4.1.1 Lower Respiratory Tract Infections
Ciprofloxacin tablets are indicated in adult patients for treatment of lower respiratory tract infections
caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis,
Pseudomonas aeruginosa, Haemophilus influenzae, Haemophilus parainfluenzae, or Streptococcus
pneumoniae.
Ciprofloxacin tablets are not a drug of first choice in the treatment of presumed or confirmed
pneumonia secondary to Streptococcus pneumoniae.
Ciprofloxacin tablets are indicated for the treatment of acute exacerbations of chronic bronchitis
(AECB) caused by Moraxella catarrhalis.
Because fluoroquinolones, including ciprofloxacin tablets, have been associated with serious adverse
reactions [see WARNINGS AND PRECAUTIONS (4.1 to 4.15)] and for some patients AECB is selflimiting,
reserve ciprofloxacin tablets for treatment of AECB in patients who have no alternative
treatment options.

4.1.2 Urinary Tract Infections
Urinary Tract Infections in Adults
Ciprofloxacin tablets are indicated in adult patients for treatment of urinary tract infections caused
by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus
mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter koseri, Citrobacter freundii,
Pseudomonas aeruginosa, methicillin-susceptible Staphylococcus epidermidis, Staphylococcus
saprophyticus, orEnterococcus faecalis.
Acute Uncomplicated Cystitis
Ciprofloxacin tablets are indicated in adult female patients for treatment of acute uncomplicated
cystitis caused by Escherichia coli or Staphylococcus saprophyticus.
Because fluoroquinolones, including ciprofloxacin tablets, have been associated with serious adverse
reactions [see WARNINGS AND PRECAUTIONS (4.1 to 4.15)] and for some patients acute
uncomplicated cystitis is self-limiting, reserve ciprofloxacin tablets for treatment of acute
uncomplicated cystitis in patients who have no alternative treatment options.
Complicated Urinary Tract Infection and Pyelonephritis in Pediatric Patients
Ciprofloxacin tablets are indicated in pediatric patients aged one to 17 years of age for treatment of
complicated urinary tract infections (cUTI) and pyelonephritis due to Escherichia coli [see USE IN
SPECIFIC POPULATIONS (5.2)].
Although effective in clinical trials, ciprofloxacin tablets are not a drug of first choice in the pediatric
population due to an increased incidence of adverse reactions compared to controls, including
reactions related to joints and/or surrounding tissues. Ciprofloxacin tablets, like other
fluoroquinolones, is associated with arthropathy and histopathological changes in weight-bearing
joints of juvenile animals [see WARNINGS AND PRECAUTIONS (4.12), UNDESIRABLE EFFECTS
(4.8), USE IN SPECIFIC POPULATIONS (5.2) and NONCLINICAL TOXICOLOGY (5.3)]..

4.1.3 Acute Sinusitis
Ciprofloxacin tablets are indicated in adult patients for treatment of acute sinusitis caused
by Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis.
Because fluoroquinolones, including ciprofloxacin tablets, have been associated with serious adverse
reactions [see WARNINGS AND PRECAUTIONS (4.1 to 4.15)] and for some patients acute sinusitis is
self-limiting, reserve ciprofloxacin tablets for treatment of acute sinusitis in patients who have no
alternative treatment options.

4.1.4 Pediatric Use
Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the pediatric
population due to an increased incidence of adverse reactions compared to controls. Quinolones,
including ciprofloxacin, cause arthropathy (arthralgia, arthritis), in juvenile animals [see WARNINGS
AND PRECAUTIONS (4.12) and NONCLINICAL TOXICOLOGY (5.3)].
Complicated Urinary Tract Infection and Pyelonephritis
Ciprofloxacin is indicated for the treatment of cUTI and pyelonephritis due to Escherichia coli in
pediatric patients 1 to 17 years of age. Although effective in clinical trials, ciprofloxacin is not a drug
of first choice in the pediatric population due to an increased incidence of adverse reactions compared
to the controls, including events related to joints and/or surrounding tissues [see UNDESIRABLE
EFFECTS (4.8)].
Inhalational Anthrax (Post-Exposure)
Ciprofloxacin is indicated in pediatric patients from birth to 17 years of age, for inhalational anthrax
(post-exposure). The risk-benefit assessment indicates that administration of ciprofloxacin to pediatric
patients is appropriate [see DOSAGE AND ADMINISTRATION (4.2)].
Plague
Ciprofloxacin is indicated in pediatric patients from birth to 17 years of age, for treatment of plague,
including pneumonic and septicemic plague due to Yersinia pestis (Y. pestis) and prophylaxis for
plague. Efficacy studies of ciprofloxacin could not be conducted in humans with pneumonic plague for
feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in
animals. The risk-benefit assessment indicates that administration of ciprofloxacin to pediatric patients
is appropriate [see INDICATIONS AND USAGE (4.1), DOSAGE AND ADMINISTRATION (4.2)].

Dosage in Adults
The determination of dosage and duration for any particular patient must take into consideration the
severity and nature of the infection, the susceptibility of the causative microorganism, the integrity of
the patient’s host-defense mechanisms, and the status of renal and hepatic function. Ciprofloxacin
tablets may be administered to adult patients when clinically indicated at the discretion of the
physician
1 .Generally ciprofloxacin should be continued for at least 2 days after the signs and symptoms of
infection have disappeared, except for inhalational anthrax (post-exposure).
2 .Used in conjunction with metronidazole.
3. Begin drug administration as soon as possible after suspected or confirmed exposure.

Dosage in Pediatric Patients
Dosing and initial route of therapy (that is, IV or oral) for cUTI or pyelonephritis should be determined
by the severity of the infection. Ciprofloxacin tablets should be administered as described in Table 3.
1. The total duration of therapy for cUTI and pyelonephritis in the clinical trial was determined
by the physician. The mean duration of treatment was 11 days (range 10 to 21 days).
2. Begin drug administration as soon as possible after suspected or confirmed exposure.
3. Begin drug administration as soon as possible after suspected or confirmed exposure to Y.
pestis.

