Cipro-Sol I.V. Infusion USP is indicated for the treatment of the following infections. Special
attention should be paid to available information on resistance to Ciprofloxacin before
commencing therapy.
Consideration should be given to official guidance on the appropriate use of antibacterial
agents.
Adults
• Lower respiratory tract infections due to Gram-negative bacteria
- Exacerbations of chronic obstructive pulmonary disease.
- Broncho-pulmonary infections in cystic fibrosis or in bronchiectasis.
- Pneumonia.
• Chronic suppurative otitis media
• Acute exacerbation of chronic sinusitis especially if these are caused by Gram-negative
bacteria
• Urinary tract infections
• Epididymo-orchitis including cases due to Neisseria gonorrhoeae

• Pelvic inflammatory disease including cases due to Neisseria gonorrhoeae
In the above genital tract infections when thought or known to be due to Neisseria
gonorrhoeae it is particularly important to obtain local information on the prevalence
of resistance to Cipro-Sol I.V. Infusion USP and to confirm susceptibility based on
laboratory testing.
• Infections of the gastro-intestinal tract (e.g. travellers` diarrhoea)
• Intra-abdominal infections
• Infections of the skin and soft tissue caused by Gram-negative bacteria
• Malignant external otitis
• Infections of the bones and joints
• Treatment of infections in neutropenic patients
• Prophylaxis of infections in neutropenic patients
• Inhalation anthrax (post-exposure prophylaxis and curative treatment)
Children and adolescents
• Broncho-pulmonary infections in cystic fibrosis caused by Pseudomonas aeruginosa
• Complicated urinary tract infections and pyelonephritis
• Inhalation anthrax (post-exposure prophylaxis and curative treatment)
Ciprofloxacin may also be used to treat severe infections in children and adolescents when
this is considered to be necessary.
Treatment should be initiated only by physicians who are experienced in the treatment of
cystic fibrosis and/or severe infections in children and adolescents.

The dosage is determined by the indication, the severity and the site of the infection, the
susceptibility to Ciprofloxacin of the causative organism(s), the renal function of the patient
and, in children and adolescents the body weight.
The duration of treatment depends on the severity of the illness and on the clinical and
bacteriological course.
After intravenous initiation of treatment, the treatment can be switched to oral treatment with

tablet or suspension if clinically indicated at the discretion of the physician. IV treatment
should be followed by oral route as soon as possible.
In severe cases or if the patient is unable to take tablets (e.g. patients on enteral nutrition), it is
recommended to commence therapy with intravenous Ciprofloxacin until a switch to oral
administration is possible.
Treatment of infections due to certain bacteria (e.g. Pseudomonas aeruginosa, Acinetobacter
or Staphylococci) may require higher Ciprofloxacin doses and co-administration with other
appropriate antibacterial agents.
Treatment of some infections (e.g. pelvic inflammatory disease, intra-abdominal infections,
infections in neutropenic patients and infections of bones and joints) may require coadministration
with other appropriate antibacterial agents depending on the pathogens
involved.
Adults

Children and adolescents

Geriatric patients
Geriatric patients should receive a dose selected according to the severity of the infection and
the patient`s creatinine clearance.
Renal and hepatic impairment
Recommended starting and maintenance doses for patients with impaired renal function:

In patients with impaired liver function no dose adjustment is required

Dosing in children with impaired renal and/or hepatic function has not been studied.
Method of administration
Cipro-Sol should be checked visually prior to use. It must not be used if cloudy.
Cipro-Sol should be administered by intravenous infusion. For children, the infusion
duration is 60 minutes.
In adult patients, infusion time is 60 minutes for 400 mg Ciprofloxacin and 30 minutes for
200 mg Ciprofloxacin. Slow infusion into a large vein will minimize patient discomfort
and reduce the risk of venous irritation.

Severe infections and mixed infections with Gram-positive and anaerobic pathogens
Ciprofloxacin monotherapy is not suited for treatment of severe infections and infections
that might be due to Gram-positive or anaerobic pathogens. In such infections
Ciprofloxacin must be co- administered with other appropriate antibacterial agents.

