Carbamazepine This drug, also a blocker of sodium channels like phenytoin, causes many of the same side effects as phenytoin, but to a slightly lesser degree. There is induction of hepatic enzymes and “autoindicution,” leading to declining drug levels after a few weeks of administration. Mild leukopenia is common, and there have been rare instances of pancytopenia, hepatic enzyme abnormalities, pancreatitis, hyponatremia (inappropriate antidiuretic hormone [ADH]), and, rarely, diabetes insipidus as idiosyncratic reactions. It is advisable therefore, that a complete blood count and liver function tests (some practitioners omit the latter because of the infrequency of hepatic problems) be done before or soon after treatment is instituted and that counts are rechecked regularly. Idiosyncratic rashes, some as severe as Stevens-Johnson syndrome may occur, particularly in Asian individuals carrying the HLA-B*1502 haplotype as mentioned above. It has not been considered useful to check patients for this haplotype but it may be considered in Asian patients.
Oxcarbazepine, an analogue of carbamazepine, has fewer of these side effects than the parent drug, especially marrow toxicity, but its long-term therapeutic value is not as well established. It has the advantage of being titrated upward at a more rapid rate than carbamazepine. Dose-related side effects are similar to carbamazepine but it has less hepatic enzyme induction. Some patients report weight gain after continued use. Hyponatremia has been reported in 3 percent of patients taking oxcarbazepine. Should drowsiness or increased seizure frequency occur, this complication should be suspected. Rashes occur at the same or slightly lower rate than with carbamazepine and there is considerable cross-reactivity for this side effect. Elevated cholesterol and osteoporosis are lesser effects, shared also with carbamazepine.
Valproate This drug in all its related forms is considered to be GABA-ergic, acting through glutamic acid decarboxylase, but also displaying some sodium channel blocking features. All preparations of this drug are occasionally hepatotoxic, an adverse effect that is usually (but not invariably) limited to children 2 years of age and younger. The use of valproate with hepatic enzyme-inducing drugs increases the risk of liver toxicity. However, mild elevations of serum ammonia and mild impairments of liver function tests in an adult do not require discontinuation of the drug. An increasingly emphasized problem with valproate has been weight gain during the first months of therapy. In one study there was an average addition of 5.8 kg, and even more in those disposed to obesity. In addition, menstrual irregularities and polycystic ovarian syndrome may appear in young women taking the drug, perhaps as a consequence of the aforementioned weight gain. Pancreatitis is a rare but important complication of valproate. Tremor and slight bradykinesias have been seen and they vaguely simulate parkinsonism. The major issues, however, pertain to its use in pregnancy as discussed earlier.
An intravenous form of valproate is available and may be useful in status epilepticus. The maximum recommended rate of administration is 3 mg/kg per min.