Tavflox is indicated in adults for the treatment of the following infections
(see sections 4.4 and 5.1):
• Acute bacterial sinusitis
• Acute exacerbations of chronic bronchitis
• Community-acquired pneumonia
• Complicated skin and soft tissue infections
For the above-mentioned infections Tavflox should be used only when it is considered
inappropriate to use antibacterial agents that are commonly recommended for the initial
treatment of these infections.
• Pyelonephritis and complicated urinary tract infections (see Special warnings and precautions for
use)
• Chronic bacterial prostatitis

Uncomplicated cystitis (see Special warnings and precautions for use)
• Inhalation Anthrax: post exposure prophylaxis and curative treatment (see Special warnings and
precautions for use)
Tavflox may also be used to complete a course of therapy in patients who have shown
improvement during initial treatment with intravenous levofloxacin.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Tavflox tablets are administered once or twice daily. The dosage depends on the type and severity
of the infection and the susceptibility of the presumed causative pathogen.
Tavflox tablets may also be used to complete a course of therapy in patients who have shown
improvement during initial treatment with intravenous levofloxacin; given the bioequivalence of
the parenteral and oral forms, the same dosage can be used.
Posology
The following dose recommendations can be given for Tavflox :
Dosage in patients with normal renal function (creatinine clearance > 50 ml/min)

Special populations
Impaired renal function (creatinine clearance ≤ 50 ml/min)

1 No additional doses are required after haemodialysis or continuous ambulatory peritoneal
dialysis (CAPD).
Impaired liver function
No adjustment of dose is required since levofloxacin is not metabolised to any relevant extent by
the liver and is mainly excreted by the kidneys.
Elderly Population
No adjustment of dose is required in the elderly, other than that imposed by consideration of renal
function (See Special warnings and precautions for use “Tendinitis and tendon rupture” and “QT
interval prolongation”).
Paediatric population
Tavflox is contraindicated in children and growing adolescents (see Contraindications).
Method of administration
Tavflox tablets should be swallowed without crushing and with sufficient amount of liquid. They
may be divided at the score line to adapt the dose. The tablets may be taken during meals or
between meals. Tavflox tablets should be taken at least two hours before or after iron salts, zinc
salts, magnesium- or aluminium-containing antacids, or didanosine (only didanosine formulations
with aluminium or magnesium containing buffering agents), and sucralfate administration, since
reduction of absorption can occur (see Interaction with other medicinal products and other forms
of interaction).

Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of
fluoroquinolones, particularly in the older population.
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after
consideration of other therapeutic options in patients with positive family history of aneurysm
disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection, or in
presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (e.g.
Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet’s
disease, hypertension, known atherosclerosis).
In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a
physician in an emergency department.
Methicillin-resistant S. aureus are very likely to possess co-resistance to fluoroquinolones, including
levofloxacin. Therefore levofloxacin is not recommended for the treatment of known or suspected
MRSA infections unless laboratory results have confirmed susceptibility of the organism to
levofloxacin (and commonly recommended antibacterial agents for the treatment of MRSA-infections
are considered inappropriate).

Levofloxacin may be used in the treatment of Acute Bacterial Sinusitis and Acute Exacerbation of
Chronic Bronchitis when these infections have been adequately diagnosed.
Resistance to fluoroquinolones of E. coli – the most common pathogen involved in urinary tract
infections – varies across the European Union. Prescribers are advised to take into account the local
prevalence of resistance in E. coli to fluoroquinolones.
Inhalation Anthrax: Use in human is based on in vitro Bacillus anthracis susceptibility data and on
animal experimental data together with limited human data. Treating physicians should refer to
national and/or international consensus documents regarding the treatment of anthrax.
Tendinitis and tendon rupture
Tendinitis may rarely occur. It most frequently involves the Achilles tendon and may lead to tendon
rupture. Tendinitis and tendon rupture, sometimes bilateral, may occur within 48 hours of starting
treatment with levofloxacin and have been reported up to several months after discontinuation of
treatment. The risk of tendinitis and tendon rupture is increased in patients aged over 60 years, in
patients receiving daily doses of 1000 mg and in patients using corticosteroids. The daily dose should
be adjusted in elderly patients based on creatinine clearance (see Posology and method of
administration). Close monitoring of these patients is therefore necessary if they are prescribed
levofloxacin. All patients should consult their physician if they experience symptoms of tendinitis. If
tendinitis is suspected, treatment with levofloxacin must be halted immediately, and appropriate
treatment (e.g. immobilisation) must be initiated for the affected tendon (see Contraindications and
Undesirable effects).

