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Gemifloxacin Mesylate

Gemifloxacin (C18H20FN5O4 CH4O3S), a naphthyridine derivative, is a synthetic fluoroquinolone anti-infective agent.

Uses

Respiratory Tract Infections

Acute Bacterial Exacerbation of Chronic Bronchitis

Gemifloxacin is used for the treatment of acute bacterial exacerbation of chronic bronchitis caused by susceptible strains of Streptococcus pneumoniae, Haemophilus influenzae, H. parainfluenzae, or Moraxella catarrhalis. In several randomized, double-blind, active-controlled studies in patients with acute exacerbation of chronic bronchitis, clinical response (defined as sufficient improvement in or resolution of signs and symptoms at day 13-24 without further need for anti-infectives) was achieved in 86-94% of those receiving oral gemifloxacin (320 mg once daily for 5 days) and in 93, 85, or 85% of those receiving oral amoxicillin and clavulanate potassium (500 mg of amoxicillin 3 times daily for 7 days), oral clarithromycin (500 mg twice daily for 7 days), or oral levofloxacin (500 mg once daily for 7 days), respectively.

Community-Acquired Pneumonia

Gemifloxacin is used for the treatment of community-acquired pneumonia (CAP) of mild to moderate severity caused by S. pneumoniae (including multidrug-resistant strains), H. influenzae, M. catarrhalis, Mycoplasma pneumoniae, Chlamydia pneumoniae, or Klebsiella pneumoniae.

In several controlled and uncontrolled studies in patients with clinically and radiographically documented CAP, clinical response was achieved in 89-92% of patients receiving oral gemifloxacin (320 mg once daily) for 7 days. In 22 patients with CAP caused by multidrug-resistant S. pneumoniae, clinical and bacteriologic response was achieved in 87% of patients receiving a 7-day regimen of the drug.

The rate of clinical response reported with oral gemifloxacin (320 mg once daily for 7-14 days) was similar to that reported with oral amoxicillin and clavulanate potassium (500 mg of amoxicillin 3 times daily for 10 days) or oral trovafloxacin (200 mg once daily for 7-14 days).

In studies evaluating a 7-day regimen of oral gemifloxacin in patients with mild to moderate CAP, the bacterial eradication rate was 88% in those with S. pneumoniae infection, 86% in those with H. influenzae, 100% in those with M. catarrhalis, and 93-96% in those with C. pneumoniae or M. pneumoniae infection. In 22 patients with CAP caused by multidrug-resistant S. pneumoniae, the bacterial eradication rate was 100% in those with isolates resistant to penicillin, second generation cephalosporins, or co-trimoxazole; 84% in those with isolates resistant to macrolides (i.e., clarithromycin, erythromycin); and 81% in those with isolates resistant to tetracycline. In 13 patients with infections caused by K. pneumoniae, the bacterial eradication rate was 85% and there were at least 2 reports of clinical failure (one had bacteriologic recurrence) in patients with mild CAP caused by this gram-negative bacteria.

Some clinicians, including the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA), suggest that fluoroquinolones with enhanced activity against S. pneumoniae (e.g., gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin) are drugs of choice for the treatment of CAP in adults.

However, there is disagreement over the role of these drugs in the outpatient treatment of CAP. The IDSA recommends monotherapy with these oral fluoroquinolones as one of several possible regimens for empiric outpatient treatment of acute CAP in immunocompetent adults, but the ATS suggests that these agents not be used for outpatient treatment of CAP in immunocompetent adults without cardiopulmonary disease or other modifying factors that would increase the risk of multidrug-resistant S. pneumoniae.

To limit emergence of fluoroquinolone-resistant strains, the US Centers for Disease Control and Prevention (CDC) suggests that use of these oral fluoroquinolones in the outpatient treatment of CAP be reserved for when other anti-infectives are ineffective or cannot be used or when highly penicillin-resistant S. pneumoniae (penicillin MIC greater than or equal to 2 mcg/mL) are identified as the cause of infection. For further information on treatment of CAP.

Gemifloxacin

Dosage and Administration

Administration

Gemifloxacin is administered orally once daily without regard to meals. Gemifloxacin tablets should be swallowed intact with copious amounts (i.e., at least 100 mL) of liquid and should not be chewed, crushed, or broken. Gemifloxacin should be administered at least 2 hours before or 3 hours after aluminum- or magnesium-containing antacids; dietary supplements containing metal cations such as zinc or iron (e.g., multivitamins, ferrous sulfate); or buffered didanosine preparations. These drugs may substantially interfere with the absorption of gemifloxacin, resulting in systemic concentrations considerably lower than desired.

General Dosage

Dosage of gemifloxacin mesylate is expressed in terms of gemifloxacin. Dosage and duration of gemifloxacin therapy, particularly in patients with renal or hepatic impairment, should not exceed those recommended by the manufacturer.

Respiratory Tract Infections

For the treatment of acute bacterial exacerbation of chronic bronchitis or community-acquired pneumonia (CAP), the usual adult dosage of gemifloxacin is 320 mg once daily. The usual duration of therapy is 5 days for the treatment of acute bacterial exacerbation of chronic bronchitis or 7 days for CAP.

Special Populations

Dosage of gemifloxacin should be reduced in patients with creatinine clearance of 40 mL/minute or less, including patients on hemodialysis or those receiving chronic ambulatory peritoneal dialysis (CAPD). These patients should be given a dosage of 160 mg once daily. Because gemifloxacin is partially removed by hemodialysis, the drug should be administered to patients undergoing hemodialysis after the end of the dialysis period. The manufacturer states that no dosage adjustment is necessary in patients with mild (Child Pugh class A), moderate (Child Pugh class B), or severe (Child Pugh class C) hepatic impairment. Adjustments in gemifloxacin dosage based solely on age are not necessary for geriatric patients older than 65 years of age.

