Is Isoniazid Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use Isoniazid? Is Isoniazid safe for nursing mother and child? Does Isoniazid extracts into breast milk? Does Isoniazid has any long term or short term side effects on infants? Can Isoniazid influence milk supply or can Isoniazid decrease milk supply in lactating mothers?

It is excreted into breast milk in clinically non-significant amount, in any case, much lower than the doses commonly used in newborns and infants (Snider 1984, Singh 2008). No significant problems have been observed in infants whose mothers were treated. (Drobac 2005). An infant whose mother was treated with anti-TBC drugs during pregnancy and lactation for 7 months, presented moderately high levels of liver transaminases along with a normal clinical and developmental course (Peters 2008). The plasma levels measured in any of those infants were undetectable or very low. Several medical societies and consensus of expert panels consider safe the use of this medication while breastfeeding (Dautzenberg 1988, Tran 1998, Blumberg 2003, Schram 2005, WHO 2007, Singh 2008, Baquero-Artigao 2015, Malhamé 2016).American Academy of Pediatrics: medication usually compatible with breastfeeding.WHO List of Essential Medicines 2002: compatible with breastfeeding. The addition of Vitamin B6 (Pyridoxine) to treatment of mother-infant dyad should be evaluated, especially in cases of malnutrition, diabetes, other diseases or a new pregnancy (Blumberg 2003, Steichen 2006, Baquero-Artigao 2015, 2016 Principi Di 2016).

The Centers for Disease Control and Prevention and other professional organizations state that breastfeeding should not be discouraged in women taking isoniazid. Nursing mothers who are taking isoniazid should take 25 mg of oral pyridoxine daily.[1][2][3] Because of the low levels of isoniazid in breastmilk and safe administration directly to infants, it is unlikely to cause adverse reactions in infants, but infants should be monitored for rare instances jaundice. Giving the maternal once-daily dose before the infant's longest sleep period will decrease the dose the infant receives. The amount of isoniazid in milk is insufficient to treat tuberculosis in the breastfed infant. If breastfed infants are treated with isoniazid, they should also receive pyridoxine 1 mg/kg daily.[4]

In one uncontrolled study, 6-beta-hydroxycortisol levels were measured in 10 male infants whose mothers had tuberculosis and took ethambutol 1 gram daily plus isoniazid 300 mg daily and the infants of mothers (apparently without tuberculosis) who took no chronic drug therapy. The infants of mothers taking the antituberculars had consistently lower 6-beta-hydroxycortisol levels on 8 occasions at 15-day intervals from 90 to 195 days of age, but these differences were statistically significant on days 120 and 195 only. The authors attributed the lower levels to inhibition of hepatic metabolism of cortisol to 6-beta-hydroxycortisol by the antitubercular drugs in milk.[10] However, ethambutol is not known to inhibit drug metabolism, so if the effect occurs it is more likely caused by isoniazid. One woman taking rifampin 450 mg, isoniazid 300 mg and ethambutol 1200 mg daily during pregnancy and rifampin 450 mg and isoniazid 300 mg for the first 7 months of lactation (extent not stated). The infant was born with mildly elevated serum liver enzymes which persisted for to 1 (alanine transferase) to 2 years (aspartate transaminase), but had no other adverse reactions.[11] Isoniazid was used as part of multi-drug regimens to treat 2 pregnant women with multidrug-resistant tuberculosis during the second and third trimesters of pregnancy and postpartum. Their two infants were breastfed (extent and duration not stated). At age 3.9 and 4.6 years, the children were developing normally except for a mild speech delay in one.[12] Two mothers in Turkey were diagnosed with tuberculosis at the 30th and 34th weeks of pregnancy. They immediately started isoniazid 300 mg, rifampin 600 mg, pyridoxine 50 mg daily for 6 months, plus pyrazinamide 25 mg/kg and ethambutol 25 mg/kg daily for 2 months. Both mothers breastfed their infants (extent not stated). Their infants were given isoniazid 5 mg/kg daily for 3 months prophylactically. Tuberculin skin tests were negative after 3 months and neither infant had tuberculosis at 1 year of age. No adverse effects of the drugs were mentioned.[13]