Transfer of isoniazid from circulation to breast milk in lactating women on chronic therapy for tuberculosis.

Isoniazid is the most widely used first line antituberculosis drug. It is considered safe during lactation, but limited data are available on the transfer of isoniazid from circulation to milk in lactating women, which can provide an assessment of extent of exposure to the nursling. The study documents the transfer pattern and milk to plasma (M : P) ratio of isoniazid at a steady state. Peak plasma and milk concentrations of isoniazid were reached within 1 h and the projected exposure of the drug to the infant is much lower than the prophylactic dose, supporting its safety during breast feeding. To determine milk to plasma (M : P) ratios and infant dose (absolute and relative) for isoniazid in lactating women on antituberculosis therapy. Concentrations of isoniazid in plasma and milk were measured in exclusively breast feeding women taking 300 mg day(-1) as treatment for tuberculosis. Peak plasma and milk concentrations of isoniazid were observed at 1 h. A mean M : P(AUC) value of 0.89 (95% CI 0.7, 1.1) was calculated for isoniazid from seven women over 24 h. The mean absolute infant dose was estimated to be 89.9 mug kg day(-1) (95% CI 65.6, 114) and the relative infant dose was 1.2% of the weight adjusted maternal dose. The mean relative dose of isoniazid (1.2%) transmitted to the infant via breast milk is below the 10% notional level of concern. These data suggest that isoniazid therapy is safe during breastfeeding.