Description

Gemifloxacin, a naphthyridine derivative, is a synthetic fluoroquinolone anti-infective agent. Like all other commercially available fluoroquinolones, gemifloxacin contains a fluorine at the C-6 position.

However, gemifloxacin contains a naphthyridine nucleus rather than the quinolone nucleus contained in most other fluoroquinolones (e.g., ciprofloxacin, gatifloxacin, levofloxacin, lomefloxacin, moxifloxacin, norfloxacin, ofloxacin, sparfloxacin). The pyrrolidine ring at the C-7 position and the 8-methoxyamino moiety on the naphthyridine nucleus of gemifloxacin appear to enhance activity against gram-positive organisms (e.g., Streptococcus pneumoniae); however, the drug has reduced activity against Pseudomonas aeruginosa. Gemifloxacin is active in vitro and in clinical infections against most strains of Streptococcus pneumoniae (including multidrug-resistant strains), Haemophilus influenzae, H. parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Chlamydia pneumoniae, and Mycoplasma pneumoniae.

Gemifloxacin also has in vitro activity against Staphylococcus aureus (oxacillin-susceptible strains only), S. pyogenes (group A b-hemolytic streptococci), Acinetobacter lwoffi, K. oxytoca, Legionella pneumophila, and Proteus vulgaris; however, the safety and efficacy of the drug in infections caused by these bacteria have not been established in adequate and well-controlled clinical trials. Gemifloxacin has greater activity in vitro against S. pneumoniae (including penicillin- and macrolide-resistant strains) than many other fluoroquinolones (e.g., ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin, sparfloxacin, trovafloxacin).

Although gemifloxacin may have in vitro activity against many gram-negative bacteria (e.g., H. influenzae, M. catarrhalis) and the etiologic agents of atypical pneumonia (e.g., C. pneumoniae, M. pneumoniae, Legionella) that is equal to or greater than that of these other fluoroquinolones, gemifloxacin is less active than ciprofloxacin in vitro against many Enterobacteriaceae and Ps. aeruginosa. The relevance of these in vitro data to the treatment of clinical infections remains to be determined. Like other fluoroquinolone anti-infective agents, gemifloxacin inhibits DNA synthesis in susceptible organisms via inhibition of type II DNA topoisomerases (DNA gyrase, topoisomerase IV). However, unlike many other fluoroquinolones, gemifloxacin targets both DNA gyrase and topoisomerase IV in susceptible S. pneumoniae.

Although cross-resistance can occur between gemifloxacin and other fluoroquinolones, gemifloxacin may be active against some strains of S. pneumoniae resistant to ciprofloxacin and other fluoroquinolones. Gemifloxacin is rapidly absorbed from the GI tract following oral administration. The oral bioavailability of gemifloxacin is 71%, and peak plasma concentrations of the drug generally are attained within 0.5 -2 hours. Gemifloxacin has an elimination half-life of about 7 hours and may be administered once daily. Gemifloxacin is excreted in feces and urine; following oral administration of the drug in healthy individuals, approximately 61 or 36% of the dose was excreted in feces or urine, respectively, as unchanged drugs and metabolites. Cytochrome P-450 (CYP) isoenzymes do not appear to play an important role in gemifloxacin metabolism. Gemifloxacin does not inhibit CYP isoenzymes, suggesting that the drug is unlikely to alter the pharmacokinetics of drugs metabolized by these enzymes.

Advice to Patients

Importance of taking gemifloxacin with copious amounts (i.e., at least 100 mL) of fluid to prevent formation of highly concentrated urine. Importance of taking gemifloxacin at least 2 hours before or 3 hours after aluminum- or magnesium-containing antacids; dietary supplements containing metal cations such as zinc or iron (e.g., multivitamins, ferrous sulfate); or didanosine chewable/dispersible buffered tablets, buffered powder for oral solution, or pediatric powder for oral solution prepared as an admixture with antacid. Importance of taking gemifloxacin exactly as prescribed and continuing therapy for the entire treatment course. Importance of reporting persistent or worsening symptoms of infection. Importance of informing their clinician if they have a history of or experience palpitations or fainting spells while on gemifloxacin.

Risk of photosensitivity or hypersensitivity reactions. Importance of avoiding unnecessary exposure to strong sunlight or artificial (UV) light (e.g., sunlamps, solariums) and using a broad-spectrum sunscreen when in bright sunlight; discontinue gemifloxacin and inform a clinician at the first appearance of a sunburn-like reaction or skin eruption, rash, or any other sign of hypersensitivity.

Risk of dizziness or somnolence; if dizziness occurs, importance of avoiding activities that require mental alertness or coordination, and not operating hazardous machinery or a motor vehicle.

Risk of adverse musculoskeletal effects. Importance of informing a clinician if pain, tenderness, or rupture of a tendon occurs; importance of resting and avoiding exercise until the diagnosis of tendinitis or tendon rupture has been excluded. Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, especially other drugs that may affect the QT interval such as cisapride (currently commercially available under a limited-access protocol only), erythromycin, antipsychotic agents, and tricyclic antidepressants. Importance of women informing clinicians if they are or plan to become pregnant or to breast-feed.

Overview

For additional information until a more detailed monograph is developed and published, the manufacturer’s labeling should be consulted. It is essential that the manufacturer’s labeling be consulted for more detailed information on usual cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Preparations

Gemifloxacin Mesylate Oral Tablets, film- 320 mg (of gemifloxacin) Factive®, (with povidone) coated Genesoft

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