(levofloxacin)
DESCRIPTION
(Levofloxacin)
is a synthetic broad-spectrum
antibacterial
agent.
ically,
levofloxacin, a
chiral fluorinated
is. the pure
(-)(S)-enantiomer of the
racemic
drug
with
chemical
(MS)g-fluoro-2.
3-dihydro-3-methyl-10-
(4-methyl-1- piperazinyl)-7-oxo-7H-pýrido [1,2,3,-de) (1.4) benzoxazine-
6-carboxylic
acid. Its molecular formula is CuH,FN,O, and the structural formula is:
СООН
THERAPEUTIC
INDICATIONS
Lefox
(Levofloxacin) is indicated, for the treatment of adults (>18 years of age)
with mild.
moderate,
and severe
caused by
susceptible
strains
designated
micro-organisms
in the conditions listed below:
Acute bacterial
sinusitis
Acute bacterial
exacerbation of chronic bronchitis
Community-
acquired pneumonia and nosocomial pneumonia
Complicated skin
and skin structure infections
Uncomplicated
skin and skin structure infections
Chronic
bacterial prostatitis
Complicated
urinary tract infections
Uncomplicated
urinary tract infections
neute
pyelonepinus
Inhalational
anthrax, post-exposure
Plague
DOSAGE AND
ADMINISTRATION
presumed,
causative pathogen.
Leflox
(Levofloxacin) should be swallowed without crushing and with sufficient amount
of liquid.
Leffox
(Levofloxacin) Tablets should be administered at least two hours before or two
hours after antacids containing magnesium, aluminum, as well as sucralfate,
metal cations such as iron, and multivitamin preparations with zinc or
didanosine chewable/buffered tablets or the pediatric powder for oral solution.
The dosage guidelines as per the infection are given as
Dosage in adult
patients with normal renal function
Levofloxacin
QUALITATIVE AND
QUANTITATIVE COMPOSITION
Leflox
(Levofloxacin) is available for oral administration as:
Leflox Tablets
250mg
Each film-coated
tablet contains:
Levofloxacin
USP...250mg
Leflox Tablets
500mg
mach nim-coaled
labiel cultallo.
Levofloxacin
USP...500mg
Leflox Tablets
750mg
Each film-coated
tablet contains:
Levofloxacin
USP...750mg
CLINICAL
PHARMACOLOGY
Mechanism of Action
Levofloxacin is
the L-isomer of the racemate, ofloxacin, a quinolone antimicrobial agent. The
antibactenal
activity of ofloxacin resides primanly in the
L-Isomer. The
main mechanism of
action of
levofloxacin involves the inhibition of bacterial topoisomerase IV and DNA
gyrase (both or which are type Il topoisomerases), enzymes required for DNA
replication, transcription, repair and recombination. Levofloxacin has in vitro
activity against the following gram-negative and gram-positive micro-organisms.
It is often bactericidal at concentrations equal to or slightly greater than
inhibitory concentration. It is generally considered to be about twice as
active as its isomer, ofloxacin.
Levofloxacin has
been shown to be active against most strains of the following micro-organisms
both in vitro and in clinical infections.
Commonly
susceptible species
Aerobic
Gram-positive bacteria
Staphylococcus
aureus methicillin-susceptible,
Staphylococcus
saprophyticus,
Streptococci
group C and G,
Streptococcus agalactiae,
Streptococcus
pneumoniae,
Streptococcus
pyogenes.
Aerobic Gram-
negative bacteria
Burkholderia
Eikenella
corrodens,
Haemophilus influenzae;
Haemophilus
para-influenzae,
Klebsiella oxytoca, Klebsiella pneumoniae, Moraxella catarrhalis, Pasteurella
multocida, Proteus vulgaris, Providencia rettgeri.
Anaerobic
bacteria Peptostreptococcus.
Other
Chlamydophila
pneumoniae,
Chlamydophila
psittaci,
Chlamydia trachomatis,
pneumophila,
Mycoplasma pneumoniae, Mycoplasma hominis, Ureaplasma urealyticum.
Species for
which acquired resistance may be a problem
Aerobic
Gram-positive bacteria
Enterococcus
faecalis, Staphylococcus aureus methicillin-resistant, Coagulase negative
Staphylococcus
spp.
Aerobic Gram-
negative bacterian
Acinetonaren
Citrovacer
reundit.
Enterobacter
aerogenles,
Enterobacter
agglomerans,
Enterobacter cloacae, Escherichia coli, Morganella morganii, Proteus mirabilis,
Providencia stuartii, Pseudomonas aeruginosa, Serratia marcescens.
