Ciclodin IV Infusion Vial

Ciclodin IV is a colorless to slightly yellow, clear liquid.
Each mL contains: Ciprofloxacin, USP 2 mg (As Hydrochloride).

Pharmacotherapeutic group: Fluoroquinolones. ATC code: J01MA02.
Pharmacodynamics: 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 (C_max) 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.
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: See Table 1.

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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: See Table 2.

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Pharmacokinetics: Absorption: Following an intravenous infusion of ciprofloxacin, the mean maximum serum concentrations were achieved at the end of infusion. Pharmacokinetics of ciprofloxacin were 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 given every 12 hours, produced an equivalent area under the serum concentration time curve (AUC).
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: Ciprofloxacin is largely excreted unchanged both renally and, to a smaller extent, faecally. (See Table 3.)

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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 C_max and AUC were not age-dependent (above one year of age). No notable increase in C_max and AUC upon multiple dosing (10 mg/kg three times daily) was observed.
In 10 children with severe sepsis C_max 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%.

For the treatment of wide range of infections including anthrax, biliary tract infections, bone and joint infections, gastro-enteritis (traveler's diarrhea), gonorrhoea, lower respiratory-tract infections and urinary-tract infections. Used also as prophylaxis for meningococcal meningitis and surgical infections.

Adult: 100 mg to 400 mg twice daily, given over 30 to 60 minutes as a solution containing the equivalent of 1-2 mg/mL.
Children: 4-8 mg/kg twice daily is suggested.
10 mg/kg twice daily up to maximum of 400 mg twice daily (for exacerbation of cystic fibrosis associated with Pseudomonas aeruginosa infection).
Not generally recommended for other uses in children and adolescents unless considered essential or as prescribed by the physician.

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 hematuria. 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 hemodialysis 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.

Contraindicated to some patients who experience tendon pain, inflammation or rupture and the treatment should be discontinued to prevent tendon damage.

Ciprofloxacin should be used with caution in patients with epilepsy or a history of CNS disorders. Should not be used in children, adolescents, pregnant women, or breastfeeding mothers or use only if the benefits outweigh the risk.
Healthcare professionals are advised to avoid prescribing fluoroquinolones to patients who have aortic aneurysm or at risk for an aortic aneurysm, such as patients with peripheral atherosclerotic vascular disease, hypertension, certain genetic conditions such as Marfan syndrome and Ehlers-Danlos syndrome, and elderly patients. The benefit of using fluoroquinolones to these patients should be assessed by the prescribers prior to initiation of therapy. It should be prescribed to these patients only when no other treatment options are available.

Use with caution in pregnant women or breastfeeding mothers or use only if the benefits outweighs the risk.

Ciprofloxacin is generally well tolerated.
Blood and lymphatic system disorders: Haematological disturbance including haemolytic anemia, or agranulocytosis.
Psychiatric disorders: More rarely, hallucinations, psychotic reactions, depression, and convulsions.
Nervous system disorders: The most common on the CNS are headache, dizziness, restlessness, drowsiness, insomnia, nightmares and other sensory disturbances.
Gastrointestinal disorders: Gastrointestinal disturbances include nausea, vomiting, diarrhoea, abdominal pain, and dyspepsia are the most frequent side effects. Pseudomembranous colitis has been reported rarely.
Hepatobiliary disorder: Elevated liver enzyme values, jaundice and hepatitis.
Skin and subcutaneous tissue disorders: Rash, pruritus, hypersensitivity-type reactions have been included, rarely, vasculitis, erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis.
Musculoskeletal and connective tissue disorders: Myalgia and sweating. Pain and irritation may occur at the site of injection accompanied rarely by phlebitis or thrombophlebitis.
Renal and urinary disorders: Anaphylaxis, transient increase in serum creatinine or blood urea nitrogen and occasionally acute renal failure, interstitial nephritis, and crystalluria.

Aluminum, magnesium or iron reduces absorption of Ciprofloxacin. It also decreases the clearance of theophylline, increases blood concentrations of midazolam according to some isolated reports. The urinary excretion of Ciprofloxacin reduced by probenecid. When used simultaneously with azlocillin, it has resulted in higher and more prolonged concentration of Ciprofloxacin. Changes in pharmacokinetics of fluoroquinolones such as Ciprofloxacin have been reported when given with histamine H2 antagonist, possibly due to the change in gastric pH, but do not seem to be of much of clinical significance.
Theophylline interferes with metabolism of caffeine, enhances effects of oral anticoagulants warfarin, glibenclamide, probenecid, metoclopramide and its derivatives.

Store at temperatures not exceeding 30°C.

Quinolones

J01MA02 - ciprofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.

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