Carbamazepine during pregnancy

Rosa, F.W. (1991) Spina bifida in infants of women treated with carbamazepine during pregnancy. N Egl J Med 324 674—677. 

Iqbal MM, Sohhan T, Mahmud SZ The effects of lithium, valproic acid, and carbamazepine during pregnancy and lactation. J Toxicol Clin Toxicol 2001 39 381. [PMID 11527233]... 

A. Omoy, E. Cohen, Outcome of children born to epileptic mothers treated with carbamazepine during pregnancy. Arch. Dis. Child 75 517-520, 1996. 

Some cases of neonatal seizures, respiratory depression, vomiting, and diarrhea have been reported in infants whose mothers received carbamazepine during pregnancy... 

Because the safe use of carbamazepine during pregnancy has not been established, caution should be used in prescribing carbamazepine during the first trimester of pregnancy or in women of reproductive age. Carbamazepine may cause craniofacial deformities, spina bifida (0.5% to 1%), and low birth weight. Carbamazepine is excreted in breast milk (the milk-to-maternal plasma ratio of carbamazepine is about 0.4)." There are two case reports of transient cholestatic hepatitis and jaundice in nursing infants. 

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. 

The miscellaneous anticonvulsants are contraindicated in patients with known hypersensitivity to any of the dru. Carbamazepine is contraindicated in patients with bone marrow depression or hepatic or renal impairment and during pregnancy (Category D). Valproic acid is not administered to patients with renal impairment or during pregnancy (Category D). Oxcarbazepine (Trileptal), a miscellaneous anticonvulsant, may exacerbate dementia... 

Anti-epileptic drugs, such as phenytoin, carbamazepine and valproate, may lead to neural tube defects if administered during pregnancy. Concurrent administration of folate supplements, such as folic acid, is recommended. 

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... 

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. 

Atypical antipsychotics may be preferable to lithium or anticonvulsants such as carbamazepine if treatment of bipolar disorder is required during pregnancy... 

With current information, carbamazepine seems to be the safest drug for use during pregnancy. Data on lamotrigine (more recently introduced) are increasing but it has not been shown to be strongly associated with malformations. 

Neonates require close monitoring if their mothers received enzyme inducers such as phenytoin, pheno-barbital, carbamazepine, or rifampin during pregnancy... 

Neonates require close monitoring if their mothers received enzyme inducers such as phenytoin, phenobar-bital, carbamazepine, or rifampin during pregnancy or if they need one of these drugs themselves. Examples of drugs that inhibit the metabolism of other medications include cimetidine, erythromycin, and ketoconazole." ... 

For patients who experience a breakthrough episode, the medication dose should first be optimized. When first-line medications at optimal dose fail to control symptoms, recommended treatment options include the addition of another first-line medication. Alternative treatment options include adding carbamazepine or oxcarbazepine in lieu of an additional first-line medication, adding an antipsychotic if not already prescribed, or changing from one antipsychotic to another. Of the antipsychotics, clozapine may be particularly effective for treatment of refractory illness. Electroconvulsive therapy (ECT) may also be considered for patients with severe or treatment-resistant illness. In addition, ECT is a potential treatment for patients with mixed episodes or for severe mania experienced during pregnancy. 

Carbamazepine Manufacturer recommends CBC and platelets (and possibly reticulocyte counts and serum iron) at baseline, and that subsequent monitoring be individualized by the clinician (e.g., CBC, platelet counts, and liver function tests every 2 weeks during the first 2 months of treatment, then every 3 months if normal). Monitor more closely if patient exhibits hematologic or hepatic abnormalities or if the patient is receiving a myelotoxic drug discontinue if platelets are less than 100,000/mm3, if white blood cell (WBC) count is less than 3,000/mm3 or if there is evidence of bone marrow suppression or liver dysfunction. Serum electrolyte levels should be monitored in the elderly or those at risk for hyponatremia. Carbamazepine interferes with some pregnancy tests. 

Before beginning treatment with carbamazepine, liver function tests, a complete blood count with platelets and reticulocytes, and a pregnancy test should be performed. Long-term monitoring of carbamazepine therapy includes periodic assessment of liver function tests, complete blood count, reticulocyte count, and carbamazepine levels. These should be performed every 2 months during the first 6 months of treatment and every 6-12 months thereafter. 

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