Is 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine Safe in Breastfeeding

I am a breastfeeding mother and i want to know if it is safe to use 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine? Is 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine safe for nursing mother and child? Does 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine extracts into breast milk? Does 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine has any long term or short term side effects on infants? Can 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine influence milk supply or can 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine decrease milk supply in lactating mothers?

As high as therapeutic levels of this drug have been found in the serum of infants (35-50% of maternal serum level). Side-effects were not observed, neither developmental nor IC derangements at long term follow-up among hundreds of children of treated mothers. A case was published of apnea in a newborn baby whose mother was on a very high dose of 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine (850 mg a-day). During pregnancy, it increases the clearance of 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine and other antiepileptic medication that warrants an increase in dosage in this period. After birth, the serum level rapidly increases with a risk of harm on both the mother and the infant, whenever dose is not reduced to that previous from pregnancy. An infant, 1 1/2 months old, whose mother was on 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine, resulted affected with Abstinence Syndrome soon after sudden weaning.

Occasional adverse reactions have been reported in infants who receive 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine in milk, but long-term exposure does not appear to affect infant growth and development. Breastfed infants whose mothers are taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine have relatively high plasma 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine levels. Neonates are particularly at risk for high plasma levels because their ability to metabolize the drug by glucuronidation is limited, plasma protein binding is relatively low, and maternal plasma and milk levels can rise dramatically in the immediate postpartum period if the dosage is not reduced to the prepregnancy dosage.[1][2] If 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine is required by the mother, it is not necessarily a reason to discontinue breastfeeding, because many infants have been breastfed without adverse reactions. However, breastfed infants should be carefully monitored for side effects such as apnea, rash, drowsiness or poor sucking, including measurement of serum levels to rule out toxicity if there is a concern. Monitoring of the platelet count and liver function may also be advisable. If an infant rash occurs, breastfeeding should be discontinued until the cause can be established.

One infant was exclusively breastfed from day 2 of life during maternal 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine 300 mg daily, which was decreased at 6 weeks postpartum to 200 mg daily and 50% formula was introduced. Examinations every 4 weeks showed normal development and no evidence of mental retardation or neurologic deficits. An electroencephalogram at 4 weeks of age showed no signs of pathology.[2] A breastfed infant whose mother was taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine 300 mg daily during pregnancy and postpartum had no observable adverse effects up to 5 months of age.[3] The same authors reported 9 previously unreported infants who were breastfed during maternal 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine therapy (dosage range 100 to 800 mg daily) with no adverse effects.[5][6] Thirty-five pregnancies in 34 mothers who were taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine during pregnancy were monitored. An unstated fraction of them breastfed their infants. No adverse effects in infants were observed.[4] An exclusively breastfed infant whose mother was taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine 200 mg and levetiracetam 2.5 g daily during pregnancy and lactation appeared healthy to the investigators throughout the 6- to 8-week study period.[22] The breastfed infant of a woman taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine 300 mg daily developed normally during the first 4 months of life and no adverse effects were observed.[23] A 6-week-old infant developed apparent withdrawal symptoms after abrupt weaning by a mother who was taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine 200 mg daily during late pregnancy and postpartum. Symptoms included loss of appetite, neuromotor hyperexcitability and irritability. Symptoms occurred 2 weeks after weaning and were completely alleviated within 48 hours after instituting 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine 1 mg/kg daily in the infant. Neuromotor development of the infant normalized 1 month after discontinuing therapy.[24] The reaction is rated as probably caused by 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine in breastmilk. Six infants with a median age of 4.1 months (range 0.1 to 5.1 months) were breastfed during maternal use of 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine in an average dosage of 6.3 mg/kg daily. Five were exclusively breastfed and one was about 50% breastfed. No adverse effects were noted by the mothers or the attending pediatricians. A clinical pediatric assessment in 3 of the infants also revealed no adverse effects.[7] Thirty infants whose mothers were taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine were followed during breastfeeding. None of the infants developed a rash. Among infants who were monitored by laboratory testing, no abnormalities in liver tests, electrolytes (n = 10) or hematocrits (n = 8) were noted. Elevated platelet counts were observed in 7 of 8 infants tested (average age 3.8 weeks, range 2 to 10 weeks), with no adverse clinical effects.[9] A mother was taking 875 mg of 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine daily at term and her dosage was slowly reduced by 25 mg daily at weekly intervals beginning 2 weeks postpartum. Her infant was fully breastfed and on day 16 postpartum while she was taking 850 mg daily, the infant experienced a severe apneic episode requiring cardiac compressions to maintain perfusion and was responsive only to painful stimuli. The infant's mother was taking a high dosage and had extensive drug excretion into breastmilk, and the infant's serum concentration was at the high end of the therapeutic range for children, but the fact that no adverse effects had occurred prior to day 16 could not be explained. 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine was assessed to be the probable causes of the apneic episode.[11] Three women with bipolar disorder breastfed their infants during pregnancy and breastfeeding. One took 50 mg daily at term and increased her dose to 200 mg within one month. She reportedly breastfed her infant exclusively for 12 months. An unrelated infant rash occurred at 4 months of age, but the infant's growth and development were normal at 18 months of age. Another woman took 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine 250 mg daily while she breastfed (extent not stated) her infant for several weeks. The infant's growth and development were normal at 18 months of age. The third mother also took 250 mg daily while breastfeeding (extent not stated) for at least 15 months. At 4 months of age, the infant developed a rash on the neck that resolved spontaneously; the infant's growth and development were normal at 15 months of age.[25] Five breastfed preterm infants were reported whose mothers were taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine. Transient elevation of liver enzymes occurred in twins whose mother was taking other unspecified medications for bipolar disorder. No adverse effects were seen in the other infants.[19] A prospective cohort study in Norway followed infants of mothers who took antiepileptic drugs during pregnancy and lactation and compared to infants with mothers with untreated epilepsy and infants with fathers who took antiepileptics as control groups. Of the 223 mothers studied, 71 were taking 6-(2,3-Dichlorophenyl)-1,2,4-triazine-3,5-diamine monotherapy. Infants were assessed at 6, 18 and 36 months of age. Continuous breastfeeding in children of women using antiepileptic drugs was associated with no greater impaired d