Noroxin® is indicated for the treatment of adults with upper and lower tract infections, specifically
complicated and uncomplicated cystitis, pyelitis and pyelonephritis the following infections caused
by susceptible strains of the designated microorganisms:
Escherichia coli
Klebsiella pneumonia
Unspecified Klebsiella spp.
Unspecified Enterobacter spp.
Unspecified Citrobacter spp.
Proteus mirabilis
Staphylococcus aureus
Streptococcus faecalis
Pseudomonas aeruginosa
In cases of uncomplicated acute bacterial cystitis, limit the use of NORFLOXACIN to circumstances
where no other treatment options are available. A urine culture should be obtained prior to
Fluoroquinolones, including Noroxin®, have been associated with disabling and potentially irreversible
serious adverse reactions that have occurred together including:
o Tendinitis and tendon rupture
o Peripheral neuropathy
o Central nervous system effects
Discontinue Noroxin® immediately and avoid the use of fluoroquinolones, including Noroxin®, in patients
who experience any of these serious adverse reactions. Fluoroquinolones, including Noroxin®, may
exacerbate muscle weakness in patients with myasthenia gravis. Avoid Noroxin® in patients with known
history of myasthenia gravis.
Because fluoroquinolones, including Noroxin®, have been associated with serious adverse reactions,
reserve Noroxin® for use in patients who have no alternative treatment options for uncomplicated
urinary tract infections (including cystitis).
treatment to ensure norfloxacin susceptibility.
Sexually transmitted diseases
The treatment of adults with gonococcal urethritis, or cervicitis due to penicillinase producing and
non-penicillinase producing Neisseria gonorrhoeae.
Prostatitis
Prostatitis due to Escherichia coli.
Limit the use of Noroxin® to patients where no other treatment options exist AND where Noroxin®
susceptibility is demonstrated, OR Noroxin® susceptibility is highly likely, typically greater than or
equal to 95%, based on local susceptibility patterns.
To reduce the development of drug-resistant bacteria and maintain the effectiveness of Noroxin®
and other antibacterial drugs, Noroxin® should be used only to treat infections that are proven or
strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information
are available, they should be considered in selecting or modifying antibacterial therapy. In the
absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric
selection of therapy.

Noroxin® tablets should be taken at least one hour before or at least two hours after a meal or
ingestion of milk and/or other dairy products. Multivitamins, other products containing iron or zinc,
antacids containing magnesium and aluminum, sucralfate, or didanosine, chewable/buffered
tablets or the pediatric powder for oral solution, should not be taken within 2 hours of
administration of norfloxacin.
Noroxin® tablets should be taken with a glass of water. Patients receiving Noroxin® should be well
hydrated.
Susceptibility of the causative organism to Noroxin® should be tested; however, therapy may be
initiated before obtaining the results of these tests.
Normal Renal Function
The recommended daily dose of Noroxin® is as described in the following chart:
Infection Description Unit Dose Frequency Duration Daily Dose
Urinary Tract
Uncomplicated UTI's
(cystitis) due to E. coli,
K. pneumoniae, or P.
mirabilis
400 mg q12h 3 days 800 mg
Uncomplicated
UTI's due to other
indicated organisms
400 mg q12h 7-10 days 800 mg
Complicated UTI's 400 mg q12h 10-21 days 800 mg
Sexually Transmitted
Diseases
Uncomplicated
Gonorrhea
800 mg single dose 1 day 800 mg
Prostatitis Acute or Chronic 400 mg q12h 28 days 800 mg
Renal impairment:
Noroxin® may be used for the treatment of urinary tract infections in patients with renal

insufficiency who do not require hemodialysis.
In patients with a creatinine clearance rate of 30 mL/min/1.73 m2 or less, the recommended dosage
is one 400-mg tablet once daily for the duration given above. At this dosage, the urinary
concentration exceeds the MICs for most urinary pathogens susceptible to norfloxacin, even when
the creatinine clearance is less than 10 mL/min/1.73 m2.
When only the serum creatinine level is available, the following formula (based on sex, weight, and
age of the patient) may be used to convert this value into creatinine clearance. The serum
creatinine should represent a steady state of renal function.
Males: (weight in kg) × (140 – age)
(72) × serum creatinine (mg/100 mL)
Females: (0.85) × (above value)
The administration of Noroxin® to anuric patients is not recommended.
Elderly
Elderly patients being treated for urinary tract infections who have a creatinine clearance of greater
than 30 mL/min/1.73 m2 should receive the dosages recommended under “Normal Renal Function”.
Elderly patients being treated for urinary tract infections who have a creatinine clearance of 30
mL/min/1.73 m2 or less should receive 400 mg once daily as recommended under “Renal
Impairment”.
Pediatrics
The safety and efficacy of Noroxin® in pre-pubertal children have not been established.
Noroxin® should be used in patients in whom epiphyseal closure has not occurred (see Warnings).

