Is Divalproex Sodium Safe in Breastfeeding

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

It is excreted in breast milk in clinically non-significant amount without problems in the short or long term in infants whose mothers were treated. Plasma levels of these infants were undetectable or very low. Cognitive development did not suffer any alteration. An infant was presented with thrombocytopenic purpura and anemia who recovered after removing valproate in the mother. However, doubts were raised on whether it was instead a post-viral reaction that led to idiopathic thrombocytopenic purpura. The administration of valproic acid does not affect prolactin levels. The American Academy of Pediatrics rates it as usual compatible with breastfeeding medication.WHO List of Essential Medicines 2002: compatible with breastfeeding.

Divalproex is converted to valproic acid in the body. Breastfeeding during valproic acid monotherapy does not appear to adversely affect infant growth or development, and breastfed infants had higher IQs and enhanced verbal abilities than nonbreastfed infants at 6 years of age in one study.[1] If divalproex is required by the mother, it is not necessarily a reason to discontinue breastfeeding. Because of the low levels of divalproex and valproic acid in breastmilk and infant serum, no definite adverse reactions to either drug during breastfeeding have been reported. Theoretically, breastfed infants are at risk for valproic acid-induced hepatotoxicity, so infants should be monitored for jaundice and other signs of liver damage during maternal therapy. A questionable case of thrombocytopenia has been reported with valproic acid, so monitor the infant for unusual bruising or bleeding. One author recommends monitoring infant serum valproate levels, platelets and liver enzymes during therapy.[2] Combination therapy with sedating anticonvulsants or psychotropics may result in infant sedation or withdrawal reactions.

An mother with epilepsy was taking valproic acid 2.4 g daily and primidone 250 mg 3 times daily during pregnancy and postpartum. During the second week postpartum, her breastfed infant was sedated. Breastfeeding was stopped and the drowsiness cleared.[3] The sedation was possibly caused by primidone in breastmilk although valproic acid might have contributed by increasing primidone levels. Petechiae, thrombocytopenia, anemia, and mild hematuria occurred in a 2.5-month-old breastfed infant whose mother was taking valproic acid 600 mg twice daily. The petechiae resolved 8 days after discontinuing breastfeeding. The authors believed the adverse effect to be caused by valproic acid in breastmilk.[14] However, other authors believe that these symptoms were more likely caused by idiopathic thrombocytopenic purpura following a viral infection.[17] Two breastfed infants aged 1 and 3 months whose mothers were taking valproic acid monotherapy 750 and 500 mg daily developed normally and had no abnormal laboratory values. Their plasma levels were 6% and 1.5% or their mother's serum levels, respectively.[15] Six breastfed infants whose mothers were taking valproic acid 750 or 1000 mg daily had no adverse reactions to valproic acid in breastmilk.[17] An exclusively breastfed infants whose mother was taking valproate 1.8 g, topiramate 300 mg, and levetiracetam 2 g, daily during pregnancy and lactation appeared healthy to the investigators throughout the 6- to 8-week study period.[18] In a long-term study on infants exposed to anticonvulsants during breastfeeding, no difference in average intelligence quotient at 3 years of age was found between infants who were breastfed (n = 11) and those not breastfed (n = 24) when their mothers were taking valproate.[19]