Levofloxacin 500 MG Film-Coated Tablets SMPC - Taj Pharmaceuticals

Levofloxacin 500 mg Fil m-coated Tabl ets SMPC, Taj Phar maceuticals
Levofloxacin Taj Phar ma : Uses, Side Effects, Interactions, Pictures, Warnings, Levofloxacin Dosage & Rx Info | Levofloxacin Uses, Side Effects -: Indications, Side Effects, Warnings, Levofloxacin - Drug Information - Taj Phar ma, Le vofloxacin dose Taj pharmaceuticals Levofloxacin interactions, Taj Pharmaceutical Levo floxacin contraindications, Levofloxacin price, Levofloxacin Taj Pharma Levofloxacin 500 mg Fil m-coated Tablets SMPC- Taj Phar ma . Stay connected to all updated on Levofloxacin Taj Pharmaceuticals Taj pharmac euticals Hyderabad.
• Uncomplicated cystitis (see section 4.4)

RX
• Inhalation Anthrax: postexposure prophylaxis
LEVOFLOXACIN and curative treatment (see section 4.4)
Levofloxacin Tablets may also be used to
FILM COATED complete a course of therapy in patients who
TABLETS have shown improvement during initial
treatment with intravenous levofloxacin.
500MG Consideration should be given to official
1.NAME OF THE MEDICINAL PRODUCT guidance on the appropriate use of antibacterial
agents.
Levofloxacin 500 mg Film-coated Tablets
4.2 Posology and method of administration
2. QUALITATIVE AND QUANTITATIVE
COMPOSITION Levofloxacin Tablets are administered once or
twice daily. The dosage depends on the type and
Each film coated tablet contains 500 mg of severity of the infection and the sensitivity of the
levofloxacin as active substance corresponding presumed causative pathogen.
to 512.46 mg of levofloxacin hemihydrate.
Treatment time
For the full list of excipients, see section 6.1.
The duration of therapy varies according to the
3. PHARMACEUTICAL FORM course of the disease (see table below). As with
Film-coated tablet antibiotic therapy in general, administration of
Levofloxacin Tablets should be continued for a
For 500 mg tablets: Pink coloured, capsule minimum of 48 to 72 hours after the patient has
shaped, biconvex, film coated tablet with break become afebrile or evidence of bacterial
line on both sides. eradication has been obtained.
The tablet can be divided into equal doses.
Indication Daily dose
Duration of
4. CLINICAL PARTICULARS regimen
treatment (according
(according to
to severity)
severity)
4.1 Therapeutic indications
Acute bacterial
Levofloxacin Tablets is indicated in adults for sinusitis
500 mg once daily 10 - 14 days
the treatment of the following infections (see
Acute bacterial
sections 4.4 and 5.1): exacerbations of 500 mg once daily 7 - 10 days
chronic bronchitis
• Acute bacterial sinusitis
Community-
500 mg once or
• Acute exacerbations of chronic bronchitis acquired
pneumonia
twice daily
7 - 14 days
• Community-acquired pneumonia Pyelonephritis 500 mg once daily 7 - 10 days

Complicated
• Complicated skin and soft tissue infections urinary tract 500 mg once daily 7 - 14 days
infections
For the above-mentioned infections Uncomplicated
Levofloxacin Tablets should be used only when 250 mg once daily 3 days
cystitis
it is considered inappropriate to use antibacterial Chronic bacterial
500 mg once daily 28 days
agents that are commonly recommended for the prostatitis
initial treatment of these infections. Complicated Skin
500 mg once or
and soft tissue 7 - 14 days
twice daily
• Pyelonephritis and complicated urinary tract infections
infections (see section 4.4) Inhalation Anthrax 500 mg once daily 8 weeks
• Chronic bacterial prostatitis

