Teratogenic anticonvulsants

Phenobarbital, carbamazepine, and phenytoin potentially reduce efficacy of OCs, and many anticonvulsants are known teratogens. The use of condoms in conjunction with high-estrogen OCs or intrauterine devices (IUDs) may be considered for women taking these drugs. 

Peterson CL, Laniel MA (2004) Histones and histone modifications. Curr Biol 14 R546-R551 Phiel CJ, Zhang F, Huang EY, Guenther MG, Lazar MA, Klein PS (2001) Histone deacetylase is a direct target of valproic acid, a potent anticonvulsant, mood stabilizer, and teratogen. J Biol Chem 276 36734-36741... 

Carbamazepine exerts its anticonvulsant activity through its own action on voltage sensitive sodium channels and those of its relatively stable 10-11-epoxide. The compound shows a number of potential toxicities including skin rash, hepatic necrosis and teratogenicity. It is possible the 10-11-epoxide is the causative agent, but struc-... 

Valproate, carbamazepine, and other anticonvulsants pose teratogenic risks. Despite this, treatment should continue during pregnancy, as the potential threat to the fetus by a seizure is greater However, it is mandatory to administer the lowest dose affording safe and effective prophylaxis. Concurrent high-dose administration of folate may... 

Hauck, R.-S. and Nau, H. (1996) Asymmetric synthesis and enantioselective teratogenicity of 2-n-propyl-4-pentenoic acid (4-ene-VPA), an active metabolite of the anticonvulsant drug, valproic acid. Toxicol. Lett. 49 41-48. 

Bojic U, Elmazaar MMA, Hauck R-S, et al. Further branching of valproate-related carboxylic acids reduces the teratogenic activity, but not anticonvulsant effect. Chem Res Toxicol 1996 9 866-870. 

Use of anticonvulsants in combination may cause a higher prevalence of teratogenic effects than anticonvulsant monotherapy... 

SAFETY PROFILE Poison by ingestion and intraperitoneal routes. Human systemic effects by ingestion somnolence, hemorrhage, changes in teeth and supporting structures. Human mutation data reported. An experimental teratogen. An FDA proprietary drug used as an anticonvulsant. When heated to decomposition it emits toxic fiimes of NOx. 

Of the newer anticonvulsants, lamotrigine, gabapentin, tiagabine, and vigabatrin have little or no teratogenic potential in animals, whereas oxcarbazepine and topira-mate are teratogenic in rodents. However, animal studies are not necessarily apphcable to humans and chnical data are stiU insufficient to assess the effects of newer drugs on the development of the human fetus (153). 

The incidence of neonatal abnormalities in mothers taking anticonvulsant treatment is 70/ 1000 live births (Frederick, 1973). This is 2.4 times the spontaneous rate in the general population (29 abnormalities/1000 live births). Thus, even using a known low-incidence teratogen could cause 40 additional cases/1000 live births, but to determine that accurately would require many thousands of female patient exposures to be detectable against the spontaneous background incidence. 

---