Clostridium difficile-associated disease
Diarrhoea, particularly if severe, persistent and/or bloody, during or after treatment with levofloxacin
(including several weeks after treatment), may be symptomatic of Clostridium difficile-associated
disease (CDAD). CDAD may range in severity from mild to life threatening, the most severe form of
which is pseudomembranous colitis (see Undesirable effects). It is therefore important to consider
this diagnosis in patients who develop serious diarrhoea during or after treatment with levofloxacin.
If CDAD is suspected or confirmed, levofloxacin should be stopped immediately and appropriate
treatment initiated without delay. Anti-peristaltic medicinal products are contraindicated in this
clinical situation.
Patients predisposed to seizures
Quinolones may lower the seizure threshold and may trigger seizures. Levofloxacin is contraindicated
in patients with a history of epilepsy (see Contraindications) and, as with other quinolones, should be
used with extreme caution in patients predisposed to seizures or concomitant treatment with active
substances that lower the cerebral seizure threshold, such as theophylline (see Interaction with other
medicinal products and other forms of interaction). In case of convulsive seizures (see Undesirable
effects), treatment with levofloxacin should be discontinued.
Patients with G-6- phosphate dehydrogenase deficiency
Patients with latent or actual defects in glucose-6-phosphate dehydrogenase activity may be prone to
haemolytic reactions when treated with quinolone antibacterial agents. Therefore, if levofloxacin has
to be used in these patients, potential occurrence of haemolysis should be monitored.
Patients with renal impairment
Since levofloxacin is excreted mainly by the kidneys, the dose of Tavflox should be adjusted in
patients with renal impairment (see Posology and method of administration).
Hypersensitivity reactions
Levofloxacin can cause serious, potentially fatal hypersensitivity reactions (e.g. angioedema up to
anaphylactic shock), occasionally following the initial dose (see Undesirable effects). Patients should
discontinue treatment immediately and contact their physician or an emergency physician, who will
initiate appropriate emergency measures.
Severe bullous reactions
Cases of severe bullous skin reactions such as Stevens-Johnson syndrome or toxic epidermal
necrolysis have been reported with levofloxacin (see Undesirable effects). Patients should be advised
to contact their doctor immediately prior to continuing treatment if skin and/or mucosal reactions
occur.
Dysglycaemia
As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and
hyperglycaemia have been reported, usually in diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g., glibenclamide) or with insulin. Cases of hypoglycaemic coma
have been reported. In diabetic patients, careful monitoring of blood glucose is recommended (see
Undesirable effects).
Prevention of photosensitisation
Photosensitisation has been reported with levofloxacin (see Undesirable effects). It is recommended
that patients should not expose themselves unnecessarily to strong sunlight or to artificial UV rays
(e.g. sunray lamp, solarium), during treatment and for 48 hours following treatment discontinuation
in order to prevent photosensitisation.
Patients treated with Vitamin K antagonists
Due to possible increase in coagulation tests (PT/INR) and/or bleeding in patients treated with
levofloxacin in combination with a vitamin K antagonist (e.g. warfarin), coagulation tests should be
monitored when these drugs are given concomitantly (see Interaction with other medicinal products
and other forms of interaction).
Psychotic reactions
Psychotic reactions have been reported in patients receiving quinolones, including levofloxacin. In
very rare cases these have progressed to suicidal thoughts and self-endangering behavioursometimes
after only a single dose of levofloxacin (see Undesirable effects). In the event that the
patient develops these reactions, levofloxacin should be discontinued and appropriate measures
instituted. Caution is recommended if levofloxacin is to be used in psychotic patients or in patients
with history of psychiatric disease.
QT interval prolongation
Caution should be taken when using fluoroquinolones, including levofloxacin, in patients with known
risk factors for prolongation of the QT interval such as, for example:
- congenital long QT syndrome
- concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III
antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics).
- uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesemia)
- cardiac disease (e.g. heart failure, myocardial infarction, bradycardia)
Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore,
caution should be taken when using fluoroquinolones, including levofloxacin, in these populations.
(See Posology and method of administration "Elderly", Interaction with other medicinal products and
other forms of interaction, Undesirable effects, and Overdose).