Streptococcal Infections (including Streptococcus pneumoniae)
Ciprofloxacin is not recommended for the treatment of streptococcal infections due to
inadequate efficacy.

Genital tract infections
Epididymo-orchitis and pelvic inflammatory diseases may be caused by fluoroquinoloneresistant
Neisseria gonorrhoeae. Ciprofloxacin should be co-administered with another appropriate
antibacterial agent unless Ciprofloxacin -resistant Neisseria gonorrhoeae can be excluded.
If clinical improvement is not achieved after 3 days of treatment, the therapy should be
reconsidered.

Intra-abdominal infections
There are limited data on the efficacy of Ciprofloxacin in the treatment of post-surgical
intra-abdominal infections.

Travellers’ diarrhoea
The choice of Ciprofloxacin should take into account information on resistance to
Ciprofloxacin in relevant pathogens in the countries visited.

Infections of the bones and joints
Ciprofloxacin should be used in combination with other antimicrobial agents depending
on the results of the microbiological documentation.

Inhalational anthrax
Use in humans is based on in-vitro susceptibility data and on animal experimental data
together with limited human data. Treating physicians should refer to national and /or
international consensus documents regarding the treatment of anthrax.

Children and adolescents
The use of Ciprofloxacin in children and adolescents should follow available official
guidance. Ciprofloxacin treatment should be initiated only by physicians who are
experienced in the treatment of cystic fibrosis and/or severe infections in children and
adolescents.

Ciprofloxacin has been shown to cause arthropathy in weight-bearing joints of immature
animals. Safety data from a randomized double-blind study on Cipro-Sol I.V. Infusion
USP use in children (Cipro-Sol I.V. Infusion USP: n=335, mean age = 6.3 years;
comparators: n=349, mean age = 6.2 years; age range = 1 to 17 years) revealed an
incidence of suspected drug-related arthropathy (discerned from joint-related clinical
signs and symptoms) by Day +42 of 7.2% and 4.6%. Respectively, an incidence of drugrelated
arthropathy by 1-year follow-up was 9.0% and 5.7%. The increase of suspected
drug-related arthropathy cases over time was not statistically significant between groups.
Treatment should be initiated only after a careful benefit/risk evaluation, due to possible
adverse events related to joints and/or surrounding tissue.

Broncho-pulmonary infections in cystic fibrosis
Clinical trials have included children and adolescents aged 5-17 years. More limited
experience is available in treating children between 1 and 5 years of age.
Complicated urinary tract infections and pyelonephritis
Ciprofloxacin treatment of urinary tract infections should be considered when other
treatments cannot be used, and should be based on the results of the microbiological
documentation.
Clinical trials have included children and adolescents aged 1-17 years.

Other specific severe infections
Other severe infections in accordance with official guidance, or after careful benefit-risk
evaluation when other treatments cannot be used, or after failure to conventional therapy
and when the microbiological documentation can justify a Cipro-Sol I.V. Infusion USP
use.
The use of Cipro-Sol I.V. Infusion USP for specific severe infections other than those
mentioned above has not been evaluated in clinical trials and the clinical experience is
limited. Consequently, caution is advised when treating patients with these infections.

Hypersensitivity
Hypersensitivity and allergic reactions, including anaphylaxis and anaphylactoid
reactions, may occur following a single dose (see section 4.8) and may be life-threatening.
If such reaction occurs, Ciprofloxacin should be discontinued and an adequate medical
treatment is required.

Musculoskeletal System
Ciprofloxacin should generally not be used in patients with a history of tendon
disease/disorder related to quinolone treatment. Nevertheless, in very rare instances, after
microbiological documentation of the causative organism and evaluation of the
risk/benefit balance, Ciprofloxacin may be prescribed to these patients for the treatment
of certain severe infections, particularly in the event of failure of the standard therapy or
bacterial resistance, where the microbiological data may justify the use of Ciprofloxacin.
Tendinitis and tendon rupture (especially Achilles tendon), sometimes bilateral, may
occur with Ciprofloxacin, as soon as the first 48 hours of treatment. The risk of
tendinopathy may be increased in elderly patients or in patients concomitantly treated
with corticosteroids (see section 4.8).
At any sign of tendinitis (e.g. painful swelling, inflammation), Ciprofloxacin treatment
should be discontinued. Care should be taken to keep the affected limb at rest.
Ciprofloxacin should be used with caution in patients with myasthenia gravis (see section 4.8).