Dosage Modifications in Patients with Renal Impairment
Ciprofloxacin is eliminated primarily by renal excretion; however, the drug is also metabolized and
partially cleared through the biliary system of the liver and through the intestine. These alternative
pathways of drug elimination appear to compensate for the reduced renal excretion in patients with
renal impairment. Nonetheless, some modification of dosage is recommended, particularly for patients
with severe renal dysfunction.

When only the serum creatinine concentration is known, the following formulas may be used to
estimate creatinine clearance:
Men - Creatinine clearance (mL/min) = Weight (kg) x (140–age)
72 x serum creatinine (mg/dL)
Women - 0.85 x the value calculated for men.
The serum creatinine should represent a steady state of renal function. In patients with severe
infections and severe renal impairment, a unit dose of 750 mg may be administered at the intervals
noted above. Patients should be carefully monitored. Pediatric patients with moderate to severe renal
insufficiency were excluded from the clinical trial of cUTI and pyelonephritis. No information is
available on dosing adjustments necessary for pediatric patients with moderate to severe renal
insufficiency (that is, creatinine clearance of < 50 mL/min/1.73 m2).

4.4.1 Disabling and Potentially Irreversible Serious Adverse Reactions Including Tendinitis and
Tendon Rupture, Peripheral Neuropathy, and Central Nervous System Effects:
Fluoroquinolones, including ciprofloxacin, 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 ciprofloxacin. Patients of any age or without pre-existing risk factors have experienced these
adverse reactions [see Warnings and Precautions (4.4.2, 4.4.3, 4.4.4)]. Discontinue ciprofloxacin
immediately at the first signs or symptoms of any serious adverse reaction. In addition, avoid the use
of fluoroquinolones, including ciprofloxacin, in patients who have experienced any of these serious
adverse reactions associated with fluoroquinolones.

4.4.2 Tendinitis and Tendon Rupture:
Fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of tendinitis
and tendon rupture in all ages [see Warnings and Precautions (4.4) and Undesirable effects (4.8)].
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 ciprofloxacin, 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. Discontinue ciprofloxacin immediately if the patient experiences pain,
swelling, inflammation or rupture of a tendon. Avoid fluoroquinolones, including ciprofloxacin, in
patients who have a history of tendon disorders or have experienced tendinitis or tendon rupture [see
Undesirable effects (4.8)]

4.4.3 Peripheral Neuropathy
Fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of peripheral
neuropathy. Cases of sensory or sensorimotor axonal polyneuropathy affecting small and/or large
axons resulting in paresthesias, hypoesthesias, dysesthesias and weakness have been reported in
patients receiving fluoroquinolones, including ciprofloxacin. Symptoms may occur soon after
initiation of ciprofloxacin and may be irreversible in some patients [see Warnings and Precautions
(4.4.1) and Undesirable effects (4.8)].
Discontinue ciprofloxacin 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 ciprofloxacin, in patients who have previously experienced peripheral neuropathy [see
Undesirable effects (4.8)].

4.4.4 Central Nervous System Effects
Fluoroquinolones, including ciprofloxacin, have been associated with an increased risk of central
nervous system (CNS) effects, including: convulsions, increased intracranial pressure (including
pseudotumor cerebri), and toxic psychosis. Ciprofloxacin may also cause central nervous system
(CNS) events including: nervousness, agitation, insomnia, anxiety, nightmares, paranoia, dizziness,
confusion, tremors, hallucinations, depression, and psychotic reactions have progressed to suicidal
ideations/thoughts and self-injurious behavior such as attempted or completed suicide. These
reactions may occur following the first dose. Advise patients receiving ciprofloxacin tablets to
inform their healthcare provider immediately if these reactions occur, discontinue the drug, and
institute appropriate care. Ciprofloxacin, like other fluoroquinolones, is known to trigger seizures or
lower the seizure threshold. As with all fluoroquinolones, use ciprofloxacin with caution in epileptic
patients and patients with known or suspected CNS disorders that may predispose to seizures or
lower the seizure threshold (for example, severe cerebral arteriosclerosis, previous history of
convulsion, reduced cerebral blood flow, altered brain structure, or stroke), or in the presence of
other risk factors that may predispose to seizures or lower the seizure threshold (for example, certain
drug therapy, renal dysfunction). Use ciprofloxacin when the benefits of treatment exceed the risks,
since these patients are endangered because of possible undesirable CNS side effects. Cases of status
epilepticus have been reported. If seizures occur, discontinue ciprofloxacin [see Undesirable effects
(4.8) and Drug Interactions (4.5)].

4.4.5 Exacerbation of Myasthenia Gravis
Fluoroquinolones, including ciprofloxacin, 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 ciprofloxacin in patients with known
history of myasthenia gravis [see Undesirable effects (4.8)].

4.4.6 Other Serious and Sometimes Fatal Adverse Reactions
Other serious and sometimes fatal adverse reactions, some due to hypersensitivity, and some due to
uncertain etiology, have been reported in patients receiving therapy with quinolones,
administration of multiple doses. Clinical manifestations may include one or more of the following:
• Fever, rash, or severe dermatologic reactions (for example, 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.
Discontinue ciprofloxacin immediately at the first appearance of a skin rash, jaundice, or any other
sign of hypersensitivity and supportive measures instituted [see Undesirable effects (4.8)].

4.4.7 Hypersensitivity Reactions
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions, some following the first
dose, have been reported in patients receiving fluoroquinolone therapy, including ciprofloxacin.
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. Serious anaphylactic reactions require immediate emergency treatment
with epinephrine and other resuscitation measures, including oxygen, intravenous fluids, intravenous
antihistamines, corticosteroids, pressor amines, and airway management, including intubation, as
indicated [see Undesirable effects (4.8)]

4.4.8 Hepatotoxicity
Cases of severe hepatotoxicity, including hepatic necrosis, life-threatening hepatic failure, and fatal
events, have been reported with ciprofloxacin. Acute liver injury is rapid in onset (range 1–39 days),
and is often associated with hypersensitivity. The pattern of injury can be hepatocellular, cholestatic,
or mixed. Most patients with fatal outcomes were older than 55 years old. In the event of any signs
and symptoms of hepatitis (such as anorexia, jaundice, dark urine, pruritus, or tender abdomen),
discontinue treatment immediately There can be a temporary increase in transaminases, alkaline
phosphatase, or cholestatic jaundice, especially in patients with previous liver damage, who are
treated with ciprofloxacin [see Undesirable effects (4.8)].