Warnings
Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and Tendon
Rupture, Peripheral Neuropathy, and neuropsychiatric effects.
Fluoroquinolones, including Noroxin®, have been associated with disabling and potentially
irreversible serious adverse reactions from different body systems that can occur together in the
same patient. Commonly seen adverse reactions include tendinitis, tendon rupture, arthralgia,
myalgia, peripheral neuropathy, and central nervous system effects (hallucinations, anxiety,
depression, insomnia, severe headaches, and confusion). These reactions can occur within hours to
weeks after starting Noroxin®. Patients of any age or without pre-existing risk factors have
experienced these adverse reactions. Discontinue Noroxin® immediately at the first signs or
symptoms of any serious adverse reaction. In addition, avoid the use of fluoroquinolones, including
Noroxin®, in patients who have experienced any of these serious adverse reactions associated with
fluoroquinolones.
Tendinopathy and Tendon Rupture:
Fluoroquinolones, including Noroxin®, have been associated with an increased risk of tendinitis and
tendon rupture in all ages. This adverse reaction most frequently involves the Achilles tendon, and
has also been reported with the rotator cuff (the shoulder), the hand, the biceps, the thumb, and
other tendons. Tendinitis or tendon rupture can occur within hours or days of starting Noroxin®, or
as long as several months after completion of fluoroquinolone therapy. Tendinitis and tendon

rupture can occur bilaterally.
The risk of developing fluoroquinolone-associated tendinitis and tendon rupture is increased in
patients over 60 years of age, in patients taking corticosteroid drugs, and in patients with kidney,
heart or lung transplants. Other factors that may independently increase the risk of tendon rupture
include strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid
arthritis. Tendinitis and tendon rupture have also occurred in patients taking fluoroquinolones who
do not have the above risk factors.
Tendon rupture can occur during or after completion of therapy cases occurring up to several months
after completion of therapy have been reported.
Discontinue Noroxin® immediately if the patient experiences pain, swelling, inflammation or rupture
of a tendon. Avoid fluoroquinolones, including Noroxin®, in patients who have a history of tendon
disorders or have experienced tendinitis or tendon rupture. Patients should be advised to rest at the
first sign of tendinitis or tendon rupture, and to contact their healthcare provider regarding changing
to a non-quinolone antimicrobial drug.
Exacerbation of Myasthenia Gravis:
Fluoroquinolones, including Noroxin®, have neuromuscular blocking activity and may exacerbate
muscle weakness in patients with myasthenia gravis. Post-marketing serious adverse reactions,
including deaths and requirement for ventilatory support, have been associated with
fluoroquinolone use in patients with myasthenia gravis. Avoid Noroxin® in patients with known
history of myasthenia gravis.
Safety in Children, Adolescents, Nursing mothers, and during Pregnancy: THE SAFETY AND
EFFICACY OF ORAL NORFLOXACIN IN PEDIATRIC PATIENTS, ADOLESCENTS (UNDER THE AGE OF
18), PREGNANT WOMEN, AND NURSING MOTHERS HAVE NOT BEEN ESTABLISHED. (See
PRECAUTIONS, Pediatric Use, Pregnancy, and Nursing Mothers subsections.)
The oral administration of single doses of norfloxacin, 6 times (the recommended human clinical dose
(on a mg/kg basis based on a patient weight of 50kg), 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 erosions of the cartilage in bearing joints and other signs of
arthropathy in immature animals of various species.
Central Nervous System Effects/Disorders:
Fluoroquinolones, including Noroxin®, have been associated with an increased risk of central nervous
system (CNS) effects, including convulsions, increased intracranial pressure (including pseudo tumor
cerebri), and toxic psychoses. Quinolones may also cause CNS stimulation which may lead to tremors,
restlessness, lightheadedness, confusion, and hallucinations. 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.
Hypersensitivity Reactions:
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first dose,
have been reported in patients receiving quinolone therapy, including Noroxin®. Some reactions
were accompanied by cardiovascular collapse, loss of consciousness, tingling, pharyngeal or facial
edema, dyspnea, urticaria and itching. Only a few patients had a history of hypersensitivity reactions.
If an allergic reaction to norfloxacin occurs, discontinue the drug. Serious acute hypersensitivity
reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous fluids,
antihistamines, corticosteroids, pressor amines, and airway management, including intubation,
should be administered as indicated.

