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

Logo CIFLOC 250 (tablets)
CIFLOC 500 (tablets)
CIFLOC 750 (tablets)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

CIFLOC 250 (tablets)
CIFLOC 500 (tablets)
CIFLOC 750 (tablets)

COMPOSITION:
CIFLOC 250:
Each tablet contains ciprofloxacin hydrochloride equivalent to 250 mg
ciprofloxacin.
CIFLOC 500: Each tablet contains ciprofloxacin hydrochloride equivalent to 500 mg ciprofloxacin.
CIFLOC 750: Each tablet contains ciprofloxacin hydrochloride equivalent to 750 mg ciprofloxacin.

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

PHARMACOLOGICAL ACTION
Ciprofloxacin is a synthetic, 4-quinolone derivative and inhibits gyrase-mediated DNA supercoiling.
It has in vitro bactericidal activity against the following Gram-negative and Gram-positive organisms. In vitro sensitivity does not necessarily imply in vivo efficacy.
Acinetobacter Haemophilus influenzae Proteus vulgaris Streptococcus pyogenes
Aeromonas Haemophilus para-influenzae Providencia rettgeri Streptococcus species
Brucella Hafnia Providencia stuartii Vibrio
Campylobacter jejuni Klebsiella species Pseudomonas aeruginosa Viridans streptococci
Citrobacter freundii Listeria Salmonella enteritidis Yersinia
Citrobacter species Moraxella catarrhalis Serratia marcescens 
Corynebacterium Morganella morganii Shigella flexneri 
E. coli Neisseria gonorrhoea Shigella sonnei 
Edwardsiella Pasteurella Staphylococcus aureus 
Enterobacter cloacae Plesiomonas Staphylococcus epidermidis 
Enterobacter species Proteus mirabilis Streptococcus faecalis 

The following organisms show varying degrees of in vitro sensitivity to ciprofloxacin:
Alcaligenes, Enterococcus faecalis, Flavobacterium, Gardnerella, Legionella, Mycobacterium fortuitum, Mycobacterium tuberculosis, Mycoplasma hominis, Streptococcus agalactiae, Chlamydia.

The following organisms are usually resistant:
Enterococcus faecium, Ureaplasma urealyticum, Nocardia asteroides.

With a few exceptions anaerobes are moderately sensitive (e.g. Peptococcus, Peptostreptococcus) to resistant (e.g. Bacteriodes, Treponema pallidum).

Pharmacokinetics
Ciprofloxacin is well absorbed and peak serum levels are obtained within 1 - 3 hours after oral dosing. The absolute oral bioavailability is approximately 70% with no substantial loss by first pass metabolism.
Food does not impair oral absorption, but may delay the time to peak serum concentrations.
Distribution of ciprofloxacin is wide and the volume of distribution high, indicating extensive tissue penetration. Ciprofloxacin is present in lung, skin, fat, muscle, cartilage and bone. It is also present in active form in the saliva, nasal and bronchial secretions, sputum, skin blister fluid, lymph, peritoneal fluid, prostatic secretions, cerebrospinal fluid and the aqueous humor. High concentrations are achieved in bile.
Protein binding is low and ranges from 20 to 40%.
Ciprofloxacin is eliminated principally by urinary excretion, but non-renal excretion may account for about a third of elimination and includes hepatic metabolism, biliary excretion and possibly transluminal secretions across the intestinal mucosa.
Elimination occurs primarily by the kidneys and mainly during the first 12 hours after dosing. Excretion is virtually complete after 24 hours; about 40% to 50% is excreted in urine as unchanged drug and about 15% as metabolites. Renal clearance is approximately 300 mL/minute.
The elimination half-life of unchanged ciprofloxacin is 3 - 5 hours. The elimination kinetics are linear; after repeated dosing at 12 hourly intervals and once steady state has been reached no accumulation occurs.

INDICATIONS
Ciprofloxacin is indicated for the treatment of the following infections caused by ciprofloxacin sensitive bacteria:
Lower Respiratory Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae and Haemophilus para-influenzae.
Urinary Tract Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter freundii, Pseudomonas aeruginosa, Staphylococcus epidermidis and Streptococcus faecalis.
Skin and Soft Tissue Infections caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Streptococcus pyogenes.
Gastro-intestinal Infections: Infective diarrhoea caused by E. coli, Campylobacter jejuni, Shigella flexneri and Shigella sonnei.
Bone Infections: Osteomyelitis due to susceptible Gram-negative organisms.
Gonorrhoea: Ciprofloxacin is ineffective against Treponema pallidum.
In the treatment of infections caused by Pseudomonas aeruginosa, an aminoglycoside must be administered concomitantly.