The following dose recommendations can be should be taken at least two hours before or after
given for Levofloxacin Tablets: iron salts, zinc salts, magnesium- or aluminium-
containing antacids, or didanosine (only
Dosage in patients with normal renal function
didanosine formulations with aluminium or
(creatinine clearance > 50 ml/min) magnesium containing buffering agents), and
sucralfate administration since reduction of
Special Populations absorption can occur (see section 4.5).
Impaired renal function (creatinine clearance 4.3 Contraindications
≤ 50 ml/min) Levofloxacin Tablets must not be used:
Dosage regimen • in patients hypersensitive to levofloxacin or
250 mg/24 h
500
500 mg/12 h
other quinolones or to any of the excipients
Creatinine clearance mg/24 h listed in section 6.1,
First
First dose: 250 First dose: 500
mg
dose: 500
mg • in patients with epilepsy,
mg
Then: • in patients with history of tendon disorders
Then:125 Then:250
50-20 ml/min 250 related to fluoroquinolone administration,
mg/24h mg/12 h
mg/24 h
Then: 125
Then:
Then:125
• in children or growing adolescents
19-10 ml/min 125
mg/48 h mg/12 h
mg/24 h • during pregnancy,
< 10 ml/min (including
Then: 125
Then:
Then:125 • in breast-feeding women.
haemodialysis and 125
mg/48 h mg/24 h
CAPD)1 mg/24 h
4.4 Special Warnings and precautions for use
1
No additional doses are required after
Epidemiologic studies report an increased risk of
haemodialysis or continuous ambulatory
aortic aneurysm and dissection after intake of
peritoneal dialysis (CAPD).
fluoroquinolones, particularly in the older
Impaired liver function population.
No adjustment of dosage is required since Therefore, fluoroquinolones should only be used
levofloxacin is not metabolised to any relevant after careful benefit-risk assessment and after
extent by the liver and is mainly excreted by the consideration of other therapeutic options in
kidneys. patients with positive family history of
aneurysm disease, or in patients diagnosed with
Elderly population pre-existing aortic aneurysm and/or aortic
No adjustment of dosage is required in the dissection, or in presence of other risk factors or
elderly, other than that imposed by consideration conditions predisposing for aortic aneurysm and
of renal function (see section 4.4 “Tendinitis and dissection (e.g. Marfan syndrome, vascular
tendon rupture” and “QT interval Ehlers-Danlos syndrome, Takayasu arteritis,
prolongation”). giant cell arteritis, Behcet's disease,
hypertension, known atherosclerosis).
Paediatric population
In case of sudden abdominal, chest or back pain,
Levofloxacin is contraindicated in children and patients should be advised to immediately
growing adolescents (see section 4.3). consult a physician in an emergency department.
Method of administration Methicillin-resistant Staphylococcus aureus
Levofloxacin Tablets should be swallowed (MRSA)
without crushing and with sufficient amount of Methicillin-resistant S. aureus are very likely to
liquid. They may be divided at the score line to possess co-resistance to fluoroquinolones,
adapt the dose. The tablets may be taken during including levofloxacin. Therefore levofloxacin is
meals or between meals. Levofloxacin Tablets
not recommended for the treatment of known or Diarrhoea, particularly if severe, persistent
suspected MRSA infections unless laboratory and/or bloody, during or after treatment with
results have confirmed susceptibility of the Levofloxacin (including several weeks after
organism to levofloxacin (and commonly treatment), may be symptomatic of Clostridium
recommended antibacterial agents for the difficile-associated disease (CDAD). CDAD
treatment of MRSA-infections are considered may range in severity from mild to life
inappropriate). threatening, the most severe form of which is
pseudomembranous colitis (see section 4.8). It is
Levofloxacin may be used in the treatment of
therefore important to consider this diagnosis in
Acute Bacterial Sinusitis and Acute patients who develop serious diarrhoea during or
Exacerbation of Chronic Bronchitis when these after treatment with levofloxacin. If CDAD is
infections have been adequately diagnosed. suspected or confirmed, Levofloxacin Tablets
Resistance to fluoroquinolones of E. coli – the should be stopped immediately and appropriate
most common pathogen involved in urinary tract treatment initiated without delay (e.g. oral
infections – varies across the European Union. metronidazole or vancomycin). Medicinal
Prescribers are advised to take into account the products inhibiting the peristalsis are
