Ciprofloxacin film-coated tablets are indicated for the treatment of the following infections (see sections 4.4 and 5.1).
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
• Genital tract infections
• gonococcal uretritis and cervicitis due to susceptible Neisseria gonorrhoeae
• epididymo-orchitis including cases due to Neisseria gonorrhoeae
• pelvic inflammatory disease including infections due to Neisseria gonorrhoeae
• 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
• Prophylaxis of invasive infections due to Neisseria meningitidis
• Inhalation anthrax (post-exposure prophylaxis and curative treatment)
Ciprofloxacin may be used in the management of neutropenic patients with fever that is suspected to be due to a bacterial infection.

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 (see sections 4.4 and 5.1).

Posology
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.
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 co-administration with other appropriate antibacterial agents depending on the pathogens involved.

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.

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 a change in sensation to light touch, pain, or temperature)
Peripheral neuropathy can occur at any time during treatment with fluoroquinolones (may occur soon after these drugs are taken) and can last for months to years after the drug is stopped or be permanent.
If a patient develops symptoms of peripheral neuropathy, the fluoroquinolone should be stopped and the patient should be switched to another non-fluoroquinolone anti- bacterial drug, unless the benefit of continued treatment with a fluoroquinolone outweighs the risk.
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 coadministered with other appropriate antibacterial agents.

Streptococcal Infections (including Streptococcus pneumonia
Ciprofloxacin is not recommended for the treatment of streptococcal infections due to inadequate efficacy.
Genital tract infections
Gonococcal uretritis, cervicitis, epididymo-orchitis and pelvic inflammatory disease may be caused by fluoroquinolones-resistant Neisseria gonorrhoeae isolates.
Therefore, ciprofloxacin should be administered for the treatment of gonococcal uretritis or cervicitis only if ciprofloxacin-resistant Neisseria gonorrhoeae can be excluded.
For epididymo-orchitis and pelvic inflammatory diseases, empirical ciprofloxacin should only be considered in combination with another appropriate antibacterial agent (e.g. a cephalosporin) unless ciprofloxacin-resistant Neisseria gonorrhoeae can be excluded. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered.
Urinary tract infections
Resistance to fluoroquinolones of Escherichia coli- the most common pathogen involved in urinary tract infections – varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in Escherichia coli to fluoroquinolones.
The single dose of ciprofloxacin that may be used in uncomplicated cystitis in pre-menopausal women is expected to be associated with lower efficacy than the longer treatment duration. This is all the more to be taken into account as regards the increasing resistance level of Escherichia coli to quinolones.
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.
Paediatric population
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 randomised double-blind study on ciprofloxacin use in children (ciprofloxacin: 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 drug-related 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 (see section 4.8).

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 in 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 guidelines, 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 ciprofloxacin use.
The use of ciprofloxacin 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 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 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. Inflammation and ruptures of tendon may occur even up to several months after discontinuation of ciprofloxacin therapy. 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 because symptoms can be exacerbated (see section 4.8).
Photosensitivity
Ciprofloxacin has been shown to cause photosensitivity reactions. Patients taking ciprofloxacin should be advised to avoid direct exposure to either extensive sunlight or UV irradiation during treatment (see section 4.8).
Central Nervous System
Ciprofloxacin like other quinolones are known to trigger seizures or lower the seizure threshold. Cases of status epilepticus have been reported. Ciprofloxacin should be used with caution in patients with CNS disorders which may be predisposed to seizure. If seizures occur ciprofloxacin should be discontinued (see section 4.8). Psychiatric reactions may occur even after the first administration of ciprofloxacin. In rare cases, depression or psychosis can progress to suicidal ideations/thoughts culminating in attempted suicide or completed suicide. In the occurrence of such cases, ciprofloxacin should be discontinued.
Cases of polyneuropathy (based on neurological symptoms such as pain, burning, sensory disturbances or muscle weakness, alone or in combination) have been reported in patients receiving ciprofloxacin. Ciprofloxacin should be discontinued in patients experiencing symptoms of neuropathy, including pain, burning, tingling, numbness and/or weakness in order to prevent the development of an irreversible condition (see section 4.8).

