INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo CIPROCINA Intravenous Infusion

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form)

CIPROCINA Intravenous Infusion

COMPOSITION
CIPROCINA: Each mL of the infusion contains
ciprofloxacin lactate equivalent to 2 mg of ciprofloxacin.

PHARMACOLOGICAL CLASSIFICATION
A.20.1.1. Broad and medium spectrum antibiotics.

PHARMACOLOGICAL ACTION
Ciprofloxacin is a synthetic fluoroquinolone antibiotic. It is bactericidal and acts by inhibiting the A-subunit of DNA-gyrase which is essential in the reproduction of bacterial DNA.
Pharmacokinetics
After oral administration, ciprofloxacin plasma levels are dose related and peak at 0,5 to 2 hours.
The absolute bioavailability is approximately 70%. Protein binding is 40%. Forty to fifty percent is excreted in urine as unchanged ciprofloxacin. Approximately 15% of a single dose is eliminated as metabolites. Elimination is primarily renal and mainly during the first 12 hours after dosing. Renal clearance is approximately 300 mL/minute. The elimination half-life of unchanged ciprofloxacin is 3 to 5 hours. The elimination kinetics is linear.
Micro-organism resistant to ciprofloxacin
Enterococcus faecium; Norcardia asteroides; Ureaplasma urealyticum; Peptostreptococcus species; Peptococcus species; Bacteroides; Treponema pallidum.

INDICATIONS
CIPROCINA is indicated for the treatment of the following infections, when caused by susceptible organisms:
Lower Respiratory Tract Infections caused by
Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa.
Urinary Tract Infections caused by
Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Providencia rettgeri, Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus epidermidis, Streptococcus faecalis.
Skin and Soft Tissue Infections caused by
Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Morganella morganii, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pyogenes.
Gastro-intestinal Infections
Infective diarrhoea caused by Campylobacter jejuni, Escherichia coli, Shigella flexneri and Shigella sonnei.
Bone Infections
Osteomyelitis due to susceptible Gram-negative organisms.
Gonorrhoea

CONTRA-INDICATIONS
CIPROCINA is contra-indicated in patients with a history of hypersensitivity to ciprofloxacin, any other quinolones, or any of the inactive ingredients.
Pregnancy and lactation.
CIPROCINA is contra-indicated in children under the age of 18 years.
Experimental evidence indicates lesions of the cartilage of weight-bearing joints in immature members of certain animal species.

WARNINGS
CIPROCINA should be used with caution in patients with a history of convulsive disorders.
Crystalluria related to the use of CIPROCINA has been observed. Patients receiving CIPROCINA should be well hydrated and excessive alkalinity of the urine should be avoided.
In treatment of infections caused by Pseudomonas aeruginosa, an aminoglycoside must be administered concomitantly (see “DOSAGE AND DIRECTIONS FOR USE”).

INTERACTIONS
Concurrent administration of CIPROCINA with theophylline may lead to elevated plasma concentrations of theophylline and prolongation of its elimination half-life. This may result in increased risk of theophylline-related toxicity. If concomitant use cannot be avoided, plasma levels of theophylline should be monitored and dosage adjustments made as appropriate.
Concomitant administration of the non-steroidal anti-inflammatory medicine fenbufen with quinolones may increase the risk of central nervous system stimulation and seizures.
Monitoring of serum creatinine concentrations is advised in patients on concomitant cyclosporine therapy, as transient increases in serum creatinine concentrations have been observed.
The simultaneous administration of CIPROCINA and warfarin may lead to warfarin toxicity; therefore the INR should be closely monitored.
Concurrent administration of CIPROCINA and glibenclamide can potentiate the action of glibenclamide, leading to hypoglycaemia.
Probenecid interferes with renal secretion of CIPROCINA. Co-administration of probenecid and CIPROCINA increases the CIPROCINA serum concentrations. Metoclopramide accelerates the absorption of CIPROCINA, resulting in shorter time to reach maximum plasma concentrations.

PREGNANCY AND LACTATION
Safety in pregnancy and lactation has not been established (see “CONTRA-INDICATIONS”).

