Mechanism of action:

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:

Following an intravenous infusion of ciprofloxacin the mean maximum serum concentrations were achieved at the end of infusion,Ciprofloxacin is largely excreted unchanged both renally and, to a smaller extent, faecally.

Dosage and administrations:

After intravenous initiation of treatment, the treatment can be switched to oral treatment with tablets or suspension if clinically indicated by the physician. IV treatment should be followed by oral route as soon as possible.Treatment of infections due to certain bacteria (e.g. Pseudomonas aeruginosa, Acinetobacteror 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.

Paediatricpopulation:

Dosing in children with impaired renal and/or hepatic function has not been studied.

Elderly patients: Elderly patients should receive a dose selected according to the severity of the infection and the patient`s creatinine clearance.

Patients with renal impairment: Recommended starting and maintenance doses for patients with impaired renal function:

Patients with hepaticimpairment: In patients with impaired liver function no dose adjustment is required.

Method of administration

Ciprofloxacin solution for infusion should be checked visually prior to use. It must not be used if cloudy.

Ciprofloxacin 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 solution for infusion and 30 minutes for 200 mg Ciprofloxacin solution for infusion. Slow infusion into a large vein will minimize patient discomfort and reduce the risk of venous irritation. The infusion solution can be infused either directly or in parallel with other compatible infusion solutions.

Overdose:

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. In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation

Drug Interaction:

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)

Probenecid: Probenecid interferes with renal secretion of ciprofloxacin. The co-administration increases ciprofloxacin serum concentrations.

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

Theophylline: Concurrent administration of ciprofloxacin and theophylline can cause an undesirable increase in serum theophylline concentration, serum theophylline concentrations should be checked and the theophylline dose reduced as necessary

Other  xanthine derivatives: On concurrent administration of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline), raised serum concentrations of these xanthine derivatives were reported.

Phenytoin: The coadministration may result in increased or reduced serum levels of phenytoin such that monitoring of drug levels is recommended.

Ciclosporin: A transient rise in the concentration of serum creatinine was observed when ciprofloxacin and ciclosporin 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 anti-coagulant effects. The INR should be monitored frequently during and shortly after co-administration of ciprofloxacin with a vitamin K antagonist (e.g., warfarin, acenocoumarol, phenprocoumon, or fluindione).

Lidocaine: possible interaction with ciprofloxacin associated with side effects may occur upon concomitant administration.

Sildenafil: caution should be used when ciprofloxacin used concomitantly with sildenafil taking into consideration the risks and the benefits.

Cytochrome P450

Ciprofloxacin inhibits CYP1A2 which may cause increased serum concentration of concomitantly administered substances metabolised by this enzyme (e.g. theophylline, clozapine,olanzapineropinirole, tizanidine, duloxetine). 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

Ropinirole: Monitoring of ropinirole-related side effects and dose adjustment as appropriate is recommended during and shortly after co-administration with ciprofloxacin.

Clozapine: Clinical surveillance and appropriate adjustment of clozapine dosage during and shortly after co administration with ciprofloxacin are advised

Incompatibilities with other solutions:

Unless compatibility with other solutions/drugs has been confirmed, the infusion solution must always be administered separately.  Ciprofloxacin infusion has been shown to be compatible solution for infusion (  Ringer's solution, Sodium chloride (0.9%), Glucose (5%) and (10%) and Fructose (10%) ) when infused in parallel

When ciprofloxacin infusion solutions are mixed with compatible infusion solutions, for microbial reasons and light sensitivity these solutions must be administered shortly after admixture

Warnings and precautions:

• 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.
• Ciprofloxacin is not recommended for the treatment of streptococcal infectionsdue to inadequate efficacy.
• There are limited data on the efficacy of ciprofloxacin in the treatment of post-surgical intra-abdominal infections
• The ability to drive or to operate machinery may be impaired due to central nervous system effects.
• Genital tract infections: 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 varies; Prescribers are advised to take into account the local prevalence of resistance in Escherichia coli to fluoroquinolones.
• Travellers' diarrhea: The choice of ciprofloxacin should take into account information on resistance to ciprofloxacin in relevant pathogens in the countries visited.
• Inhalational anthrax: 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. Treatment should be initiated only after a careful benefit/risk evaluation, due to possible adverse events related to joints and/or surrounding tissue. 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 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. Tendinitis and tendon rupture (especially Achilles tendon), sometimes bilateral, may occur with ciprofloxacin, even within 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 corticosteroid. 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
• Photosensitivity:Ciprofloxacin has been shown to cause photosensitivity reactions. Patients should be advised to avoid direct exposure to either extensive sunlight or UV irradiation during treatment .
• Central Nervous System: Ciprofloxacin like other 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 ciprofloxacin should be discontinued.Cases of polyneuropathy have been reported in patients receiving ciprofloxacin. Ciprofloxacin should be discontinued in patients experiencing symptoms of neuropathy.
• 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, 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.
• Hypoglycemia: As with other quinolones, hypoglycemia has been reported most often in diabetic patients, careful monitoring of blood glucose is recommended .
• Gastrointestinal System:The occurrence of severe and persistent diarrhea during or after treatment may indicate an antibiotic-associated colitis (life-threatening with possible fatal outcome), requiring immediate treatment .
• urinary system:Crystalluria related to the use of ciprofloxacin has been reported .Patients receiving ciprofloxacin should be well hydrated .
• Hepatobiliary system:Cases of hepatic necrosis and life-threatening hepatic failure have been reported with ciprofloxacin .In the event of any signs and symptoms of hepatic disease 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.
• 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.
• Vision disorders:If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.
• Pregnancy: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 potential risk of articular damage, ciprofloxacin should not be used during breast-feeding.

Storage conditions: keep the drug in the outer carton in order to protect from light , and store it at room temperature (15 º C – 30 º C )

How supplied: a carton box contains 100 ml vial