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According to the studies, the rank order of phototoxic potential of fluoroquinolones is as follows: enoxacin> ciprofloxacin > norfloxacin = ofloxacin = levofloxacin = gatifloxacin = moxifloxacin 1, 2.

Based on published literature, the approximate order of fluoroquinolones in which they significantly interact with theophylline is as follows: enoxacin > ciprofloxacin > norfloxacin > ofloxacin, levofloxacin, trovafloxacin, gatifloxacin, moxifloxacin.

The side-effect profile of levofloxacin was compared with that of other fluoroquinolones based on European and international data from approximately 130 million prescriptions 12. Levofloxacin was found to be very safe with a low rate of hepatic abnormalities (1/650,000). The main CNS problems associated with fluoroquinolones include dizziness, convulsions, psychosis, and insomnia. Levofloxacin, ofloxacin, and moxifloxacin reportedly have the lowest potential of inducing central nervous system (CNS) adverse events among the fluoroquinolones currently available. Cardiovascular problems were seen in 1/15 million levofloxacin prescriptions compared to 1-3% of sparfloxacin patients having QTc prolongation of greater than 500 msec. Moxifloxacin was also associated with QTc prolongation when compared to non-fluoroquinolone comparators. Nausea, vomiting, and diarrhoea remain the main adverse drug reactions associated with levofloxacin. However, the ADR rate for levofloxacin is still one of the lowest of any fluoroquinolone at 2% (compared to 2-10% for other fluoroquinolones). The tolerance profile of levofloxacin can be considered to be very good, and better than most, if not all of the fluoroquinolones available.

• Skin and Skin Structure Infections:
  Among 253 patients (129 levofloxacin, 124 ciprofloxacin), clinical success (cure and improvement) was observed in 96.1% of levofloxacin-treated patients and in 93.5% of ciprofloxacin-treated patients. Bacteriological eradication rates by pathogen were 93.2% and 91.7%, respectively. Levofloxacin eradicated 94% (66/70) of Staphylococcus aureus and 94% (17/18) of Streptococcus pyogenes isolates, compared with 93% (70/75) and 92% (12/13) for ciprofloxacin. Microbiological eradication rates by subject were approximately 93% and 90% for the levofloxacin and ciprofloxacin groups, respectively. Drug-related adverse events were reported by 8.9% of those receiving levofloxacin and 8.2% of those administered ciprofloxacin 10.
• Acute Pyelonephritis, Urinary tract infections (UTI):
  Levofloxacin 750 mg once daily for 5 days is at least as effective as ciprofloxacin 400 mg or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis 13.
  In the modified intent-to-treat (mITT) population (levofloxacin 94, ciprofloxacin 98), 83% of levofloxacin-treated and 79.6% of ciprofloxacin-treated subjects achieved microbiological eradication (difference 3.4, 95% CI 14.4%, 7.6%). In the microbiologically evaluable (ME) population (levofloxacin 80, ciprofloxacin 76), 92.5% of levofloxacin-treated vs. 93.4% of ciprofloxacin-treated subjects (difference 0.9, 95% CI 7.1%, 8.9%) achieved microbiologic eradication. Clinical success was achieved in 86.2% vs. 80.6% (mITT) and in 92.5% vs. 89.5% (ME) of levofloxacin-treated and ciprofloxacin-treated subjects, respectively. Escherichia coli was the most commonly isolated uropathogen. Few (2.1%) of the pathogens were fluoroquinolone-resistant. Adverse events (AEs) were similar to those seen previously with both agents. Potential limitations are that this analysis is based on a subset of subjects from a larger study and, because of different durations of therapy, the results may be biased against levofloxacin.
• Chronic bacterial prostatitis:
  Levofloxacin 500 mg once daily for 28 days is as effective as ciprofloxacin 500 mg twice daily for 28 days for the treatment of chronic bacterial prostatitis. The clinical success rates, including cured plus improved patients, were similar (75% for levofloxacin and 72.8% for ciprofloxacin). Microbiologic eradication rates were 75% for levofloxacin and 76.8% for ciprofloxacin 5.

