clinical Pharmacology and Therapeutics (1990) 48, 262–267; doi: 10.1038/clpt.1990.148