Photosensitivity
Ciprofloxacin has been shown to cause photosensitivity reactions. Patients taking
Cipro-Sol I.V. Infusion USP should be advised to avoid direct exposure to either
extensive sunlight or UV irradiation during treatment (see section 4.8).
Central Nervous System
Quinolones are known to trigger seizures or lower the seizure threshold. Ciprofloxacin
should be used with caution in patients with CNS disorders which may be predisposed to
seizure. If seizures occur Cipro-Sol I.V. Infusion USP should be discontinued (see section
4.8). Psychiatric reactions may occur even after the first administration of Cipro-Sol I.V.
Infusion USP. In rare cases, depression or psychosis can progress to self- endangering
behavior. In these cases, Cipro-Sol I.V. Infusion USP should be discontinued.
The mental health side effects are disturbances in attention, disorientation, agitation,
nervousness, memory impairment and serious disturbances in mental abilities called
delirium.
Peripheral nervous system
Peripheral neuropathy (serious nerve damage) is an identified risk of fluoroquinolone
drugs taken by mouth or by injection.
(Peripheral neuropathy symptoms in the arms or legs such as; pain, burning, tingling,
numbness, weakness or change in sensation to light touch, pain, or temperature).
Peripheral neuropathy can occur at anytime during treatment with fluoroquinolones (may
occur soon after these drugs are taken) and can last for months or years after the drug is
stopped or be permanent. The symptoms may occur soon after initiation of therapy and
may be irreversible. If symptoms of peripheral neuropathy including pain, burning,
tingling, numbness and / or weakness develop, patients should immediately discontinue
ciprofloxacin and contact their physician. (See possible side effects).
If a patient develops symptoms of peripheral neuropathy, the fluoroquinolone

stopped and the patient should be switched to another non-fluroquinolone antibacterial
drug, unless the benefit of continued treatment with a fluoroquinolone outweighs the risk
(see section 4.8).

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. Cipro-Sol 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 also increased Risk of ruptures or tears in the aorta blood vessel in
certain patients.
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).
Cardiac disorders
Since Ciprofloxacin is associated with cases of QT prolongation (see section 4.8), caution
should be exercised when treating patients at risk for torsades de pointes arrhythmia.
Gastrointestinal System
The occurrence of severe and persistent diarrhea during or after treatment (including
several weeks after treatment) may indicate an antibiotic-associated colitis (lifethreatening
with possible fatal outcome), requiring immediate treatment (see section 4.8).
In such cases, Ciprofloxacin should immediately be discontinued, and an appropriate
therapy initiated. Anti-peristaltic drugs are contraindicated in this situation.
Renal and urinary system
Crystalluria related to the use of Ciprofloxacin has been reported (see section 4.8).
Patients receiving Cipro-Sol I.V. Infusion USP should be well hydrated and excessive
alkalinity of the urine should be avoided.
Hepatobiliary system
Cases of hepatic necrosis and life-threatening hepatic failure have been reported with
Ciprofloxacin (see section 4.8). In the event of any signs and symptoms of hepatic disease
(such as anorexia, jaundice, dark urine, pruritus, or tender abdomen), treatment should be
discontinued.
Glucose-6-phosphate dehydrogenase deficiency
Haemolytic reactions have been reported with Ciprofloxacin in patients with glucose-6-
phosphate dehydrogenase deficiency. Cipro-Sol I.V. Infusion USP should be avoided in
these patients unless the potential benefit is considered to outweigh the possible risk. In
this case, potential occurrence of haemolysis should be monitored.
Fluoroquinolone antibiotics may cause significant decreases in blood sugar and certain
mental health side effects.
Blood sugar disturbances including high blood sugar and low blood sugar, are alread