4.4.9 Serious Adverse Reactions with Concomitant Theophylline
Serious and fatal reactions have been reported in patients receiving concurrent administration of
ciprofloxacin and theophylline. These reactions have included cardiac arrest, seizure, status
epilepticus, and respiratory failure. Instances of nausea, vomiting, tremor, irritability, or palpitation
have also occurred. Although similar serious adverse reactions have been reported in patients
receiving theophylline alone, the possibility that these reactions may be potentiated by ciprofloxacin
cannot be eliminated. If concomitant use cannot be avoided, monitor serum levels of theophylline
and adjust dosage as appropriate [see Drug Interactions (4.5)]

4.4.10 Clostridium difficile-Associated Diarrhea
Clostridium difficile (C. difficile)-associated diarrhea (CDAD) has been reported with use of nearly
all antibacterial agents, including ciprofloxacin, 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 isolates of C. difficile cause increased morbidity and mortality, as these
infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be
considered in all patients who present with diarrhea following antibacterial 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 antibacterial use not directed
against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management,
protein supplementation, antibacterial treatment of C. difficile, and institute surgical evaluation as
clinically indicated [see Undesirable effects (4.8)].

4.4.11 Prolongation of the QT Interval
Some fluoroquinolones, including ciprofloxacin, have been associated with prolongation of the QT
interval on the electrocardiogram and cases of arrhythmia. Cases of torsade de pointes have been
reported during postmarketing surveillance in patients receiving fluoroquinolones, including
ciprofloxacin. Avoid ciprofloxacin in patients with known prolongation of the QT interval, risk
factors for QT prolongation or torsade de pointes (for example, congenital long QT syndrome,
uncorrected electrolyte imbalance, such as hypokalemia or hypomagnesemia and cardiac disease,
such as heart failure, myocardial infarction, or bradycardia), and patients receiving Class IA
antiarrhythmic agents (quinidine, procainamide), or Class III antiarrhythmic agents (amiodarone,
sotalol), tricyclic antidepressants, macrolides, and antipsychotics. Elderly patients may also be more
susceptible to drug-associated effects on the QT interval [see Undesirable effects (4.8), Therapeutic
Indication (4.1.4)]
4.4.12 Musculoskeletal Disorders in Pediatric Patients and Arthropathic Effects in Animals
Ciprofloxacin is indicated in pediatric patients (less than 18 years of age) only for cUTI, prevention
of inhalational anthrax (post exposure), and plague [see Indications and Usage (4.1)]. An increased
incidence of adverse reactions compared to controls, including reactions related to joints and/or
surrounding tissues, has been observed [see Undesirable effects (4.8)]. In pre-clinical studies, oral
administration of ciprofloxacin caused lameness in immature dogs. Histopathological examination of
the weight-bearing joints of these dogs revealed permanent lesions of the cartilage. Related
quinolone-class drugs also produce erosions of cartilage of weight-bearing joints and other signs of
arthropathy in immature animals of various species [see Therapeutic Indication (4.1.4)] and
Nonclinical Toxicology (5.3.1)].

4.4.13 Photosensitivity/Phototoxicity
Moderate to severe photosensitivity/phototoxicity reactions, the latter of which may manifest as
exaggerated sunburn reactions (for example, 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 quinolones including
ciprofloxacin after sun or UV light exposure. Therefore, avoid excessive exposure to these sources of
light. Discontinue ciprofloxacin if phototoxicity occurs. [See Undesirable effects (4.8)
4.4.14 Development of Drug Resistant Bacteria
Prescribing ciprofloxacin tablets 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.

4.4.15 Potential Risks with Concomitant Use of Drugs Metabolized by Cytochrome P450 1A2
Enzymes
Ciprofloxacin is an inhibitor of the hepatic CYP1A2 enzyme pathway. Co-administration of
ciprofloxacin and other drugs primarily metabolized by CYP1A2 (for example, theophylline,
methylxanthines, caffeine, tizanidine, ropinirole, clozapine, olanzapine and zolpidem), results in
increased plasma concentrations of the co-administered drug and could lead to clinically significant
pharmacodynamic adverse reactions of the co-administered drug [see Drug Interactions (4.5) and
Clinical Pharmacology (5.1)].
4.4.16 Interference with Timely Diagnosis of Syphilis
Ciprofloxacin has not been shown to be effective in the treatment of syphilis. Antimicrobial agents
used in high dose for short periods of time to treat gonorrhea may mask or delay the symptoms of
incubating syphilis. Perform a serologic test for syphilis in all patients with gonorrhea at the time of
diagnosis. Perform follow-up serologic test for syphilis three months after ciprofloxacin treatment.
4.4.17 Crystalluria
Crystals of ciprofloxacin have been observed rarely in the urine of human subjects but more frequently
in the urine of laboratory animals, which is usually alkaline [see Nonclinical Toxicology (5.3.1)].
Crystalluria related to ciprofloxacin has been reported only rarely in humans because human urine is
usually acidic. Avoid alkalinity of the urine in patients receiving ciprofloxacin. Hydrate patients well
to prevent the formation of highly concentrated urine [see Dosage and Administration (4.2)].

4.4.18 Blood Glucose Disturbances:
Fluoroquinolones, including ciprofloxacin, have been associated with disturbances of blood glucose,
including symptomatic hyperglycemia and hypoglycemia, usually in diabetic patients receiving
concomitant treatment with an oral hypoglycemic agent (for example, glyburide) or with insulin. In
these patients, careful monitoring of blood glucose is recommended. Severe cases of hypoglycemia
resulting in coma or death have been reported. If a hypoglycemic reaction occurs in a patient being
treated with ciprofloxacin, discontinue ciprofloxacin and initiate appropriate therapy immediately [see
ADVERSE REACTIONS (6.1), DRUG INTERACTIONS (4.5)].