Anaerobic
bacteria
Bacteroides
fragilis, Bacteroides ovatus, Bacteroides thetaiotamicron, Bacteroides
vulgatus, Clostridium difficile.
Levofioxacin has
been shown to be active against Bacillus anthracis in vitro.
Pharmacokinetics
Levofioxacin is
rapidly and almost completely absorbed with absolute bioavailability of 99%
following oral use with peak plasma concentrations achieved within 1-2 hours of
a dose. The mean volume of distribution of levofloxacin ranges from 74 to 112 L
after single or multiple 500mg or 750mg doses indicating distribution into body
tissues including the bronchial mucosa and lungs, but penetration into CSF is
relatively poor. Levofloxacin is approximately 24 to 38% bound to plasma
proteins. It is only metabolised to a small degree to in-active metabolites.
The elimination half-ife of levofloxacin is 6 to 8 hours, although this may be
prolonged in patients with renal impairment. Approximately 87% of an
admihistered dose was recovered as unchanged drug in urine within, 48 hours,
whereas less than 4% of the dose was recovered in leces in 72 hours and less
than 5% of an administered dose is récovered in the urine. It is not removed by
hemodialysis or peritoneal dialysis.
Special
Population
Renal Insufficiency
Clearance of
levoloxacin is substantially reduced and plasma elimiration half-life is
substantially prolonged in patients with impaired renal function (creatinine
clearance 50mL/min), requiring dosage adjustment in such patients to avoid
accumulation, Neither hemodialysis nor continuous ambulatory peritoneal
dialysis (CAPD) is effective in removal of levoxacin from the body, indicating
that supplemental doses of levoloxacin are not required following hemodialysis
or CAPD,
(creatinine
clearance 2 50mL/min)
INDICATIONS
DOSE
EVERY 24 HOURS
DURATION (DAYS)
Acute Bacterial
Sinusitis
500mg
Toung
10 - 14
Acute Bacterial
Exacerbation of
chronic
Bronchitis
250mg to 500mg
onct Cally
7 - 10
Community
Acquired
Pneumonia
500mg
750mg
7-14
Nosocomial
Pneumonia
750mg
7-14
Uncomplicated
skin and skin soft tissue Infections
500mg
7-10
Complicated skin
and soft tissue Infections
750mg
7 - 14
Uncomplicated
Urinary
Tract Infections
250mg
Complicated
Urinary
Tract Infections
250mg
500mg
750mg
10
7-14
Acute
Pyelonephritis
250mg
500mg
750mg
10
7 - 10
Chronic
Bacterial
Prostatitis
500mg
28
Inhalational
Anthrax (Post-Exposure)
500mg
60
Plague, adult
and pediatric patients > 50kg
500mg
10 - 14
Dosage in adult
patients with impaired renal function
(creatinine
clearance < 50mL/min)
Dosage in
Normal Renal
Functions
Every 24 hours
Creatinine
Clearance
20 to 49mL/min
Creatinine
Clearance®
10 to 19mL/min
is
750mg
750mg every
48 hours
500mg
500mg initial
dose, then 250mg every
24 hours
Inhalational
Anthrax (post-exposure)
Pediatric
patients ≥ 50kg
500mg
24hr
60 days
Pediatric
patients < 50kg and 2 6 months of age
8mg/kg
(not to exceed
250mg per dose)
12hr
60 days
ADVERSE
REACTIONS
Levoffoxacin is
usually weil tolerated. However, following are the adverse effects reported
during its therapy
Common
Monilasis, insomnia, headache, dizziness, dyspnea, nausea, diartea
constipation.
vomiting,
dyspepsia, rash, pruntus, vaginitis, edema and chest pain.
thrombocytopenia,
granulogy topenia, ellergic reaction,
Loss comman
Genital monilass, ayperka typerglycemia.
hypoglycemia.
hyperkalemia,
agitation,
confusion.
halluci
lation,
nightmare, sleep disorder, anorexia, abnormal dreaming, tremor.
paresthesia,
vertigo,
hypertonia, hyperkinesias, abnormal gail, somnolence, syncope cardiac arrest,
paip
itation,
ventricular tachycardia, ventricular arhythmia, phlebitis,
stomatitis,
pancrealitis.