Other serious and sometimes fatal events, some due to hypersensitivity, and some due to uncertain
etiology, have been reported rarely in patients receiving therapy with quinolones, including
Noroxin®. These events may be severe and generally occur following the administration of multiple
doses. Clinical manifestations may include one or more of the following:
•fever, rash or severe dermatologic reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson
syndrome);
•vasculitis; arthralgia; myalgia; serum sickness;
•allergic pneumonitis;
•interstitial nephritis; acute renal insufficiency or failure;
•hepatitis; jaundice; acute hepatic necrosis or failure;
• anemia, including hemolytic and aplastic; thrombocytopenia, including thrombotic
thrombocytopenic purpura; leukopenia; agranulocytosis; pancytopenia; and/or other hematologic
abnormalities.
The drug should be discontinued immediately at the first appearance of a skin rash, jaundice, or any
other sign of hypersensitivity, and supportive measures should be instituted.
Clostridium Difficile Associated Diarrhea:
Clostridium difficile associated diarrhea (CDAD) has been reported with use of nearly all antibacterial
agents, including Noroxin® and may range in severity from mild diarrhea to fatal colitis. Treatment
with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD.
Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as
theseinfections can be refractory to antimicrobial therapy and may require colectomy. CDAD must
beconsidered in all patients who present with diarrhea following antibiotic use. Careful medical
history is necessary since CDAD has been reported to occur over two months after the administration
of antibacterial agents.
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.
Peripheral Neuropathy:
Fluoroquinolones, including Noroxin®, have been associated with an increased risk of peripheral
neuropathy. Rare Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or
large axons resulting in paresthesia, hypoesthesia, dysesthesias and weakness have been reported
in patients receiving fluoroquinolones, including Noroxin®. Symptoms may occur soon after initiation
of norfloxacin and may be irreversible in some patients. Discontinue Noroxin® immediately if the
patient experiences symptoms of peripheral neuropathy including pain, burning, tingling, numbness,
and/or weakness, or other alterations in sensations including light touch, pain, temperature, position
sense and vibratory sensation, and/or motor strength in order to minimize the development of an
irreversible condition.
Avoid fluoroquinolones, including Noroxin®, in patients who have previously experienced peripheral
neuropathy.
Syphilis Treatment:
Norfloxacin has not been shown to be effective in the treatment of syphilis. Antimicrobial agents
used in high doses for short periods of time to treat gonorrhea may mask or delay the symptoms of
incubating syphilis. All patients with gonorrhea 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
three months.

Precautions
General
Needle-shaped crystals were found in the urine of some volunteers who received either placebo, 800
mg norfloxacin, or 1600 mg norfloxacin (at or twice the recommended daily dose, respectively) while
participating in a double-blind, crossover study comparing single doses of norfloxacin with placebo.
While crystalluria is not expected to occur under usual conditions with a dosage regimen of 400 mg
twice daily, as a precaution, the daily recommended dosage should not be exceeded and the patient
should drink sufficient fluids to ensure a proper state of hydration and adequate urinary output.
Alteration in dosage regimen is necessary for patients with impaired renal function. (See Posology
and method of Administration section).
Moderate to severe photosensitivity/phototoxicity reactions
The latter of which may manifest as exaggerated sunburn reactions (e.g., burning, erythema,
exudation, vesicles, blistering, edema) involving areas exposed to light (typically the face, "V" area of
the neck, extensor surfaces of the forearms, dorsa of the hands), can be associated with the use of
quinolone antibiotics after sun or UV light exposure. Therefore, excessive exposure to these sources
of light should be avoided. Drug therapy should be discontinued if phototoxicity occurs.
Rarely, hemolytic reactions have been reported in patients with latent or actual defects in glucose-
6-phosphate dehydrogenase activity who take quinolone antibacterial agents, including norfloxacin.
Prescribing Noroxin® in the absence of a proven or strongly suspected bacterial infection or a
prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the
development of drug-resistant bacteria.
Effects on ability to drive and use machines
Norfloxacin can cause dizziness and lightheadedness and, therefore, patients should know how they
react to norfloxacin before they operate an automobile or machinery or engage in activities requiring
mental alertness and coordination.
Cardiac Disorders
Caution should be taken when using fluoroquinolones, including norfloxacin, 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 antiarrhythmic,
tricyclic antidepressants, Macrolides, antipsychotics).
- Uncorrected electrolyte imbalance (e.g. hypokalemia, hypomagnesaemia).
- 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 norfloxacin, in
these populations.
Carcinogenesis, mutagenesis
No increase in neoplastic changes was observed with norfloxacin as compared to controls in a study
in rats, lasting up to 96 weeks at doses 8-9 times the usual human dose (on a mg/kg basis).
Norfloxacin was tested for mutagenic activity in a number of in vivo and in vitro tests. Norfloxacin
had no mutagenic effect in the dominant lethal test in mice and did not cause chromosomal