included as a warning in most fluoroquinolone drug labels; however, to add that
hypoglycemia can lead to coma.
Resistance
During or following a course of treatment with Cipro-Sol I.V. Infusion USP bacteria that
demonstrate resistance to Ciprofloxacin may be isolated, with or without a clinically
apparent superinfection. There may be a particular risk of selecting for Ciprofloxacin -

resistant bacteria during extended durations of treatment and when treating nosocomial
infections and/or infections caused by Staphylococcus and Pseudomonas species.
Cytochrome P450
Ciprofloxacin inhibits CYP1A2 and thus may cause increased serum concentration of
concomitantly administered substances metabolised by this enzyme (e.g. theophylline,
clozapine, ropinirole, tizanidine). Co-administration of Cipro-Sol I.V. Infusion USP and
tizanidine is contra-indicated. Therefore, patients taking these substances concomitantly
with Ciprofloxacin should be monitored closely for clinical signs of overdose, and
determination of serum concentrations (e.g. of theophylline) may be necessary (see
section 4.5).
Methotrexate
The concomitant use of Ciprofloxacin with methotrexate is not recommended (see section
4.5).
Interaction with tests
The in-vitro activity of Ciprofloxacin against Mycobacterium tuberculosis might give
false negative bacteriological test results in specimens from patients currently taking
Cipro-Sol I.V. Infusion USP.
Injection Site Reaction
Local intravenous site reactions have been reported with the intravenous administration of
Ciprofloxacin. These reactions are more frequent if the infusion time is 30 minutes or
less. These may appear as local skin reactions which resolve rapidly upon completion of
the infusion. Subsequent intravenous administration is not contraindicated unless the
reactions recur or worsen.
Sodium chloride load
In patients for whom sodium intake is of medical concern (patients with congestive heart
failure, renal failure, nephrotic syndrome, etc.), the additional sodium load should be
taken into account.

Effects of other medicinal products on Cipro-Sol I.V. Infusion USP:
Drugs known to prolong QT interval
Ciprofloxacin, like other fluoroquinolones, should be used with caution in patients
receiving drugs known to prolong QT interval (e.g. Class IA and III anti- arrhythmics,
tricyclic antidepressants, macrolides, antipsychotics) (see section 4.4).
Probenecid
Probenecid interferes with renal secretion of Ciprofloxacin. Co-administration of
probenecid and Ciprofloxacin increases Ciprofloxacin serum concentrations.
Effects of Cipro-Sol I.V. Infusion USP on other medicinal products:
Tizanidine

Tizanidine must not be administered together with Ciprofloxacin (see section 4.3).
In a clinical study with healthy subjects, there was an increase in serum tizanidine
concentration (Cmax increase: 7-fold, range: 4 to 21-fold; AUC increase: 10-fold, range:
6 to 24-fold) when given concomitantly with Ciprofloxacin. Increased serum tizanidine
concentration is associated with a potentiated hypotensive and sedative effect.
Methotrexate
Renal tubular transport of methotrexate may be inhibited by concomitant administration
of Ciprofloxacin, potentially leading to increased plasma levels of methotrexate and
increased risk of methotrexate-associated toxic reactions. The concomitant use is not
recommended (see section 4.4).
Theophylline
Concurrent administration of Ciprofloxacin and theophylline can cause an undesirable
increase in serum theophylline concentration. This can lead to theophylline-induced side
effects that may rarely be life threatening or fatal. During the combination, serum
theophylline concentrations should be checked and the theophylline dose reduced as
necessary (see section 4.4).
Other xanthine derivatives
On concurrent administration of Ciprofloxacin and caffeine or pentoxifylline
(oxpentifylline), raised serum concentrations of these xanthine derivatives were reported.
Phenytoin
Simultaneous administration of Ciprofloxacin and phenytoin may result in increased or
reduced serum levels of phenytoin such that monitoring of drug levels is recommended.
Oral anticoagulants
Simultaneous administration of Ciprofloxacin with warfarin may augment its anticoagulant
effects. There have been many reports of increases in oral anti-coagulant
activity in patients receiving antibacterial agents, including fluoroquinolones. The risk
may vary with the underlying infection, age and general status of the patient so that the
contribution of the fluoroquinolone to the increase in INR (international normalised ratio)
is difficult to assess. It is recommended that the INR should be monitored frequently
during and shortly after co-administration of Ciprofloxacin with an oral anticoagulant
agent.
Ropinirole
It was shown in a clinical study that concomitant use of ropinirole with Ciprofloxacin, a
moderate inhibitor of the CYP450 1A2 isozyme, results in an increase of Cmax and AUC
of ropinirole by 60% and 84%, respectively. Monitoring of ropinirole-related side effects
and dose adjustment as appropriate is recommended during and shortly after coadministration
with Ciprofloxacin (see section 4.4).