local prevalence of resistance in E. coli to contraindicated in this clinical situation.
fluoroquinolones. Patients predisposed to seizures
Inhalation Anthrax: Use in humans is based on Quinolones may lower the seizure threshold and
in vitro Bacillus anthracis susceptibility data and may trigger seizures. Levofloxacin is
on animal experimental data together with contraindicated in patients with a history of
limited human data. Treating physicians should
epilepsy (see section 4.3) and, as with other
refer to national and/or international consensus
quinolones, should be used with extreme caution
documents regarding the treatment of anthrax.
in patients predisposed to seizures, or
Tendinitis and tendon rupture concomitant treatment with active substances
that lower the cerebral seizure threshold, such as
Tendinitis may rarely occur. It most frequently theophylline (see section 4.5). In case of
involves the Achilles tendon and may lead to convulsive seizures (see section 4.8), treatment
tendon rupture. Tendinitis and tendon rupture, with levofloxacin should be discontinued.
sometimes bilateral, may occur within 48 hours
of starting treatment with levofloxacin and have Patients with G-6- phosphate dehydrogenase
been reported up to several months after deficiency
discontinuation of treatment. The risk of Patients with latent or actual defects in glucose-
tendinitis and tendon rupture is increased in 6-phosphate dehydrogenase activity may be
patients aged over 60 years, in patients receiving
prone to haemolytic reactions when treated with
daily doses of 1000 mg and in patients using quinolone antibacterial agents. Therefore, if
corticosteroids. The daily dose should be levofloxacin has to be used in these patients,
adjusted in elderly patients based on creatinine potential occurrence of haemolysis should be
clearance (see section 4.2). Close monitoring of monitored.
these patients is therefore necessary if they are
prescribed Levofloxacin. All patients should Patients with renal impairment
consult their physician if they experience
symptoms of tendinitis. If tendinitis is suspected, Since levofloxacin is excreted mainly by the
treatment with Levofloxacin must be halted kidneys, the dose of Levofloxacin Tablets
immediately, and appropriate treatment (e.g. should be adjusted in patients with renal
immobilisation) must be initiated for the impairment. (see section 4.2).
affected tendon (see sections 4.3 and 4.8). Hypersensitivity reactions
Clostridium difficile-associated disease Levofloxacin can cause serious, potentially fatal
hypersensitivity reactions (e.g. angioedema to
anaphylactic shock), occasionally following the single dose of levofloxacin (see section 4.8). In
initial dose (see section 4.8). Patients should the event that the patient develops these
discontinue treatment immediately and contact reactions, levofloxacin should be discontinued
their physician or an emergency physician, who and appropriate measures instituted. Caution is
will initiate appropriate emergency measures. recommended if levofloxacin is to be used in
psychotic patients or in patients with a history of
Severe bullous reactions psychiatric disease.
Cases of severe bullous skin reactions such as
QT interval prolongation
Stevens-Johnson syndrome or toxic epidermal
necrolysis have been reported with levofloxacin Caution should be taken when using
(see section 4.8). Patients should be advised to fluoroquinolones, including levofloxacin, in
contact their doctor immediately prior to patients with known risk factors for prolongation
continuing treatment if skin and/or mucosal of the QT interval such as, for example:
reactions occur.
- congenital long QT syndrome
Dysglycaemia
-concomitant use of drugs that are known to
As with all quinolones, disturbances in blood prolong the QT interval (e.g. Class IA and III
glucose, including both hypoglycaemia and antiarrhythmics, tricyclic antidepressants,
hyperglycaemia have been reported, usually in macrolides, antipsychotics).
diabetic patients receiving concomitant
treatment with an oral hypoglycaemic agent - uncorrected electrolyte imbalance (e.g.
hypokalemia, hypomagnesemia)
(e.g., glibenclamide) or with insulin. Cases of
hypoglycaemic coma have been reported. In - cardiac disease (e.g. heart failure, myocardial
diabetic patients, careful monitoring of blood infarction, bradycardia)
glucose is recommended (see section 4.8).
Elderly patients and women may be more