aberrations in hamsters or rats at doses 30-60 times the usual human dose (on a mg/kg basis).
Norfloxacin had no mutagenic activity in vitro in the Ames microbial mutagen test, Chinese hamster
fibroblasts and V-79 mammalian cell assay. Although norfloxacin was weakly positive in the Recassay
for DNA repair, all other mutagenic assays were negative including a more sensitive test (V-
79).
Aortic aneurysm and dissection, and heart valve regurgitation/incompetence
Epidemiologic studies report an increased risk of aortic aneurysm and dissection, particularly in
elderly patients, and of aortic and mitral valve regurgitation after intake of fluoroquinolones. Cases
of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of
regurgitation/incompetence of any of the heart valves have been reported in patients receiving
fluoroquinolones (see section 4.8).
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 congenital heart valve disease, or in patients diagnosed with pre-existing aortic aneurysm
and/or aortic dissection, or heart valve disease, or in presence of other risk factors or conditions
predisposing
- for both aortic aneurysm and dissection and heart valve regurgitation/incompetence
(e.g. connective tissue disorders such as Marfan syndrome or vascular Ehlers-Danlos
syndrome, Turner syndrome, Behcet's disease, hypertension, rheumatoid arthritis)
or additionally for aortic aneurysm and dissection ( e.g. vascular disorders such as
Takayasu arteritis or giant cell arteritis, or known atherosclerosis, or Sjögren’s
syndrome) or additionally
- for heart valve regurgitation/incompetence (e.g. infective endocarditis).
- The risk of aortic aneurysm and dissection, and their rupture may also be increased
in patients treated concurrently with systemic corticosteroids.
- In case of sudden abdominal, chest or back pain, patients should be advised to
immediately consult a physician in an emergency department.
Patients should be advised to seek immediate medical attention in case of acute
dyspnea, new onset of heart palpitations, or development of oedema of the
abdomen or lower extremities.

Quinolones, including norfloxacin, have been shown in vitro to inhibit CYP1A2. Concomitant use with
drugs metabolized by CYP1A2 (e.g., caffeine, clozapine, ropinirole, tacrine, theophylline,
tizanidine) may result in increased substrate drug concentrations when given in usual doses.
Patients taking any of these drugs concomitantly with norfloxacin should be carefully
monitored.
Elevated plasma levels of theophylline have been reported with concomitant quinolone use. There
have been reports of theophylline-related side effects in patients on concomitant therapy with
norfloxacin and theophylline. Therefore, monitoring of theophylline plasma levels should be
considered and dosage of theophylline adjusted as required.
Elevated serum levels of cyclosporine have been reported with concomitant use of cyclosporine with
norfloxacin. Therefore, cyclosporine serum levels should be monitored and appropriate cyclosporine
dosage adjustments made when these drugs are used concomitantly.
Quinolones, including norfloxacin, may enhance the effects of oral anticoagulants, including warfarin
or its derivatives or similar agents. When these products are administered concomitantly,
prothrombin time or other suitable coagulation tests should be closely monitored.

The concomitant administration of quinolones including norfloxacin with glyburide (a sulfonylurea
agent) has, on rare occasions, resulted in severe hypoglycemia. Therefore, monitoring of blood
glucose is recommended when these agents are co-administered.
Diminished urinary excretion of norfloxacin has been reported during the concomitant
administration of probenecid and norfloxacin.
The concomitant use of nitrofurantoin is not recommended since nitrofurantoin may antagonize the
antibacterial effect of Noroxin® in the urinary tract.
Multivitamins, or other products containing iron or zinc, antacids or sucralfate, should not be
administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because
they may interfere with absorption resulting in lower serum and urine levels of norfloxacin.
Didanosine chewable/buffered tablets or the pediatric powder for oral solution should not be
administered concomitantly with, or within 2 hours of, the administration of norfloxacin, because
these products may interfere with absorption resulting in lower serum and urine levels of
norfloxacin.
Some quinolones have also been shown to interfere with the metabolism of caffeine. This may lead
to reduced clearance of caffeine and a prolongation of the plasma half-life that may lead to
accumulation of caffeine in plasma when products containing caffeine are consumed while taking
norfloxacin. Ingestion of caffeine-containing medications (e.g. certain analgesics) should be avoided
where possible.
Oral nutritional solutions and dairy products (milk or milk products such as yoghurt) reduce the
absorption of norfloxacin. Norfloxacin should therefore be taken at least 1 hour before or 2 hours
after such products.
The concomitant administration of a non-steroidal anti-inflammatory drug (NSAID) with a quinolone,
including norfloxacin, may increase the risk of CNS stimulation and convulsive seizures. Therefore,
Noroxin® should be used with caution in individuals receiving NSAIDS concomitantly. On the basis
of animal studies, concomitant administration of quinolones and fenbufen can cause seizures. Coadministration
of quinolones and fenbufen should therefore be avoided.
Norfloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs
known to prolong the QT interval (e.g. Class IA and III anti-arrhythmic, tricyclic antidepressants,
macrolides, antipsychotics).

