INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
ORPIC 250 mg TABLETS
ORPIC 500 mg TABLETS
ORPIC 750 mg TABLETS

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

ORPIC 250 mg TABLETS
ORPIC 500 mg TABLETS
ORPIC 750 mg TABLETS

COMPOSITION:
Each tablet contains:
ORPIC 250 mg TABLETS:
291 mg ciprofloxacin hydrochloride, equivalent to 250 mg ciprofloxacin
ORPIC 500 mg TABLETS:
582 mg ciprofloxacin hydrochloride, equivalent to 500 mg ciprofloxacin
ORPIC 750 mg TABLETS:
873 mg 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. 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 asteroides 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 absorbed from the gastro-intestinal tract. Oral bioavailability is approximately 70% and a peak plasma concentration is achieved 0,5 to 2 hours after oral dosing. Absorption may be delayed by the presence of food, but is not substantially affected overall. The plasma half-life is about 3,5 to 4,5 hours and there is evidence of moderate accumulation. Half-life may be prolonged in severe renal failure and to some extent in the elderly.
Plasma protein binding ranges from 20 to 40%. Ciprofloxacin is widely distributed in the body and tissue penetration is extensive. It appears in the cerebrospinal fluid, but the concentrations are only about 10% of those in the plasma when the meninges are not inflamed.
Ciprofloxacin crosses the placenta, and is distributed into the breast milk. High concentrations are achieved in the bile.
Ciprofloxacin is eliminated principally by urinary excretion, but non-renal clearance may account for about a third of elimination and includes hepatic metabolism, biliary excretion, and possibly transluminal secretion across the intestinal mucosa. Urinary excretion is by active tubular secretion as well as glomerular filtration and is virtually complete within 24 hours.
About 40 to 50% of an oral dose is excreted unchanged in the urine and about 15% as metabolites Faecal excretion over 5 days has accounted for 20 to 35% of an oral dose.
At least four active metabolites have been identified. Oxociprofloxacin appears to be the major urinary metabolite, and sulphociprofloxacin is the primary faecal metabolite.
Only small amounts of ciprofloxacin are removed by haemodialysis or peritoneal dialysis.

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.

ORPIC 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.

ORPIC is contra-indicated in patients who are hypersensitive to ciprofloxacin or other quinolones.

WARNINGS:
ORPIC must be used cautiously in patients with a history of convulsive disorders.
As crystalluria has been reported in patients taking ORPIC, patients must be well hydrated.
Excessive alkalinity of the urine should be avoided.

DOSAGE AND DIRECTIONS FOR USE:
ORPIC tablets should be swallowed whole with plenty of liquid. ORPIC 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.

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 peripheralneuropathy.
* In some patients, these side-effects have been reported after the first dose of ciprofloxacin. ORPIC 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 ORPIC 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.
ORPIC 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 ORPIC and warfarin may intensify the action of warfarin.
Concurrent administration of ORPIC and glibenclamide has been reported to intensify the hypoglycaemic effects of glibenclamide.
Probenecid interferes with the renal secretion of ORPIC, and concurrent administration would increase the serum concentration of ciprofloxacin.
Metoclopramide accelerates the absorption of ORPIC, resulting in a shorter time to reach maximum plasma concentrations. This had no effect on the bioavailability of ORPIC.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
In the event of acute, excessive oral overdosage, 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.

IDENTIFICATION:
ORPIC 250 mg TABLETS:
A white to off-white, film-coated, round, biconvex tablet.
ORPIC 500 mg TABLETS:
A white to off-white, film-coated, round, biconvex tablet.
ORPIC 750 mg TABLETS:
A white to off-white, film-coated, ovoid, biconvex tablet, bisected on one side.

PRESENTATION:
ORPIC 250 mg TABLETS: Blister packs of 6 and 10 tablets.
ORPIC 500 mg TABLETS: Blister packs of 10 tablets.
ORPIC 750 mg TABLETS: Blister packs of 10 tablets.

STORAGE INSTRUCTIONS:
Store below 25°C.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
ORPIC 250 mg TABLETS: 35/20.1.1/0101
ORPIC 500 mg TABLETS: 35/20.1.1/0102
ORPIC 750 mg TABLETS: 35/20.1.1/0103

NAME AND BUSINESS ADDRESS OF APPLICANT:
PHARMACARE LIMITED
7 Fairclough Road
Korsten
Port Elizabeth
6020
South Africa

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
12/10/2000

D666
A&S PRINTERS

New addition to this site: February 2004
Source: Community Pharmacy
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