Divalproex sodium Pregnancy and Breastfeeding Warnings
Divalproex sodium Pregnancy Warnings
To provide information regarding the effects of in utero exposure to divalproex sodium, physicians are advised to recommend that pregnant patients taking divalproex sodium enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/. Animal studies have revealed evidence of embryofetotoxicity. Exposure to valproate in utero increases the risk of neural tube defects and other structural abnormalities. The risk of spina bifida following in utero valproate exposure has been estimated to be approximately 1 to 2%. There is also an increased risk of other major birth defects such as craniofacial defects and cardiovascular malformations. A fetal valproate syndrome which includes defects of the face, heart, and limbs has also been described. A four-fold increase in congenital malformations has been reported among infants with valproic acid-exposed mothers compared with those treated with other antiepileptic monotherapies (as a group). Fatal hepatic failures, in a newborn and in an infant, have been reported following the maternal use of valproate during pregnancy. FDA notified healthcare professionals that children born to mothers who take the divalproex sodium or related products during pregnancy have an increased risk of lower cognitive test scores than children exposed to other antiseizure medications during pregnancy. One study has reported that both valproic acid and its principal metabolites are found in amniotic fluid. In that study of 52 pregnancies in epileptic women taking valproic acid, 5 fetal neural tube defects were reported. Maternal serum levels of valproate were significantly higher in pregnancies which resulted in a neural tube defect than in pregnancies which resulted in normal infants. An in vitro study of the teratogenic effects of valproic acid has suggested that valproic acid may disrupt chondrogenesis by reducing mitosis and altering matrix production. Two workers have suggested that periconceptional vitamin supplementation, particularly with vitamins containing calcium pantothenate, may reduce the risk of neural tube closure defects in women receiving valproic acid therapy. One recent patient series has suggested that benzodiazepines may amplify the teratogenic effects of valproic acid. Two cases of omphalocele along with the typical dysmorphic features of the fetal valproate syndrome have been reported in newborns whose mothers were receiving valproic acid therapy. A recent case report has suggested that valproic acid may cause hydranencephaly. FDA pregnancy category D: There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks. FDA pregnancy category X: Studies in animals or humans have demonstrated fetal abnormalities and/or there is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience, and the risks involved in use of the drug in pregnant women clearly outweigh potential benefits.
FDA pregnancy category D for treating epilepsy and manic episodes associated with bipolar disorder. FDA pregnancy category X for treating migraine headaches. Use of divalproex sodium is not recommended during pregnancy. If divalproex sodium is used during pregnancy, or if the patient becomes pregnant while receiving divalproex sodium, the patient should be apprised of the potential hazard to the fetus.
Divalproex sodium Breastfeeding Warnings
A decision should be made to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Yes (1 to 10% of serum concentration)
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