Prevention of photosensitisation sensitive to QTc-prolonging medications.
Therefore, caution should be taken when using
Photosensitisation has been reported with
levofloxacin (see section 4.8). It is fluoroquinolones, including levofloxacin, in
these populations.
recommended that patients should not expose
themselves unnecessarily to strong sunlight or to (see section 4.2 Elderly, section 4.5, section 4.8,
artificial UV rays (e.g. sunray lamp, solarium), section 4.9).
during treatment and for 48 hours following
treatment discontinuation in order to prevent Peripheral neuropathy
photosensitisation. Sensory or sensorimotor peripheral neuropathy
Patients treated with Vitamin K antagonists have been reported in patients receiving
fluoroquinolones, including levofloxacin, which
Due to possible increase in coagulation tests can be rapid in its onset (see section 4.8).
(PT/INR) and/or bleeding in patients treated Levofloxacin should be discontinued if the
with levofloxacin in combination with a vitamin patient experiences symptoms of neuropathy in
K antagonist (e.g. warfarin), coagulation tests order to prevent the development of an
should be monitored when these drugs are given irreversible condition.
concomitantly (see section 4.5).
Hepatobiliary disorders
Psychotic reactions
Cases of hepatic necrosis up to fatal hepatic
Psychotic reactions have been reported in failure have been reported with levofloxacin,
patients receiving quinolones, including primarily in patients with severe underlying
levofloxacin. In very rare cases these have diseases, e.g. sepsis (see section 4.8). Patients
progressed to suicidal thoughts and self- should be advised to stop treatment and contact
endangering behaviour- sometimes after only a their doctor if signs and symptoms of hepatic
disease develop such as anorexia, jaundice, dark administered concomitantly with Levofloxacin
urine, pruritus or tender abdomen. Tablets. Concurrent administration of
fluoroquinolones with multi-vitamins containing
Exacerbation of myasthenia gravis
zinc appears to reduce their oral absorption. It is
Fluoroquinolones, including levofloxacin, have recommended that preparations containing
neuromuscular blocking activity and may divalent or trivalent cations such as iron salts,
exacerbate muscle weakness in patients with zinc salts or magnesium- or aluminium-
myasthenia gravis. Postmarketing serious containing antacids, or didanosine
adverse reactions, including deaths and the (only didanosine formulations with aluminium
requirement for respiratory support, have been or magnesium containing buffering
associated with fluoroquinolone use in patients agents) should not be taken 2 hours before or
with myasthenia gravis. Levofloxacin is not after Levofloxacin Tablets administration (see
recommended in patients with a known history section 4.2). Calcium salts have a minimal effect
of myasthenia gravis. on the oral absorption of levofloxacin.
Vision disorders Sucralfate
If vision becomes impaired or any effects on the The bioavailability of Levofloxacin Tablets is
eyes are experienced, an eye specialist should be significantly reduced when administered
consulted immediately (see sections 4.7 and together with sucralfate. If the patient is to
4.8). receive both sucralfate and Levofloxacin
Tablets, it is best to administer sucralfate 2 hours
Superinfection after the Levofloxacin Tablets administration
The use of levofloxacin, especially if prolonged, (see section 4.2).
may result in overgrowth of non-susceptible Theophylline, fenbufen or similar non-steroidal
organisms. If superinfection occurs during anti-inflammatory drugs
therapy, appropriate measures should be taken.
No pharmacokinetic interactions of levofloxacin
Interference with laboratory tests were found with theophylline in a clinical study.
In patients treated with levofloxacin, However a pronounced lowering of the cerebral
determination of opiates in urine may give false- seizure threshold may occur when quinolones
positive results. It may be necessary to confirm are given concurrently with theophylline, non-
positive opiate screens by more specific method. steroidal anti-inflammatory drugs, or other
agents which lower the seizure threshold.
Levofloxacin may inhibit the growth
of Mycobacterium tuberculosis and, therefore, Levofloxacin concentrations were about 13 %
may give false-negative results in the higher in the presence of fenbufen than when
bacteriological diagnosis of tuberculosis. administered alone.
4.5 Interaction with other medicinal Probenecid and cimetidine