4.5 Interaction with other medicinal products and other forms of interaction:
Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated metabolism. Coadministration
of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in
increased plasma concentrations of these drugs and could lead to clinically significant adverse events
of the co-administered drug.

4.6 Fertility, pregnancy and lactation
Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Ciprofloxacin should not be
used during pregnancy unless the potential benefit justifies the potential risk to both fetus and mother.
An expert review of published data on experiences with ciprofloxacin use during pregnancy by
TERIS–the Teratogen Information System–concluded that therapeutic doses during pregnancy are
unlikely to pose a substantial teratogenic risk (quantity and quality of data=fair), but the data are insufficient to state that there is no risk.2A controlled prospective observational study followed 200
women exposed to fluoroquinolones (52.5% exposed to ciprofloxacin and 68% first trimester
exposures) during gestation.3 In utero exposure to fluoroquinolones during embryogenesis was not
associated with increased risk of major malformations. The reported rates of major congenital
malformations were 2.2% for the fluoroquinolone group and 2.6% for the control group (background
incidence of major malformations is 1 to 5%). Rates of spontaneous abortions, prematurity and low
birth weight did not differ between the groups and there were no clinically significant musculoskeletal
dysfunctions up to one year of age in the ciprofloxacin exposed children. Another prospective followup
study reported on 549 pregnancies with fluoroquinolone exposure (93% first trimester
exposures).4 There were 70 ciprofloxacin exposures, all within the first trimester. The malformation
rates among live-born babies exposed to ciprofloxacin and to fluoroquinolones overall were both
within background incidence ranges. No specific patterns of congenital abnormalities were found. The
study did not reveal any clear adverse reactions due to in utero exposure to ciprofloxacin. No
differences in the rates of prematurity, spontaneous abortions, or birth weight were seen in women
exposed to ciprofloxacin during pregnancy.2, 3 However, these small postmarketing epidemiology
studies, of which most experience is from short term, first trimester exposure, are insufficient to
evaluate the risk for less common defects or to permit reliable and definitive conclusions regarding the
safety of ciprofloxacin in pregnant women and their developing fetuses. Reproduction studies have
been performed in rats and mice using oral doses up to 100 mg/kg (0.6 and 0.3 times the maximum
daily human dose based upon body surface area, respectively) and have revealed no evidence of harm
to the fetus due to ciprofloxacin. In rabbits, oral ciprofloxacin dose levels of 30 and 100 mg/kg
(approximately 0.4- and 1.3-times the highest recommended therapeutic dose based upon body surface
area) produced gastrointestinal toxicity resulting in maternal weight loss and an increased incidence of
abortion, but no teratogenicity was observed at either dose level. After intravenous administration of
doses up to 20 mg/kg (approximately 0.3-times the highest recommended therapeutic dose based upon
body surface area), no maternal toxicity was produced and no embryotoxicity or teratogenicity was
observed.

Due to its neurological effects, ciprofloxacin may affect reaction time. Thus, the ability to drive or to
operate machinery may be impaired.

What are the possible side effects of ciprofloxacin tablets?
Ciprofloxacin tablets may cause serious side effects, including:
See “What is the most important information I should know about ciprofloxacin tablets?”
Serious allergic reactions. Serious allergic reactions, including death, can happen in people
taking fluoroquinolones, including ciprofloxacin tablets, even after only 1 dose. Stop taking
ciprofloxacin tablets and get emergency medical help right away if you get any of the following
symptoms of a severe allergic reaction:
hives
trouble breathing or swallowing
swelling of the lips, tongue, face
throat tightness, hoarseness
rapid heartbeat
faint
skin rash

Skin rash may happen in people taking ciprofloxacin tablets even after only 1 dose. Stop taking
ciprofloxacin tablets at the first sign of a skin rash and call your healthcare provider. Skin rash may be
a sign of a more serious reaction to ciprofloxacin tablets.
Liver damage (hepatotoxicity). Hepatotoxicity can happen in people who take ciprofloxacin
tablets. Call your healthcare provider right away if you have unexplained symptoms such as:
nausea or vomiting
stomach pain
fever
weakness
abdominal pain or tenderness
itching
unusual tiredness
loss of appetite
light colored bowel movements
dark colored urine
yellowing of your skin or the whites of your eyes
Stop taking ciprofloxacin tablets and tell your healthcare provider right away if you have yellowing of
your skin or white part of your eyes, or if you have dark urine. These can be signs of a serious reaction
to ciprofloxacin tablets (a liver problem).

Intestine infection (Pseudomembranous colitis). Pseudomembranous colitis can happen with
many antibacterial medicines, including ciprofloxacin tablets. Call your healthcare provider right
away if you get watery diarrhea, diarrhea that does not go away, or bloody stools. You may have
stomach cramps and a fever. Pseudomembranous colitis can happen 2 or more months after you
have finished your antibacterial medicine.
Serious heart rhythm changes (QT prolongation and torsade de pointes). Tell your healthcare
provider right away if you have a change in your heart beat (a fast or irregular heartbeat), or if you
faint. Ciprofloxacin tablets may cause a rare heart problem known as prolongation of the QT
interval. This condition can cause an abnormal heartbeat and can be very dangerous. The chances
of this event are higher in people:
who are elderly
with a family history of prolonged QT interval
with low blood potassium (hypokalemia)
who take certain medicines to control heart rhythm (antiarrhythmics)
Joint Problems. Increased chance of problems with joints and tissues around joints in children
under 18 years old can happen. Tell your child’s healthcare provider if your child has any joint
problems during or after treatment with ciprofloxacin tablets.
Sensitivity to sunlight (photosensitivity). See “What should I avoid while taking ciprofloxacin
tablets?”
Changes in blood sugar
People who take ciprofloxacin and other fluoroquinolone medicines with oral anti-diabetes
medicines or with insulin can get low blood sugar (hypoglycemia) and high blood sugar
(hyperglycemia). Follow your healthcare provider's instructions for how often to check your blood
sugar. If you have diabetes and you get low blood sugar while taking ciprofloxacin, stop taking
ciprofloxacin and call your healthcare provider right away. Your antibiotic medicine may need to
be changed.
The most common side effects of ciprofloxacin tablets include:

nausea, diarrhea, changes in liver function tests, vomiting, rash
Tell your healthcare provider about any side effect that bothers you, or that does not go away.
These are not all the possible side effects of ciprofloxacin tablets. For more information, ask your
healthcare provider or pharmacist.
Pediatric population
- Although effective in clinical trials, ciprofloxacin is not a drug of first choice in the pediatric
population due to an increased incidence of adverse reactions compared to controls. Quinolones,
including ciprofloxacin, cause arthropathy (arthralgia, arthritis), in juvenile animals [see WARNINGS
AND PRECAUTIONS (4.12) and NONCLINICAL TOXICOLOGY (5.3)].