Fertility
Norfloxacin did not adversely affect the fertility of male and female mice at oral doses up to 30
times
the usual human dose (on a mg/kg basis).
Pregnancy
Teratogenic Effects.
Pregnancy Category C.
Norfloxacin has been shown to produce embryonic loss in monkeys when given in doses 10 times2
the maximum daily total human dose (on a mg/kg basis). At this dose, peak plasma levels obtained
in monkeys were approximately 2 times those obtained in humans. There has been no evidence
of a teratogenic effect in any of the animal species tested (rat, rabbit, mouse, monkey) at 6-50
times the maximum daily human dose (on a mg/kg basis). There are, however, no adequate and
well-controlled studies in pregnant women. Norfloxacin should be used during pregnancy only if the
potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is generally known that quinolones pass into mothers’ milk. It is not known whether norfloxacin,
specifically, is excreted in human milk.
When a 200-mg dose of Noroxin® was administered to nursing mothers, norfloxacin was not
detected in human milk. However, because the dose studied was low, because other drugs in this
class are secreted in human milk, and because of the potential for serious adverse reactions from
norfloxacin in nursing infants, a decision should be made to discontinue nursing or to discontinue
the drug, taking into account the importance of the drug to the mother.

Pediatric Use
The safety and effectiveness of oral norfloxacin in pediatric patients and adolescents below the age
of 18 years have not been established. Norfloxacin causes arthropathy in juvenile animals of several
animal species. (See SPECIAL WARNINGS AND PRECAUTIONS section)
Geriatric Use
Geriatric patients are at increased risk for developing severe tendon disorders including tendon
rupture when being treated with a fluoroquinolone such as Noroxin®. This risk is further increased
in patients receiving concomitant corticosteroid therapy. Tendinitis or tendon rupture can involve
the Achilles, hand, shoulder, or other tendon sites and can occur during or after completion of
therapy; cases occurring up to several months after fluoroquinolone treatment have been reported.
Caution should be used when prescribing Noroxin® to elderly patients, especially those on
corticosteroids. Patients should be informed of this potential side effect and advised to discontinue
Noroxin® and contact their healthcare provider if any symptoms of tendinitis or tendon rupture occur
(see Boxed Warning; WARNINGS; and ADVERSE REACTIONS, Post-Marketing). Of the 340 subjects in
one large clinical study of Noroxin® for treatment of urinary tract infections, 103 patients were 65
and older, 77 of whom were 70 and older; no overall differences in safety and effectiveness were
evident between these subjects and younger subjects. In clinical practice, no difference in the type
of reported adverse experiences have been observed between the elderly and younger patients
except for a possible increased risk of tendon rupture in elderly patients receiving concomitant
corticosteroids (see SPECIAL WARNINGS and PRECAUTIONS section). In addition, increased risk for
other adverse experiences in some older individuals cannot be ruled out (see Undesirable Effects
section).
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this
drug may be greater in patients with impaired renal function. Because elderly patients are more likely
to have decreased renal function, care should be taken in dose selection, and it may be useful to
monitor renal function (see POSOLOGY and METHOD OF ADMINISTRATION). A pharmacokinetic
study of Noroxin® in elderly volunteers (65 to 75 years of age with normal renal function for their
age) was carried out (see CLINICAL PHARMACOLOGICAL PROPERTIES). In general, elderly patients
may be more susceptible to drug-associated effects of the QTc interval. Therefore, precaution should
be taken when using Noroxin® concomitantly with drugs that can result in prolongation of the QTc
interval (e.g., class IA or class III antiarrhythmic) or in patients with risk factors for torsade de pointes
(e.g., known QTc prolongation, uncorrected hypokalemia).