Peripheral neuropathy
Peripheral sensory neuropathy and peripheral sensory motor neuropathy have been reported in
patients receiving fluoroquinolones, including levofloxacin, which can be rapid in its onset (see
Undesirable effects). Levofloxacin should be discontinued if the patient experiences symptoms of
neuropathy in order to prevent the development of an irreversible condition.
Hepatobiliary disorders
Cases of hepatic necrosis up to fatal hepatic failure have been reported with levofloxacin, primarily in
patients with severe underlying diseases, e.g. sepsis (see Undesirable effects). Patients should be
advised to stop treatment and contact their doctor if signs and symptoms of hepatic disease develop
such as anorexia, jaundice, dark urine, pruritus or tender abdomen.
Exacerbation of myasthenia gravis
Fluoroquinolones, including levofloxacin, have neuromuscular blocking activity and may exacerbate
muscle weakness in patients with myasthenia gravis. Postmarketing serious adverse reactions,
including deaths and the requirement for respiratory support, have been associated with
fluoroquinolone use in patients with myasthenia gravis. Levofloxacin is not recommended in patients
with a known history of myasthenia gravis.
Vision disorders
If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be
consulted immediately (see Effects on ability to drive and use machines and Undesirable effects).
Superinfection
The use of levofloxacin, especially if prolonged, may result in overgrowth of non-susceptible
organisms. If superinfection occurs during therapy, appropriate measures should be taken.
Interference with laboratory tests
In patients treated with levofloxacin, determination of opiates in urine may give false-positive results.
It may be necessary to confirm positive opiate screens by more specific method.
Levofloxacin may inhibit the growth of Mucobacterium tuberculosis and, therefore, may give falsenegative
results in the bacteriological diagnosis of tuberculosis.