Complicated Urinary Tract Infection and Pyelonephritis
Ciprofloxacin is indicated for the treatment of cUTI and pyelonephritis due to Escherichia coli in
pediatric patients 1 to 17 years of age. Although effective in clinical trials, ciprofloxacin is not a drug
of first choice in the pediatric population due to an increased incidence of adverse reactions compared
to the controls, including events related to joints and/or surrounding tissues [see UNDESIRABLE
EFFECTS (4.8)].
Inhalational Anthrax (Post-Exposure)
Ciprofloxacin is indicated in pediatric patients from birth to 17 years of age, for inhalational anthrax
(post-exposure). The risk-benefit assessment indicates that administration of ciprofloxacin to pediatric
patients is appropriate [see DOSAGE AND ADMINISTRATION (4.2)].
Plague
Ciprofloxacin is indicated in pediatric patients from birth to 17 years of age, for treatment of plague,
including pneumonic and septicemic plague due to Yersinia pestis (Y. pestis) and prophylaxis for
plague. Efficacy studies of ciprofloxacin could not be conducted in humans with pneumonic plague for
feasibility reasons. Therefore, approval of this indication was based on an efficacy study conducted in
animals. The risk-benefit assessment indicates that administration of ciprofloxacin to pediatric patients
is appropriate [see INDICATIONS AND USAGE (4.1), DOSAGE AND ADMINISTRATION (4.2)

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.

In the event of acute overdosage, reversible renal toxicity has been reported in some cases. Empty the
stomach by inducing vomiting or by gastric lavage. Observe the patient carefully and give supportive
treatment, including monitoring of renal function, urinary pH and acidify, if required, to prevent
crystalluria and administration of magnesium, aluminum, or calcium containing antacids which can
reduce the absorption of ciprofloxacin. Adequate hydration must be maintained. Only a small amount
of ciprofloxacin (less than 10%) is removed from the body after hemodialysis or peritoneal dialysis.

5.1 Pharmacodynamics properties:
Pharmacotherapeutic group: Fluoroquinolones, ATC code: J01MA02
Mechanism of action:
As a fluoroquinolone antibacterial agent, the bactericidal action of ciprofloxacin results from the
inhibition of both type II topoisomerase (DNA-gyrase) and topoisomerase IV, required for bacterial
DNA replication, transcription, repair and recombination.
Pharmacokinetic /Pharmacodynamic relationship:
Efficacy mainly depends on the relation between the maximum concentration in serum (Cmax) and the
minimum inhibitory concentration (MIC) of ciprofloxacin for a bacterial pathogen and the relation
between the area under the curve (AUC) and the MIC.
Mechanism of resistance:
In-vitro resistance to ciprofloxacin can be acquired through a stepwise process by target site mutations
in both DNA gyrase and topoisomerase IV. The degree of cross-resistance between ciprofloxacin and
other fluoroquinolones that results is variable. Single mutations may not result in clinical resistance,
but multiple mutations generally result in clinical resistance to many or all active substances within the
class.
Impermeability and/or active substance efflux pump mechanisms of resistance may have a variable
effect on susceptibility to fluoroquinolones, which depends on the physiochemical properties of the
various active substances within the class and the affinity of transport systems for each active
substance. All in-vitro mechanisms of resistance are commonly observed in clinical isolates.
Resistance mechanisms that inactivate other antibiotics such as permeation barriers (common in
Pseudomonas aeruginosa) and efflux mechanisms may affect susceptibility to ciprofloxacin. Plasmidmediated
resistance encoded by qnr-genes has been reported.

Spectrum of antibacterial activity:
Breakpoints separate susceptible strains from strains with intermediate susceptibility and the latter from resistant strains:

1 Staphylococcus spp. - breakpoints for ciprofloxacin relate to high dose therapy.
* Non-species-related breakpoints have been determined mainly on the basis of PK/PD data and are
independent of MIC distributions of specific species. They are for use only for species that have not
been given a species-specific breakpoint and not for those species where susceptibility testing is not
recommended.
The prevalence of acquired 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.
Groupings of relevant species according to ciprofloxacin susceptibility (for Streptococcus species see
section 4.4)

COMMONLY SUSCEPTIBLE SPECIES
Aerobic Gram-positive micro-organisms
Bacillus anthracis (1)
Aerobic Gram-negative micro-organisms
Aeromonas spp.
Brucella spp.
Citrobacter koseri
Francisella tularensis
Haemophilus ducreyi
Haemophilus influenzae*
Legionella spp.
Moraxella catarrhalis*
Neisseria meningitidis
Pasteurella spp.
Salmonella spp.*
Shigella spp.*
Vibrio spp.
Yersinia pestis
Anaerobic micro-organisms
Mobiluncus
Other micro-organisms
Chlamydia trachomatis ($)
Chlamydia pneumoniae ($)
Mycoplasma hominis ($)
Mycoplasma pneumoniae ($)

