Hematological monitoring during therapy with carbamazepine in children

Carbamazepine (CBZ) is being prescribed more frequently for treatment of children and adults with generalized tonicclonic and partial complex seizures. Early reports of aplastic anemia in elderly patients treated with this drug led to concern about its potential hematological toxicity. A variety of other hematological abnormalities have also been described in association with CBZ therapy, including agranulocytosis, thrombocytopenia, and transient leukopenia. The drug labeling recommends frequent blood tests and includes strict guidelines for discontinuation of therapy if relatively minor abnormalities occur, for example, total white blood cell count (WBC) less than 4,000 per cubic millimeter. Several authors have questioned the validity and practicality of these guidelines El]. In fact, routine monitoring is not practiced at certain epilepsy centers. The major objection raised is that routine monitoring does not help predict which patients will develop severe idiosyncratic drug reactions. It has been suggested that children are less likely than adults to develop hematological abnormalities while receiving CBZ therapy, but few large pediatric series have been reported. T o determine the incidence and severity of hematological problems associated with CBZ, we reviewed the records of 200 children who attended the Pediatric Neurology Clinic at the University of Michigan Medical Center from 1978 to 1982 [4}. We compared two groups of patients. Group 1 consisted of 125 children in whom therapy was initiated before age 12 (39 were less than 6 years old); group 2 included 75 children who were between 12 and 17 years old at the start of therapy. Mean duration of treatment (18 months), mean CBZ level (6 CLgiml), and mean number of other anticonvulsants (1.5) were the same for the two groups. N o patient developed any symptomatic hematological problem. The Table summarizes the results of hematological surveillance in these children. Leukopenia (WBC less than 4,000 per cubic millimeter) was the most frequently noted abnormality and was almost twice as common in the younger age group. In most patients leukopenia resolved while CBZ therapy was continued, but 4 of the 200 had persistent or recurrent leukopenia while taking the drug. The drug was discontinued in 3 patients because of leukopenia. There was no detectable clinical difference between the patients in whom the drug was stopped and those for whom the decision was made to continue treatment. Based on our experience and published series [3], it appears that CBZ is a relatively safe drug for children with seizures. However, although it is possible that leukopenia was sometimes unrelated to CBZ, its occurrence in a minority of patients merits further investigation and suggests that hematological surveillance is appropriate. Although reports in the literature are inconsistent about the value of routine blood counts in preventing or altering the outcome of Hematological Abnormalities in Children Treated with Carbamazepine for Seizures