• Urinary Tract Infections:
  Once-daily levofloxacin is as effective as and has a superior tolerability profile than lomefloxacin in the treatment of complicated UTIs 11.
  Microbiologic eradication rate of pathogens was 95.5% for levofloxacin and 91.7% for lomefloxacin. At the 5 to 9-day post-therapy visit, symptoms were completely resolved in 84.8% of levofloxacin-treated patients and were decreased in 8.2% (93.0% clinical success). Among the lomefloxacin-treated patients, complete resolution was seen in 82.4%, with decreased symptoms in 6.1% (88.5% clinical success). Side effects were reported by 10 (2.6%) and 18 (5.2%) levofloxacin- and lomefloxacin-treated patients, respectively. Compared with levofloxacin-treated patients, more lomefloxacin-treated patients experienced photosensitivity reactions and dizziness. Nausea was more frequent in the levofloxacin-treated group. Six patients in each treatment group had a gastrointestinal side effects (1.7%); rash was reported more frequently with lomefloxacin than with levofloxacin. Discontinuation because of side effects was occured in 8 (3.4%) levofloxacin- and 14 (6.1%) lomefloxacin-treated patients.
• Acute Pyelonephritis:
  Predominant organism was E. coli Eradication rates similar 95%(Le) 95%(Lo) Relapse rates were similar Clinical cure (microbiologic and clinical success) rates 92%(Le) 80%(Lo) Rates of clinical success (cure plus improvement) were similar Adverse events 2%(Le) 5%(Lo) 9

• Bacterial exacerbation of chronic obstructive pulmonary disease (COPD).
  In the study levofloxacin and clarithromycin showed similar exacerbation-free intervals. The bacteriological eradication rate was significantly higher with the levofloxacin treatment 4.
• Community-acquired pneumonia:
  Clarithromycin ER has equivalent efficacy and tolerability to the levofloxacin in the treatment of community-acquired pneumonia 7.
  Of 299 patients randomized and treated, 252 were clinically evaluable (128 clarithromycin ER, 124 levofloxacin). Clinical cure rates were 88% (113/128) and 86% (107/124), and radiographic success rates were 95% (117/123) and 88% (104/118) for clarithromycin ER and levofloxacin, respectively. Both treatment regimens were effective in resolving and improving clinical signs and symptoms of CAP. Bacteriologic cure rates were 86% (80/93) and 88% (85/97) for clarithromycin ER and levofloxacin, respectively.
• Acute sinusitis:
  The study showed that, in the treatment of acute sinusitis, daily levofloxacin therapy is as effective as twice-daily clarithromycin therapy with more complete clearing of symptoms and a more tolerable side-effect profile 8.
  The proportion of cured patients was higher in the levofloxacin (40.8%) than in the clarithromycin group (29.0%). Of patients receiving levofloxacin and clarithromycin, 22.5% and 39.3%, respectively, experienced adverse events related or possibly related to the study therapy.

• Acute bacterial exacerbations of chronic bronchitis.
  Standard 5-day course of oral azithromycin was clinically and bacteriologically equivalent to a 7-day course of oral levofloxacin in the treatment of ABECB. Favorable results were demonstrated in 89% of patients receiving azithromycin and in 92% of patients receiving levofloxacin by day 4 of therapy. At day 24 favorable responses were approximately 82% and 86%, respectively. The bacterial eradication rates of respiratory pathogens were 96% for azithromycin and 85% for levofloxacin 6. Both treatments are well-tolerated, with the majority of adverse events being GI in nature.
• Community-acquired pneumonia:
  A single 2 g dose of azithromycin microspheres is at least as effective as a 7-day course of levofloxacin in the treatment of mild to moderate community-acquired pneumonia 16.
  The cure rates were 89.7% for azithromycin microspheres and 93.7% for levofloxacin. Bacteriologic success at test of cure in the "bacteriologic per protocol" population was 90.7% for azithromycin microspheres and 92.3% for levofloxacin. Both medications were well tolerated. The incidence of side effects was 19.9% for azithromycin and 12.3% for levofloxacin.
• Sinusitis:
  Single 2 g dose azithromycin microspheres has efficacy comparable to 10 days of levofloxacin in the treatment of acute bacterial sinusitis 17.
  Clinical success rates were 94.5% with azithromycin-microspheres and 92.8% with levofloxacin. In patients with Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, clinical cure rates were 97.3%, 96.3%, and 100%, respectively, for the azithromycin and 92.3%, 100%), and 90.9%, respectively, for the levofloxacin.

