Convulzor Use In Pregnancy & Lactation

Use in Pregnancy: ER tablet: Teratogenic Effects: Pregnancy Category D.
Fetal Risk Summary: 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). 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 cognitive test scores than children exposed to either another antiepileptic drug in utero or to non-antiepileptic drugs in utero.
In animal studies, offspring had structural malformations similar to those seen in humans and demonstrated behavioral deficits.
Clinical Considerations: Neural tube defects are the congenital malformation most strongly associated with maternal valproate use. The risk of spina bifida following in utero valproate exposure is generally estimated as 1-2%, compared to an estimated general population risk for spina bifida of about 0.06 to 0.07% (6 to 7 in 10,000 births).
To prevent major seizures, women with epilepsy should not discontinue Valproic Acid abruptly, as this can precipitate status epilepticus with resulting maternal and fetal hypoxia and threat to life. Even minor seizures may pose some hazard to the developing embryo or fetus. However, discontinuation of the drug may be considered prior to and during pregnancy in individual cases if the seizure disorder severity and frequency do not pose a serious threat to the patient.
Available prenatal diagnostic testing to detect neural tube and other defects should be offered to pregnant women using valproate.
Evidence suggests that folic acid supplementation prior to conception and during the first trimester of pregnancy decreases the risk for congenital neural tube defects in the general population. It is not known whether the risk of neural tube defects in the offspring of women receiving valproate is reduced by folic acid supplementation. Dietary folic acid supplementation both prior to conception and during pregnancy should be routinely recommended for patients using valproate.
Patients taking valproate may develop clotting abnormalities. A patient who had low fibrinogen when taking multiple anticonvulsants including valproate gave birth to an infant with afibrinogenemia who subsequently died of hemorrhage. If valproate is used in pregnancy, the clotting parameters should be monitored carefully.
Patients taking valproate may develop hepatic failure. Fatal cases of hepatic failure in infants exposed to valproate in utero have also been reported following maternal use of valproate during pregnancy.
Syrup: See Contraindications and Women of childbearing potential and Usage in pregnancy under Precautions.
Risks associated with valproic acid: In humans Valproic acid may produce teratogenic effects, such as neural tube defects (e.g. spina bifida) in the offspring of human females receiving the drug during pregnancy. There are data that suggest an increased incidence of congenital malformations associated with the use of valproic acid during pregnancy. Therefore, valproic acid should be considered for women of childbearing potential only after the risks have been thoroughly discussed with the patient and weighed against the potential benefits of treatment.
There are multiple reports in the clinical literature that indicate the use of antiepileptic drugs during pregnancy results in an increased incidence of birth defects in the offspring. Therefore, antiepileptic drugs should be administered to women of childbearing potential only if they are clearly shown to be essential in the management of their disease.
The incidence of neural tube defects in the fetus may be increased in mothers receiving valproate during the first trimester of pregnancy. The United States Centers for Disease Control (CDC) has estimated the risk of valproic acid exposed women having children with spina bifida to be approximately 1-2%.
Other congenital anomalies (e.g., craniofacial defects, cardiovascular malformations, hypospadias and anomalies involving various body systems), compatible and incompatible with life, have been reported.
There was an increased incidence of congenital malformations in children born to epileptic women exposed to valproate monotherapy during pregnancy. Available data indicate dose-dependency of this effect.
Valproate can cause decreased IQ scores following in utero exposure. Published epidemiological studies have indicated that children exposed to valproate in utero have lower cognitive test scores than children exposed in utero to either another antiepileptic drug or to no antiepileptic drugs.
There have been reports of developmental delay, autism and/or autism spectrum disorder in the offspring of women exposed to valproic acid during pregnancy.
Exposure in utero to valproate products has been associated with cerebral atrophy with varying degrees/manifestations of neurological compromise, including developmental delays and psychomotor impairment (see Adverse reactions).
In animals: Animal studies have demonstrated valproate-induced teratogenicity. Increased frequencies of malformations, as well as intrauterine growth retardation and death, have been observed in mice, rats, rabbits, and monkeys following prenatal exposure to valproate. Malformations of the skeletal system are the most common structural abnormalities produced in experimental animals, but neural tube closure defects have been seen in mice exposed to maternal plasma valproate concentrations exceeding 230 mcg/mL (2.3 times the upper limit of the human therapeutic range) during susceptible periods of embryonic development.
Risks in the neonates: Pregnant women taking valproate may develop clotting abnormalities, including thrombocytopenia, hypofibrinogenemia, and/or decrease in other coagulation factors, which may result in hemorrhagic complications in the neonate including death (see Thrombocytopenia and General under Precautions).
If valproate is used in pregnancy, the clotting parameters should be monitored carefully.
Hepatic failure, resulting in the death of a newborn and of an infant, has been reported following the use of valproate during pregnancy.
Cases of hypoglycemia have been received for neonates whose mothers have taken valproate during pregnancy.
Tests to detect neural tube and other defects using current accepted procedures should be considered a part of routine prenatal care in childbearing women receiving valproate.
Antiepileptic drugs should not be discontinued abruptly in patients in whom the drug is administered to prevent major seizures because of the strong possibility of precipitating status epilepticus with attendant hypoxia and threat to life. In individual cases, where the severity and frequency of the seizure disorder are such that the removal of medication does not pose a serious threat to the patient, discontinuation of the drug may be considered prior to and during pregnancy, although it cannot be said with any confidence that even minor seizures do not pose some hazard to the developing embryo or fetus.
Use in Lactation: Syrup: Valproate is excreted in breast milk. Concentrations in breast milk have been reported to be 1-10% of serum concentrations. It is not known what effect this would have on a nursing infant. Consideration should be given to discontinuing nursing when valproic acid is administered to a nursing woman (see Usage in pregnancy under Precautions).