RESUMEN
The current literature on the effects of clozapine on pregnancy is limited, and no cases of pregnant Japanese women have been reported. Decreased variability in the fetal heart rate due to clozapine exposure has been reported in countries other than Japan, but its association with serum concentrations of clozapine has not been documented. In this case, a 29-year-old Japanese primipara with treatment-resistant schizophrenia taking clozapine 250 mg/day experienced pregnancy. The pregnancy progressed without complications. At 40 weeks and 2 days of gestation, the patient developed premature rupture of membranes, and decreased variability in the fetal heart rate and variable deceleration were observed, leading to an emergency cesarean section. The neonate had no congenital malformations, metabolic disorders, seizures, floppy infant syndrome, leukopenia, or neutropenia. Serum concentrations of clozapine and norclozapine (N-desmethylclozapine), measured in the mother and in the neonate immediately after birth, suggested that clozapine and norclozapine were transported to the fetus during pregnancy. Based on these observations, the present case suggests that high fetal serum concentrations of clozapine and norclozapine may affect fetal heart rate. This case report concludes that, with careful monitoring, Japanese women taking clozapine can deliver successfully and emphasizes the importance of monitoring serum clozapine concentrations and fetal cardiac function throughout pregnancy, with particular attention to the later stages.
RESUMEN
PURPOSE: We studied the efficacy and safety of bortezomib (BOR) for treatment of multiple myeloma in comparison with thalidomide (THAL) by reference to adverse events, and searched for laboratory markers that could be used for prognostication of patients. METHODS: Biochemical data of patients receiving BOR and THAL for treatment of multiple myeloma at the Japanese Red Cross Narita Hospital were investigated retrospectively, after obtaining Institutional Review Board approval. Judgment of curative effects complied with the effects criteria of the International Myeloma Working Group (IMWG). RESULTS: BOR showed a higher rate of effectiveness than THAL for refractory multiple myeloma, and its effects were rapid. BOR treatment prolonged the survival time of THAL-resistant patients. The efficacy of BOR was unrelated to patient age, the number of previous therapeutic regimens, or the disease period. After medication with BOR, patients in whom it had been effective tended to show an increase of the serum alkaline phosphatase (ALP) level. Thrombocytopenia (86.2%) and leucopenia (69.0%) were observed at high frequencies, but no previously unreported adverse events or fatalities were associated with BOR therapy. CONCLUSION: It is suggested that BOR has therapeutic efficacy for multiple myeloma as a first-line medical treatment and/or for patients with THAL resistance, and can improve prognosis and survival. Since serum ALP elevation was observed in many patients for whom BOR was effective, this may be a predictor of BOR efficacy.