Vol.58 No.S-2 October 2010
Safety profile of pediatric tosufloxacin
1)Department of Pharmacology, Jikei University School of Medicine, 3-25-8 Nishi-Shinbashi, Minato-ku, Tokyo, Japan
(present: Department of Infectious Diseases and Infection Control, Jikei University School of Medicine)
2)Formerly: Kawasaki Municipal Hospital (†Deceased)
3)Kawasaki RA&IM Clinic
4)Department of Research Project Studies, Kitasato Institute for Life Sciences
Abstract
A safety profile was evaluated in 235 pediatric subjects - 63 with pneumonia and 172 with otitis media - included in the safety analyses in the two Phase III clinical studies of tosufloxacin(TFLX) granules.
Adverse events were reported by 62.6% (147 of 235) and adverse drug reactions by 26.4% (62 of 235) of the subjects. Vomiting (4.3%, 10 of 235), diarrhea (3.4%, 8 of 235), and loose stools (2.1%, 5 of 235) were the most frequently reported adverse drug reactions. Two cases of arthralgia, a joint-related adverse drug reaction concerned in the use of quinolone antibiotics in pediatric subjects, were reported to be mild and resolved rapidly. The one-year follow-up for the occurrence of joint disorders showed joint-related adverse events reported by 9.6% (22 of 230) of subjects. All these cases were estimated unrelated to TFLX administration except for one relationship, that was unknown. No serious adverse drug reactions were reported and all adverse events rapidly disappeared or resolved after discontinuation or completion of dosing. No convulsions or hypoglycaemia were reported.
The correlation evaluated between pharmacokinetic parameters-AUC and Cmax-and adverse drug reactions showed the adverse drug reaction's incidence to be increased with higher AUC and Cmax. No clear relationships were observed between pharmacokinetic parameters and vomiting, diarrhea (including loose stool), or arthralgia, but thirst and anorexia were possibly correlated with Cmax.
Although two mild arthralgia were reported, no clinically significant adverse drug reactions were observed and the pediatric use of TFLX granule does not raise any serious safety concerns. However, TFLX granule is the first fluoroquinolone antibiotics indicated for pneumonia and otitis media in pediatric patients in Japan, so it should be carefully used balancing risks and benefits in clinical practice.
Key word
tosufloxacin, child, adverse event, safety
Received
May 25, 2010
Accepted
August 20, 2010
Jpn. J. Chemother. 58 (S-2): 78-88, 2010
