Epilepsan ECC Use In Pregnancy & Lactation

Fertility, Pregnancy and lactation: Divalproex sodium is contraindicated as treatment for epilepsy during pregnancy unless there is no suitable alternative to treat epilepsy. Divalproex Sodium is contraindicated for use in women of childbearing potential unless the measures for prevention of pregnancy as mentioned in CONTRAINDICATIONS and PRECAUTIONS are met.
Valproate was shown to cross the placental barrier both in animal species and in humans.
Pregnancy Exposure Risk related to Divalproex Sodium: Both valproate monotherapy and Divalproex Sodium polytherapy are associated with abnormal pregnancy outcomes. Available data suggest that antiepileptic polytherapy including Divalproex Sodium is associated with a greater risk of congenital malformations than Divalproex Sodium monotherapy.
Congenital malformations: Children of epileptic women exposed to Valproate monotherapy during pregnancy suffer from congenital malformations. The most common types of malformations include neural tube defects, facial dysmorphism, cleft lip and palate, craniostenosis, cardiac, renal and urogenital defects, limb defects (including bilateral aplasia of the radius), and multiple anomalies involving various body systems.
In utero exposure to Valproate may also result in hearing impairment/loss due to ear and/or nose malformations (secondary effect) and/or to direct toxicity on the hearing function.
Cases describe both unilateral and bilateral deafness or hearing impairment. Monitoring of signs and symptoms of ototoxicity is recommended.
Developmental disorders: Exposure to Divalproex Sodium in utero can have adverse effects on mental and physical development of the exposed children. The exact gestational period of risk for these effects is uncertain and the possibility of a risk throughout the entire pregnancy cannot be excluded. Although the role of confounding factors cannot be excluded, there is evidence in children exposed to Divalproex Sodium that the risk of intellectual impairment may be independent from maternal IQ. Children exposed to Valproate in utero are at increased risk of autistic spectrum disorder, childhood autism, and increased risk of developing attention deficit/hyperactivity disorder (ADHD).
Female children, female adolescents and woman of childbearing potential: If a Woman wants to plan a Pregnancy: For epilepsy indication: During pregnancy, maternal tonic clonic seizures and status epilepticus with hypoxia may carry a particular risk of death for mother and the unborn child.
For epilepsy indication: In women planning to become pregnant or who are pregnant, valproate therapy should be reassessed.
For epilepsy indication: If a woman plans a pregnancy or becomes pregnant, valproate therapy should be stopped.
For epilepsy indication: In women planning to become pregnant all efforts should be made to switch to appropriate alternative treatment prior to conception, if possible.
If a woman plans a pregnancy: For the indication epilepsy, if a woman is planning to become pregnant, a specialist (preferably) experienced in the management of epilepsy, must reassess Divalproex Sodium. Valproic Acid therapy and consider alternative treatment options. Every effort should be made to switch to appropriate alternative treatment prior to conception, and before contraception is discontinued [see PRECAUTIONS]. If switching is not possible, the woman should receive further counselling regarding the Divalproex Sodium risks for the unborn child to support her informed decision making regarding family planning.
Pregnant women: Divalproex sodium as treatment for epilepsy is contraindicated in pregnancy unless there is no suitable alternative treatment [see CONTRAINDICATIONS, WARNINGS, and PRECAUTIONS], as evaluated and decided by the treating physician. If a woman using Divalproex Sodium becomes pregnant, she must be immediately referred to a specialist (preferably) to consider alternative treatment options. During pregnancy, maternal tonic clonic seizures and status epilepticus with hypoxia may carry a particular risk of death for mother and the unborn child.
If, despite the known risks of Divalproex Sodium in pregnancy and after careful consideration of alternative treatment preferably by the specialist, in exceptional circumstances a pregnant woman must receive Divalproex Sodium for epilepsy, it is recommended to: Use the lowest effective dose and divide the daily dose of Divalproex Sodium into several small doses to be taken throughout the day. The use of a prolonged release formulation may be preferable to other treatment formulations in order to avoid high peak plasma concentrations [see DOSAGE & ADMINISTRATION].
Fetal Risk: Valproate can cause major congenital malformations, particularly neural tube defects (e.g spina bifida). In addition, valproate can cause decreased IQ scores following in utero exposures. All patients with a Divalproex Sodium exposed pregnancy and their partners should consider specialized prenatal monitoring to detect the possible occurrence of neural tube defects or other malformations. The available evidence does not suggest that folate supplementation before the pregnancy may prevent the risk of neural tube defects which may occur in all pregnancies.
Risk in the neonate: Cases of hemorrhagic syndrome have been reported very rarely in neonates whose mothers have taken Divalproex Sodium during pregnancy. This hemorrhagic syndrome is related to thrombocytopenia, hypofibrinogenemia and/or to a decrease in other coagulation factors. Afibrinogenemia has also been reported and may be fatal. However, this syndrome must be distinguished from the decrease of the vitamin-K factors induced by phenobarbital and enzymatic inducers. Therefore, platelet count, fibrinogen plasma level, coagulation tests and coagulation factors should be investigated in neonates.
Cases of hypoglycaemia have been reported in neonates whose mothers have taken Divalproex Sodium during the third trimester of their pregnancy.
Cases of hypothyroidism have been reported in neonates whose mothers have taken Divalproex Sodium during pregnancy.
Withdrawal syndrome (such as, in particular, agitation, irritability, hyperexcitability, jitteriness, hyperkinesia, tonicity disorders, tremor, convulsions and feeding disorders) may occur in neonates whose mothers have taken valproate during the last trimester of their pregnancy.
Lactation: Divalproex Sodium is excreted in human milk with a concentration ranging from 1% to 10% of maternal serum levels. Hematological disorders have been shown in breastfed newborns/infants of treated women. A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from Divalproex Sodium therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.
Fertility: Amenorrhoea, polycystic ovaries and increased testosterone levels have been reported in women using Divalproex Sodium [see ADVERSE REACTIONS]. Divalproex Sodium administration may also impair fertility in men. Case reports indicate that fertility dysfunctions are reversible after treatment discontinuation.