Vol.59 No.6 November 2011

Safety and efficacy of levofloxacin 500 mg once a day

Seiji Hori¹⁾, Kazuhiro Uchino²⁾, Hiroki Yamaguchi²⁾, Takuyuki Matsumoto²⁾, Kyoko Kuroyanagi²⁾, Sanae Yoshida²⁾, Megumi Takahashi²⁾, Hiroko Kodama²⁾, Satoko Hamajima²⁾, Rie Yonemochi³⁾, Fumiaki Kobayashi⁴⁾, Naoki Yamanouchi⁴⁾, Tadamichi Suzuki³⁾, Tomoo Shiozawa²⁾ and Fumie Yamaguchi²⁾

¹⁾Department of Infectious Diseases and Infection Control, Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo, Japan
²⁾Post Marketing Studies Management Department, Daiichi Sankyo Company, Limited
³⁾Pharmacovigilance Department, Daiichi Sankyo Company, Limited
⁴⁾Clinical Data and Biostatistics Department, Daiichi Sankyo Company, Limited

Abstract

Levofloxacin(LVFX) was approved for administration at a dose of 500 mg once a day in April 2009 based on pharmacokinetic and pharmacodynamic theory. A use-results survey on LVFX 500 mg/day was performed from October 2009 to September 2010. Survey forms for 32,200 patients were collected from 4,547 medical institutions nationwide. Safety was examined in 29,880 patients and efficacy in 28,800 patients.
The incidence of adverse drug reactions(ADRs) was 1.61%. The major ADRs were gastrointestinal disorders such as diarrhea and nausea at 0.64%, abnormalities in laboratory tests including increased levels of alanine aminotransferase and aspartate aminotransferase at 0.31%, skin and subcutaneous tissue disorders such as exanthema and drug eruption at 0.19%, and nervous system disorders such as vertigo at 0.17%. The types and incidences of ADR were not much different from those for LVFX 100 mg 2-3 times/day.
Nonsteroidal anti-inflammatory drugs of the phenyl acetate and propionate types, which require caution when co-administered with LVFX, were used concomitantly by 13.7% of patients but no increases in incidences of central nervous system ADRs were observed.
For patients with renal dysfunction (Ccr<50 mL/min), when the dosage and administration were adjusted as shown in the package insert, no dose-dependent central nervous system ADRs were found and the efficacy was maintained at more than 85%. However, when the dosage and administration were not adjusted, central nervous system ADRs such as convulsions were observed in patients who were taking 500 mg/day as a consecutive dose.
The overall efficacy rate was 96.0% and by types of infections, it was 96.3% for respiratory tract infections, 95.7% for urinary tract or genital infections, 94.7% for otorhinolaryngologic infections, 96.8% for dermatological infections, 97.6% for intestinal tract infections, 96.3% for surgical and orthopedic infections, 96.1% for obstetric and gynecological infections, 95.8% for dental and oral surgical infections, 93.8% for biliary tract infections and 96.9% for ophthalmologic infections.
The above findings indicated that the safety of LVFX 500 mg/day was basically the same as 100 mg 2-3 times/day. The overall efficacy was 96.0% and efficacy in each of the different fields of infection exceeded 90%. The validity of adjustment of the dosage and administration based on renal function shown in the package insert for patients with renal dysfunction was confirmed.

Key word

levofloxacin, safety, efficacy, postmarketing surveillance

Received

July 28, 2011

Accepted

August 29, 2011

Jpn. J. Chemother. 59 (6): 614-633, 2011