DOSAGE AND DIRECTIONS FOR USE
In the treatment of infections caused by Pseudomonas aeruginosa, an aminoglycoside must be administered concomitantly.
CIPROCINA IV
Dosage and Duration of Treatment
The dosage of CIPROCINA IV is determined by the severity and type of infection, the sensitivity of the causative organism(s) and the age, mass and renal function of the patient.
Adults: The usual dose is 100 to 200 mg IV every 12 hours.
For severe and/or complicated infections 400 mg may be administered every 12 hours.
Intravenous therapy should be discontinued as soon as oral ciprofloxacin therapy can be substituted. The normal duration of intravenous therapy is up to 7 days.
In cystic fibrosis patients, the normal dose is 200 mg IV every 12 hours. The low body mass of these patients should however, be taken into consideration when determining dosage (5 to 10 mg/kg/day).
Directions for Intravenous Administration
CIPROCINA IV should be administered by intravenous infusion over a period of 60 minutes. Slow infusion into large vein will minimise 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.
Compatibility and Stability
CIPROCINA IV is compatible with various intravenous solutions, including sterile water for injection, 0,9% sodium chloride solution, 5% and 10 % dextrose solutions, 5% dextrose with 0,225% or 0,45% sodium chloride solutions, Ringer’s solution and Ringer’s Lactate solution. If CIPROCINA IV has been mixed with one of the above compatible solutions, for microbiological reasons and light sensitivity, these solutions should be administered shortly after admixture.
Important Incompatibilities Unless compatibility with other infusion solutions or medicines has been confirmed, they should always be administered separately. Signs of incompatibility include precipitation, clouding and discolouration.
Incompatibility will present with all infusion solutions and medicines that are physically or chemically unstable at the pH of the ciprofloxacin infusion solutions (3.9 to 4.5), e.g. penicillins and heparin solutions, especially on combination with solutions adjusted to an alkaline pH.
ANY REMAINING SOLUTION MUST BE DISCARDED.
Impaired Renal or Liver Function
In patients with reduced renal function, the half-life of ciprofloxacin may be prolonged.
The dosage needs to be adjusted as shown below.
For patients with renal impaired and hepatic insufficiency, monitoring of medicine serum levels provides the most reliable basis for dose adjustment.
Dose Adjustment of Ciprofloxacin for Patients with Renal or Hepatic Impairment
1.
Kidney insufficiency
        1.1 Clcr >31 mL/min/1,73 m2: Max 800 mg/day intravenously.
        1.2 Clcr <30 mL/min/1,73 m2: Max 400 mg/day intravenously.
        1.3 Impaired renal function and haemodialysis: As in 1.2 above; after dialysis on dialysis days.
2. Renal impairment and CAPD (chronic ambulatory peritoneal dialysis)
        2.1 Addition of CIPROCINA IV solution to the dialysate (intraperitoneal): 50 mg ciprofloxacin per litre of dialysate administered 4 times a day.
3. Hepatic impairment
        No dose adjustments.
4. Hepatic and renal impairment
        As in 1.1 and 1.2 above.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
Side-effects
Gastro-intestinal disorders
Frequent: Nausea, diarrhoea, vomiting, dyspepsia, abdominal pain.
Less frequent: The development of severe and persistent diarrhoea may indicate pseudomembranous colitis, requiring immediate treatment. In such cases CIPROCINA must be discontinued and appropriate therapy initiated (e.g. vancomycin, orally 4 x 250 mg/day).
Eye disorders
Less frequent: Visual disturbances (e.g. diplopia, colour vision).
Ear and labyrinth disorders
Less frequent: Tinnitus, transient impairment of hearing –especially at high frequencies.
Blood and lymphatic system disorders
Less frequent: Eosinophilia, leucocytopenia, granulocytopenia, anaemia, thrombocytopenia, leucocytosis, thrombocytosis, haemolytic anaemia, altered prothrombin values.
Skin subcutaneous tissue disorders
Less frequent: Urticaria, rashes and photosensitivity (blisters, sensation of skin burning), erythema nodosum and erythema exsudativum multiforme (minor), Stevens–Johnson syndrome, Lyell’s syndrome, punctate skin haemorrhages (petechiae), haemorrhagic bullae and papules with signs of vascular involvement (vasculitis).
Nervous system disorders
Frequent: Dizziness, headache, tiredness, nervousness, agitation, and trembling.
