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 Cravit
Composition
Each film coated tablet contains :Levofloxacin hemihydrate equivalent to
Levofloxacin 250 mg or 500 mg.
Description
Cravit Tablet 250mg : Round shallow convex and pink film coated tablet; has
KALBE emboss on one side and break line on the other side.
Cravit Tablet
500mg : Biconvex and pink film coated tablet; has circle and KALBE emboss on
one side and break-line on the other side.
Actions
Pharmacology: The main mechanism of action of levofloxacin is inhibition of
DNA gyrase. It is 2-fold stronger than that of ofloxacin. There is not much
difference between MIC and MBC. The activity of levofloxacin is
bactericidal. In the observation of bacterial morphology, bacteriolysis can
be seen in the concentration around MIC.
Cravit shows clinical efficacy on respiratory tract infections,
genitourinary tract infections, biliary tract infections, intestinal tract
infections and other various infections in the surgical, gynecological,
dermatological, otorhinolaryngological, ophthalmological, and dental and
oral surgery fields.
Microbiology: Cravit is a broad-spectrum quinolone antibacterial agent
containing levofloxacin, optically active (-)-S-form of racemate ofloxacin
synthesized by Daiichi Pharmaceutical Co., Ltd. Cravit shows broad and
potent antibacterial activities against gram-positive bacteria, e.g.
Staphylococcus sp, Streptococcus pneumoniae, Streptococcus pyogenes,
Streptococcus hemolyticus, Enterococcus sp, and gram-negative bacteria, e.g.
E. coli, Klebsiella, Serratia, and Proteus spp,
Pseudomonas aeruginosa,
Haemophilus influenzae. Moreover, Cravit has antibacterial activities
against Peptostreptococcus sp of anaerobic bacteria and Chlamydia trachomatis.
Pharmacokinetics: Absorption: Levofloxacin is rapidly and essentially
completely absorbed after oral administration. Peak plasma concentrations
are usually attained 1-2 hrs after oral dosing. The absolute bioavailability
of a 500- and 750-mg tablet of levofloxacin are both approximately 99%,
demonstrating complete oral absorption of levofloxacin. Following a single
i.v. dose of levofloxacin to healthy volunteers, the mean ± SD peak plasma
concentration attained was 6.2 ± 1.0 µg/mL after a 500mg dose infused over
60 min and 11.5 ± 4.0 µg/mL after a 750mg dose infused over 90 min.
Oral administration with food slightly prolongs the time to peak
concentration by approximately 1 hr and slightly decreases the peak
concentration by approximately 14%. Therefore, levofloxacin can be
administered without regard to food.
Distribution: The mean volume of distribution of levofloxacin generally
ranges from 74-112 L after single and multiple 500or 750-mg doses,
indicating widespread distribution into body tissues. Levofloxacin reaches
its peak levels in skin tissues and in blister fluid of healthy subjects at
approximately 3 hrs after dosing. The skin tissue biopsy to plasma AUC ratio
is approximately 2 and the blister fluid to plasma AUC ratio is
approximately 1 following multiple once-daily oral administration of 750-
and 500-mg levofloxacin, respectively, to healthy subjects. Levofloxacin
also penetrates well into lung tissues. Lung tissue concentrations were
generally 2- to 5-fold higher than plasma concentrations and ranged from
approximately 2.4-11.3 µg/g over a 24-hr period after a single 500-mg oral
dose.
In vitro, over a clinically relevant range (1-10 µg/mL) of serum/plasma
levofloxacin concentrations, levofloxacin is approximately 24-38% bound to
serum proteins across all species studied, as determined by the equilibrium
dialysis method. Levofloxacin is mainly bound to serum albumin in humans.
Levofloxacin binding to serum proteins is independent of the drug
concentration.
Metabolism: Levofloxacin is stereochemically stable in plasma and urine and
does not invert metabolically to its enantiomer, D-ofloxacin. Levofloxacin
undergoes limited metabolism in humans and is primarily excreted as
unchanged drug in the urine. Following oral administration, approximately
87% of an administered dose was recovered as unchanged drug in urine within
48 hrs, whereas <4% of the dose was recovered in feces in 72 hrs. Less than
5% of an administered dose was recovered in the urine as the desmethyl and
N-oxide metabolites, the only metabolites identified in humans. These
metabolites have little relevant pharmacological activity.
