Moxifloxacin Tablets (Avelox-Bayer)

By William T. Elliott, MD, FACP, and James Chan, PharmD, PhD

In december 1999, the fda approved moxifloxacin, a new, once-daily quinolone for the treatment of respiratory tract infections. The new antibacterial agent will be marketed by the Bayer Corporation as Avelox. Moxifloxacin is a 8-methoxyfluoroquinolone with antibacterial activity against gram-positive, gram-negative, and anaerobic bacteria with good activity against common respiratory pathogens such as Streptococcus pneumoniae, Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae, and Moraxella catarrhalis.

Indications

Moxifloxacin is approved for the treatment of adults (³ 18 years of age) with the following infections caused by susceptible strains of microorganisms:1 acute bacterial sinusitis caused by S. pneumoniae, H. influenzae, or M. catarrhalis; acute bacterial exacerbation of chronic bronchitis caused by S. pneumoniae, H. influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Staphylococcus aureus, or M. catarrhalis; community-acquired pneumonia (mild to moderate severity) caused by S. pneumoniae, H. influenzae, M. pneumoniae, C. pneumoniae, or M. catarrhalis.

Dosage

The recommended dose is 400 mg once daily. The duration is five days for acute bacterial exacerbation of chronic bronchitis and 10 days for acute bacterial sinusitis and community-acquired pneumoniae. The tablets may be taken with a liberal amount of fluid without regard to meals. The dose should be taken at least four hours before or eight hours after antacids (magnesium or aluminum based), sucralfate, didanosine buffered tablets or pediatric powder, and metal cations such as iron and zinc, including multivitamins.1

Dosage adjustment is not necessary in patients with renal insufficiency. However, moxifloxacin is not recommended in patients with moderate or severe hepatic insufficiency.1

Potential Advantages

In vitro data suggest that moxifloxacin is more active than sparfloxacin, levofloxacin, and ofloxacin against S. pneumoniae with intermediate resistance to penicillin.2 These isolates were selected from blood cultures of patients with pneumococcal pneumonia. The MIC90 (0.25 mg/L) was one dilution lower than sparfloxacin, three dilutions lower than levofloxacin, and four dilutions slower than ofloxacin. As with other fluoroquinolones, moxifloxacin achieves good tissue levels. Concentrations three hours post-dose in respiratory tissue (e.g., bronchial mucosa, epithelial lining, alveolar macrophages) and sinus mucosa average at least 1.7 (range, 1.7-21.1) times that of plasma concentrations.1 Gram-positive microorganisms resistant to other fluoroquinolones may be susceptible to moxifloxacin.1 Moxifloxacin is approved for a five-day course for the acute exacerbation of chronic bronchitis compared to 7-10 days for other regimens.

Potential Disadvantages

Moxifloxacin has been reported to prolong the QT interval. The effect may increase with increasing concentration.1 In clinical trials, the mean prolongation of QTc was 6 ± 26 msec. The drug should be avoided in patients receiving Class 1A or III antiarrhythmics, patients with proarrhythmic conditions, or patients taking drugs which can prolong QT intervals (e.g., erythromycin, cisapride).

Common side effects related to moxifloxacin include nausea (8%), diarrhea (6%), dizziness (3%), and headache, abdominal pain, and vomiting each at 2%.1

Comments

Moxifloxacin is a new 8-methoxyfluoroquinolone with a broad spectrum of activity including gram-negative and gram-positive anaerobes.4,5 It is particularly effective against common respiratory pathogens including resistant S. pneumoniae. The efficacy and safety of moxifloxacin in these infections were based on several randomized, controlled, double-blind, comparative trials. Moxifloxacin (400 mg daily for 5 days) was compared to clarithromycin (500 mg twice daily for 10 days) for the treatment of acute bacterial exacerbation of chronic bronchitis and (400 mg daily for 10 days) in clinically and radiologically documented community-acquired pneumonia.1 In the chronic bronchitis trial, clinical success was comparable at 7-17 days post-therapy, 89% (n = 501). Similar results were reported for community pneumonia, 95% clinical success for moxifloxacin and clarithromycin (n = 382), and 89% for moxifloxacin compared to amoxicillin (1 g three times daily) (n = 362).1,5 In a multinational study (n = 649), moxifloxacin (400 mg for 5 days) was comparable to clarithromycin (500 mg for 7 days) in acute exacerbation of chronic bronchitis, although bacteriological success favored moxifloxacin.3 However, bacteriological success was assessed in only 35% of the clinically evaluable patients. In the treatment of acute bacterial sinusitis, moxifloxacin (400 mg for 10 days) and cefuroxime axetil (250 mg twice daily for 10 days) were found to be comparable in clinical cure assessed 7-14 days post-therapy, 90% vs. 89%.6

Moxifloxacin is priced at $44 for a five-day course or $87 for a 10-day course.

Clinical Implications

Several new quinolones have been introduced to the market as "ideal agents" to treat various respiratory tract infections with particular focus activity against drug-resistant S. pneumoniae. Moxifloxacin is the fifth quinolone to be approved for treating various respiratory tract infections (others being levofloxacin, sparfloxacin, grepafloxacin, and trovafloxacin, with gatifloxacin to follow). None of the older agents has emerged as the "ideal agent." Sparfloxacin has been associated with photosensitivity and prolongation of QT intervals. Glaxo Wellcome has voluntarily withdrawn grepafloxacin from the market due to increased risk of torsade de pointes. The FDA has issued a health advisory to physicians concerning the risk of severe liver toxicity due to trovafloxacin. Levofloxacin, which may be less active against S. pneumoniae, is not associated with these toxicities and is recommended by some experts as a good choice for older patients with underlying disease.9 Moxifloxacin carries the potential to prolong QT intervals, which will bear close watching.

Fluoroquinolones should be prescribed prudently. They should not be prescribed for respiratory syndromes when an antibiotic is not appropriate or in infections where other classes of antibiotics are more appropriate. The increased prevalence of S. pneumoniae with reduced susceptibility to fluoroquinolones has been seen in Canada as well as in other countries.7,8

References

1. Avelox Product Information. Bayer Corporation. December 1999.

2. Reinert RR, et al. J Antimicrob Chemother 1998; 42(6):803-806.

3. Wilson R, et al. J Antimicrob Chemother 1999;44(4): 501-513.

4. Dalhoff A, et al. Chemotherapy 1996;42(6):410-425.

5. Balfone JA, et al. Drugs 1999;57(3):363-373.

6. Burke T, et al. Clin Ther 1999;21(10):1664-1677.

7. Chen DK, et al. N Engl J Med 1999;341(4):233-239.

8. Linares J, et al. N Engl J Med 1999;341(4):1546-1547.

9. Anonymous. The Medical Letter 1999;41(1064):95-104.