SPECIES FOR WHICH ACQUIRED RESISTANCE MAY BE A PROBLEM
Aerobic Gram-positive micro-organisms
Enterococcus faecalis ($)
Staphylococcus spp. *(2)
Aerobic Gram-negative micro-organisms
Acinetobacter baumannii+
Burkholderia cepacia+*
Campylobacter spp.+*
Citrobacter freundii*
Enterobacter aerogenes
Enterobacter cloacae*
Escherichia coli*
Klebsiella oxytoca
Klebsiella pneumoniae*
Morganella morganii*
Neisseria gonorrhoeae*
Proteus mirabilis*
Proteus vulgaris*
Providencia spp.
Pseudomonas aeruginosa*
Pseudomonas fluorescens
Serratia marcescens*
Anaerobic micro-organisms
Peptostreptococcus spp.
Propionibacterium acnes
INHERENTLY RESISTANT ORGANISMS
Aerobic Gram-positive micro-organisms
Actinomyces
Enteroccus faecium
Listeria monocytogenes
Aerobic Gram-negative micro-organisms
Stenotrophomonas maltophilia
Anaerobic micro-organisms
Excepted as listed above
Other micro-organisms
Mycoplasma genitalium
Ureaplasma urealitycum
* Clinical efficacy has been demonstrated for susceptible isolates in approved clinical indications
+ Resistance rate ≥ 50% in one or more EU countries
($): Natural intermediate susceptibility in the absence of acquired mechanism of resistance
(1): Studies have been conducted in experimental animal infections due to inhalations of Bacillus anthracis spores;
these studies reveal that antibiotics starting early after exposition avoid the occurrence of the disease if the treatment
is made up to the decrease of the number of spores in the organism under the infective dose. The recommended use
in human subjects is based primarily on in-vitro susceptibility and on animal experimental data together with limited
human data. Two-month treatment duration in adults with oral ciprofloxacin given at the following dose, 500 mg

5.2 Pharmacokinetic Properties:
Absorption
The absolute bioavailability of ciprofloxacin when given as an oral tablet is approximately 70% with
no substantial loss by first pass metabolism. Ciprofloxacin maximum serum concentrations
(Cmax) and area under the curve (AUC) are shown in the chart for the 250 mg to 1000 mg dose range (Table 12).
Table 12: Ciprofloxacin Cmax and AUC Following Administration of Single Doses of
Ciprofloxacin Tablets to Healthy Subjects

Maximum serum concentrations are attained 1 to 2 hours after oral dosing. Mean concentrations 12
hours after dosing with 250, 500, or 750 mg are 0.1, 0.2, and 0.4 mcg/mL, respectively. The serum
elimination half-life in subjects with normal renal function is approximately 4 hours. Serum
concentrations increase proportionately with doses up to 1000 mg. A 500 mg oral dose given every
12 hours has been shown to produce an AUC equivalent to that produced by an intravenous infusion of
400 mg ciprofloxacin given over 60 minutes every 12 hours. A 750 mg oral dose given every 12 hours
has been shown to produce an AUC at steady-state equivalent to that produced by an intravenous
infusion of 400 mg given over 60 minutes every 8 hours. A 750 mg oral dose results in a Cmax similar
to that observed with a 400 mg intravenous dose. A 250 mg oral dose given every 12 hours produces
an AUC equivalent to that produced by an infusion of 200 mg ciprofloxacin given every 12 hours
(Table 13).

1. AUC 0–12h
2. AUC 24h = AUC 0–12h x 2
3. AUC 24h = AUC 0–8h x 3

Table 13: Steady-state Cmax and AUC of Ciprofloxacin Following Administration of Multiple Oral
and IV Ciprofloxacin Doses to Healthy Subjects
Food
When ciprofloxacin tablet is given concomitantly with food, there is a delay in the absorption of the
drug, resulting in peak concentrations that occur closer to 2 hours after dosing rather than 1 hour. The
overall absorption of ciprofloxacin tablet, however, is not substantially affected. Avoid concomitant
administration of ciprofloxacin with dairy products (like milk or yogurt) or calcium-fortified juices
alone since decreased absorption is possible; however, ciprofloxacin may be taken with a meal that
contains these products. With oral administration, a 500 mg dose, given as 10 mL of the 5%
ciprofloxacin suspension (containing 250 mg ciprofloxacin/5 mL) is bioequivalent to the 500 mg
tablet. A 10 mL volume of the 5% ciprofloxacin suspension (containing 250 mg ciprofloxacin/5 mL) is
bioequivalent to a 5 mL volume of the 10% ciprofloxacin suspension (containing 500 mg
ciprofloxacin/5 mL).
Distribution
The binding of ciprofloxacin to serum proteins is 20% to 40% which is not likely to be high enough to
cause significant protein binding interactions with other drugs.
After oral administration, ciprofloxacin is widely distributed throughout the body. Tissue
concentrations often exceed serum concentrations in both men and women, particularly in genital
tissue including the prostate. Ciprofloxacin is present in active form in the saliva, nasal and bronchial
secretions, mucosa of the sinuses, sputum, skin blister fluid, lymph, peritoneal fluid, bile, and prostatic
secretions. Ciprofloxacin has also been detected in lung, skin, fat, muscle, cartilage, and bone. The
drug diffuses into the cerebrospinal fluid (CSF); however, CSF concentrations are generally less than
10% of peak serum concentrations. Low levels of the drug have been detected in the aqueous and vitreous humors of the eye.

Metabolism
Four metabolites have been identified in human urine which together account for approximately 15%
of an oral dose. The metabolites have antimicrobial activity, but are less active than unchanged
ciprofloxacin. Ciprofloxacin is an inhibitor of human cytochrome P450 1A2 (CYP1A2) mediated
metabolism. Co-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2
results in increased plasma concentrations of these drugs and could lead to clinically significant
adverse events of the co-administered drug [see CONTRAINDICATIONS (4.3), WARNINGS AND
PRECAUTIONS (4.9, 4.15)].
Excretion
The serum elimination half-life in subjects with normal renal function is approximately 4 hours.
Approximately 40 to 50% of an orally administered dose is excreted in the urine as unchanged drug.
After a 250 mg oral dose, urine concentrations of ciprofloxacin usually exceed 200 mcg/mL during the
first two hours and are approximately 30 mcg/mL at 8 to 12 hours after dosing. The urinary excretion of ciprofloxacin is virtually complete within 24 hours after dosing. The renal clearance of ciprofloxacin, which is approximately 300 mL/minute, exceeds the normal glomerular filtration rate of 120 mL/minute. Thus, active tubular secretion would seem to play a significant role in its elimination.
Co-administration of probenecid with ciprofloxacin results in about a 50% reduction in the
ciprofloxacin renal clearance and a 50% increase in its concentration in the systemic circulation.
Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after
oral dosing, only a small amount of the dose administered is recovered from the bile as unchanged
drug. An additional 1% to 2% of the dose is recovered from the bile in the form of metabolites.
Approximately 20% to 35% of an oral dose is recovered from the feces within 5 days after dosing.
This may arise from either biliary clearance or transintestinal elimination.