Clozapine
Following concomitant administration of 250 mg Ciprofloxacin with clozapine for 7 days,
serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and
31%, respectively. Clinical surveillance and appropriate adjustment of clozapine dosage
during and shortly after co- administration with Ciprofloxacin are advised (see section 4.4).
Glibenclamide
In particular cases, concurrent administration of Ciprofloxacin and glibenclamide
containing medicinal products can intensify the action of glibenclamide (hypoglycaemia).
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 an increase of
AUC and Cmax of duloxetine. Although no clinical data are available on a possible
interaction with Ciprofloxacin, similar effects can be expected upon concomitant
administration (see section 4.4).
Lidocaine
It was demonstrated in healthy subjects that concomitant use of lidocaine containing
medicinal products with Ciprofloxacin, a moderate inhibitor of CYP450 1A2 isozyme,
reduces clearance of intravenous lidocaine by 22%. Although lidocaine treatment was
well tolerated, a possible interaction with Ciprofloxacin associated with side effects may
occur upon concomitant administration.
Sildenafil
Cmax and AUC of sildenafil were increased approximately twofold in healthy subjects
after an oral dose of 50 mg given concomitantly with 500 mg Ciprofloxacin. Therefore,
caution should be used prescribing Cipro-Sol I.V. Infusion USP concomitantly with
sildenafil taking into consideration the risks and the benefits.

Pregnancy
Pregnancy Category C.
Animal studies do not indicate direct or indirect harmful effects with respect to
reproductive toxicity. In juvenile and prenatal animals exposed to quinolones,
The data that are available on administration of ciprofloxacin to pregnant women
indicates no malformative or feto/neonatal toxicity of ciprofloxacin. effects on immature
cartilage have been observed, thus, it cannot be excluded that the drug could cause
damage to articular cartilage in the human immature organism / foetus (see section 5.3).

As a precautionary measure, it is preferable to avoid the use of ciprofloxacin during
pregnancy.
Lactation
Ciprofloxacin is excreted in breast milk. Due to the potential risk of articular damage,
Ciprofloxacin should not be used during breast-feeding.
 

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

The most commonly reported adverse drug reactions (ADRs) are nausea, diarrhea, vomiting, transient increase in transaminases, rash, and injection and infusion site reactions. ADRs derived from clinical studies and post-marketing surveillance with Cipro-Sol I.V. Infusion USP sorted by categories of frequency are listed below.

An overdose of 12 g has been reported to lead to mild symptoms of toxicity. An acute overdose of 16 g has been reported to cause acute renal failure. Symptoms in overdose consist of dizziness, tremor, headache, tiredness, seizures, hallucinations, confusion, abdominal discomfort, renal and hepatic impairment as well as crystalluria and haematuria.
Reversible renal toxicity has been reported. Apart from routine emergency measures, it is recommended to monitor renal function, including urinary pH and acidify, if required, to prevent crystalluria. Patients should be kept well hydrated. Only a small quantity of Ciprofloxacin (<10%) is eliminated by haemodialysis or peritoneal dialysis.