Excretion: Levofloxacin is excreted largely as unchanged drug in the urine.
The mean terminal plasma elimination halflife of levofloxacin ranges from
approximately 6-8 hrs following single or multiple doses of levofloxacin
given orally or intravenously. The mean apparent total body clearance and
renal clearance range from approximately 144-226 mL/min and 96-142 mL/min,
respectively. Renal clearance in excess of the glomerular filtration rate
suggests that tubular secretion of levofloxacin occurs in addition to its
glomerular filtration. Concomitant administration of either cimetidine or
probenecid results in approximately 24% and 35% reduction in the
levofloxacin renal clearance, respectively, indicating that secretion of
levofloxacin occurs in the renal proximal tubule. No levofloxacin crystals
were found in any of the urine samples freshly collected from subjects
receiving levofloxacin.
Special Populations: Geriatric: There are no significant differences in
levofloxacin pharmacokinetics between young and elderly subjects when the
subjects' differences in creatinine clearance are taken into consideration.
Following a 500-mg oral dose of levofloxacin to healthy elderly subjects
(66-80 years), the mean terminal plasma elimination half-life of
levofloxacin was about 7.6 hrs, as compared to approximately 6 hrs in
younger adults. The difference was attributable to the variation in renal
function status of the subjects and was not believed to be clinically
significant. Drug absorption appears to be unaffected by age. Levofloxacin
dose adjustment based on age alone is not necessary.
Pediatric: The pharmacokinetics of levofloxacin in pediatric subjects have
not been studied.
Gender: There are no significant differences in levofloxacin
pharmacokinetics between male and female subjects when subjects' differences
in creatinine clearance are taken into consideration. Following a 500-mg
oral dose of levofloxacin to healthy male subjects, the mean terminal plasma
elimination half-life of levofloxacin was about 7.5 hrs, as compared to
approximately 6.1 hrs in female subjects. This difference was attributable
to the variation in renal function status of the male and female subjects
and was not believed to be clinically significant. Drug absorption appears
to be unaffected by the gender of the subjects. Dose adjustments based on
gender alone is not necessary.
Race: The effect of race on levofloxacin pharmacokinetics was examined
through a covariate analysis performed on data from 72 subjects: 48 white
and 24 nonwhite. The apparent total body clearance and apparent volume of
distribution were not affected by the race of the subjects.
Renal Insufficiency: Clearance of levofloxacin is substantially reduced and
plasma elimination half-life is substantially prolonged in patients with
impaired renal function (creatinine clearance <50 mL/min), requiring dosage
adjustment in such patients to avoid accumulation. Neither hemodialysis nor
continuous ambulatory peritoneal dialysis (CAPD) is effective in removal of
levofloxacin from the body, indicating that supplemental doses of
levofloxacin are not required following hemodialysis or CAPD. (See
Precautions and Dosage & Administration.)
Hepatic Insufficiency: Pharmacokinetic studies in hepatically impaired
patients have not been conducted. Due to the limited extent of levofloxacin
metabolism, the pharmacokinetics of levofloxacin are not expected to be
affected by hepatic impairment.
Bacterial Infection: The pharmacokinetics of levofloxacin in patients with
serious community-acquired bacterial infections are comparable to those
observed in healthy subjects.
Drug Interactions: The potential for pharmacokinetic drug interactions
between levofloxacin and theophylline, warfarin, cyclosporine, digoxin,
probenecid, cimetidine, sucralfate and antacids has been evaluated. (See
Drug Interactions.)
Electrocardiogram: In a study of 48 healthy volunteers receiving single
doses of levofloxacin 500, 1000 and 1500 mg and placebo, a dose-related
increase from baseline to post-dose of average QTc was observed. These
changes were not statistically significant from placebo for the 500-mg dose,
variably statistically significant for the 1000-mg dose depending on the
correction method used and statistically significant for the 1500-mg dose
(see Precautions).
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