Cipocil
CIPOCIL?TABLETS
Ciprofloxacin Hydrochloride Tablets 500 mg
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COMPOSITION
Each tablet contains:
Ciprofloxacin Hydrochloride Tablets 500 mg
582 mg ciprofloxacin hydrochloride, equivalent to 500 mg ciprofloxacin
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PHARMACOLOGICAL CLASSIFICATION
Broad and medium spectrum antibiotics -
PHARMACOLOGICAL ACTION
Ciprofloxacin is a synthetic 4-quinolone derivative. Ciprofloxacin is bactericidal and acts by inhibiting the A subunit of DNA gyrase (topoisomerase) which is essential in the reproduction of bacterial DNA.
Spectrum of activity: (See Indications)
Streptococci and enterococci are less susceptible. Enterococcus faecium, Ureaplasma urealyticum, Nocardia astcroides are usually resistant.
Most anaerobic bacteria, including Bacteroides fragilis, Clostridium difficile and Treponema pallidum are resistant to ciprofloxacin, although some (eg Peptococcus, Peptostreptococcus) may be moderately sensitive.
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 I-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.
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INDICATIONS
Ciprofloxacin is indicated for the treatment of infections caused by ciprofloxacin-sensitive organisms:
Lower Respiratory Tract Infections
caused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzae and Haemophilus parainfluenzae.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 Escherichia coli, Campylobacter jejuni, Shigella flexneri, and Shigella sonnei.Bone Infections
Osteomyelitis due to sensitive gram-negative organisms.Gonorrhoea
Ciprofloxacin is not effective 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 Hydrochloride Tablets is contra-indicated in children under 18 years of age and in growing adolescents, except where the benefits of the treatment outweigh the risks.
Species variable, reversible lesions of the cartilage of weight-bearing joints have been reported in immature members of certain animal species during animal studies. Ciprofloxacin Hydrochloride Tablets is contra-indicated in patients who are hypersensitive to ciprofloxacin or other quinolones.
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WARNINGS
Ciprofloxacin Hydrochloride Tablets must be used cautiously in patients with a history of convulsive disorders.
As crystalluria has been reported in patients taking Ciprofloxacin Hydrochloride Tablets, patients must be well hydrated.
Excessive alkalinity of the urine should be avoided.
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DOSAGE AND DIRECTIONS FOR USE
Ciprofloxacin Hydrochloride Tablets should be swallowed whole with plenty of liquid. Ciprofloxacin Hydrochloride Tablets may be taken with or without meals.Dosage:
The dosage range is 250 mg to 750 mg twice daily.
Elderly patients should receive as low a dose as possible; this will depend on the severity of the condition being treated and on the patient's creatinine clearance.
In patients with reduced renal function, the half-life of ciprofloxacin is prolonged and the dosage must be adjusted.
Infections of the lower respiratory tract:
Mild to moderate: 250 to 500 mg twice daily.
Severe or complicated: 750 mg twice daily.
The dosage in cystic fibrosis patients is 750 mg twice daily.
The low bodymass of these patients should be considered when determining dose (7.5 mg to 15.0 mg/kg/day).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.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 to 6 weeks or longer.Gonorrhoea:
A single dose of 250 mg.Duration of treatment:
The duration or treatment depends on the severity of the infection, the clinical response and the bacteriological results.
For acute infections the usual treatment period is 5 to 10 days. More prolonged therapy may be required for severe and complicated infections.
Generally, treatment should be continued for at least 3 days after the signs and symptoms of the infection have disappeared. The duration of treatment for acute uncomplicated cystitis in women is 3 days.
Treatment of streptococcal infections must continue for at least 10 days due to the risk of late complications.
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SIDE EFFECTS AND SPECIAL PRECAUTIONS
Side-effects:
Gastro-intestinal:
Nausea, vomiting, diarrhoea, abdominal pain, dyspepsia, flatulence and anorexia. Pseudomembranous colitis has been reported.If severe and persistent diarrhoea appears during treatment, a doctor must be consulted since this could be due to a serious gastro-intestinal condition (pseudomembranous colitis) which would require immediate treatment. Ciprofloxacin must be discontinued and appropriate therapy initiated (for example vancomycin 250 mg x 4 daily, orally). Medicines that inhibit peristalsis are contra-indicated.
