P&T Portfolio: Factive

June 16, 2003

P&T Portfolio - Factive - Gemifloxacin mesylate tablets - new antibiotic.

 

HEALTH-SYSTEM EDITION

P & T PORTFOLIO

Generic name

Gemifloxacin

Proprietary name/manufacturer

Factive/GeneSoft

FDA-approved indications

Gemifloxacin is approved for the treatment of acute bacterial exacerbation of chronic bronchitis (ABECB) caused by S. pneumoniae, H. influenzae, H. parainfluenzae, or M. catarrhalis and for the treatment of mild to moderate community-acquired pneumonia (CAP) caused by S. pneumoniae (including penicillin-resistant strains), H. influenzae, M. catarrhalis, M. pneumoniae, C. pneumoniae, or K. pneumoniae.

Pharmacology

Gemifloxacin is a fluoroquinolone antimicrobial with a unique chemical structure that confers enhanced activity against gram-positive pathogens without significantly compromising gram-negative activity. Gemifloxacin exerts its bactericidal effects by inhibiting DNA synthesis through the inhibition of both DNA gyrase and topoisomerase IV, which are essential for bacterial growth. The mechanism of action of quinolones is different from that of macrolides, beta-lactams, aminoglycosides, or tetracyclines, and, therefore, microorganisms resistant to these classes of drugs may be susceptible to gemifloxacin and other quinolones.

Efficacy

Several controlled clinical trials have demonstrated the efficacy of oral gemifloxacin given once daily for the treatment of ABECB and CAP. Clinical response rates for gemifloxacin in these studies have approximated 85%-90% for both ABECB and CAP. Gemifloxacin appears to be similar in efficacy to clarithromycin, amoxicillin/clavulanate, sequential IV ceftriaxone/oral cefuroxime, trovafloxacin, and levofloxacin for the treatment of ABECB. A cost-effectiveness study showed gemifloxacin as more cost-effective compared with clarithromycin in the treatment of acute exacerbations of chronic bronchitis (AECB). For the treatment of CAP, gemifloxacin also appears to be similar in efficacy to amoxicillin/clavulanate, and trovafloxacin. Oral gemifloxacin also appears to be similar in efficacy to sequential therapy with IV ceftriaxone/oral cefuroxime in treating patients with CAP.

Warnings

• Safety and effectiveness in children, adolescents, and pregnant or lactating women have not been established.

• Gemifloxacin may prolong the QT interval. Avoid the drug in patients with a history of prolongation of the QTc interval, patients with uncorrected electrolyte disorders, and patients receiving class 1A, or class III antiarrhythmic agents.

• Serious and occasionally fatal hypersensitivity and/or anaphylactic reactions have been reported in patients receiving fluoroquinolone therapy.

• Fluoroquinolones have been shown to cause arthropathy and osteochondrosis in immature rats and dogs.

• CNS effects have been reported infrequently. Use with caution in patients with CNS diseases such as epilepsy or patients predisposed to convulsions.

Pharmacokinetics

Oral bioavailability71%
Protein binding60%-70%
Volume of distribution4.1 L/kg
MetabolismLimited metabolism by the liver to minor metabolites
ExcretionFeces (61%); urine (36%)
Half-life7 hours

 

Adverse effects

The most common adverse effects, occurring in less than 5% of patients, included: diarrhea, rash, nausea, headache, abdominal pain, vomiting, and dizziness.

Drug interactions

• Antacid containing aluminum and magnesium

• Didanosine chewable/buffered tablets or pediatric oral solution

• Iron

• Sucralfate

• Zinc

Conclusion/comments

Gemifloxacin, one of three new third-generation fluoroquinolone agents, demonstrated efficacy in the once-daily treatment of ABECB and CAP. As many as 13 million people in the United States suffer from AECB, with mortality rates in hospitalized patients as high as 30%. One-half to two-thirds of AECB episodes involve bacterial infection. In addition, there are as many as four million cases of CAP in the nation each year, and it is the leading cause of death due to infections.

 

Published June 2003. Content based on medical literature and product information available at that time.

 

 

P&T Portfolio: Factive. Drug Topics Jun. 16, 2003;147:HSE21.