CONTRA-INDICATIONS
Safety during pregnancy and lactation has not been established.
Children under 18 years and in growing adolescents, except where the benefits of treatment exceed the risks. Experimental evidence indicates that, species variable reversible lesions of the cartilage of weight bearing joints has been seen in immature members of certain animal species.
Patients who have shown hypersensitivity to ciprofloxacin or any other quinolones.

WARNINGS
CIFLOC should be used with caution in patients with a history of convulsive disorders or a history of CNS disorders.
Crystalluria related to the use of ciprofloxacin has been observed. Patients receiving ciprofloxacin should be well hydrated and excessive alkalinity of the urine should be avoided.

DOSAGE AND DIRECTIONS FOR USE
CIFLOC
tablets should be swallowed whole with plenty of liquid and may be taken with or without meals.
Dosage and Duration of Treatment:
The dosage range is 250 - 750 mg twice daily. The duration of treatment depends upon the severity and nature of the infection.
For acute uncomplicated cystitis in women, the treatment period is 3 days. Generally, treatment should be continued for at least 3 days after the signs and symptoms of the infection have disappeared.
For acute infections the usual treatment period is 5 - 10 days. For severe and complicated infections more prolonged therapy may be required.
In streptococcal infections the treatment must last at least 10 days because of the risk of late complications.
Infections of the lower respiratory tract:
Mild to moderate - 250 to 500 mg twice daily; severe or complicated - 750 mg twice daily.
In cystic fibrosis patients the dose is 750 mg twice daily. The low body mass of these patients should, however be taken into consideration when determining dosage (7,5 to 15 mg/kg/day).
Infections of the urinary tract:
Acute uncomplicated cystitis - 250 mg twice daily; severe or complicated –500 mg twice daily.
Infections of the skin:
Mild to moderate - 500 mg twice daily, severe or complicated –750 mg twice daily.
Infectious diarrhoea:
500 mg twice daily.
Bone infections:
Mild to moderate - 500 mg twice daily; severe or complicated - 750 mg twice daily. Treatment may be required for 4 - 6 weeks or longer.
Gonorrhoea:
A single dose of 250 mg.

Elderly patients should receive a dose as low as possible; this will depend on the severity of the illness and on the creatinine clearance.
If the patient is unable to take ciprofloxacin tablets, because of the severity of his illness or for other reasons, it is recommended to commence the therapy with intravenous ciprofloxacin. After intravenous administration the treatment can be continued orally.

Impaired Renal or Liver Functions:
In patients with reduced renal function, the half-life of ciprofloxacin is prolonged and the dose needs to be adjusted.
For patients with changing renal function or patients with renal impairment and hepatic insufficiency, monitoring of drug serum levels provide the most reliable basis for dose adjustment.

Dose adjustment of ciprofloxacin for patients with kidney and/or liver insufficiency.
1. Kidney insufficiency:
  CL
cr >31 mL/min/1,73 m² <60 mL/min/1,73 m²
  CL
cr<30 mL/min/1,73 m²
  Impaired renal function and haemodialysis
        
        Max 1000 mg/day.
        Max 500 mg/day.
        Max 500 mg/day on days after dialysis.
2. Impaired renal function and CAPD
  Oral administration of either ciprofloxacin 500 mg tablet or 2 x 250 mg tablets is indicated.
  For CAPD patients with peritonitis, the recommended daily oral dose is 500 mg 4 times daily.
3.  Liver function disturbances No dose adjustments.
4.   Liver and kidney insufficiency As in point 1 above.

