Carbamazepine teratogenicity

Amore BM, Kalhom TF, Skiles GL, et al. Characterization of carbamazepine metabolism in a mouse model of carbamazepine teratogenicity. Drug Metab Dispos 1997 25 953-962. 

Diav-Citrin O, Shechtman S, Arnon J, Ornoy A. Is carbamazepine teratogenic A prospective controlled study of 210 pregnancies. Neurology 2001 57(2) 321. ... 

Mebendazole is contraindicated in patients witii known hypersensitivity. Mebendazole is also contraindicated during pregnancy (Category C). The drug, like albendazole, has exhibited embryotoxic and teratogenic effects in experimental animals. Administration of mebendazole with tiie hydantoins and carbamazepine may reduce plasma levels of mebendazole. 

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. 

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... 

Because of the potential for hematological and hepatic toxicity, carbamazepine should not be administered to patients with liver disease or thrombocytopenia or to those at risk for agranulocytosis. For this reason, carbamazepine is strictly contraindicated in patients receiving clozapine. Because of reports of teratogenicity, including increased risks of spina bifida (Rosa 1991), microcephaly (Bertol-lini et al. 1987), and craniofacial defects (Jones et al. 1989), carbamazepine is relatively contraindicated in pregnant women. Pretreatment evaluation should include a complete blood count and determination of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. 

Mebendazole is teratogenic in animals and therefore contraindicated in pregnancy. It should be used with caution in children younger than 2 years of age because of limited experience and rare reports of convulsions in this age group. Plasma levels may be decreased by concomitant use of carbamazepine or phenytoin and increased by cimetidine. Mebendazole should be used with caution in patients with cirrhosis. 

The most serious toxicities associated with carbamazepine use are idiosyncratic skin rashes, hematological disorders, hepatotoxicity, and teratogenicity (80). On the basis of studies with mice, teratogenicity is most likely related to formation of arene oxide and/or quinone-like metabolites of carbamazepine (83),... 

As with carbamazepine, phenytoin also causes idiosyncratic toxic effects, including hematological and connective tissue toxicities, hepatotoxicity, and teratogenicity (89). Although some of these toxicities have been hypothesized to be caused by P450 oxidative metabolism (92,93) or peroxidase-mediated reactions (94,95), mechanisms for these toxic effects in humans are unknown. 

Lindhout D, Hoppener RJEA, Meinardi H. Teratogenicity of antiepileptic drug combinations with special emphasis on epoxidation of carbamazepine. Epilepsia 1984 25 77-83. 

Adverse effects These are primarily related to CNS and Gl disturbances. They include impaired concentration, dizziness, ataxia, diplopia, somnolence, nervousness, and confusion, as well as nausea and weight loss. Renal stones have been reported in 1.5 percent of patients. Topiramate is teratogenic in animals, and should be avoided during pregnancy. Inducers of drug metabolism such as phenytoin and carbamazepine decrease topiramate serum concentrations by approximately 50 percent. Topiramate decreases ethinyl estradiol concentrations of oral contraceptive preparations, and individuals should supplement the amount of ethinyl estradiol. 

Oxcarbazepine is structurally similar to carbamazepine, A/hich is thought to be teratogenic in humans... 

Data from various studies in 1255 patients exposed to carbamazepine have been analysed to evaluate its potential teratogenicity (73). There was an increased rate of congenital anomalies, mainly neural tube defects, cardiovascular and urinary tract anomalies, and cleft palate. The combination of carbamazepine with other antiepileptic drugs was more teratogenic than carbamazepine monotherapy. Because this study was retrospective, the conclusions should not be seen as definitive. 

The Israeh Teratogen Information Service has prospectively followed 210 pregnancies with exposure to carbamazepine in the first trimester (74). The outcomes were... 

Matalon S, Schechtman S, Goldzweig G, Ornoy A. The teratogenic effect of carbamazepine a meta-analysis of 1255 exposures. Reprod Toxicol 2002 16(1) 9-17. 

Carbamazepine is possible lithium alternative. However, recent findings indicate that it is less safe than previously thought probable teratogen. 

Some mood stabilizers have an increased teratogenic risk during the first trimester (e.g., carbamazepine, lithium, oxcarbazepine, and valproate) this risk is greater if the patient is on multiple agents... 

Carbamazepine is an anticonvulsant beneficial in the treatment of bipolar I disorder, and, as in the case of valproate, it may be more advantageous than lithium in non-classical bipolar conditions such as mixed mood states and rapid cycling conditions. It appears to have a teratogenic effect and, like valproate, has been associated with an increased risk of neural tube defects. ... 

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