Specific Populations
Elderly
Pharmacokinetic studies of the oral (single dose) and intravenous (single and multiple dose) forms of
ciprofloxacin indicate that plasma concentrations of ciprofloxacin are higher in elderly subjects (older
than 65 years) as compared to young adults. Although the Cmax is increased 16% to 40%, the increase
in mean AUC is approximately 30%, and can be at least partially attributed to decreased renal
clearance in the elderly. Elimination half-life is only slightly (~20%) prolonged in the elderly. These
differences are not considered clinically significant.
Renal Impairment
In patients with reduced renal function, the half-life of ciprofloxacin is slightly prolonged. Dosage
adjustments may be required [see DOSAGE AND ADMINISTRATION (4.2)].
Hepatic Impairment
In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in
ciprofloxacin pharmacokinetics have been observed. The kinetics of ciprofloxacin in patients with
acute hepatic insufficiency, have not been fully studied.
Pediatrics
Following a single oral dose of 10 mg/kg ciprofloxacin suspension to 16 children ranging in age from
4 months to 7 years, the mean Cmax was 2.4 mcg/mL (range: 1.5 mcg/mL to 3.4 mcg/mL) and the
mean AUC was 9.2 mcg*hr/mL (range: 5.8 mcg*hr/mL to 14.9 mcg*h/mL). There was no apparent
age-dependence, and no notable increase in Cmax or AUC upon multiple dosing (10 mg/kg three times
a day). In children with severe sepsis who were given ciprofloxacin IV (10 mg/kg as a 1-hour
intravenous infusion), the mean Cmax was 6.1 mcg/mL (range: 4.6 mcg/mL to 8.3 mcg/mL) in 10
children less than 1 year of age; and 7.2 mcg/mL (range: 4.7 mcg/mL to 11.8 mcg/mL) in 10 children
between 1 year and 5 years of age. The AUC values were 17.4 mcg*hr/mL (range: 11.8 mcg*hr/mL to
32 mcg*hr/mL) and 16.5 mcg*hr/mL (range: 11 mcg*hr/mL to 23.8 mcg*hr/mL) in the respective age
groups. These values are within the range reported for adults at therapeutic doses. Based on population
pharmacokinetic analysis of pediatric patients with various infections, the predicted mean half-life in
children is approximately 4 hours to 5 hours, and the bioavailability of the oral suspension is
approximately 60%.

Drug-Drug Interactions
Antacids
Concurrent administration of antacids containing magnesium hydroxide or aluminum hydroxide may
reduce the bioavailability of ciprofloxacin by as much as 90% [see DOSAGE AND
ADMINISTRATION (4.2)].

Histamine H2-receptor antagonists
Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of
ciprofloxacin.
Metronidazole
The serum concentrations of ciprofloxacin and metronidazole were not altered when these two drugs
were given concomitantly.
Tizanidine
In a pharmacokinetic study, systemic exposure of tizanidine (4 mg single dose) was significantly
increased (Cmax 7-fold, AUC 10-fold) when the drug was given concomitantly with ciprofloxacin
(500 mg twice a day for 3 days). Concomitant administration of tizanidine and ciprofloxacin is
contraindicated due to the potentiation of hypotensive and sedative effects of
tizanidine [see CONTRAINDICATIONS (4.3)].
Ropinirole
In a study conducted in 12 patients with Parkinson’s disease who were administered 6 mg ropinirole
once daily with 500 mg ciprofloxacin twice-daily, the mean Cmax and mean AUC of ropinirole were
increased by 60% and 84%, respectively. Monitoring for ropinirole-related adverse reactions and
appropriate dose adjustment of ropinirole is recommended during and shortly after co-administration
with ciprofloxacin [see WARNINGS AND PRECAUTIONS (4.9)].
Clozapine
Following concomitant administration of 250 mg ciprofloxacin with 304 mg clozapine for 7 days,
serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%,
respectively. Careful monitoring of clozapine associated adverse reactions and appropriate adjustment
of clozapine dosage during and shortly after co-administration with ciprofloxacin are advised.
Sildenafil
Following concomitant administration of a single oral dose of 50 mg sildenafil with 500 mg
ciprofloxacin to healthy subjects, the mean Cmax and mean AUC of sildenafil were both increased
approximately two-fold. Use sildenafil with caution when co-administered with ciprofloxacin due to
the expected two-fold increase in the exposure of sildenafil upon co-administration of ciprofloxacin.
Duloxetine
In clinical studies it was demonstrated that concomitant use of duloxetine with strong inhibitors of the
CYP450 1A2 isozyme such as fluvoxamine, may result in a 5-fold increase in mean AUC and a 2.5-
fold increase in mean Cmax of duloxetine.

Lidocaine
In a study conducted in 9 healthy volunteers, concomitant use of 1.5 mg/kg IV lidocaine with
ciprofloxacin 500 mg twice daily resulted in an increase of lidocaine Cmax and AUC by 12% and
26%, respectively. Although lidocaine treatment was well tolerated at this elevated exposure, a
possible interaction with ciprofloxacin and an increase in adverse reactions related to lidocaine may occur upon concomitant administration.

Metoclopramide
Metoclopramide significantly accelerates the absorption of oral ciprofloxacin resulting in a shorter time to reach maximum plasma concentrations. No significant effect was observed on the bioavailability of ciprofloxacin. Omeprazole
When ciprofloxacin was administered as a single 1000 mg dose concomitantly with omeprazole (40 mg once daily for three days) to 18 healthy volunteers, the mean AUC and Cmax of ciprofloxacin were reduced by 20% and 23%, respectively. The clinical significance of this interaction has not been determined.

