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

Abstract

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• 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. WHAT THIS STUDY ADDS• 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. AIMTo determine milk to plasma (M : P) ratios and infant dose (absolute and relative) for isoniazid in lactating women on antituberculosis therapy. METHODSConcentrations of isoniazid in plasma and milk were measured in exclusively breast feeding women taking 300 mg day -1 as treatment for tuberculosis. RESULTSPeak plasma and milk concentrations of isoniazid were observed at 1 h. A mean M : PAUC 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 mg kg day -1 (95% CI 65.6, 114) and the relative infant dose was 1.2% of the weight adjusted maternal dose. CONCLUSIONSThe 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.

Isoniazid metabolism and hepatotoxicity

“…After absorption, INH diffuses into all tissues and body fluids rapidly, including cerebrospinal fluid, saliva, pleural and peritoneal exudates, bronchi and pulmonary alveoli 49 , 50 , 51 , 52 . INH also can be excreted into breast milk 53 , 54 .…”

Study of NAT2 Gene Polymorphisms in an Indian Population

“…Plasma was separated from blood cells by centrifugation and stored at -201C until analysis. Estimation of isoniazid in plasma was carried out using a reverse phase-high performance liquid chromatography (HPLC) method as described previously by Singh et al [27] The plasma standard curves were linear over the range 0.25-10 mg mL, with a correlation coefficient of 0.997 between isoniazid concentration and peak area. The intra-day and inter-day coefficients of variation for the plasma assay were 4-10% at 0.5 mg mL and 2-6.4% at 4 mg mL, respectively.…”

Latent Tuberculosis in Pregnancy: A Systematic Review

“…Finally, one cross-sectional study examined the presence of INH in breast milk among lactating women during treatment for LTBI [ 27 ]. Peak INH concentrations in plasma and breast milk were measured one hour after administration.…”

“…Peak INH concentrations in plasma and breast milk were measured one hour after administration. Although some isoniazid did penetrate into breast milk, there was considerable inter-individual variability; the calculated mean relative infant dose of 1.2% of weight-adjusted maternal dose was deemed safe [ 27 ]. The authors further suggested that lactating women wait at least one-hour interval to breastfeed, after ingesting INH.…”