Cardiac disorders
Caution should be taken when using fluoroquinolones including ciprofloxacin, 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 anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics)
• uncorrected electrolyte imbalance (e.g. hypokalaemia, 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 ciprofloxacin, in these populations. (See section 4.2 Elderly patients, section 4.5, section 4.8 and section 4.9).
Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population.
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection, or in presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet's disease, hypertension, known atherosclerosis).
In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.
Hypoglycaemia
As with other quinolones, hypoglycaemia has been reported most often in diabetic patients, predominantly in the elderly population. In all diabetic patients, careful monitoring of blood glucose is recommended (see section 4.8).

Gastrointestinal System
The occurrence of severe and persistent diarrhoea during or after treatment (including several weeks after treatment) may indicate an antibiotic-associated colitis (life-threatening 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 ciprofloxacin should be well hydrated and excessive alkalinity of the urine should be avoided.
Impaired renal function
Since ciprofloxacin is largely excreted unchanged via renal pathway dose adjustment is needed in patients with impaired renal function as described in section 4.2 to avoid an increase in adverse drug reactions due to accumulation of ciprofloxacin.
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. Ciprofloxacin 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.

Resistance
During or following a course of treatment with ciprofloxacin 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 Pseudominas species.
Cytochrome P450
Ciprofloxacin inhibits CYP1A2 and thus may cause increased serum concentration of concomitantly administered substances metabolized by this enzyme (e.g. theophylline, clozapine, olanzapine, ropinirole, tizanidine, duloxetine, agomelatine). Co-administration of ciprofloxacin 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 ciprofloxacin.
Vision disorders
If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.

Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population.
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or
aortic dissection, or in presence of other risk factors or conditions predisposing for aortic aneurysm and dissection ( e.g. Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet's disease, hypertension, known atherosclerosis).
In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.

Effects of other products on ciprofloxacin Chelation Complex Formation
The simultaneous administration of ciprofloxacin (oral) and multivalent cation-containing drugs and mineral supplements (e.g. calcium, magnesium, aluminium, iron), polymeric phosphate binders (e.g. sevelamer or lanthanum carbonate), sucralfate or antacids, and highly buffered drugs (e.g. didanosine tablets) containing magnesium, aluminium or calcium reduces the absorption of ciprofloxacin. Consequently, ciprofloxacin should be administered either 1 – 2 hours before or at least 4 hours after the preparation.
The restriction does not apply to antacids belonging to the class of H2 receptor blockers. Food and Dairy Products
Dietary calcium as part of a meal does not significantly affect absorption. However, the concurrent administration of dairy products or mineral-fortified drinks alone (e.g. milk, yoghurt, calcium-fortified orange juice) with ciprofloxacin should be avoided because absorption of ciprofloxacin may be reduced.

Probenecid
Probenecid interferes with renal secretion of ciprofloxacin. Coadministration of probenecid and ciprofloxacin increases ciprofloxacin serum concentrations. Metoclopramide
Metoclopramide accelerates the absorption of ciprofloxacin (oral) resulting in a shorter time to reach maximum plasma concentrations. No effect was seen on the bioavailability of ciprofloxacin. Omeprazole
Concomitant administration of ciprofloxacin and omeprazole containing medicinal products results in a slight reduction of Cmax and AUC of ciprofloxacin. Effects of ciprofloxacin 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. Agomelatine
In clinical studies, it was demonstrated that fluvoxamine, as a strong inhibitor of the CYP450 1A2 isoenzyme, markedly inhibits the metabolism of agomelatine resulting in a 60-fold increase of agomelatine exposure. Although no clinical data are available for a possible interaction with ciprofloxacin, a moderate inhibitor of CYP450 1A2, similar effects can be expected upon concomitant administration ('Cytochrome P450' in section 'Special warnings and precautions for use).