products and other forms of interaction Probenecid and cimetidine had a statistically
Effect of other medicinal products on significant effect on the elimination of
levofloxacin levofloxacin. The renal clearance of
levofloxacin was reduced by cimetidine (24 %)
Iron salts, zinc salts, magnesium- or aluminium- and probenecid (34 %). This is because both
containing antacids, didanosine drugs are capable of blocking the renal tubular
Levofloxacin absorption is significantly reduced secretion of levofloxacin. However, at the tested
when iron salts, or magnesium- or aluminium- doses in the study, the statistically significant
containing antacids, or didanosine (only kinetic differences are unlikely to be of clinical
didanosine formulations with aluminium or relevance.
magnesium containing buffering agents) are
Caution should be exercised when levofloxacin Meals

is coadministered with drugs that effect the
tubular renal secretion such as probenecid and There is no clinically relevant interaction with
cimetidine, especially in renally impaired food. Levofloxacin Tablets may therefore be
patients. administered regardless of food intake.
Other relevant information 4.6 Fertility, Pregnancy and lactation

Pregnancy
Clinical pharmacology studies have shown that
the pharmacokinetics of levofloxacin were not There are limited amount of data with respect to
affected to any clinically relevant extent when the use of levofloxacin in pregnant women.
levofloxacin was administered together with the Animal studies do not indicate direct or indirect
following drugs: harmful effects with respect to reproductive
- calcium carbonate toxicity (see section 5.3). However in the
absence of human data and due to that
- digoxin experimental data suggest a risk of damage by
fluoroquinolones to the weight-bearing cartilage
- glibenclamide
of the growing organism, levofloxacin must not
- ranitidine. be used in pregnant women (see sections 4.3 and
5.3).
Effect of levofloxacin on other medicinal
products Breast-feeding
Ciclosporin Levofloxacin tablets are contraindicated in
breast-feeding women. There is insufficient
The half-life of ciclosporin was increased by 33 information on the excretion of levofloxacin in
% when coadministered with levofloxacin. human milk; however other fluoroquinolones are
Vitamin K antagonists excreted in breast milk. In the absence of human
data and due to that experimental data suggest a
Increased coagulation tests (PT/INR) and/or risk of damage by fluoroquinolones to the
bleeding, which may be severe, have been weight-bearing cartilage of the growing
reported in patients treated with levofloxacin in organism, levofloxacin must not be used in
combination with a vitamin K antagonist (e.g. breast-feeding women (see sections 4.3 and 5.3).
warfarin). Coagulation tests, therefore, should be
monitored in patients treated with vitamin K Fertility
antagonists (see section 4.4). Levofloxacin caused no impairment of fertility
Drugs known to prolong the QT interval or reproductive performance in rats.
Levofloxacin, like other fluoroquinolones, 4.7 Effects on ability to drive and use
should be used with caution in patients receiving machines
drugs known to prolong the QT interval (e.g. Some undesirable effects (e.g. dizziness/vertigo,
Class IA and III antiarrhythmics, tricyclic drowsiness, visual disturbances) may impair the
antidepressants, macrolides, antipsychotic). (See patient's ability to concentrate and react, and
section 4.4 QT interval prolongation). therefore may constitute a risk in situations
where these abilities are of special importance
Other relevant information (e.g. driving a car or operating machinery).
In a pharmacokinetic interaction study, 4.8 Undesirable Effects
levofloxacin did not affect the pharmacokinetics The information given below is based on data
of theophylline (which is a probe substrate for from clinical studies in more than 8300 patients
CYP1A2), indicating that levofloxacin is not a and on extensive post marketing experience.
CYP1A2 inhibitor.
Frequencies are defined using the following
Other forms of interactions convention: very common (≥ 1/10), common (≥
1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), Extrapyramid

rare (≥ 1/10,000, < 1/1,000), very rare (< al disorder
Ageusia
1/10,000), not known (cannot be estimated from Syncope
the available data). Benign
intracranial
Within each frequency grouping, undesirable hypertension
effects are presented in order of decreasing Eye Visual Transient
disorders disturbances vision loss
seriousness. such as (see section
blurred 4.4)
System Commo Uncom Rare Not known vision (see
organ n mon (≥1/10,000 (cannot be section 4.4)
class (≥1/100 (≥1/1,000 to <1/1,000) estimated
to <1/10 to from Ear and Vertigo Tinnitus Hearing loss
) <1/100) available Labyrinth Hearing
data) disorders impaired
Infections Fungal Cardiac Tachycardia, Ventricular

and infection disorders Palpitation tachycardia,
infestation including which may
s Candida result in
infection cardiac arrest
Pathoge Ventricular
n arrhythmia
resistanc and torsade
e de pointes
(reported
Blood and Leukope Thrombocyt Pancytopenia predominantly
lymphatic nia openia Agranulocytos in patients
system Eosinoph Neutropenia is with risk
disorders ilia Haemolytic factors of QT
anaemia prolongation),
Immune Angioedema Anaphylactic electrocardiog
system Hypersensiti shocka ram QT
disorders vity (see Anaphylactoid prolonged
section 4.4) shock a (see (see sections
section 4.4) 4.4 and 4.9)
Metabolis Anorexia Hypoglycae Hyperglycae Vascular Hypotension
m and mia mia disorders
nutrition particularly Hypoglycaemi Respirator Dyspnoe Bronchospas
disorders in diabetic c coma (see y, thoracic a m
patients (see section 4.4) and Pneumonitis
section 4.4) mediastina allergic
Psychiatric Insomnia Anxiety Psychotic Psychotic l disorders
disorders Confusio reactions disorders with Gastro- Diarrhoe Abdomin Diarrhoea –
nal state (with e.g. self- intestinal a al pain haemorrhagic
Nervous hallucination endangering disorders Vomiting Dyspepsi which in very
ness , paranoia) behaviour Nausea a rare cases
Depression including Flatulenc may be
Agitation suicidal e indicative of
Abnormal ideation or Constipat enterocolitis,
dreams suicide ion including
Nightmares attempt (see pseudomemb
section 4.4) ranous colitis
Nervous Headach Somnole Convulsion Peripheral (see section
system e nce (see sensory 4.4)
disorders Dizzines Tremor sections 4.3 neuropathy Pancreatitis
s Dysgeusi and 4.4) (see section Hepatobili Hepatic Blood Jaundice and
a Paraesthesi 4.4) ary enzyme bilirubin severe liver
a Peripheral disorders increase increase injury,
sensory motor d d including
neuropathy (ALT/AS cases with
(see section T, fatal acute
4.4) alkaline liver failure,
Parosmia phosphat primarily in
including ase, patients with
anosmia GGT) severe
Dyskinesia underlying
diseases (see important. It allows continued monitoring of the

