Use of Phenytoin, Phenobarbital Carbamazepine, Levetiracetam Lamotrigine and Valproate in Pregnancy and Breastfeeding: Risk of Major Malformations, Dose-dependency, Monotherapy vs Polytherapy, Pharmacokinetics and Clinical Implications

Kaplan, Yusuf Cem; Demir, Ömer

doi:10.2174/1570159x19666210211150856

Cited by 24 publications

(32 citation statements)

References 97 publications

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“…Although there are studies showing that CBZ causes malformations in the fetus, such as growth retardation, hypothyroidism, thrombocytopenia, mental retardation, immunoendocrine disorders, heart defects, and neural tube defects, 22,27,29,42,43 there are also pregnancy registry studies showing that it does not increase the risk of fetal malformation 44 …”

Section: Discussionmentioning

confidence: 99%

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods

et al. 2022

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Objective This study was carried out to determine the effect of intrauterine carbamazepine (CBZ) exposure on fetal bone development during pregnancy. Methods In the study, 24 female Wistar pregnant rats were used. Rats were 20 weeks old. They had an average body weight of 150–200 g. Pregnant rats were randomly selected and divided (n = 6) into a control group, low‐dose CBZ (10 mg/kg/day) group, medium‐dose CBZ (25 mg/kg/day) group, and high‐dose CBZ (50 mg/kg/day) group. The ossification length (mm) and ossification area (mm2) of the long bones of the fetuses in the experimental and control groups were calculated. The densities of alkaline phosphatase (AP) and tartrate‐resistant acid phosphatase (TRAP) were analyzed. The ossification regions of the femurs of the fetuses were examined under a light microscope. Microstructural images of the femurs were evaluated with scanning electron microscope photographs. The densities of minerals involved in the ossification process were analyzed. Results According to the results of the study, all three doses of CBZ caused loss of ossification areas, and it was observed that this bone loss also increased statistically significantly depending on the dose increase (p < .05). Calcium concentration decreased in the CBZ groups. When the electron microscope images were examined, it was determined that the cartilage matrix of the CBZ groups was thinned. In the histological evaluation of the groups, narrowing of the primary bone collar and smaller bone spicules in the ossification region compared to the control group were noted due to the increase in dose in the CBZ groups. In immunohistochemical staining, it was observed that the TRAP and AP expression values of the femurs were the lowest in the CBZ groups. These decreases were also statistically significant when compared with the control group. Significance It was revealed with both microscopic and macroscopic findings that exposure to intrauterine CBZ negatively affected ossification and bone growth.

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Section: Discussionmentioning

confidence: 99%

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods

et al. 2022

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“…An increased dosage of sodium valproate and topiramate is associated with even more incidence of significant congenital morbidities. Multidrug therapy, including medications like sodium valproate and topiramate, results in a higher incidence of significant morbidities [33]. Assessing risk patterns of other antiepileptics by referring to consistent research studies, the least number of malformations are observed with lamotrigine and levetiracetam, which include no or slight incidences of structural deformities, no organ-centric deformities except for an increased incidence of oral clefts in single drug therapy of lamotrigine, but this is not observed in all studies.…”

Section: Prevention and Reduction Of Sodium Valproate Usage In Pregna...mentioning

confidence: 99%

Measures to Mitigate Sodium Valproate Use in Pregnant Women With Epilepsy

Ranjith¹,

Joshi²

2022

Cureus

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Sodium valproate is a sodium salt of valproic acid. It is often used in the medical treatment of several conditions like epilepsy, bipolar disorder, mania, and migraines. This review debates whether the usage of valproic acid is appropriate in pregnancy. It also lists the various neonatal deformities and other teratogenic effects the said drug presents due to prenatal exposure to the drug and the implications of continuing drug therapy in certain situations. We should often weigh the outcomes and implement it only in conditions where its use is inevitable. It also includes the importance of awareness among middle-aged women with mental illness regarding the teratogenic effects of sodium valproate use and the relevance of discussion by physicians with patients regarding the usage of this drug despite being aware of the complications. It also explores other treatment options and modalities that can be used in the place of valproic acid for epilepsy and bipolar disorder in pregnant women and women of the reproductive age group, and how we can mitigate the usage of this drug by implementing various measures by referring to various guidelines present in different areas of the world. In summary, this article explores the numerous teratogenic effects sodium valproate presents in pregnancy, alternative medications, and treatment options instead of valproate. It also enumerates conditions where valproate use is necessary and how we can reduce and prevent the usage of valproate in pregnancy by opting for pregnancy prevention programs during valproate use and various other guidelines.

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“…RID is a function of MP ratio and maternal drug clearance, and the safety threshold is 5–10%. However, RID higher than 10% is not necessarily a taboo for breastfeeding ( 18 , 19 ). It should be noted that M/P ratio is not necessarily proportional to RID.…”

Section: Metabolic Pathway Of Asms and The Influence Of Asms In Human...mentioning

confidence: 99%

“…M/P ratio ranging from 0.18–0.45 and RID ranging from 0.6–7.7% ( 20 ). The evaluation of adverse reactions in infants exposed to phenytoin through breast milk found that in most cases, there were no serious adverse reactions ( 19 ). There a report that breastfeeding under treatment with phenytoin led to methemoglobinemia ( 28 ).…”

Section: Metabolic Pathway Of Asms and The Influence Of Asms In Human...mentioning

confidence: 99%

Management of anti-seizure medications in lactating women with epilepsy

et al. 2022

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Epilepsy is a common neurological disease. At present, there are about 70 million epilepsy patients in the world, half of them are women, and 30–40% of women with epilepsy are of childbearing potential. Patients with epilepsy who are of childbearing potential face more challenges, such as seizures caused by hormonal fluctuations and the risk of adverse effects on the mother and baby from taking anti-seizure medications (ASMs). Breast milk is one of the best gifts that a mother can give her baby, and breastfeeding can bring more benefits to the baby. Compared with healthy people, people with epilepsy have more concerns about breastfeeding because they are worried that ASMs in their milk will affect the growth and development of the baby, and they are always faced with the dilemma of whether to breastfeed after childbirth. Regarding, whether women with epilepsy can breastfeed while taking ASMs, and whether breastfeeding will adversely affect the baby is still an important topic of concern for patients and doctors. This article reviews the existing research on breastfeeding-related issues in women with epilepsy to guide clinical practice, and improve the breastfeeding compliance of women with epilepsy.

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Use of Phenytoin, Phenobarbital Carbamazepine, Levetiracetam Lamotrigine and Valproate in Pregnancy and Breastfeeding: Risk of Major Malformations, Dose-dependency, Monotherapy vs Polytherapy, Pharmacokinetics and Clinical Implications

Cited by 24 publications

References 97 publications

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods

Bone development in offspring of pregnant rats treated with carbamazepine: Evaluation by three different methods

Measures to Mitigate Sodium Valproate Use in Pregnant Women With Epilepsy

Management of anti-seizure medications in lactating women with epilepsy

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