Less frequent: Insomnia, peripheral paralgesia, sweating, unsteady gait, convulsions, increase in intracranial pressure, anxiety states, nightmares, confusion, hallucinations, psychotic reactions (even progressing to self-endangering behaviour), depression.
In some instances, these reactions occurred after the first administration of ciprofloxacin.
In these cases CIPROCINA must be discontinued and the medical practitioner informed immediately.
Musculoskeletal, connective tissue and bone disorders
Less frequent: Joint pain, joint swelling, general feeling of weakness and myalgia (which may be of special importance in patients with myasthenia gravis) and tendosynovitis, cases of anchillotendinitis. Partial or complete rupture of the achilles tendon occurred in predominantly elderly patients on treatment with systemic glucocorticoids.
At sign of an anchillotendinitis (or any tendonitis) (e.g. painful swelling) the administration of CIPROCINA should be discontinued and a medical practitioner should be consulted.
Cardiovascular system
Less frequent: Tachycardia, flushing, migraine, syncope.
Genitourinary system
Less frequent: Crystalluria, interstitial nephritis, transient renal impairment including transient renal failure and haematuria. Patients receiving CIPROCINA should be well hydrated and excessive alkalinity of the urine should be avoided.
Hypersensitivity reactions
Less frequent: Anaphylactic/anaphylactoid reactions can occur (e.g. facial, vascular and laryngeal oedema, dyspnoea progressing to life-threatening shock); in some instances after the first administration. In these cases CIPROCINA has to be discontinued and appropriate medical treatment instituted.
General disorders and administration site conditions
Less frequent: Phlebitis or thrombophlebitis, local irritation and pain at the site of injection. Intravenous infusion should be administered by slow infusion over a period of 60 minutes. These reactions are more frequent if the infusion time is 30  minutes or less, or if small veins of the hands are used. These may appear as local skin reactions, which resolve rapidly upon completion of the infusion. Subsequent intravenous administration is not contra-indicated unless the reactions recur or worsen.
Influence on laboratory parameters/urinary sediment
Less frequent: There can be temporary elevations of transaminases, alkaline phosphatase or cholestatic jaundice, (especially in patients with liver damage, temporary increase in urea, creatinine or hyperbilirubinaemia).
Other
Less frequent: Impaired taste and smell, hyperglycaemia, hepatic necrosis, very seldom progressing to hepatic failure.
The ability to drive a motor vehicle or to operate machinery may be impaired by CIPROCINA. This applies particularly in combination with alcohol.
Long-term or repeated administration of CIPROCINA can lead to super infections with resistant bacteria or fungi.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
In event of acute, excessive oral over-dosage, reversible renal toxicity has been reported.
Apart from routine emergency measures, it is recommended to monitor renal function and to administer magnesium- or calcium-containing antacids, which reduce the absorption of oral CIPROCINA.
Only a small amount of ciprofloxacin (<10%) is removed from the body after haemodialysis or peritoneal dialysis.
Treatment is symptomatic and supportive.

IDENTIFICATION
CIPROCINA Intravenous Infusion is a clear colourless to slightly yellow solution practically free from visible particles.

PRESENTATION
CIPROCINA is available in 50 mL, 100 mL and 200 mL USP type II clear transparent glass bottles, with grey colour rubber stoppers and green colour flip-off seals.
OR
CIPROCINA is available in 50 mL, 100 mL and 200 mL clear, colourless PPP 200 INFU 9 bags with a connecting port and an additional port on one side, with provision for the bag to hang at the other side. The bag is vacuum packed in an outer aluminium pouch.

STORAGE INSTRUCTIONS
Store below 25ºC. Protect from light. Do not freeze.
After infusion of the required dose, any remaining solution should be discarded.
CIPROCINA is light-sensitive and should always be stored in the cardboard outer carton or aluminium pouch. No special precautions are, however, required during the 60 minutes infusion period.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER
A40/20.1.1/0114

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
Pharmaplan (Pty) Ltd
106 16th Road
Midrand

DATE OF PUBLICATION OF THE PACKAGE INSERT
5 August 2005

New addition to this site: May 2014
Source: Pharmaceutical Industry

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