section 4.4) benefit/risk balance of the medicinal product.
Hepatitis
Skin and Rash Toxic 4.9 Overdose
subcutane Pruritus epidermal
ous tissue Urticaria necrolysis According to toxicity studies in animals or
disorders b Hyperhid Stevens-
rosis Johnson clinical pharmacology studies performed with
syndrome supra-therapeutic doses, the most important
Erythema
multiforme
signs to be expected following acute overdosage
Photosensitivi of levofloxacin are central nervous system
ty reaction symptoms such as confusion, dizziness,
(see section
4.4) impairment of consciousness, and convulsive
Leukocytoclas seizures, increases in QT interval as well as
tic vasculitis gastro-intestinal reactions such as nausea and
Stomatitis
mucosal erosions.
Musculosk Arthralgi Tendon Rhabdomyoly
eletal and a disorders sis CNS effects including confusional state,
connective Myalgia (see Tendon
tissue sections 4.3 rupture (e.g. convulsion, hallucination, and tremor have been
disorders and 4.4) Achilles observed in post marketing experience.
including tendon) (see
tendinitis sections 4.3 In the event of overdose, symptomatic treatment
(e.g. Achilles and 4.4)
tendon) Ligament should be implemented. ECG monitoring should
Muscular rupture be undertaken, because of the possibility of QT
weakness Muscle
which may rupture
interval prolongation. Antacids may be used for
be of special Arthritis protection of gastric mucosa. Haemodialysis,
importance including peritoneal dialysis and CAPD, are not
in patients
with effective in removing levofloxacin from the
myasthenia body. No specific antidote exists.
gravis (see
section 4.4 ) 5. PHARMACOLOGICAL PROPERTIES
Renal and Blood Renal failure
Urinary creatinin acute (e.g. 5.1 Pharmacodynamic properties
disorders e due to
increase interstitial
d nephritis) Pharmacotherapeutic group: Antiifectives for
General Asthenia Pyrexia Pain systemic use – Antibacterials for systemic use –
disorders (including Quinolone antibasterials – Fluoroquinolones
and pain in back,
administrat chest, and Levofloxacin is a synthetic antibacterial agent of
ion site extremities)
conditions
the fluoroquinolone class and is the S (-)
a enantiomer of the racemic drug substance
Anaphylactic and anaphylactoid reactions may
ofloxacin.
sometimes occur even after the first dose
b Mechanism of action
Mucocutaneous reactions may sometimes
occur even after the first dose As a fluoroquinolone antibacterial agent,
levofloxacin acts on the DNA-DNA-gyrase
Other undesirable effects which have been
complex and topoisomerase IV.
associated with fluoroquinolone administration
include: PK/PD relationship
• attacks of porphyria in patients with porphyria. The degree of the bactericidal activity of
levofloxacin depends on the ratio of the
Reporting of suspected adverse reactions
maximum concentration in serum (Cmax) or the
Reporting suspected adverse reactions after area under the curve (AUC) and the minimal
authorisation of the medicinal product is inhibitory concentration (MIC).
Mechanism(s) of resisance 3. Strains with MIC values above the susceptible