- Effect of other medicinal products on Tavflox
- Iron salts, zinc salts, magnesium- or aluminium-containing antacids, didanosine
- Levofloxacin absorption is significantly reduced when iron salts, or magnesium- or aluminiumcontaining
antacids, or didanosine (only didanosine formulations with aluminium or magnesium
containing buffering agents) are administered concomitantly with Tavflox tablets. Concurrent
administration of fluoroquinolones with multi-vitamins containing zinc appears to reduce their oral
absorption. It is recommended that preparations containing divalent or trivalent cations such as
iron salts, zinc salts or magnesium- or aluminium-containing antacids, or didanosine (only
didanosine formulations with aluminium or magnesium containing buffering agents) should not be taken 2 hours before or after Tavflox tablet administration (see Posology and method of
administration). Calcium salts have a minimal effect on the oral absorption of levofloxacin.
- Sucralfate
- The bioavailability of Tavflox tablets is significantly reduced when administered together with
sucralfate. If the patient is to receive both sucralfate and Tavflox, it is best to administer sucralfate 2
hours after the Tavflox tablet administration (see Posology and method of administration).
- Theophylline, fenbufen or similar non-steroidal anti-inflammatory drugs
- No pharmacokinetic interactions of levofloxacin were found with theophylline in a clinical study.
However a 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 seizure threshold.
- Levofloxacin concentrations were about 13% higher in the presence of fenbufen than when
administered alone.
- Probenecid and cimetidine
- Probenecid and cimetidine had a statistically significant effect on the elimination of levofloxacin.
The renal clearance of levofloxacin was reduced by cimetidine (24%) and probenecid (34%). This is
because both drugs are capable of blocking the renal tubular secretion of levofloxacin. However, at
the tested doses in the study, the statistically significant kinetic differences are unlikely to be of
clinical relevance.
- Caution should be exercised when levofloxacin is coadministered with drugs that affect the tubular
renal secretion such as probenecid and cimetidine, especially in renally impaired patients.
- Other relevant information
- Clinical pharmacology studies have shown that the pharmacokinetics of levofloxacin were not
affected to any clinically relevant extent when levofloxacin was administered together with the
following drugs: calcium carbonate, digoxin, glibenclamide, ranitidine.
- Effect of Tavflox on other medicinal products
- Ciclosporin
- The half-life of ciclosporin was increased by 33% when coadministered with levofloxacin.
- Vitamin K antagonists
- Increased coagulation tests (PT/INR) and/or bleeding, which may be severe, have been reported in
patients treated with levofloxacin in combination with a vitamin K antagonist (e.g. warfarin).
Coagulation tests, therefore, should be monitored in patients treated with vitamin K antagonists
(see Special warnings and precautions for use).
- Drugs known to prolong QT interval
- Levofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs
known to prolong the QT interval (e.g. Class IA and III antiarrhythmics, tricyclic antidepressants,
macrolides, antipsychotics) (See Special warnings and precautions for use QT interval prolongation).
- Other relevant information
- In a pharmacokinetic interaction study, levofloxacin did not affect the pharmacokinetics of
theophylline (which is a probe substrate for CYP1A2), indicating that levofloxacin is not a CYP1A2
inhibitor.

- Other forms of interactions
- Food
- There is no clinically relevant interaction with food. Tavflox tablets may therefore be administered
regardless of food intake.

Pregnancy
pregnancy category C
There is limited amount of data from the use of levofloxacin in pregnant women. Animal studies do
not indicate direct or indirect harmful effects with respect to reproductive toxicity (see Preclinical
safety data). However in the absence of human data and due to that experimental data suggest a
risk of damage by fluoroquinolones to the weight-bearing cartilage of the growing organism,
levofloxacin must not be used in pregnant women (see Contraindications and Preclinical safety
data).
Breast-feeding
Tavflox is contraindicated in breast-feeding women. There is insufficient information on the
excretion of levofloxacin in human milk; however, other fluoroquinolones are excreted in breast
milk. In the absence of human data and due to that experimental data suggest a risk of damage by
fluoroquinolones to the weight-bearing cartilage of the growing organism, levofloxacin must not
be used in breast-feeding women (see Contraindications and Preclinical safety data).
Fertility
Levofloxacin caused no impairment of fertility or reproductive performance in rats.

Some undesirable effects (e.g. dizziness/vertigo, drowsiness, visual disturbances) may impair the patient's ability to concentrate and react, and therefore may constitute a risk in situations where these abilities are of special importance (e.g. driving a car or operating machinery)

The information given below is based on data from clinical studies in more than 8300 patients and on
extensive post marketing experience.
Frequencies are defined using the following convention: very common (≥1/10), common (≥1/100,
<1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), not known
(cannot be estimated from the available data).
Within each frequency grouping, undesirable effects are presented in order of decreasing
seriousness.

