Ball P, Mandell L, Patou G, Dankner W, Tillotson G
School of Biomedical Sciences, St Andrews University, St Andrews, Fife, 6 Gilchrist Row, Scotland KY16 8XU, UK.
Int J Antimicrob Agents. 2004 May;23(5):421-9. doi: 10.1016/j.ijantimicag.2004.02.014.
Gemifloxacin is a broad-spectrum quinolone antibacterial with enhanced potency against Gram-positive bacteria, including multi-drug resistant Streptococcus pneumoniae, and retained potency against Gram-negative bacilli and bacterial strains resistant to other antibiotics. It has proven particularly effective in respiratory and urinary tract infection. This review presents safety data from 6775 patients included in clinical trials, receiving either the recommended 320 mg once daily oral dose of gemifloxacin, or standard dose of other quinolones, macrolides or beta-lactams (n = 5248). Studies in healthy volunteer and special populations are also reported. Adverse experiences (AEs) were observed in 44.7% of gemifloxacin-treated patients and 47.5% of those who received comparator drugs. Mild gastro-intestinal adverse drug reactions (ADRs) (diarrhoea 5.1%, nausea 3.9%) predominated. Rash, usually maculo-papular and in no case proceeding to more severe eruptions, was observed in 3.6% of those receiving gemifloxacin. A higher incidence of rash (>20%) was observed in young women and was the subject of further study. Adverse drug reactions suspected or probably related to treatment occurred in 17.4% of patients receiving gemifloxacin and in 20% of those receiving comparator antibiotics. Diarrhoea and nausea were experienced by 3.6 and 2.7%, respectively, of gemifloxacin-treated patients (4.6 and 3.2% of comparators), rash by 2.8% (0.6% of comparators) and headache by 1.2% (1.5% of comparators). Gemifloxacin-related vomiting (0.9%), dizziness (0.8%) and taste perversion (0.3%) were uncommon. Treatment discontinuation followed one or more adverse drug reactions in 2.2% of gemifloxacin-treated patients (0.9% due to rash) and 2.1% of comparator-treated patients. A total of 63 deaths (33 receiving gemifloxacin) occurred in the trial population: none were considered related to treatment. A slight prolongation in QT interval (2.56 ms (S.D. +/-24.5)) was observed in gemifloxacin-treated patients: no cardiac arrhythmias were reported. There was a low incidence of liver function tests (LFTs) classified as of potential clinical concern: gemifloxacin (0.4-1.2%), comparators (0.2-1.3%). Serious adverse events (SAEs), occurring during but not necessarily related to therapy, occurred in 3.6% of gemifloxacin-treated patients (4.3% of comparators). SAEs related to treatment agents were rare (0.4% in each group) and included rash (0.1%) and elevated liver enzymes (<0.1%). Gemifloxacin was well tolerated by the elderly, those with renal or hepatic impairment and when co-administered with omeprazole, digoxin, theophylline, warfarin (with which there were no significant interactions) and Maalox. In conclusion, gemifloxacin 320 mg once daily demonstrated a favourable safety and tolerability profile similar to that of comparator antibiotics, including other quinolones.
吉米沙星是一种广谱喹诺酮类抗菌药物,对革兰氏阳性菌,包括多重耐药肺炎链球菌,具有增强的抗菌效力,对革兰氏阴性杆菌和对其他抗生素耐药的菌株也保持抗菌效力。它已被证明在呼吸道和泌尿道感染中特别有效。本综述展示了来自6775例临床试验患者的安全性数据,这些患者接受了推荐的每日一次口服320毫克吉米沙星剂量,或其他喹诺酮类、大环内酯类或β-内酰胺类药物的标准剂量(n = 5248)。还报告了在健康志愿者和特殊人群中的研究情况。在接受吉米沙星治疗的患者中,44.7%观察到不良事件(AE),接受对照药物治疗的患者中这一比例为47.5%。轻度胃肠道药物不良反应(ADR)(腹泻5.1%,恶心3.9%)占主导。在接受吉米沙星治疗的患者中,3.6%观察到皮疹,通常为斑丘疹,且无一例发展为更严重的皮疹。在年轻女性中观察到皮疹的发生率较高(>20%),这是进一步研究的主题。在接受吉米沙星治疗的患者中,17.4%的患者出现疑似或可能与治疗相关的药物不良反应,接受对照抗生素治疗的患者中这一比例为20%。接受吉米沙星治疗的患者中,腹泻和恶心的发生率分别为3.6%和2.7%(对照药物组分别为4.6%和3.2%),皮疹发生率为2.8%(对照药物组为0.6%),头痛发生率为1.2%(对照药物组为1.5%)。与吉米沙星相关的呕吐(0.9%)、头晕(0.8%)和味觉异常(0.3%)并不常见。在接受吉米沙星治疗的患者中,2.2%(0.9%因皮疹)的患者因一种或多种药物不良反应而停药,接受对照药物治疗的患者中这一比例为2.1%。试验人群中共有63例死亡(33例接受吉米沙星治疗):无一例被认为与治疗相关。在接受吉米沙星治疗的患者中观察到QT间期略有延长(2.56毫秒(标准差±24.5)):未报告心律失常。肝功能检查结果分类为具有潜在临床关注意义的发生率较低:吉米沙星组为(0.4 - 1.2%),对照药物组为(0.2 - 1.3%)。严重不良事件(SAE),在治疗期间发生但不一定与治疗相关,在接受吉米沙星治疗的患者中发生率为3.6%(对照药物组为4.3%)。与治疗药物相关的严重不良事件很少见(每组0.4%),包括皮疹(0.1%)和肝酶升高(<0.1%)。吉米沙星在老年人、有肾或肝功能损害的患者中,以及与奥美拉唑、地高辛、茶碱、华法林(与之无显著相互作用)和氢氧化铝镁同时使用时,耐受性良好。总之,每日一次320毫克的吉米沙星显示出与对照抗生素,包括其他喹诺酮类药物相似的良好安全性和耐受性。