Single-Dose Studies
In clinical trials involving 82 healthy subjects and 228 patients with gonorrhea, treated with a single
dose of norfloxacin, 6.5% reported drug-related adverse experiences. However, the following
incidence figures were calculated without reference to drug relationship.
The most common adverse experiences (>1.0%) were: dizziness (2.6%), nausea (2.6%), headache
(2.0%), and abdominal cramping (1.6%).
Additional reactions (0.3%-1.0%) were: anorexia, diarrhea, hyperhidrosis, asthenia, anal/rectal pain,
constipation, dyspepsia, flatulence, tingling of the fingers, and vomiting.
Laboratory adverse changes considered drug-related were reported in 4.5% of patients/subjects.
These laboratory changes were: increased AST (SGOT) (1.6%), decreased W BC (1.3%), decreased
platelet count (1.0%), increased urine protein (1.0%), decreased hematocrit and hemoglobin
(0.6%), and increased eosinophils (0.6%).
Multiple-Dose Studies
In clinical trials involving 52 healthy subjects and 1980 patients with urinary tract infections or
prostatitis treated with multiple doses of norfloxacin, 3.6% reported drug-related adverse
experiences. However, the incidence figures below were calculated without reference to drug
relationship.
The most common adverse experiences (>1.0%) were: nausea (4.2%), headache (2.8%), dizziness
(1.7%), and asthenia (1.3%).
Additional reactions (0.3%-1.0%) were: abdominal pain, back pain, constipation, diarrhea, dry mouth,
dyspepsia/heartburn, fever, flatulence, hyperhidrosis, loose stools, pruritus, rash, somnolence, and
vomiting.
Less frequent reactions (0.1%-0.2%) included: abdominal swelling, allergies, anorexia, anxiety, bitter
taste, blurred vision, bursitis, chest pain, chills, depression, dysmenorrhea, edema, erythema, foot or
hand swelling, insomnia, mouth ulcer, myocardial infarction, palpitation, pruritus, renal colic, sleep
disturbances, and urticaria.
Abnormal laboratory values observed in these patients/subjects were: eosinophilia (1.5%), elevation
of ALT (SGPT) (1.4%), decreased W BC and/or neutrophil count (1.4%), elevation of AST (SGOT) (1.4%),
and increased alkaline phosphatase (1.1%).
Those occurring less frequently included increased BUN, increased LDH, increased serum creatinine,
decreased hematocrit, and glycosuria.
Post-Marketing
The most frequently reported adverse reaction in post-marketing experience is rash.
CNS effects characterized as generalized seizures, myoclonus and tremors have been reported with
Noroxin®. Visual disturbances have been reported with drugs in this class.
The following additional adverse reactions have been reported since the drug was marketed:
Hypersensitivity Reactions2
Hypersensitivity reactions have been reported including anaphylactic reactions, angioedema,
dyspnea, vasculitis, urticaria, arthritis, arthralgia and myalgia.