esophagitis,
gastroenteritis, glossitis, pseudomembraneous/C. dificie
politis,
abnormal hepatic function, increased hepatic enzymes, increased alkaline
phosphatase urticaria, arthralgia,
-To report
SUSPECTED ADVERSE REACTIONS to Getz Pharma's Pharmacovigilance
Section, please
contact at dsafety@getzpharma.com or +92-21-38636363* CONTRAINDICATIONS
Levoflaxacin is
contraindicated in patients with a hist
one chis
oator to any
patients orthe bistrol hypersensitivily to this drug and/or other
NERVOND NITIS
SYSTEM DEF
DEFECTS AND
Iroversiblendon
rupture
ediately and
avoid the use of Fluoroquinolones, including
me saverse
cacion
As
fluoroquinolones, including levofloxacin have been associated with serious
adverse reactions, reserve levofioxacin for use in patients who have no
altemative treatment-options for exacerbation of chrons.
Acute
exacerbation of chronic bronchitis
Acute sinusitis
Acute
uncomplicated cystitis
PRECAUTIONS
Tendinitis and
Tendon Rupture: Fluoroquinolones, including levofloxacin, have been associated
with an increased risk of tendinitis and tendon rupture in all ages. Tendinitis
or tendon rupture can occur within hours or days of starting levofloxacin or as
long as several months after completion of Nuoroquinolone therapy. Discontinue
levofloxacin immediately if the patient experiences pain. swelling,
inflammation or rupture of a tendon. Patients should be advised to rest at the
first sign of tendinitis or tendon rupture, and to contact their physician.
Avoid levofloxacin in patients who have a history of tendon disorders or tendon
rupture.
Peripheral
Neuropathy: Sensory or sensorimotor axonal poly neuropathy has been reported in
patents recewing
nuorogumoones.
including
levofloxacin, which can be rapid in its onset.
Levofloxacin
should be discontinued if the patient experiences symptoms of neuropathy. Avoid
Ruoroquinolones, including levofloxacin, in patients who have previously
experienced peripheral neuropathy.
Central Nervous
System Effects: Fluoroquinolones,
levofloxacin,
have been
associated with
an increased risk of central nervous system (CNS) effects. Fluoroquinolones may
also cause central nervous system stimulation. Suicidal thoughts, and attempted
or completed
cially in
patients with a medical history of depression, or an undenying
levolloxacin.
disconunue
risk factor for
depression. " these roacbons beco
nervous system
(CNS) disorder that may predispose
them to seizures
or lower the seizure threshold or in the presence of other risk factors that
may
predispose them
to solures brower te solure tiestore.
Myasthenia
Fluoroquinolones,
including levolloxacin,
have
activity and may
exacerbate
musue weakrioss
patients with
myasthenia
gravis. Avoid levolloxacin, in patients with a known history of myasthenia
grayis
Other Serious
and Sometimes Fatal Adverse Reactions: Other serious and sometimes fatal
inducing levoloxacin. Discontinue leadin patients e eving that appetrance of
skin rash,
jaundice, or any
other sign of hypersensitivity and institute supportive measures.
Hepatotoxicity:
Severe hepatotoxicity (including acute hepatitis and fatal events) have been
reported for patients treated with levofioxacin. Levofloxacin should be
discontinued immediately if the patient develops signs and symptoms of
hepatitis.
Clostridium
difficile-Associated Diarrhea: Clostridium difficile-associated diarrhea (CDAD)
has been reported with use of nearly all antibacterial agents, including
levofloxacin, and may range in severity from mild diarrhea to fatal colitis. If
CDAD is suspected or confirmed, ongoing antibiotic use not directed against C.
difficile may need to be discontinued. Appropriate fluid and electrolyte
management, protein supplementation, antibiotic treatment of C, difficile, and
surgical evaluation should be instituted as clinically indicated.
Blood Glucose
Disturbances: Disturbances of blood glucose, including symptomatic hyper and
hypoglycemia, have been reported with levofloxacin, usually in diabetic
patients receiving concomitant treatment with an oral hypoglycemic agent or
with insulin, In these patients, careful monitoring of blood glucose is
recommended.
Photosensitivity/Phototoxicity:
Moderate to severe photosensitivity/phototoxicity reactions, can be associated
with the use of fluoroquinolones after sun or UV light exposure. I herefore,
excessive exposure to these sources of light should be avoided. Drug therapy
should be
discontinued if
photosensitivity/phototoxicity occurs.
Patients with
G-6-phosphate dehydrogenase deficiency: Patients with latent or actual defects
in glucose-6-phosphate dehydrogenase activity may be prone to hemolytic
reactions when treated with quinolone antibacterial agents and so levolloxacin
should be used with caution.
