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Pharmacology Update: Gemifloxacin Tablets (Factive—Gensoft Pharmaceuticals)
By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD
Another fluoroquinolone has been added to the list of antibacterial agents for respiratory tract infections. Gemifloxacin is a broad-spectrum agent that is highly active against the most common respiratory pathogens, including penicillin and macrolide resistant Streptococcus pneumoniae. It is marketed by Gensoft as "Factive."
Gemifloxacin is indicated for the treatment of acute bacterial exacerbation of chronic bronchitis (AECB) caused by S pneumoniae, Haemophilus influenzae, H parainfluenzae, or Moraxella catarrhalis and community acquired pneumonia (of mild-to-moderate severity) caused by S pneumoniae (including penicillin-resistant strains), H influenzae, M catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumonia.1
The recommended dose is 320 mg once daily for 5 days for acute exacerbation of chronic bronchitis and 320 mg once daily for 7 days for mild-to-moderately severe community acquired pneumonia. The dose should be 160 mg daily for patient with renal dysfunction (creatinine clearance < 40 mL/min). No dosage adjustment is required in patients with hepatic dysfunction.1
Gemifloxacin may be taken without regard to meals and should be swallowed whole with a liberal amount of water.1
Gemifloxacin is supplied as 320-mg tablets.
Gemifloxacin is highly active against common respiratory pathogens. Its in vitro activity is superior to levofloxacin against S pneumoniae, against penicillin-resistant and penicillin-intermediate S pneumoniae and erythromycin-resistant S pneumoniae.2,3 Gemifloxacin is also highly active against both beta lactamase positive and negative H influenzae and M catarrhalis as well as atypical pathogens such as Legionella pneumophilia, M pneumoniae, and C pneumonia.2 Overall gemifloxacin is most active among the respiratory quinolones (eg, moxifloxacin, gatifloxacin, and levofloxacin) against S pneumoniae, H influenzae, and M catarrhalis.4 Gemifloxacin produces high drug concentrations (2-90 times that of the plasma) in bronchial mucus, epithelial lung fluid, and bronchoalveolar macrophages.1 Gemifloxacin provides high drug concentration relative to its minimum inhibitory concentration (ie, high area under the inhibition curve [AUIC] and high Cmax/MIC ratio) and is one of the highest among respiratory quinolones.5
Gemifloxacin may prolong the QT interval in some patients. It should be avoided in patients with a history of QTc interval prolongation, electrolyte abnormalities, and patients taking drugs that may prolong the QT interval.1 In clinical trials, the incidence of rash was higher in gemifloxacin patients than with comparators (eg, clarithromycin, amoxicillin/clavulanate) (2.8% vs 0.6%).1 Common sides effects include diarrhea, nausea, headache, vomiting, stomach pain, dizziness, and taste alteration.1 Gemifloxacin is indicated for mild-to-moderate community acquired pneumonia only.
Gemifloxacin is the latest entry into a previous crowded field of quinolones for respiratory infections. These include gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sparfloxacin, and trovafloxacin.
Gemifloxacin has excellent in vitro activity against common respiratory pathogens. In comparative studies (n = 1391), gemifloxacin for 5 days was found to be comparable to clarithromycin, amoxicillin/clavulanate, or levofloxacin for 7 days in clinical success in the treatment of acute bacterial exacerbation of chronic bronchitis. The clinical end point was assessed from day 13 to 24. Clinical cure ranged from 86-93.6% for gemifloxacin and 84.5-93.2% for the comparators. Gemifloxacin for 7 days was found to be comparable to amoxicillin/clavulanate for 10 days in treating community acquired pneumonia (n = 228), 88.7% and 87.6%, respectively.1 In a long-term follow-up (26 weeks) study in patients with AECB (n = 438), the percent of patients without recurrence was 71% for gemifloxacin (320 mg daily x 5 days) compared to 58.5% for clarithromycin (500 mg twice daily x 7 days) (P = 0.16).6 This is attributed to superior bacterial eradication. In a study involving hospitalized patients with mild-to-moderate acute exacerbation of chronic bronchitis, gemifloxacin (320 mg x 5 days) was reported to be comparable to sequential ceftriaxone (1 g daily up to 3 days) and oral cefuroxime (500 mg twice daily for 7 days) in clinical and bacteriological success, which may result in earlier discharge.7 Similar efficacy was reported in patients with community acquired pneumonia.8 Gemifloxacin is generally well tolerated with similar side effects and drug interactions to other fluoroquinolones. The cost of gemifloxacin was not available at the time of this review.
Gemifloxacin is the latest addition to the respiratory quinolones. It is highly active against common respiratory pathogens. The once crowded field of respiratory quinolones has been characterized by a variety of flaws. Sparfloxacin has been associated with phototoxicity, grepafloxacin with prolonged QT interval, and trovafloxacin with hepatotoxicity. While gemifloxacin may be more active in vitro than other quinolones, clinical advantage over other quinolones has not been demonstrated. Gemifloxacin should be used prudently and reserved for infections caused by susceptible microorganisms resistant to more narrow spectrum antimicrobial agents to minimize the development of resistance.
Dr. Elliott is Chair, Formulary Committee, Northern California Kaiser Permanente and Asst. Clinical Professor of Medicine, University of California-San Francisco. Dr. Chan is Pharmacy Quality and Outcomes Manager, Kaiser Permanente, Oakland, CA.
1. Factive Product Information. Gensoft Pharmaceuticals. April 2003.
2. Garcia-Garrote F, et al. J Antimicrob Chemother. 2001;47:681-4.
3. Lowe MN, Lamb HM. Drugs. 2000;59(5): 1137-1147.
4. Koeth LM, et al. Int J Antimicrob Agents. 2002;19(1):33-37.
5. Wise R. J Antimicrob Chemother. 2003;51(suppl 1): 37-42.
6. Wilson R, et al. Clin Ther. 2002;24(4):639-652.
7. Wilson R, et al. Respir Med. 2003;97(3):242-249.
8. Lode H, et al. Clin Ther. 2002;24(11):1915-1936.