breakpoint are very rare or not yet reported. The
Resistance to levofloxacin is acquired through a identification and antimicrobial susceptibility
stepwise process by target site mutations in both tests on any such isolate must be repeated and if
type II topoisomerases, DNA gyrase and the result is confirmed the isolate must be sent to
topoisomerase IV. Other resistance mechanisms a reference laboratory. Until there is evidence
such as permeation barriers (common in regarding clinical response for confirmed
Pseudomonas aeruginosa) and efflux
isolates with MIC above the current resistant
mechanisms may also affect susceptibility to breakpoint they should be reported resistant.
levofloxacin.
4. Breakpoints apply to an oral dose of 500 mg x
Cross-resistance between levofloxacin and other 1 to 500 mg x 2 and an intravenous dose of 500
fluoroquinolones is observed. Due to the mg x 1 to 500 mg x 2.
mechanism of action, there is generally no cross-
resistance between levofloxacin and other The prevalence of resistance may vary
classes of antibacterial agents. geographically and with time for selected
species and local information on resistance is
Breakpoints
desirable, particularly when treating severe
The EUCAST recommended MIC breakpoints infections. As necessary, expert advice should
for levofloxacin, separating susceptible from be sought when the local prevalence of
intermediately susceptible organisms and resistance is such that the utility of the agent in
intermediately susceptible from resistant at least some types of infections is questionable.
organisms are presented in the below table for
Commonly susceptible species
MIC testing (mg/L).
Aerobic Gram-positive bacteria
EUCAST clinical MIC breakpoints for Bacillus anthracis
levofloxacin (version 2.0, 2012-01-01): Staphylococcus aureus methicillin-susceptible
Staphylococcus saprophyticus
Pathogen Susceptible Resistant Streptococci, group C and G
Streptococcus agalactiae
Enterobacteriacae ≤1 mg/L >2 mg/L Streptococcus pneumoniae
Streptococcus pyogenes
Pseudomonas spp. ≤1 mg/L >2 mg/L
Aerobic Gram- negative bacteria
Acinetobacter spp. ≤1 mg/L >2 mg/L Eikenella corrodens
Haemophilus influenzae
Staphylococcus spp. ≤1 mg/L >2 mg/L Haemophilus para-influenzae
Klebsiella oxytoca
S.pneumoniae 1 ≤2 mg/L >2 mg/L Moraxella catarrhalis
Streptococcus Pasteurella multocida
≤1 mg/L >2 mg/L Proteus vulgaris
A,B,C,G
Providencia rettgeri
H.influenzae2,
≤1 mg/L >1 mg/L Anaerobic bacteria
3
M.catarrhalis 3
Peptostreptococcus
Non-species related
≤1 mg/L >2 mg/L Other
breakpoints 4
1 Chlamydophila pneumoniae
. The breakpoints for levofloxacin relate to high
Chlamydophila psittaci
dose therapy. Chlamydia trachomatis
2. Low-level fluoroquinolone resistance Legionella pneumophila
Mycoplasma pneumoniae
(ciprofloxacin MICs of 0.12-0.5 mg/l) may Mycoplasma hominis
occur but there is no evidence that this resistance Ureaplasma urealyticum
is of clinical importance in respiratory tract Species for which acquired resistance may be a
infections with H. influenzae. problem
Enterococcus faecalis levofloxacin has poor penetration intro cerebro-

Staphylococcus aureus methicillin-resistant# spinal fluid.
Coagulase negative Staphylococcus spp
Aerobic Gram- negative bacteria Biotransformation
Acinetobacter baumannii Levofloxacin is metabolised to a very small
Citrobacter freundii extent, the metabolites being desmethyl-
Enterobacter aerogenes
Enterobacter cloacae levofloxacin and levofloxacin N-oxide. These
Escherichia coli metabolites account for < 5 % of the dose
Klebsiella pneumoniae excreted in urine. Levofloxacin is
Morganella morganii stereochemically stable and does not undergo
Proteus mirabilis
Providencia stuartii
chiral inversion.
Pseudomonas aeruginosa Elimination
Serratia marcescens
Anaerobic bacteria Following oral and intravenous administration of
Bacteroides fragilis levofloxacin, it is eliminated relatively slowly
Inherently resistant Strains from the plasma (t½: 6 - 8 h). Excretion is
primarily by the renal route > 85 % of the
administered dose).
Enterococcus faecium
# Methicillin-resistant S. aureus are very likely The mean apparent total body clearance of
to possess co-resistance to fluoroquinolones, levofloxacin following a 500 mg single dose was
including levofloxacin. 175 +/-29.2 ml/min.
5.2 Pharmacokinetic properties There are no major differences in the
pharmacokinetics of levofloxacin following
Absorption intravenous and oral administration, suggesting
Orally administered levofloxacin is rapidly and that the oral and intravenous routes are
almost completely absorbed with peak plasma interchangeable.
concentrations being obtained within 1- 2 h. The Linearity
absolute bioavailability is 99- 100 %.
Levofloxacin obeys linear pharmacokinetics
Food has little effect on the absorption of over a range of 50 to 1000 mg.
levofloxacin.
Special populations
Steady state conditions are reached within 48
hours following a 500 mg once or twice daily Subjects with renal insufficiency
dosage regimen.
The pharmacokinetics of levofloxacin are
Distribution affected by renal impairment. With decreasing
renal function renal elimination and clearance
Approximately 30 - 40 % of levofloxacin is are decreased, and elimination half-lives
bound to serum protein. The mean volume of increased as shown in the table below:
distribution of levofloxacin is approximately 100
l after single and repeated 500 mg doses, Pharmacokinetics in renal insufficiency
indicating widespread distribution into body following single oral 500 mg dose
tissues.
Clcr [ml/min] < 20 20 - 49 50 - 80
Penetration into tissues and body fluids:
ClR [ml/min] 13 26 57
Levofloxacin has been shown to penetrate into
bronchial mucosa, epithelial lining fluid, t1/2 [h] 35 27 9
alveolar macrophages, lung tissue, skin (blister Elderly subjects
fluid), prostatic tissue and urine. However,
There are no significant differences in Cellulose microcrystalline