Reporting to National Regulatory Authority:
To reports any side effect(s):
Saudi Arabia:
-The National Pharmacovigilance and Drug Safety Centre (NPC)
• Fax: +966-11-205-7662
• Call NPC at +966-11-2038222, Ext: 2317-2356-2340.
• Reporting hotline:19999
• Toll free phone: 8002490000
• E-mail: npc.drug@sfda.gov.sa
• Website: www.sfda.gov.sa/npc
Other GCC States:
-Please contact the relevant competent authority.

According to toxicity studies in animals or clinical pharmacology studies performed with supratherapeutic
doses, the most important signs to be expected following acute overdose of Tavflox
tablets are central nervous system symptoms such as confusion, dizziness, impairment of
consciousness, and convulsive seizures, increases in QT interval as well as gastro-intestinal reactions
such as nausea and mucosal erosions.
CNS effects including confusional state, convulsion, hallucination, and tremor have been observed in
post marketing experience.
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be
undertaken, because of the possibility of QT 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.

Pharmacotherapeutic group: quinolone antibacterials, fluoroquinolones
ATC code: J01MA12
Levofloxacin is a synthetic antibacterial agent of the fluoroquinolone class and is the S (-) enantiomer
of the racemic active substance ofloxacin.
Mechanism of action

As a fluoroquinolone antibacterial agent, levofloxacin acts on the DNA-DNA-gyrase complex and
topoisomerase IV.
PK/PD relationship
The degree of the bactericidal activity of levofloxacin depends on the ratio of the maximum
concentration in serum (Cmax) or the area under the curve (AUC) and the minimal inhibitory
concentration (MIC).
Mechanism of resistance
Resistance to levofloxacin is acquired through a stepwise process by target site mutations in both
type II topoisomerases, DNA gyrase and topoisomerase IV. Other resistance mechanisms such as
permeation barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may also affect
susceptibility to levofloxacin.
Cross-resistance between levofloxacin and other fluoroquinolones is observed. Due to the
mechanism of action, there is generally no cross-resistance between levofloxacin and other classes of
antibacterial agents.
Breakpoints
The EUCAST recommended MIC breakpoints for levofloxacin, separating susceptible from
intermediately susceptible organisms and intermediately susceptible from resistant organisms are
presented in the below table for MIC testing (mg/l).
EUCAST clinical MIC breakpoints for levofloxacin (version 2.0, 2012-01-01):

4. Breakpoints apply to an oral dose of 500 mg x 1 to 500 mg x 2 and an intravenous dose of 500
mg x 1 to 500 mg x 2
The prevalence of resistance may vary geographically and with time for selected species and local
information on resistance is desirable, particularly when treating severe infections. As necessary,
expert advice should be sought when the local prevalence of resistance is such that the utility of the
agent in at least some types of infections is questionable.

Commonly susceptible species
Aerobic Gram-positive bacteria
Bacillus anthracis
Staphylococcus aureus methicillin-susceptible
Staphylococcus saprophyticus
Streptococci, group C and G
Streptococcus agalactiae
Streptococcus pneumoniae
Streptococcus pyogenes
Aerobic Gram- negative bacteria
Eikenella corrodens
Haemophilus influenzae
Haemophilus para-influenzae
Klebsiella oxytoca
Moraxella catarrhalis
Pasteurella multocida
Proteus vulgaris
Providencia rettgeri
Anaerobic bacteria
Peptostreptococcus
Other
Chlamydophila pneumoniae
Chlamydophila psittaci
Chlamydia trachomatis
Legionella 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 bacteria
Acinetobacter baumannii
Citrobacter freundii
Enterobacter aerogenes
Enterobacter cloacae

Escherichia coli
Klebsiella pneumoniae
Morganella morganii
Proteus mirabilis
Providencia stuartii
Pseudomonas aeruginosa
Serratia marcescens
Anaerobic bacteria
Bacteroides fragilis
Inherently Resistant Strains
Aerobic Gram-positive bacteria
Enterococcus faecium
# Methicillin-resistant S. aureus is very likely to possess co-resistance to fluoroquinolones, including
levofloxacin.

