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Utibid UTIBID (Norfloxacin) represents a new
generation of quinolones carboxylic acid derivatives referred to as the
Fluoroquinolones.
Composition
UTIBID 400
Each film coated tablet contains Norfloxacin USP 400 mg.
Chemistry
UTIBID (Norfloxacin) is a quinolone carboxylic acid derivative. Chemically
it is 1-ethyl-6-fluoro-1, 4-dihydro-4-OXO-7-(1-piperazinyl)-3-quinoline
carboxylic acid. Its empirical formula is C16H18FN3O3,
and the structural formula is:
It has a molecular weight of 319.33.
Microbiology
Norfloxacin has in vitro activity against a broad range of gram-positive and
gram-negative aerobic bacteria.
The fluorine atom at the 6
position provides increased potency against gram-negative organisms, and the
piperazine moiety at the 7 position is responsible for anti-pseudomonal
activity. Norfloxacin inhibits bacterial deoxyribonucleic acid synthesis and
is bactericidal. At the molecular level, three specific events are
attributed to norfloxacin in E.coli cells.
1. Inhibition of the
ATP-dependent DNA supercoiling reaction catalyzed by DNA gyrase.
2. Inhibition of the relaxation of supercoiled DNA.
3. Promotion of double-standard DNA breakage.
Resistance to Norfloxacin due to spontaneous mutation in vitro is a rare
occurrence (range 10,1 to 10.'2 cells). Resistant organisms have emerged
during therapy with Norfloxacin in less than 1 % of patients treated.
Organisms in which development of resistance is greatest are the following:
Pseudomonas aeruginosa
Klebsiella pneumoniae
Acinetobacter species
Enterococcus species
Norfloxacin has been shown to be active against most strains of the
following organisms both in vitro and in clinical infections.
Gram-positive aerobes
Enterococcus faecalis
Staphylococcus aureus
Staphylococcus epidermidis
Staphylococcus saprophyticus
Streptococcus agalactiae
Gram-negative aerobes
Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae
Esherichia coli
Klebsiella pneumoniae
Neisseria gonorrhoeae
Proteus mirabilis
Proteus vulgaris
Pseudomonas aeruginosa
Serratia marcescens
Norfloxacin has been shown to be active in vitro against most strains of the
following organisms; however, the clinical significance of these data is
unknown.
Gram-positive aerobes
Bacillus cereus
Gram-negative aerobes
Acinetobacter calcoaceticus
Aeromonas species
Alcaligenes species
Campylobacter species
Citrobacter diversus
Edwardsiella tarda
Flavobacterium species
Klebsiella oxytoca
Klebsiella rhinoscleromatis
Morganella morganii
Providencia alcalifaciens
Providencia rettgeri
Providencia stuartii
Salmonella species
Shigella species
Vibrio cholerae
Vibrio parahaemolyticus
Yersinia enterocolitica
Other
Ureaplasma urealyticum
Norfloxacin is not generally active against obligate anaerobes. It has not
been shown to be active against Treponema pallidum.
Clinical Pharmocology
Following oral administration, 30-40% of UTIBID (Norfloxacin) is rapidly
absorbed from the GI tract. Peak serum concentrations (Cmax) of 1.5 to 2.0
mcg/ml (average in some studies 1.6 mcg/ml) are achieved in 1-2 hours
(average tmax 1.5 hrs), after a 400 mg dose of Norfloxacin. With an 800 mg
dose of Norfloxacin, average Cmax was 2.4 mcg/ml.
Absorption is only slightly delayed when Norfloxacin is administered with
food. Due to the low protein binding (14%) and high lipid solubility, UTIBID
(Norfloxacin) is widely distributed to the various tissues. Liver is the
primary site of metabolism.
Six metabolites of Norfloxacin,
of lesser antimicrobial potency, are excreted unconjugated in the urine.
Liver impairment has no major effect on the pharmacokinetics of Norfloxacin.