Central Nervous System:
Headache, dizziness, tiredness, nervousness, agitation and restlessness. Other side-effects which have been reported include: tremor, drowsiness, insomnia, nightmares, visual and other sensory disturbances, anxiety states, confusion, hallucinations, psychotic reactions, depression, convulsions, sweating, unsteady gait, increase in intracranial pressure, paraesthesia and peripheral neuropathy In some patients, these side-effects have been reported after the first dose of ciprofloxacin. Ciprofloxacin Hydrochloride Tablets should be discontinued, and the doctor informed immediately.Sensory:
Impaired taste and smell. visual disturbances (e.g. diplopia, colour vision), tinnitus and transient impairment of hearing (especially at high frequencies).Hypersensitivity reactions:
Rash, pruritus and drug fever. Punctuate skin haemorrhages (petechiae), blister formation with accompanying haemorrhages (haemorrhagic bullae), small nodules (papules) with crust formation showing vascular involvement (vasculitis), erythema multiforme, erythema nodosum,. Stevens-Johnson syndrome, Lyell syndrome and toxic epidermal necrolysis have been reported.Interstitial nephritis, hepatitis, hepatic necrosis very seldom progressing to life-threatening hepatic failure have also been reported.
Anaphylactic/anaphylactoid reactions (e.g. facial, vascular and laryngeal oedema, dyspnoea progressing to life-threatening shock) have occurred after the first dose of ciprofloxacin. Ciprofloxacin must be discontinued and medical treatment (e.g. treatment for shock) initiated.
Cardiovascular system:
Tachycardia, hot flushes, migraine and fainting.Other side-effects:
Joint pain, joint swelling:
The following have been reported rarely: general feeling of weakness, muscular pains, tendosynovitis, photosensitivity, transient impairment in kidney function including transient kidney failure.Achillotendinitis was observed in single cases during the administration of ciprofloxacin. Cases of partial or complete rupture of the Achilles tendon have been reported predominantly in the elderly or patients who have received prior systemic treatment with glucocorticoids. If there are any signs of achillotendinitis (e.g. painful swelling), the administration of ciprofloxacin should be discontinued and a physician 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. Leucocytosis, thrombocytosis, haemolytic anaemia and altered prothrombin values occur rarely.Laboratory parameters
Transient increases in transaminases. alkaline phosphatase. urea, serum creatinine, serum bilirubin. Cholestatic jaundice has been reported.
Individual cases of hyperglycaemia, crystalluria or haematuria have been reported.
Special precautions:
Care is necessary in patients with impaired hepatic or renal function, glucose-6-phosphate dehydrogenase deficiency, or myasthenia gravis . The ability to drive or operate machinery may be impaired by ciprofloxacin, especially when alcohol is also taken.
Interactions:
Concurrent administration of Ciprofloxacin Hydrochloride Tablets with theophylline may lead to elevated plasma theophylline concentrations and prolongation of the elimination half-life of theophylline. This may result in an increased risk of theophylline-related adverse reactions. If concomitant use cannot be avoided, plasma levels of theophylline should be monitored and appropriate dosage adjustments made.
Ciprofloxacin Hydrochloride Tablets should be administered 1-2 hours before, or at least 4 hours after taking iron preparations or 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 medicine 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 Hydrochloride Tablets and warfarin may intensify the action of warfarin.
Concurrent administration of Ciprofloxacin Hydrochloride Tablets and glibenclamide has been reported to intensify the hypoglycaemic effects of glibenclamide.
Probenecid interferes with the renal secretion of Ciprofloxacin Hydrochloride Tablets, and concurrent administration would increase the serum concentration of ciprofloxacin.
Metoclopramide accelerates the absorption of Ciprofloxacin Hydrochloride Tablets, resulting in a shorter time to reach maximum plasma concentrations. This had no effect on the bioavailability of Ciprofloxacin Hydrochloride Tablets.
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KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
In the event of acute, excessive oral over dosage, reversible renal toxicity has been reported. Apart from routine emergency measures, it is recommended that renal function be monitored and magnesium and calcium containing antacids be administered in order to reduce the absorption of ciprofloxacin.
Only a small amount of ciprofloxacin (<10 ) is removed from the body after haemodialysis or peritoneal dialysis. Treatment is symptomatic and supportive.
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STORAGE INSTRUCTIONS
Store below 25?C.
KEEP OUT OF REACH OF CHILDREN.