Patients treated
with Vitamin K antagonista: Due to possible increase in coagulation tests
(PT/INR) and/or
patients treated
wih levofloxacin in combination with a vitamin K
concomita go
wartarn), coagulation lost should be monitored when these drugs are given
Congenital long
QT syndrome
Concomitant use
of drugs that
are known to prolong the OT interval (o.g. Class IA and II
antarhythmic,
tricyclic antidepressants, macrolides)
Uncorrected
electrolyte Imbalance (e.g. hypokalemia, hyporagnesemia)
Cardiac disease
(a g., heart failuré, myocardial infarction, bradycardia)
Opiates: In
patients treated with levofloxacin, determination of opiates in unne may give
false postive results. It may be necessary to confirm positive opiate screens
by more specific method.
Hepatobillary
disordars: Patients should be advised to stop treatment and contact their
doctor if signs and symptoms of hepatic disense develop such as anorexia.
jaundice, dark urine, prunitus or lender abdomen.
Renal
Insufficiency: Clearance of levofloxacin is substantially reduced and plasma
olimination half-ife is substantially prolonged in patients with
Impaired renal
function (creatinine clearance
<50mL/min),
requiring dosage adjustment in such patients to avoid accumulation. Neither
hemodialysis nor continuous ambulatory pantoneal dialysis (CAPD) is effoctive
in romoval of (evoling he mon e or icating that supplemenlal doses of
levoloxacin are not required Psychotic Reactions: Psychotic reactions have been
reported in patients recerving quinolonios, including levoffoxaon. Caution is
recommended if levofloxacin is to be used in psychotic patients or inpatients
with a history of psychiatric disease.
Vision
Disorders: If vision bacomes impaired or any effecis on the eyes are
experienced, an eye specialist should be consulted immediately.
/sms, reserve
levofoxacin for use only when there are no
uscula koltal i
oria in parole at a many an one of mean peralate
patients
receiving levoronen
tendon rupture
occur.
Pregnancy
There are no
adequate and well-controlled studies in pregnant women. Levofloxacin should be
used during pregnancy only if the potential benefit justifies the potential
risk to the fetus Nursing Mothers
Because of the
potential for serious adverse reactions from levofloxacin in nursing infants, a
decision should be made whether to discontinue nursing or to discontinue the
drug, taking into account the importance of the drug to the mother.
DRUG
INTERACTIONS
Antacids, Sucralfate.
Metal Cations. Multivitamins: Concurrent administration of levofloxacin with
antacids containing magnesium, or aluminium, as well as sucralfate metal
cations such as iron and multivitamin preparations with zin or didanosine may
interfere with the gastrointestinal absorption of levofloxacin resulting in
systemic levels considerably lower than desired. These agents should be taken
at least 2 hours before or 2 hours after levofloxacin administration,
Theophylline,
fenbufen or similar non-steroidal anti-inflammatory drugs: Pronounced lowering
of the cerebral seizure threshold may occur when quinolones
are given
concurrently
with
theophylline,
non-steroidal anti-inflammatory drugs,
or other agents
which lower the setzure
threshold.
Levofloxacin concentrations were about 13% higher in the presence of fenbufen
than when administered alone.
Probenecid and
Cimetidine: Caution should be exercised when levofloxacin is co-administered
with drugs that affect the tubular renal secretion such as probenecid and cimetidine,
especially in renally impaired patients.
Cyclosporine:
The half-life of ciclosporine was increased by 33% when co-administered with
evoloxacin.
Warfarin: There
have been reports in patients that levofloxacin enhances the effects of
warfarin.
Prothrombin
time, International Normalized Ratio. (INR) or other suitable anticoagulation
lests should be closely monitored if levofloxacin is administered concomitantly
with warfarin. Patients should also be monitored for evidence of bleeding
OVERDOSAGE
In the event of
overdose, symptomatic treatment should be implemented, ECG monitoring should be
undertaken, because of the possibility of OT interval prolongation. Antacids
may be used for protection of gastric mucosa. Haemodialysis, including
peritoneal dialysis and CAPD, are not effective in removing levofloxacin from
the body, No specific antidote exists.
STORAGE
Do not store
above 30°C.
Protect from
sunlight & moisture:
The expiration
date refers to the product correctly stored at the required conditions.
HOW SUPPLIED
Leflox
(Levofloxacin) Tablets 250mg are available in blister pack of 10'.
Lefox
(Levofloxacin) Tablets 500mg are available in blister pack of 105.
Lefox
(Levofloxacin) Tablets 750mg are avallable in blister pack of 10's.
Keep
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