• Acute bacterial exacerbations of chronic bronchitis (ABECB):
  The clinical response was rated a success, with the patient cured or improved in 94.6% of those receiving levofloxacin and 92.6% of the cefuroxime axetil group. All of the symptoms of bronchitis were resolved in more than 86% of the patients, with the exception of shortness of breath, which resolved in 69.7% of levofloxacin-treated and 72.4% of cefuroxime axetil-treated patients. Resolution or improvement of abnormalities on thoracic auscultation were noted in 85% or more of patients, with the exception of diminished breath sounds, which were resolved or improved in 62.5% of levofloxacin-treated and 55.2% of cefuroxime axetil-treated patients 3.
• Community-acquired pneumonia:
  Levofloxacin is superior to ceftriaxone and/or cefuroxime axetil in the treatment of community-acquired pneumonia 14.
  Clinical success was higher with levofloxacin treatment (96%) compared with the ceftriaxone and/or cefuroxime axetil (90%). In patients with typical respiratory pathogens the bacteriologic eradication rates were higher with levofloxacin (98%) compared with the ceftriaxone and/or cefuroxime axetil (85%). Levofloxacin eradicated 100% of the most frequently reported respiratory pathogens (i.e., H. influenzae and S. pneumoniae) and provided a >98% clinical success rate in patients with atypical pathogens. Side effects were reported in 5.8% of patients receiving levofloxacin and in 8.5% of patients receiving ceftriaxone and/or cefuroxime axetil. Gastrointestinal and central and peripheral nervous system adverse events were the most common events reported with each treatment.
• Sinusitis:
  Levofloxacin is more effective than cefuroxime for the treatment of sinusitis 15.
  In the study the treatment success rates were 97.4% for patients who received levofloxacin and 92.8% for patients who received cefuroxime. The resolution rates of bacteria were 91.6% and 80.0%, respectively.

• Rhinosinusitis:
  Cefdinir is effective as the levofloxacin in the treatment of acute rhinosinusitis 17.
  Clinical cure rate at the test-of-cure visit in the cefdinir group was 83% and in the levofloxacin group 86%. Cefdinir and levofloxacin were comparable in the treatment of moderate to severe infections. The incidence of drug side effects was generally comparable in the 2 treatment groups, although there were significant differences between cefdinir and levofloxacin in the incidence of vaginal moniliasis in women (11% vs 0%), diarrhea (8% vs 1%), and insomnia (0% vs 4%).