Urine is the major route of
excretion of UTIBID. 30% of the drug is excreted unchanged in the urine.
Renal clearance of UTIBID is high
(about 2 to 21/2 times the glomerular filtration rate) and urinary
concentrations of Norfloxacin are about 100 to 300 times the simultaneous
serum concentrations. Urinary concentrations of Norfloxacin is in excess of
MIC of most of the urinary pathogens for about 12 to 24 hours after a single
400 mg dose. In addition to glomerular filtration, there is also active
tubular secretion of Norfloxacin. As the glomerular filtration rate falls,
the mean serum elimination half-life tends to increase and necessitates
dosage adjustment in moderate to severe renal impairment.
The serum elimination half-lives
of Norfloxacin reported in various studies have ranged from 3.5 to 6.5
hours.
The average values for above with
moderate renal failure are reportedly 6.5 hours and with more severe forms
-arid renal impairment have been reported to be about 7.7 hours.
Indications and Usage
UTIBID is indicated for the treatment of adults with the following
infections caused by susceptible strains of the designed microorganisms.
Urinary tract infections
Uncomplicated urinary tract infections (including cystitis due to
Enterococcus faecalis. Esacherichia coli, Klebsiella pneumoniae, Proteus
mirabilis, Pseudomonos aeruginosa, Citrobacter freundii, Enterobacter
aerogenes, Enterobacter cloacae, Proteus vulgaris, Staphylococcus aureus or
Streptococcus agalactiae.
Complicated urinary tract
infections due to enterococcus faecalis, Esherichia colt, Klebsiella
pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, or Serratia
marcescens.
Sexually transmitted disease
Uncomplicated urethral and cervical gonorrhoea due to Neisseria gonorrhoeae.
Contraindications
UTIBID is contraindicated in patients with a history of hypersensitivity to
Norfloxacin or the other members of the quinolone group of antibacterial
agents.
Warnings
The safety and efficacy of oral Norfloxacin in children, adolescents (under
the age of 18), pregnant women, and nursing mothers have not been
established.
The oral administration of single
dose of Norfloxacin 6 times the recommended human clinical dose (on a mg/kg
basis), caused lameness in immature dogs.
Histologic examination of the weight bearing joints of these dogs revealed
permanent lesions of the cartilage. Other quinolones also produced erosion
of the cartilage in weight-bearing joints and other signs of arthropathy in
immature animals of various species. Norfloxacin has not been shown to be
effective in the treatment of syphilis. Antimicrobial agents used in high
doses for short period of time to great gonorrhoea may mask or delay the
symptoms of incubating syphilis. All patients with gonorrhoea should have a
serologic test for syphilis, at the time of diagnosis. Patients treated with
Norfloxacin should have a follow-up serologic test for syphilis after 3
months.
Serious and occasionally fatal hypersensitivity (anaphylactoid or
anaphylactic) reactions may occur. If an allergic reaction to Norfloxacin
occurs, discontinue the drug. Serious acute hypersensitivity reactions may
require immediate emergency treatment with epinephrine. Oxygen, intravenous
fluids, antihistamines and airway management, including intubation should be
administered as indicated.
Convulsions have been reported in
patients receiving Norfloxacin. Convulsions, increased intracranial
pressure, and toxic psychoses have been reported in patients receiving drugs
in this class. Quinolones, may also cause central nervous system (CNS)
stimulation, which may lead to tremors, restlessness, lightheadedness,
confusion and hallucination.
If these reactions occur in
patients receiving Norfloxacin, the drug should be discontinued and
appropriate measures instituted.
The effects of Norfloxacin on
brain function or on the electrical activity of the brain have not been
tested. Therefore, until more information becomes available, Norfloxacin,
like all other quinolones, should be used with caution in patients with
known or suspected CNS disorders, such as severe cerebral arteriosclerosis,
epilepsy and other factors which predispose to seizures.
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