levofloxacin kinetics between young and elderly
Magnesium stearate
subjects, except those associated with
differences in creatinine clearance. Silica colloidal anhydrous
Gender differences Tablet coating:
Separate analysis for male and female subjects Hypromellose E5 Talc
showed small to marginal gender differences in
levofloxacin pharmacokinetics. There is no Titanium dioxide (E171)
evidence that these gender differences are of Macrogol 400
clinical relevance.
Yellow ferric oxide (E172)
5.3 Preclinical safety data
Red ferric oxide (E172)
Non-clinical data reveal no special hazard for
humans based on conventional studies of single 6.2 Incompatibilities
dose toxicity, repeated dose toxicity, Not applicable.
carcinogenic potential and toxicity to 6.3 Shelf life
reproduction and development. 3 years.
Levofloxacin caused no impairment of fertility 6.4 Special precautions for storage
or reproductive performance in rats and its only This medicinal product does not require any
effect on fetuses was delayed maturation as a special storage conditions.
result of maternal toxicity.
6.5 Nature and contents of container
Levofloxacin did not induce gene mutations in
bacterial or mammalian cells but did induce Tablets are packed in PVC/aluminium blisters.
chromosome aberrations in Chinese hamster
For 500 mg, the tablets are provided in pack
lung cells in vitro. These effects can be
sizes of 1, 2, 5, 7, 10, 30, 50, 200 and 500
attributed to inhibition of topoisomerase II. In
tablets.
vivo tests (micronucleus, sister chromatid
exchange, unscheduled DNA synthesis, Not all pack sizes may be marketed.
dominant lethal tests) did not show any
genotoxic potential. 6.6 Special precautions for disposal and
other handling
Studies in the mouse showed levofloxacin to
have phototoxic activity only at very high doses. No special requirements.
Levofloxacin did not show any genotoxic Any unused product or waste material should be
potential in a photomutagenicity assay, and it disposed of in accordance with local
reduced tumour development in a requirements.
photocarcinogenity study.
7. MANUFACTURER:
In common with other fluoroquinolones,
levofloxacin showed effects on cartilage
(blistering and cavities) in rats and dogs. These
findings were more marked in young animals.
Manufactured in India by:
6. PHARMACEUTICAL PARTICULARS TAJ PHARMACEUTICALS LTD.
Mumbai, India
6.1 List of excipients At: 615, GIDC, Kerala, Bavla, Dist. Ahmedabad
Tablet core: 438225, Gujarat, INDIA
Povidone
This leaflet was last revised in October 2019
Crospovidone (Type-B)

Levofloxacin 500 MG Film-Coated Tablets SMPC - Taj Pharmaceuticals

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

Levofloxacin 500 MG Film-Coated Tablets SMPC - Taj Pharmaceuticals

Uploaded by

Copyright:

Available Formats

Levofloxacin 500 mg Fil m-coated Tabl ets SMPC, Taj Phar maceuticals

• Uncomplicated cystitis (see section 4.4)

• Community-acquired pneumonia Pyelonephritis 500 mg once daily 7 - 10 days

• Chronic bacterial prostatitis

4.5 Interaction with other medicinal Probenecid and cimetidine

Caution should be exercised when levofloxacin Meals

Other relevant information 4.6 Fertility, Pregnancy and lactation

1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), Extrapyramid

Infections Fungal Cardiac Tachycardia, Ventricular

diseases (see important. It allows continued monitoring of the

Mechanism(s) of resisance 3. Strains with MIC values above the susceptible

Enterococcus faecalis levofloxacin has poor penetration intro cerebro-

There are no significant differences in Cellulose microcrystalline

You might also like