Skin
Toxic epidermal necrolysis, Stevens-Johnson syndrome and erythema multiform, exfoliative
dermatitis, photosensitivity/phototoxicity reactions, leukocytoclastic vasculitis, drug rash with
eosinophilia and systemic symptoms (DRESS syndrome).
Gastrointestinal
Pseudomembranous colitis, hepatitis, jaundice including cholestatic jaundice and elevated liver
function tests, pancreatitis (rare), stomatitis. The onset of pseudomembranous colitis symptoms may
occur during or after antibacterial treatment.
Hepatic
Hepatic failure, including fatal cases.
Cardiovascular1
On rare occasions, prolonged QTc interval and ventricular arrhythmia including torsade de pointes.
Renal
Interstitial nephritis, renal failure.
Nervous System/Psychiatric2
Peripheral neuropathy that may be irreversible, Guillain-Barre syndrome, ataxia, paresthesia,
hypoesthesia, psychic disturbances including psychotic reactions and confusion.
Musculoskeletal2
Tendinitis, tendon rupture; exacerbation of myasthenia gravis (see WARNINGS, Exacerbation of
myasthenia gravis); elevated creatine kinase (CK), muscle spasms.
Hematologic
Neutropenia; leukopenia; agranulocytosis; hemolytic anemia, sometimes associated with glucose-6-
phosphate dehydrogenase deficiency; thrombocytopenia.
Special Senses2
Hearing loss, tinnitus, diplopia, dysgeusia. uveitis
Fluoroquinolones may cause significant decreases in blood sugar and certain mental health side
effects.
Blood sugar disturbance: hypoglycemia can lead to coma
The mental health side effects are:
Disturbances in attention, Disorientation, Agitation, Nervousness, Memory impairment, Delirium.
Other adverse events reported with quinolones include: agranulocytosis, albuminuria, candiduria,
crystalluria, cylindruria, dysphagia, elevation of blood glucose, elevation of serum cholesterol,
elevation of serum potassium, elevation of serum triglycerides, hematuria, hepatic necrosis,
symptomatic hypoglycemia, nystagmus, postural hypotension, prolongation of prothrombin time,
1 Cases of aortic aneurysm and dissection, sometimes complicated by rupture (including fatal ones), and of regurgitation/incompetence
of any of the heart valves have been reported in patients receiving fluoroquinolones (see section 4.4).
Other adverse events reported with quinolones include: agranulocytosis, albuminuria, candiduria, crystalluria, cylindruria, dysphagia,
elevation of blood glucose, elevation of serum cholesterol, elevation of serum potassium, elevation of serum triglycerides, hematuria,
hepatic necrosis, symptomatic hypoglycemia, nystagmus, postural hypotension, prolongation of prothrombin time, and vaginal
candidiasis.
2 Very rare cases of prolonged (up to months or years), disabling and potentially irreversible serious drug reactions affecting several,
sometimes multiple, system organ classes and senses (including reactions such as tendonitis, tendon rupture, arthralgia, pain in
extremities, gait disturbance, neuropathies associated with paresthesia, depression, fatigue, memory impairment, sleep disorders, and
impairment of hearing, vision, taste and smell) have been reported in association with the use of quinolones and fluoroquinolones in
some cases irrespective of pre-existing risk factors (see Section 4.4).

and vaginal candidiasis.
To report any side effect(s):
Saudi Arabia:
The National Pharmacovigilance and Drug Safety Center (NPC)
Fax: +966-11-205-7662
Call NPC at +966-11-2038222, Ext: 2317-2356--2340
Reporting hotline: 19999
Email: npc.drug@sfda.gov.sa
Website: www. sfda.gov.sa/npc

No significant lethality was observed in male and female mice and rats at single oral doses up to
4 g/kg.
In the event of acute over dosage, the stomach should be emptied by inducing vomiting or by gastric
lavage, and the patient carefully observed and given symptomatic and supportive treatment.
Adequate hydration must be maintained.

Mechanism of Action
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-stranded DNA breakage.
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 antipseudomonal activity.
Drug Resistance
Resistance to norfloxacin due to spontaneous mutation in vitro is a rare occurrence (range: 10-9 to
10-12 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 spp.
Enterococcus spp.
For this reason, when there is a lack of satisfactory clinical response, repeat culture and susceptibility
testing should be done. Nalidixic acid-resistant organisms are generally susceptible to norfloxacin in
vitro; however, these organisms may have higher minimum inhibitory concentrations (MICs) to
norfloxacin than nalidixic acid-susceptible strains. There is generally no cross-resistance between
norfloxacin and other classes of antibacterial agents. Therefore, norfloxacin may demonstrate
activity against indicated organisms resistant to some other antimicrobial agents including the
aminoglycosides, penicillins, cephalosporins, tetracyclines, macrolides, and sulfonamides, including

combinations of sulfamethoxazole and trimethoprim. Antagonism has been demonstrated in vitro
between norfloxacin and nitrofurantoin.
Activity in vitro and in vivo
Norfloxacin has in vitro activity against a broad range of gram-positive and gram-negative aerobic
bacteria.
Norfloxacin has been shown to be active against most strains of the following microorganisms 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
Escherichia coli
Klebsiella pneumonia
Neisseria gonorrhoeae
Proteus mirabilis
Proteus vulgaris
Pseudomonas aeruginosa
Serratia marcescens
The following in vitro data are available, but their clinical significance is unknown.
Norfloxacin exhibits in vitro MICs of ≤4 μg/mL against most (≥90%) strains of the following
microorganisms; however, the safety and effectiveness of norfloxacin in treating clinical infections
due to these microorganisms have not been established in adequate and well-controlled clinical
trials.
Gram-negative aerobes:
Citrobacter diversus
Edwardsiella tarda
Enterobacter agglomerans
Haemophilus ducreyi
Klebsiella oxytoca
Morganella morganii
Providencia alcalifaciens
Providencia rettgeri
Providencia stuartii
Pseudomonas fluorescens
Pseudomonas stutzeri
Other:
Ureaplasma urealyticum
Noroxin® is not generally active against obligate anaerobes. Norfloxacin has not been shown to be active against Treponema pallidum.