SIDE EFFECTS AND SPECIAL PRECAUTIONS
The following side-effects have been observed:
Effects on the gastrointestinal tract
  Nausea, diarrhoea, vomiting, dyspepsia, abdominal pain, flatulence, anorexia in the event of severe and persistent diarrhoea during or after treatment: a doctor must be consulted since this symptom can hide a serious intestinal disease (pseudomembranous colitis) requiring immediate treatment. In such cases ciprofloxacin must be discontinued and appropriate therapy initiated (e.g. vancomycin, orally 4 x 250 mg/day). Medicines that inhibit peristalsis are contraindicated.
Effects on the nervous system
  Dizziness, headache, tiredness, nervousness, agitation, trembling.
  Infrequently: insomnia, peripheral paralgesia, sweating, unsteady gait, convulsions, increase in intracranial pressure, anxiety states, nightmares, confusion, depression, hallucinations, in individual cases psychotic reactions (even progressing to self endangering behaviour). In some instances, these reactions occurred already after the first administration of ciprofloxacin. In these cases ciprofloxacin has to be discontinued and the doctor should be informed immediately.
Reactions on sensory organs
  Impaired taste and smell visual disturbances (e.g. diplopia, colour vision), tinnitus transitory impairment of hearing, especially at high frequencies.
Hypersensitivity reactions
  Skin reactions e.g. rashes, pruritus, drug fever.
  Infrequently: punctate skin haemorrhages (petechiae), blister formation with accompanying haemorrhages (haemorrhagic bullae) and small nodules (papules) with crust formation showing vascular involvement vasculitis), Erythema nodosum, erythema exsudativum multiforme (minor), Stevens-Johnson Syndrome, Lyell Syndrome.
  Interstitial nephritis, hepatitis and hepatic necrosis very seldom progressing to life-threatening hepatic failure.
  Anaphylactic/anaphylactoid reactions (e.g. facial, vascular and laryngeal oedema, dyspnoea progressing to life-threatening shock), in some instances after the first administration.
  In these cases ciprofloxacin has to be discontinued and medical treatment (e.g. treatment for shock) is required.
Effects on the cardiovascular system
  Tachycardia, hot flushes, migraine, fainting.
Other side effects
  Joint pain, joint swelling.
  Less frequently: general feeling of weakness, muscular pains, tendosynovitis, photosensitivity, transient impairment in kidney function including transient kidney failure.
  In single cases during the administration of ciprofloxacin, achillotendinitis was observed. Cases of partial or complete rupture of the achilles tendon have been reported predominantly in the ederly on prior systemic treatment with glucocorticoids. Therefore, at any signs of an achillotendinitis (e.g. painful swelling) the administration of ciprofloxacin should be discontinued and a physician be consulted.
  Long-term or repeated administration of ciprofloxacin can lead to superinfections with resistant bacteria or yeast-like fungi.
Effects on the blood and blood constituents
  Eosinophilia, leucocytopenia, granulocytopenia, anaemia, thrombocytopenia.
  Very rarely: leucocytosis, thrombocytosis, haemolytic anaemia, altered prothrombin values.
Influence on laboratory parameters/urinary sediment
  There can be a temporary increase in transaminases, alkaline phosphatase or cholestatic jaundice, especially in patients with previous liver damage, temporary increase in urea, creatinine or bilirubin in the serum; in individual cases: hyperglycaemia, crystalluria or haematuria.

Other information
Ciprofloxacin may impair the ability to drive or operate machinery, especially when alcohol is also taken.
Care is necessary in patients with impaired hepatic or renal function, glucose-6-phosphate dehydrogenase deficiency, or myasthenia gravis.
Exposure to strong sunlight or sunlamps should be avoided.
Interactions
Concurrent administration of ciprofloxacin 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 adverse reactions. If concomitant use cannot be avoided, plasma levels of theophylline should be monitored and dosage adjustments made as appropriate.
CIFLOC tablets should be administered 1 - 2 hours before, or at least 4 hours after taking iron preparations, antacids containing magnesium, aluminium, calcium or sucralfate as interference with absorption may occur. This restriction does not apply to antacids belonging to the class of H2 receptor blockers.
Concomitant administration of the non-steroidal anti-inflammatory drug fenbufen with quinolones has been reported to increase the risk of central nervous system stimulation and convulsive seizures.
Monitoring of serum creatinine concentrations is advised in patients on concomitant cyclosporin therapy, as transient increases in serum creatinine concentrations have been observed.
The simultaneous administration of ciprofloxacin and warfarin may intensify the action of warfarin.
In particular cases, concurrent administration of ciprofloxacin and glibenclamide can intensify the action of glibenclamide (hypoglycaemia).
Probenecid interferes with renal secretion of ciprofloxacin. Co-administration of probenecid and ciprofloxacin increases the ciprofloxacin serum concentrations.
Metoclopramide accelerates the absorption of ciprofloxacin, resulting in a shorter time to reach maximum plasma concentrations. No effect was seen on the bioavailability of ciprofloxacin.

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

IDENTIFICATION
CIFLOC 250: White oval shaped film-coated tablets embossed with ‘R’on one side and ‘126’on other side.
CIFLOC 500: White oval shaped film-coated tablets embossed with ‘R’on one side and ‘127’ on other side.
CIFLOC 750: White to off-white, capsule-shaped film-coated tablets embossed ‘R’on one side and ‘128’on other side.

PRESENTATION
CIFLOC 250: 10 tablets packed into PVC/aluminium blister packs
CIFLOC 500: 10 tablets packed into PVC/aluminium blister packs
CIFLOC 750: 10 tablets packed into PVC/aluminium blister packs

STORAGE INSTRUCTIONS
Store below 25ºC. KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS
CIFLOC 250
:         34/20.1.1/308
CIFLOC 500:         34/20.1.1/309
CIFLOC 750:         34/20.1.1/310

NAME AND BUSINESS ADDRESS OF HOLDER OF THE REGISTRATION CERTIFICATE
Dr. Reddy’s Laboratories (Pty) Ltd.
3rd Floor, TA Bank Building
160 Jan Smuts Avenue
Rosebank
2196

DATE OF PUBLICATION OF THIS PACKAGE INSERT
April 2001

New addition to this site: October 2006
Source: Pharmaceutical Industry

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