INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
CIFRAN 250 Tablets
CIFRAN 500 Tablets
CIFRAN 750 Tablets

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

CIFRAN 250 Tablets
CIFRAN 500 Tablets
CIFRAN 750 Tablets

COMPOSITION:
Cifran 250 Tablets
Each film coated tablet contains
Ciprofloxacin hydrochloride
equivalent to ciprofloxacin         250 mg
Cifran 500 Tablets
Each film coated tablet contains
Ciprofloxacin hydrochloride
equivalent to ciprofloxacin         500 mg
Cifran 750 Tablets
Each film coated tablet contains
Ciprofloxacin hydrochloride
equivalent to ciprofloxacin         750 mg

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.1 Broad and medium spectrum antibiotics

MECHANISM OF ACTION
Fluoroquinolones bring about their bactericidal action by inhibiting the bacterial DNA gyrase enzyme. DNA gyrase is responsible for continuous introduction of negative supercoils into DNA. This is an ATP dependent reaction that requires both strands of the DNA to be cut to permit passage of a segment of DNA through the break; the break is then resealed. Fluoroquinolones decrease the introduction of negative supercoils into DNA and cause rapid cessation of DNA synthesis by interfering with the propagation of DNA replication.
Antibacterial Spectrum
The antibacterial spectrum of ciprofloxacin includes Gram-negative and Gram-positive organisms viz. Acinetobacter, Aeromonas, Campylobacter jejuni, Citrobacter freundii , Citrobacter species, Corynebacterium, Edwardsiella, Enterobacter cloacae, Enterobacter species, Listeria, Morganella morganii, E.coli, Klebsiella spp., Salmonella enteritidis., P. mirabilis, P. vulgaris, Yersinia, Ps. aeruginosa, Shigella flexneri, Shigella sonnei, Hafnia, H. influenzae, H. para-influenzae, N. gonorrhoeae, M. catarrhalis, Vibrio, Staph. aureus (including methicillin resistant strains), Staph. epidermidis, Strep. pyogenes, Strep. species, Brucella, Pasteurella, Plesiomonas, Providencia rettgeri, Providencia stuartii, Serratia marcescens.
In vitro sensitivity does not necessarily imply in vivo efficacy.
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 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 pallidium).
Pharmacokinetics
Ciprofloxacin is well absorbed when given orally with a bioavailability of 70%. The mean peak plasma concentrations achieved after oral administration of 250 mg, 500 mg and 750 mg of ciprofloxacin are 1.2 mcg/mL, 2.4 mcg/mL and 4.3 mcg/mL respectively, achieved within 1-2 hours of administration. Absorption is delayed when ciprofloxacin is given with a meal.
Plasma protein binding ranges from 20 to 40%. Ciprofloxacin is widely distributed throughout the body viz. lung, skin, fat, muscle, cartilage, bone and genital tissues including the prostate. It is present in active form in saliva, nasal and bronchial secretions, sputum, skin blister fluid, lymph, peritoneal fluid, bile and prostatic secretions.
Ciprofloxacin is partly metabolised in the liver. About 50% of an oral dose is recovered unchanged in the urine and 15% as active metabolites viz. oxociprofloxacin. The rest undergoes biliary excretion and transluminal secretion across the intestinal mucosa.
The plasma elimination half-life is about 3.5 - 4.5 hrs. The half-life may be prolonged in severe renal insufficiency and in the elderly.

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.
Ciprofloxacin is contra-indicated in 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.
Ciprofloxacin is contra-indicated in patients who have shown hypersensitivity to ciprofloxacin or any other quinolones.

WARNING
Ciprofloxacin should be used with caution in patients with a history of convulsive 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:
Ciprofloxacin 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 of the infection, clinical respone and bacteriological findings. 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 to 10 days with ciprofloxacin tablets.
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).
Infectious diarroea: 500 mg twice daily.
Infections of the urinary tract: Acute uncomplicated cystitis - 250 mg twice daily; mild to moderate - 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.
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.
Impaired renal or liver function: In patients with reduced renal function, the half-life of ciprofloxacin is prolonged and the dosage needs to be adjusted.
For patients with changing renal function or patients with renal impairment and hepatic insufficiency, monitoring of drug serum levels provides the most reliable basis for dose adjustment.

Dose adjustment of ciprofloxacin for patients with kidney and/or liver insufficiency:
1.	Kidney insufficiency:
1.1	ClCR >31 mL/min/1,73m² <60 mL/min/1,73 m²	Max 1000 mg/day orally or 800 mg/day intravenously.
1.2	ClCR<30 mL/min/1,73m²	Max 500 mg/day orally or 400 mg/day intravenously
1.3	Impaired renal function and haemodialysis	As in 1.2 above, on dialysis days after dialysis
2.	Impaired renal function and CAPD
2.1	Addition of ciprofloxacin infusion solution to the dialysate (intraperitioneal): 50 mg ciprofloxacin/litre dialysate administered 4 times a day.
2.2	Oral administration of either ciprofloxacin film coated tablets as 500 mg tablet or 2 x 250 mg tablets or ciprofloxacin suspension 5% equivalent to 500 mg ciprofloxacin is indicated.
2.3	For CAPD patients with peritonitis, the recommended daily oral dose is 500 mg 4 times a day.
3.	Liver function disturbances:	No doses adjustment
4.	Liver and kidney insufficiency:	As in 1.1 and 1.2 above

SIDE-EFFECTS AND SPECIAL PRECAUTIONS :
The following side-effects have been observed:
Effects on the gastro-intestinal 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). Drugs 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 ciproflxoacin has to be discontinued and the doctor should be informed immediately.
Reactions of 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 exudativum multiforme (minor), Stevens Johnson Syndrome, Lyell Syndrome.
Intestitial nephritis, hepatitis, 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 adminsitration. 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. Very rarely: 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 elderly 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:
Even when the medicine is taken as prescribed, it can affect the speed of reaction to such an extent that the ability to drive or to operate machinery is impaired. This applies particularly in combination with alcohol.
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.
Ciprofloxacin 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 nonsteroidal 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:
Cifran 250 Tablets:
White, round, film-coated tablets embossed with `250' on one side and plain on the other side, with intact coating.
Cifran 500 Tablets:
White caplet shaped, film-coated tablets embossed with `500' on one side and plain on other other side, with intact coating.
Cifran 750 Tablets:
White caplet shaped, film-coated tablets embossed with `750' on one side and plain on other other side, with intact coating.

PRESENTATION:

Cifran 250 Tablets :	Carton containing blister strip of 10 tablets
Cifran 500 Tablets :	Carton containing blister strip of 10 tablets
Cifran 750 Tablets :	Carton containing blister strip of 10 tablets

STORAGE INSTRUCTIONS:
Store below 25°C, protected from moisture.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:

Cifran 250 Tablets:	33/20.1.1/0365
Cifran 500 Tablets:	33/20.1.1/0366
Cifran 750 Tablets:	33/20.1.1/0367

NAME AND BUSINESS ADDRESS OF APPLICANT:
RANBAXY (SA) (PTY) LTD
3rd Floor, Outspan House
1006 Lenchen Avenue North
Centurion

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
July 1999

5033491

Updated on this site: November 2001
Current: April 2005
Source: Hospital Pharmacy
SAEPI HOME PAGE      TRADE NAME INDEX      GENERIC NAME INDEX      FEEDBACK
Information presented by Malahyde Information Systems © Copyright 1996-2006