In fasting healthy volunteers, at least 30-40% of an oral dose of Noroxin® is absorbed. Absorption
is rapid following single doses of 200 mg, 400 mg and 800 mg. At the respective doses, mean peak
serum and plasma concentrations of 0.8, 1.5 and 2.4 μg/mL are attained approximately one hour
after dosing. The presence of food and/or dairy products may decrease absorption. The effective
half-life of norfloxacin in serum and plasma is 3-4 hours. Steady-state concentrations of norfloxacin
will be attained within two days of dosing.
In healthy elderly volunteers (65-75 years of age with normal renal function for their age),
norfloxacin is eliminated more slowly because of their slightly decreased renal function. Following
a single 400-mg dose of norfloxacin, the mean (± SD) AUC and Cmax of 9.8 (2.83) μg.h/mL and
2.02 (0.77) μg/mL, respectively, were observed in healthy elderly volunteers. The extent of systemic
exposure was slightly higher than that seen in younger adults (AUC 6.4 μg.h/mL and Cmax 1.5
μg/mL). Drug absorption appears unaffected. However, the effective half-life of norfloxacin in these
elderly subjects is 4 hours.
There is no information on accumulation of norfloxacin with repeated administration in elderly
patients. However, no dosage adjustment is required based on age alone. In elderly patients
with reduced renal function, the dosage should be adjusted as for other patients with renal
impairment (see Posology and Method of Administration, Renal Impairment).
The disposition of norfloxacin in patients with creatinine clearance rates greater than 30
mL/min/1.73 m2 is similar to that in healthy volunteers. In patients with creatinine clearance rates
equal to or less than 30 mL/min/1.73 m2, the renal elimination of norfloxacin decreases so that the
effective serum half-life is 6.5 hours. In these patients, alteration of dosage is necessary (see DOSAGE
AND ADMINISTRATION). Drug absorption appears unaffected by decreasing renal function.
Norfloxacin is eliminated through metabolism, biliary excretion, and renal excretion. After a single
400-mg dose of Noroxin®, mean antimicrobial activities equivalent to 278, 773, and 82 μg of
norfloxacin/g of feces were obtained at 12, 24, and 48 hours, respectively. Renal excretion occurs
by both glomerular filtration and tubular secretion as evidenced by the high rate of renal clearance
(approximately 275 mL/min). Within 24 hours of drug administration, 26 to 32% of the administered
dose is recovered in the urine as norfloxacin with an additional 5-8% being recovered in the urine
as six active metabolites of lesser antimicrobial potency. Only a small percentage (less than 1%)
of the dose is recovered thereafter. Fecal recovery accounts for another 30% of the administered
dose. In elderly subjects (average creatinine clearance 91 mL/min/1.73 m2) approximately 22% of
the administered dose was recovered in urine and renal clearance averaged 154 mL/min.
Two to three hours after a single 400-mg dose, urinary concentrations of 200 μg/mL or more are
attained in the urine. In healthy volunteers, mean urinary concentrations of norfloxacin remain
above 30 μg/mL for at least 12 hours following a 400-mg dose. The urinary pH may affect the
solubility of norfloxacin. Norfloxacin is least soluble at urinary pH of 7.5 with greater solubility
occurring at pHs above and below this value. The serum protein binding of norfloxacin is
between 10 and 15%.
The following are mean concentrations of norfloxacin in various fluids and tissues measured 1 to
4 hours post-dose after two 400-mg doses, unless otherwise indicated:
Renal Parenchyma 7.3μg/g
Prostate 2.5μg/g
Seminal Fluid 2.7μg/Ml
Testicle 1.6μg/g
Uterus/Cervix 3.0μg/g
Vagina 4.3μg/g
Fallopian Tube 1.9μg/g
Bile 6.9 μg/mL (after two 200-mg doses)

Microcrystalline cellulose,
Croscarmellose sodium,
magnesium stearate,
hydroxypropylmethylcellulose,
hydroxy-propylcellulose,
titanium dioxide,
carnauba wax.

Not applicable

Keep out of reach and sight of children.
Do not store above 30°C.
Store in the original package.
Do not use Noroxin® tablets after the expiry date stated on the carton and the blisters.
The expiry date refers to the last day of that month.

Noroxin® tablets are white, film-coated, oval-shaped biconvex tablets, one side scored, the other
engraved ‘ALG N400’.
Noroxin® is available in packs of 14 tablets.

None