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)

 

5.1 Pharmacodynamic 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 Cipro-Sol I.V. Infusion USP 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.
Plasmid-mediated 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:
EUCAST Recommendations

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

5.2 Pharmacokinetic properties
Absorption
Following an intravenous infusion of Ciprofloxacin the mean maximum serum
concentrations were achieved at the end of infusion. Pharmacokinetics of Ciprofloxacin
was linear over the dose range up to 400 mg administered intravenously.
Comparison of the pharmacokinetic parameters for a twice a day and three times a day
intravenous dose regimen indicated no evidence of drug accumulation for Ciprofloxacin
and its metabolites.
A 60-minute intravenous infusion of 200 mg Ciprofloxacin or the oral administration of
250 mg Ciprofloxacin, both given every 12 hours, produced an equivalent area under the

serum concentration time curve (AUC).
A 60-minute intravenous infusion of 400 mg Ciprofloxacin every 12 hours was
bioequivalent to a 500 mg oral dose every 12 hours with regard to AUC.

The 400 mg intravenous dose administered over 60 minutes every 12 hours resulted in a
Cmax similar to that observed with a 750 mg oral dose.
A 60-minute infusion of 400 mg Ciprofloxacin every 8 hours is equivalent with respect to
AUC to 750 mg oral regimen given every 12 hours.
Distribution
Protein binding of Ciprofloxacin is low (20-30%). Ciprofloxacin is present in plasma
largely in a non- ionised form and has a large steady state distribution volume of 2-3 L/kg
body weight.
Ciprofloxacin reaches high concentrations in a variety of tissues such as lung (epithelial
fluid, alveolar macrophages, biopsy tissue), sinuses, inflamed lesions (cantharides blister
fluid), and the urogenital tract (urine, prostate, endometrium) where total concentrations

exceeding those of plasma concentrations are reached.
Metabolism
Low concentrations of four metabolites have been reported, which were identified as:
desethyleneciprofloxacin (M 1), sulphociprofloxacin (M 2), oxociprofloxacin (M 3) and
formylciprofloxacin (M 4). The metabolites display in-vitro antimicrobial activity but to a
lower degree than the parent compound.
Ciprofloxacin is known to be a moderate inhibitor of the CYP 450 1A2 iso-enzymes.

Elimination
Ciprofloxacin is largely excreted unchanged both renally and, to a smaller extent,
faecally.

Renal clearance is between 180-300 mL/kg/h and the total body clearance is between
480-600 mL/kg/h. Ciprofloxacin undergoes both glomerular filtration and tubular
secretion. Severely impaired renal function leads to increased half lives of Ciprofloxacin
of up to 12 h.
Non-renal clearance of Ciprofloxacin is mainly due to active trans-intestinal secretion and
metabolism.
1% of the dose is excreted via the biliary route. Ciprofloxacin is present in the bile in high
concentrations.
Pediatric patients
The pharmacokinetic data in pediatric patients are limited.
In a study in children Cmax and AUC were not age-dependent (above one year of age).

No notable increase in Cmax and AUC upon multiple dosing (10 mg/kg three times
daily) was observed.
In 10 children with severe sepsis Cmax was 6.1 mg/L (range 4.6-8.3 mg/L) after a 1-hour
intravenous infusion of 10 mg/kg in children aged less than 1 year compared to 7.2 mg/L
(range 4.7-11.8 mg/L) for children between 1 and 5 years of age. The AUC values were
17.4 mg*h/L (range 11.8-32.0 mg*h/L) and 16.5 mg*h/L (range 11.0-23.8 mg*h/L) 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 approx. 4-5 hours and the bioavailability of the oral
suspension ranges from 50 to 80%.

5.3 Preclinical safety data
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 weightbearing
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.

Lactic Acid
Sodium Chloride
Water for injections

Cipro-Sol I.V. Infusion USP should not be mixed with other medicinal products.
6.3 Shelf

Do not store above 30°C, Do not refrigerate or freeze.
Keep in the original container. Protect from light.

100ml Glass Bottles.
100ml non-PVC Bag, packed in Aluminum Pouch.

For single use only. Any unused solution should be discarded.