Non-clinical data reveal no special hazards for humans based on conventional studies of single dose
toxicity, repeated dose toxicity, carcinogenic potential, or toxicity to reproduction.
Like a number of other quinolones, ciprofloxacin is phototoxic in animals at clinically relevant
exposure levels. Data on photomutagenicity/photocarcinogenicity show a weak photomutagenic or
phototumorigenic effect of ciprofloxacin in-vitro and in animal experiments. This effect was
comparable to that of other gyrase inhibitors.
Articular tolerability:
As reported for other gyrase inhibitors, ciprofloxacin causes damage to the large weight-bearing joints in immature animals. The extent of the cartilage damage varies according to age, species and dose; the damage can be reduced by taking the weight off the joints. Studies with mature animals (rat, dog) revealed no evidence of cartilage lesions. In a study in young beagle dogs, ciprofloxacin caused severe articular changes at therapeutic doses after two weeks of treatment, which were still observed after 5 months.

NONCLINICAL TOXICOLOGY
Carcinogenesis, Mutagenesis, Impairment of Fertility
Eight in vitro mutagenicity tests have been conducted with ciprofloxacin, and the test results are listed
below:
Salmonella/Microsome Test (Negative)
E. coli DNA Repair Assay (Negative)
Mouse Lymphoma Cell Forward Mutation Assay (Positive)
Chinese Hamster V79 Cell HGPRT Test (Negative)
Syrian Hamster Embryo Cell Transformation Assay (Negative)
Saccharomyces cerevisiae Point Mutation Assay (Negative)
Saccharomyces cerevisiae Mitotic Crossover and Gene Conversion Assay (Negative)
Rat Hepatocyte DNA Repair Assay (Positive)
Thus, 2 of the 8 tests were positive, but results of the following 3 in vivo test systems gave negative
results:
Rat Hepatocyte DNA Repair Assay
Micronucleus Test (Mice)
Dominant Lethal Test (Mice)
Long-term carcinogenicity studies in rats and mice resulted in no carcinogenic or tumorigenic effects due to ciprofloxacin at daily oral dose levels up to 250 mg/kg and 750 mg/kg to rats and mice,
respectively (approximately 1.7- and 2.5- times the highest recommended therapeutic dose based upon
body surface area, respectively).
Results from photo co-carcinogenicity testing indicate that ciprofloxacin does not reduce the time to
appearance of UV-induced skin tumors as compared to vehicle control. Hairless (Skh-1) mice were exposed to UVA light for 3.5 hours five times every two weeks for up to 78 weeks while concurrently being administered ciprofloxacin. The time to development of the first skin tumors was 50 weeks in mice treated concomitantly with UVA and ciprofloxacin (mouse dose approximately equal to maximum recommended human dose based upon body surface area), as opposed to 34 weeks when animals were treated with both UVA and vehicle. The times to development of skin tumors ranged
from 16 weeks to32 weeks in mice treated concomitantly with UVA and other quinolones.5
In this model, mice treated with ciprofloxacin alone did not develop skin or systemic tumors. There are no data from similar models using pigmented mice and/or fully haired mice. The clinical significance of these findings to humans is unknown.
Fertility studies performed in rats at oral doses of ciprofloxacin up to 100 mg/kg (approximately 0.7- times the highest recommended therapeutic dose based upon body surface area) revealed no evidence of impairment.

 Animal Toxicology and/or Pharmacology
Ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals of
most species tested [see Warnings and Precautions (5.12)].Damage of weight bearing joints was
observed in juvenile dogs and rats. In young beagles, 100 mg/kg ciprofloxacin, given daily for 4
weeks, caused degenerative articular changes of the knee joint. At 30 mg/kg, the effect on the joint
was minimal. In a subsequent study in young beagle dogs, oral ciprofloxacin doses of 30 mg/kg and 90
mg/kg ciprofloxacin (approximately 1.3-times and 3.5-times the pediatric dose based upon
comparative plasma AUCs) given daily for 2 weeks caused articular changes which were still observed
by histopathology after a treatment-free period of 5 months. At 10 mg/kg (approximately 0.6-times the
pediatric dose based upon comparative plasma AUCs), no effects on joints were observed. This dose
was also not associated with arthrotoxicity after an additional treatment-free period of 5 months. In
another study, removal of weight bearing from the joint reduced the lesions but did not totally prevent
them.
Crystalluria, sometimes associated with secondary nephropathy, occurs in laboratory animals dosed
with ciprofloxacin. This is primarily related to the reduced solubility of ciprofloxacin under alkaline
conditions, which predominate in the urine of test animals; in man, crystalluria is rare since human
urine is typically acidic. In rhesus monkeys, crystalluria without nephropathy was noted after single
oral doses as low as 5 mg/kg (approximately 0.07-times the highest recommended therapeutic dose
based upon body surface area). After 6 months of intravenous dosing at 10 mg/kg/day, no
nephropathological changes were noted; however, nephropathy was observed after dosing at 20
mg/kg/day for the same duration (approximately 0.2-times the highest recommended therapeutic dose
based upon body surface area).
In dogs, ciprofloxacin at 3 mg/kg and 10 mg/kg by rapid intravenous injection (15 sec.) produces
pronounced hypotensive effects. These effects are considered to be related to histamine release, since
they are partially antagonized by pyrilamine, an antihistamine. In rhesus monkeys, rapid intravenous
injection also produces hypotension but the effect in this species is inconsistent and less pronounced.
In mice, concomitant administration of nonsteroidal anti-inflammatory drugs such as phenylbutazone
and indomethacin with quinolones has been reported to enhance the CNS stimulatory effect of
quinolones. Ocular toxicity seen with some related drugs has not been observed in ciprofloxacintreated
animals.

Tablet core:
Microcrystalline Cellulose
Maize Starch
Sodium Starch Glycolate
Colloidal silicon dioxide
Talc Powder
Magnesium Stearate
Tablet coating:
HPMC 2910 - Titanium dioxide – Macrogol

Not Applicable.

Store below 30°C.

The immediate packaging material is PVC/PVDC/Alu Blister.
-Pack size: 10 Film-Coated Tablets.

This medicinal product should not be disposed of via wastewater or household waste. Any
unused medicinal product or waste material should be disposed of in accordance with local
requirements.