Pharmacology Update

Gatifloxacin Tablets and Injection (Tequin, Bristol-Myers Squibb)

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

A new extended spectrum fluoroquinolone antibiotic has been approved by the FDA. Bristol-Myers Squibb’s gatifloxacin (Tequin) is an 8-methoxyfluoroquinolone similar to moxifloxacin (Avelox). Gatifloxacin has activity against gram-positive, gram-negative, and atypical pathogens and is available in both oral and parenteral forms. The drug has a wide range of indications including upper and lower respiratory tract infections and urinary tract infections (UTIs).

Indications

Gatifloxacin is approved for the treatment of adults with the following infections caused by susceptible strains of microorganisms:1 acute bacterial exacerbation of chronic bronchitis due to Streptococcus pneumoniae, Haemophilus influenzae, H. parainfluenzae, Moraxella catarrhalis, or Staphylococcus aureus; acute sinusitis due to S. pneumoniae or H. influenzae; community-acquired pneumonia due to S. pneumoniae, H. influenzae, H. parainfluenzae, M. catarrhalis, S. aureus, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Legionella pneumophilia; uncomplicated or complicated UTIs due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis; pyelonephritis due to E. coli; and uncomplicated urethral gonococcal infections in men or cervical gonorrhea or acute, uncomplicated, rectal infections in women due to Neisseria gonorrhoeae.

Dosage

The recommended daily dose of gatifloxacin is 400 mg once a day for 7-10 days for acute bacterial exacerbation of chronic bronchitis, complicated infectious UTIs, and acute pyelonephritis. The duration of therapy is 7-14 days for community-acquired pneumonia, and 10 days for acute sinusitis. For uncomplicated UTIs (e.g., cystitis) or uncomplicated urethral gonorrhea in men or endocervical or rectal gonorrhea in women the dose is 400 mg as a single dose.1 For uncomplicated UTIs, 200 mg daily for three days is an alternative regimen.

Gatifloxacin may be taken without regard to food including milk and dietary supplements containing calcium.1 However, it should be taken at least four hours before products containing iron, zinc, or magnesium. These include antacids, multivitamins, and buffered products such as Videx.1,4

The absolute bioavailability of gatifloxacin is 96% and the oral and intravenous forms are interchangeable on a milligram basis. The injection should be administered by intravenous infusion only.1

In patients with impaired renal function (creatinine clearance < 40 mL/min) the initial dose should be 400 mg followed by 200 mg daily. Single-dose regimens do not need to be reduced.1

Gatifloxacin is marketed as 200-mg and 400-mg tablets and 200-mg (10 mg/mL, 20 mL) and 400-mg (10 mg/mL, 40 mL) single-use vials.

The drug is not for use in children younger than age 18.

Potential Advantages

In vitro studies indicate that gatifloxacin is more active against S. pneumoniae compared to levofloxacin. As with other quinolones, the MICs are not affected by susceptibility to penicillin.2 Gatifloxacin is highly selective in the inhibition of bacterial topoisomerases and has low activity against mammalian topoisomerase.5

Potential Disadvantages

Gatifloxacin is less active than ciprofloxacin against Pseudomonas species.3 Gatifloxacin may prolong the QTc interval in some patients. In normal volunteers (n = 55) the mean change in QTc was 2.9 ± 16.5 msec.1 It should be avoided in patients at risk for prolongation of QTc such as those taking class IA and III antiarrhythmics or drugs that may have the potential to prolong QTc (e.g., erythromycin, cisapride, antipsychotics, tricyclic antidepressants).1 Most common side effects include nausea (8%), diarrhea (4%), headache (4%), and dizziness (3%).3

Comments

Gatifloxacin is a new extended-spectrum fluoroquinolone with activity against gram-positive and gram-negative pathogens and anaerobes. It is slightly less active than ciprofloxacin against Enteriobacteriaceae, and less active than ciprofloxacin against P. aeruginosa.3 Gatifloxacin penetrates well into respiratory and reproductive tissue with the tissue/serum ratio of 1 or greater1,3 and has a negligible effect on P450 isoenzymes (CYP) and apparent low potential for phototoxicity. Comparative clinical trials have not been published in detail, but are available in abstract form.3 These limited data suggest that gatifloxacin (400 mg daily for 7-14 days) is similar to clarithromycin (500 mg twice daily for 7-14 days) in the clinical cure of community-acquired pneumonia (95% vs 93%). In acute maxillary sinusitis clinical cure was similar to clarithromycin (93% vs 90%). As a single dose of 400 mg or 200 mg/day for three days, the clinical cure rate is similar to ciprofloxacin (100 mg twice daily for 3 days) in uncomplicated UTI (93% vs 95% vs 93%). In the treatment of gonorrhea, gatifloxacin (400 mg as a single dose), bacterial eradication was similar to ofloxacin (400 mg as a single dose) (³ 99%). In a subset analysis, gatifloxacin (400 mg daily for 7-10 days) was reported to be more efficacious (i.e., clinical cure) than cefuroxime axetil (250 mg twice daily for 7-10 days) in the treatment of acute exacerbation of chronic bronchitis (89% vs 77%).3

Gatifloxacin 400 mg daily cost about $7 or $70 for a 10-day regimen.

Clinical Implications

Gatifloxacin is the sixth and most recent fluoroquinolone to be approved for respiratory tract infections, joining levofloxacin, sparfloxacin, grepafloxacin, trovafloxacin, and moxifloxacin. Grepafloxacin has been withdrawn from the market while trovafloxacin has been associated with liver toxicity and sparfloxacin with phototoxicity. Prolongation of the QT interval has become a class warning although the FDA concedes that the effect may vary with different agents.6 It is not clear if one of the newer 8-methoxyfluoroquinolones would emerge as an ideal "respiratory" quinolone replacing levofloxacin, which has the most clinical experience. Levofloxacin recently gained FDA approval for the treatment of penicillin-resistant S. pneumoniae in patients with community-acquired pneumonia.

These quinolones should be prescribed prudently in order to prevent development of resistant strains of bacteria. Evidence of S. pneumonia with reduced susceptibility to fluoroquinolones has already been reported.7,8

References

1. Tequin Product Information. Bristol-Myers Squibb. December 1999.

2. Blondeau JM. J Antimicrob Chemother 1999;43(suppl B):1-11.

3. Perry CM, et al. Drugs 1999;58(4):683-696.

4. Lober S, et al. Antimicrob Agents Chemother 1999; 43:1067-1071.

5. Takei M, et al. Antimicrob Agents Chemother 1998; 42:2678-2681.

6. F-D-C Reports. The Green Sheet 2000;49(7):2.

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.

Which is not true about gatifloxacin?

a. It is dosed twice a day.

b. It is available in both oral and parenteral forms.

c. It can be given as a single dose for uncomplicated UTIs and gonorrhea.

d. It is approved for the treatment of community-acquired pneumonia caused by penicillin-resistant S. pneumoniae.