Proxilev

Clear Colourless Liquid Filled in an LDPE Bottle.
Each mL contains: Ciprofloxacin USP 2 mg.

Pharmacotherapeutic group: Fluoroquinolones. ATC code: J01MA02.
Pharmacology: 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.
Spectrum of antibacterial activity: Breakpoints separate susceptible strains from strains with intermediate susceptibility and the latter from resistant strains: EUCAST Recommendations: (See table.)

Click on icon to see table/diagram/image

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 twice a day and three times a day intravenous dose regimen indicated no evidence of drug accumulation for Ciprofloxacin and its metabolites.
A 60 minutes intravenous infusion of 200 mg Ciprofloxacin given every 12 hours, produced an equivalent area under the serum concentration time curve (AUC).
A 60 minutes 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 C_max similar to that observed with a 750 mg oral dose.
A 60 minutes 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 (M1), sulphociprofloxacin (M2), oxociprofloxacin (M3) and formylciprofloxacin (M4). 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.

Severe infections of the urinary and gastrointestinal tracts including Campylobacter jejuni, Shigella spp. or Salmonella spp.
Susceptible sexually transmitted diseases e.g., gonococcal (including penicillin resistant) and non gonococcal (chlamydial) urethritis.
Osteomyelitis/septicemia caused by susceptible organisms including bacterial resistant to Beta-lactams.
Severe infections of the respiratory tract due to susceptible gram-negative infections including Pseudomonas aeruginosa.
Treatment of severe infections of the urinary and gastrointestinal tracts including Campylobacter jejuni, Shigella spp. or Salmonella spp. susceptible sexually transmitted diseases; e.g., gonococcal (including penicillin resistant) and non-gonococcal (chlamydial) urethritis; osteomyelitis/septicemia caused by susceptible organisms including bacteria resistant to beta-lactams.
Severe infections of the respiratory tract due to susceptible gram-negative infections including Pseudomonas aeruginosa; treatment of multi-drug resistant typhoid fever; post-exposure prophylaxis for meningococcal disease and anthrax in adults.

Ciprofloxacin intravenous 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 intravenous infusion and 30 minutes for 200 mg Ciprofloxacin intravenous 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 after mixing with other compatible infusion solutions 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 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.

Hypersensitivity and other serious reactions: Serious and sometimes fatal reactions (for example, anaphylactic reactions) may occur after first or subsequent doses of Ciprofloxacin. Discontinue Ciprofloxacin at the first sign of skin rash, jaundice or any sign of hypersensitivity.
Hepatotoxicity: Discontinue immediately if signs and symptoms of hepatitis occur.
Clostridium difficile-Associated Diarrhea: Evaluate if colitis occurs.
QT Prolongation: Prolongation of the QT interval and isolated cases of torsade de pointes have been reported. Avoid use in patients with known prolongation, those with hypokalemia, and with other drugs that prolong the QT interval.
Risk of Aortic Aneurysm and Dissection: Epidemiologic studies report an increased rate of aortic aneurysm and dissection within two months following use of fluoroquinolones, particularly in elderly patients. The cause for the increased risk has not been identified. In patients with a known aortic aneurysm or patients who are at greater risk for aortic aneurysms, reserve Ciprofloxacin for use only when there are no alternative antibacterial treatments available.

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

Common: Vomiting, Transient increase in transaminases, Rash.
Uncommon: Thrombocytopenia, Thrombocytaemia, Confusion and disorientation, Hallucinations, Par- and dysaesthesia, Seizures, Vertigo, Visual disturbances, Hearing loss, Tachycardia, Vasodilatation, Hypotension, Transient hepatic impairment, Cholestatic icterus, Renal failure, Oedema.
Rare: Pancytopenia, Bone marrow depression, Anaphylactic shock, Psychotic reactions, Migraine, Olfactory nerve disorders, Hearing impaired, Vasculitis, Pancreatitis, Liver necrosis, Petechiae, Tendon rupture.

Probenecid: Probenecid interferes with renal secretion of Ciprofloxacin. Co-administration of Probenecid and Ciprofloxacin increases Ciprofloxacin serum concentrations.
Effects of ciprofloxacin on other medicinal products: Tizanidine: Tizanidine must not be administered together with Ciprofloxacin. In a clinical study with healthy subjects, there was an increase in serum tizanidine concentration (C_max 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.

Store at temperatures not exceeding 30°C.
The bottles should be always stored in the cardboard outer container. No special precautions are required during the normal 30-60 minute infusion period.

Quinolones

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

Rx