Zolpidem
Co-administration of ciprofloxacin may increase blood levels of zolpidem, concurrent use is not recommended. 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 (oxpentiphylline), 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.
Cyclosporin
A transient rise in the concentration of serum creatinine was observed when ciprofloxacin and cyclosporin containing medicinal products were administered simultaneously. Therefore, it is frequently (twice a week) necessary to control the serum creatinine concentrations in these patients.
Vitamin K antagonists
Simultaneous administration of ciprofloxacin with a vitamin K antagonist may augment its anticoagulant effects. The risk may vary with the underlying infection, age and general status of the patient so that the contribution of ciprofloxacin to the increase in INR (international normalized ratio) is difficult to assess. The INR should be monitored frequently during and shortly after coadministration of ciprofloxacin with a vitamin K antagonist (e.g., warfarin, acenocoumarol, phenprocoumon, or fluindione).
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).
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 AUCof 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).
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.
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 coadministration with ciprofloxacin are advised (see section 4.4).
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 ciprofloxacin concomitantly with sildenafil taking into consideration the risks and benefits.

Pregnancy
Pregnancy Category C
The data that are available on administration of ciprofloxacin to pregnant women indicates no malformative or feto/neonatal toxicity of ciprofloxacin. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. In juvenile and prenatal animals exposed to quinolones, 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.
Breast-feeding
Ciprofloxacin is excreted in breast milk. Due to the 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.

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, Exts: 2317-2356-2340.
Reporting hotline: 19999
E-mail: npc.drug@sfda.gov.sa
Website: www.sfda.gov.sa/npc
• Other GCC States:
− Please contact the relevant competent authority.

An overdose of 12g 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 of overdose may include dizziness, tremor, headaches, 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 e.g. ventricular emptying followed by medical carbon, it is recommended to monitor renal function, including urinary pH and acidify, if required, to prevent crystalluria. Patients should be kept well hydrated.
Calcium or magnesium containing antacids may theoretically reduce the absorption of ciprofloxacin in overdoses.
Only a small quantity of ciprofloxacin (<10%) is eliminated by haemodialysis or peritoneal dialysis.
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.

Pharmacotherapeutic group: Fluoroquinolones
ATC code J01M A02 Mechanism of Action:
As a fluoroquinolones 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. PK/PD 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 the susceptibility to fluoroquinolones, which depends on 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.

Absorption
Following oral administration of single doses of 250 mg, 500 mg and 750 mg of ciprofloxacin tablets, ciprofloxacin is absorbed rapidly and extensively, mainly from the small intestine, reaching maximum serum concentrations 1-2 hours later.
Single doses of 100-750 mg produced dose-dependent maximum serum concentrations (Cmax) between 0.56 and 3.7 mg/L. Serum concentration increase proportionately with doses up to 1000 mg. The absolute bioavailability is approximately 70 – 80%.

A 500 mg oral dose given every 12 hours has been shown to produce an area under the serum concentration-time curve (AUC) equivalent to that produced by an intravenous infusion of 400mg ciprofloxacin given over 60 minutes 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. Biotransformation
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
After oral administration approximately 70% of ciprofloxacin is excreted unchanged.
Excretion of ciprofloxacin (% of dose)
Oral Administration
Urine
Faeces
Ciprofloxacin
44.7
25.0
Metabolites (M1-M4)
11.3
7.5
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 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.

Paediatric patients
The pharmacokinetic data in paediatric 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 paediatric 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%.

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.

Core Tablet:
- Maize Starch.
- Microcrystalline Cellulose
- Croscarmellose Sodium
- Colloidal Silicon Dioxide
- Talc
- Magnesium Stearate
Coating Material:
- Propylene Glycol
- Polysorbate 80
- Simethicone
- Purified Water
- Opadry white 03H28604 which contains (Hydroxy Propyl Methyl Cellulose & Titanium
Dioxide).

Not applicable.

Do not store above 30 °C. Protect from light.

Immediate Container: Aluminum-PVC/PVDC blister
Secondary Container: Carton & PIL

Keep out of the reach of children.