• Levofloxacin (Levaquin) Medical Facts

• 1. Hooper DC. Pharmacology of the fluroquinolones. Up to Date. March 2, 2000.
• 2. Lipsky BA, Baker CA. Fluroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis 1999;28:352-364.
• 3. Petitpretz P, Chone' C, Tre'molie`res F; Investigator Study Group. Levofloxacin 500 mg once daily versus cefuroxime 250 mg twice daily in patients with acute exacerbations of chronic obstructive bronchitis: clinical efficacy and exacerbation-free interval. Int J Antimicrob Agents. 2007 Jul;30(1):52-9. Epub 2007 May 18. PubMed
• 4. Lode H, Eller J, Linnhoff A, Ioanas M; Evaluation of Therapy-Free Interval in COPD Patients Study Group. Levofloxacin versus clarithromycin in COPD exacerbation: focus on exacerbation-free interval. Eur Respir J. 2004 Dec;24(6):947-53. PubMed
• 5. Bundrick W, Heron SP, Ray P, Schiff WM, Tennenberg AM, Wiesinger BA, Wright PA, Wu SC, Zadeikis N, Kahn JB. Levofloxacin versus ciprofloxacin in the treatment of chronic bacterial prostatitis: a randomized double-blind multicenter study. Urology. 2003 Sep;62(3):537-41. PubMed
• 6. Amsden GW, Baird IM, Simon S, Treadway G. Efficacy and safety of azithromycin vs levofloxacin in the outpatient treatment of acute bacterial exacerbations of chronic bronchitis. Chest. 2003 Mar;123(3):772-7. PubMed
• 7. Gotfried MH, Dattani D, Riffer E, Devcich KJ, Busman TA, Notario GF, Palmer RN. A controlled, double-blind, multicenter study comparing clarithromycin extended-release tablets and levofloxacin tablets in the treatment of community-acquired pneumonia. Clin Ther. 2002 May;24(5):736-51. PubMed
• 8. Lasko B, Lau CY, Saint-Pierre C, Reddington JL, Martel A, Anstey RJ. Efficacy and safety of oral levofloxacin compared with clarithromycin in the treatment of acute sinusitis in adults: a multicentre, double-blind, randomized study. The Canadian Sinusitis Study Group. J Int Med Res. 1998 Dec;26(6):281-91. PubMed
• 9. Richard GA, Klimberg IN, Fowler CL, Callery-D'Amico S, Kim SS. Levofloxacin versus ciprofloxacin versus lomefloxacin in acute pyelonephritis. Urology. 1998 Jul;52(1):51-5. PubMed
• 10. Nicodemo AC, Robledo JA, Jasovich A, Neto W. A multicentre, double-blind, randomised study comparing the efficacy and safety of oral levofloxacin versus ciprofloxacin in the treatment of uncomplicated skin and skin structure infections. Int J Clin Pract. 1998 Mar;52(2):69-74. PubMed
• 11. Klimberg IW, Cox CE 2nd, Fowler CL, King W, Kim SS, Callery-D'Amico S.A controlled trial of levofloxacin and lomefloxacin in the treatment of complicated urinary tract infection. Urology. 1998 Apr;51(4):610-5. PubMed
• 12. Carbon C. Comparison of side effects of levofloxacin versus other fluoroquinolones. Chemotherapy. 2001;47 Suppl 3:9-14; discussion 44-8. PubMed
• 13. Klausner HA, Brown P, Peterson J, Kaul S, Khashab M, Fisher AC, Kahn JB. A trial of levofloxacin 750 mg once daily for 5 days versus ciprofloxacin 400 mg and/or 500 mg twice daily for 10 days in the treatment of acute pyelonephritis. Curr Med Res Opin. 2007 Sep 18. PubMed
• 14. File TM Jr, Segreti J, Dunbar L, Player R, Kohler R, Williams RR, Kojak C, Rubin A. A multicenter, randomized study comparing the efficacy and safety of intravenous and/or oral levofloxacin versus ceftriaxone and/or cefuroxime axetil in treatment of adults with community-acquired pneumonia. Antimicrob Agents Chemother. 1997 Sep;41(9):1965-72. PubMed
• 15. Li XP, Qin ZM, Zheng RH, Tan QL, Zhou YY, Zhu L, Yin AF. Comparison of the effectiveness of levofloxacin and cefuroxime for the treatment of sinusitis. PubMed
• 16. D'Ignazio J, Camere MA, Lewis DE, Jorgensen D, Breen JD. Novel, single-dose microsphere formulation of azithromycin versus 7-day levofloxacin therapy for treatment of mild to moderate community-acquired Pneumonia in adults. Antimicrob Agents Chemother. 2005 Oct;49(10):4035-41. PubMed
• 17. Henry DC, Kapral D, Busman TA, Paris MM. Cefdinir versus levofloxacin in patients with acute rhinosinusitis of presumed bacterial etiology: a multicenter, randomized, double-blind study. Clin Ther. 2004 Dec;26(12):2026-33. PubMed