2002 Volume 50 Issue 10 Pages 730-747
We retrospectively studied risk factors and incidence of adverse effects of cefoselis on the central nervous system.Cefoselis is a broad-spectrum injectable antibiotic.Subjects were all patients treated with cefoselis at 4, 120 institutions where cefoselis was delivered during 3 months from the date of initial marketing to the day of the “Dear Dr.” letter announcement. Of these institutions, 1, 254 took part in the investigation and 10, 641 patients were enrolled in the study, with about half of the 21, 119 patients regarded as having been treated with cefoselis over this period.
1.The case-control study on risk factors for adverse effects in the central nervous system indicated that the Mantel-Haenszel estimate of the odds ratio of exposure to dialysis or renal failure was 23.1 (95% confidential interval: 11.9-44.7), demonstrating that dialysis or renal failure was an obvious risk factor. Another similar study on risk factors for renal disorder was conducted by excluding patients with dialysis or renal failure, and indicated a Mantel-Haenszel estimate of the odds ratio of 1.5 (95% confidence interval: 0.5-5.1), which was not statistically significant.
2.Adverse effects on the central nervous system were observed in 93 of the 10, 174 patients (0.91%), while adverse effects were observed in 48 of the 9, 879 patients (0.49%) remaining after excluding patients with dialysis or renal failure for whom the cefoselis use was contraindicated. Logistic regression analysis showed 3 additional risk factors for adverse effects on the central nervous system: renal disorder severity, age, and daily dose.We estimated the incidence of adverse effects using the logistic regression model with these 3 factors for patients under 65 years old with cefoselis at the standard dosage, i.e., 1 g twice a day. The estimated incidence varied as follows: 0.05-0.18%in patients without renal disorder, 0.09-0.31%in those with mild renal disorder, 0.16-0.56%in those with moderate renal disorder, and 0.28-1.00% in those with severe renal disorder. The incidence of adverse effects in patients aged 65 years or more was estimated to vary as follows when cefoselis was administered at the initial standard dose for elderly patients (0.5 g twice a day): 0.07-0.24% in patients without renal disorder, 0.12-0.44% in those with mild renal disorder, 0.22-0.78%in those with moderate renal disorder, and 0.40-1.38%in those with severe renal disorder.
3.Our results indicate that the incidence of adverse effects on the central nervous system due to cefoselis varies with renal disorder severity, age, and daily dose. The dose of cefoselis should therefore be determined based on renal disorder severity and patient age.