Absorption
Orally administered levofloxacin is rapidly and almost completely absorbed with peak plasma
concentrations being obtained within 1 - 2 h. The absolute bioavailability is 99 - 100 %.
Food has little effect on the absorption of levofloxacin.
Steady state conditions are reached within 48 hours following a 500 mg once or twice daily dosage
regimen.
Distribution
Approximately 30 - 40 % of levofloxacin is bound to serum protein.
The mean volume of distribution of levofloxacin is approximately 100 l after single and repeated 500
mg doses, indicating widespread distribution into body tissues.
Penetration into tissues and body fluids:
Levofloxacin has been shown to penetrate into bronchial mucosa, epithelial lining fluid, alveolar
macrophages, lung tissue, skin (blister fluid), prostatic tissue and urine. However, levofloxacin has
poor penetration into cerebro-spinal fluid.
Biotransformation
Levofloxacin is metabolised to a very small extent, the metabolites being desmethyl-levofloxacin and
levofloxacin N-oxide. These metabolites account for <5 % of the dose and are excreted in urine.
Levofloxacin is stereochemically stable and does not undergo chiral inversion.
Elimination
Following oral and intravenous administration of levofloxacin, it is eliminated relatively slowly from
the plasma (t½ : 6 - 8 h). Excretion is primarily by the renal route (>85 % of the administered dose).
The mean apparent total body clearance of levofloxacin following a 500 mg single dose was 175 +/-
29.2 ml/min.
There are no major differences in the pharmacokinetics of levofloxacin following intravenous and oral
administration, suggesting that the oral and intravenous routes are interchangeable.
Linearity
Levofloxacin obeys linear pharmacokinetics over a range of 50 to 1000 mg.
Special populations
Subjects with renal insufficiency

 The pharmacokinetics of levofloxacin are affected by renal impairment. With decreasing renal
function renal elimination and clearance are decreased, and elimination half-lives increased as shown
in the table below:
Pharmacokinetics in renal insufficiency following single oral 500 mg dose

Elderly subjects
There are no significant differences in levofloxacin pharmacokinetics between young and elderly
subjects, except those associated with differences in creatinine clearance.
Gender differences
Separate analysis for male and female subjects showed small to marginal gender differences in
levofloxacin pharmacokinetics. There is no evidence that these gender differences are of clinical
relevance.

Non-clinical data reveal no special hazard for humans based on conventional studies of single dose
toxicity, repeated dose toxicity, carcinogenic potential and toxicity to reproduction and
development.
Levofloxacin caused no impairment of fertility or reproductive performance in rats and its only
effect on fetuses was delayed maturation as a result of maternal toxicity.
Levofloxacin did not induce gene mutations in bacterial or mammalian cells but did induce
chromosome aberrations in Chinese hamster lung cells in vitro. These effects can be attributed to
inhibition of topoisomerase II. In vivo tests (micronucleus, sister chromatid exchange, unscheduled
DNA synthesis, dominant lethal tests) did not show any genotoxic potential.
Studies in the mouse showed levofloxacin to have phototoxic activity only at very high doses.
Levofloxacin did not show any genotoxic potential in a photomutagenicity assay, and it reduced
tumour development in a photocarcinogenity study.
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.

Tavflox 500 mg film-coated tablets contain the following excipients

Tablet core:
Crosspovidone 
Pharmacoat 
Microcrystalline cellulose 
Sodium stearyl fumarete 
Tablet coating:
Opadry Pink (03F34510)[Hypromellose-
Titanium Dioxide-Talc-Macrogol-red iron
oxide- yellow Iron oxide

Not Applicable

-Store below 30°C.
-keep in the original package in order to protect from light and moisture.

-The immediate packaging material is PVC/PVDC/Alu Blister.
-Pack size: 5 Film-Coated Tablets.

As for all medicines, any unused medicinal product should be disposed of accordingly and in
compliance with local environmental regulations.