The Basics
What is Divalproex?
Used to treat epilepsy to stop seizures. Also used to treat the manic phase of bipolar disorder (manic-depressive illness) and helps prevent migraine headaches.
Brand names for Divalproex
Depakote
How Divalproex is classified
Anticonvulsants, Antimanic Agents
Divalproex During Pregnancy
Divalproex pregnancy category
Category DNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Divalproex while pregnant
All pregnancies have a background risk of birth defects (about 3%), pregnancy loss (about 15%), or other adverse outcomes regardless of drug exposure. Maternal valproate use during pregnancy for any indication increases the risk of congenital malformations, particularly neural tube defects, but also malformations involving other body systems (e.g., craniofacial defects, cardiovascular malformations, hypospadias, limb malformations). The risk of major structural abnormalities is greatest during the first trimester; however, other serious developmental effects can occur with valproate use throughout pregnancy. The rate of congenital malformations among babies born to epileptic mothers who used valproate during pregnancy has been shown to be about four times higher than the rate among babies born to epileptic mothers who used other anti-seizure monotherapies . Several published epidemiological studies have indicated that children exposed to valproate in utero have lower IQ scores than children exposed to either another antiepileptic drug in utero or to no antiepileptic drugs in utero . An observational study has suggested that exposure to valproate products during pregnancy may increase the risk of autism spectrum disorders. In this study, children born to mothers who had used valproate products during pregnancy had 2.9 times the risk (95% confidence interval [CI]: 1.7-4.9) of developing autism spectrum disorders compared to children born to mothers not exposed to valproate products during pregnancy. The absolute risks for autism spectrum disorders were 4.4% (95% CI: 2.6%-7.5%) in valproate-exposed children and 1.5% (95% CI: 1.5%-1.6%) in children not exposed to valproate products. Because the study was observational in nature, conclusions regarding a causal association between in utero valproate exposure and an increased risk of autism spectrum disorder cannot be considered definitive. In animal studies, offspring with prenatal exposure to valproate had structural malformations similar to those seen in humans and demonstrated neurobehavioral deficits.
Taking Divalproex While Breastfeeding
What are recommendations for lactation if you're taking Divalproex?
Divalproex is converted to valproic acid in the body. Valproic acid levels in breastmilk are low and infant serum levels range from undetectable to low. 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. 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.
Maternal / infant drug levels
Divalproex is converted to valproic acid in the body. Valproic acid levels in breastmilk are low and infant serum levels range from undetectable to low. 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. 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.
Possible effects of Divalproex on milk supply
Relevant published information was not found as of the revision date.
Possible alternatives to Divalproex
None listed
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. Meador KJ, Baker GA, Browning N et al. Effects of breastfeeding in children of women taking antiepileptic drugs. Neurology. 2010;75:1954-60. PMID: 21106960
2. Stowe ZN. The use of mood stabilizers during breastfeeding. J Clin Psychiatry. 2007;68 Suppl 9:22-8. PMID: 17764381
3. Espir MLE, Benton P, Will E et al. Sodium valproate (Epilim) – some clinical and pharmacological aspects. In: Legg NJ, ed. Clinical and pharmacological aspects of sodium valproate in the treatment of epilepsy: proceedings of a symposium. 1976;145-51.
4. Alexander FW. Sodium valproate and pregnancy. Arch Dis Child. 1979;54:240. Letter. PMID: 373647
5. Dickinson RG, Harland RC, Lynn RK et al. Transmission of valproic acid (Depakene) across the placenta: half-life of the drug in mother and baby. J Pediatr. 1979;94:832-5. PMID: 376803
6. Bardy AH, Granstrom M-L, Hiilesmaa VK. Valproic acid and breast-feeding. In: Janz D, Bossi L, Dam M et al., eds. Epilepsy, pregnancy and the child. New York: Raven Press, 1982:359-60.
7. Froescher W, Eichelbaum M, Niesen M et al. Antiepileptic therapy with carbamazepine and valproic acid during pregnancy and lactation period. In: Dam M, ed. Advances in epileptology: XIIth epilepsy international symposium. New York: Raven Press, 1981:581-8.
8. von Unruh GE, Froescher W, Hoffmann F et al. Valproic acid in breast milk: how much is really there? Ther Drug Monit. 1984;6:272-6. PMID: 6438834
9. Nau H, Rating D, Koch S et al. Valproic acid and its metabolites: placental transfer, neonatal pharmacokinetics, transfer via mother’s milk and clinical status in neonates of epileptic mothers. J Pharmacol Exp Ther. 1981;219:768-77. PMID: 6795343
10. Nau H, Helge H, Luck W. Valproic acid in the perinatal period: decreased maternal serum protein binding results in fetal accumulation and neonatal displacement of the drug and metabolites. J Pediatr. 1984;104:627-34. PMID: 6423793
11. Philbert A, Pedersen B, Dam M. Concentration of valproate during pregnancy, in the newborn and in breast milk. Acta Neurol Scand. 1985;72:460-3. PMID: 3936331
12. Meyer FP, Quednow B, Potrafki A et al. [The perinatal pharmacokinetics of anticonvulsant drugs]. Zentralbl Gynakol. 1988;110:1195-205. PMID: 3239295
13. Tsuru N, Maeda T, Tsuruoka M. Three cases of delivery under sodium valproate-placental transfer, milk transfer and probable teratogenicity of sodium valproate. Jpn J Psychiatry Neurol. 1988;42:89-96. PMID: 3135429
14. Kacirova I, Grundmann M, Brozmanova H. Valproic acid concentrations in nursing mothers, mature milk, and breastfed infants in monotherapy and combination therapy. Epilepsy Behav. 2019;95:112-16. PMID: 31035102
15. Stahl MM, Neiderud J, Vinge E. Thrombocytopenic purpura and anemia in a breast-fed infant whose mother was treated with valproic acid. J Pediatr. 1997;130:1001-3. PMID: 9202628
16. Wisner KL, Perel JM. Serum levels of valproate and carbamazepine in breastfeeding mother-infant pairs. J Clin Psychopharmacol. 1998;18:167-9. PMID: 9555601
17. Birnbaum CS, Cohen LS, Bailey JW et al. Serum concentrations of antidepressants and benzodiazepines in nursing infants: a case series. Pediatrics. 1999;104:e11. PMID: 10390297
18. Piontek CM, Baab S, Peindl KS et al. Serum valproate levels in 6 breastfeeding mother-infant pairs. J Clin Psychiatry. 2000;61:170-2. PMID: 10817100
19. Johannessen SI, Helde G, Brodtkorb E. Levetiracetam concentrations in serum and in breast milk at birth and during lactation. Epilepsia. 2005;46:775-7. PMID: 15857447
20. Meador KJ, Baker GA, Browning N et al. Effects of breastfeeding in children of women taking antiepileptic drugs. Neurology. 2010;75:1954-60. PMID: 21106960
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
