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CIPROBAY® IV (Infusion)
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CIPROBAY® 250, 500, 750 (Tablets)
CIPROBAY® IV (Infusion)
CIPROBAY® Suspension 5%
SCHEDULING STATUS:
S4
PROPRIETARY NAME
(and dosage form):
CIPROBAY® 250, 500, 750 (Tablets)
CIPROBAY® IV (Infusion)
CIPROBAY® Suspension 5%
COMPOSITION:
CIPROBAY 250tablet contains 291 mg ciprofloxacinhydrochloride monohydrate, equivalent to 250 mg ciprofloxacin.
CIPROBAY 500tablet contains 582 mg ciprofloxacin hydrochloride monohydrate, equivalent to 500 mg ciprofloxacin.
CIPROBAY 750tablet contains 873 mg ciprofloxacin hydrochloride monohydrate, equivalent to 750 mg ciprofloxacin.
CIPROBAY IVcontains 2,54 mg ciprofloxacin lactate equivalent to 2,0 mg ciprofloxacin per mL in 0,9% sodium chloride solution.
CIPROBAY Suspension 5% when reconstituted as directed with the suspension diluent, each 5 mL CIPROBAY Suspension 5% contains ciprofloxacin microcapsules equivalent to 250 mg ciprofloxacin.
PHARMACOLOGICAL CLASSIFICATION:
A. 20.1.1. Broad and medium spectrum antibiotics.
PHARMACOLOGICAL ACTION:
Ciprofloxacin is a synthetic, 4-quinolone derivative with in vitrobactericidal activity against the following Gram-negative and Gram-positive organisms. In vitrosensitivity does not necessarily imply in vivoefficacy.
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 gonorrhoeae Shigella sonnei
Edwardsiella Pasteurella Staphyloccocus aureus
Enterobacter cloacae Plesiomonas Staphylococcus epidermidis
Enterobacter species Proteus mirabilis Streptococcus faecalis
The following organisms show varying degrees of in vitrosensitivity 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 pallidum).
The pharmacokinetics of ciprofloxacin suspension is very similar to that of ciprofloxacin tablets.
Ciprofloxacin plasma levels are dose-related and peak 0,5-2 hours after oral dosing. The absolute oral bioavailability is approximately 70% with no substantial loss by first pass metabolism. 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, bile secretions, prostatic secretions, cerebrospinal fluid and the aqueous humor. Protein binding is low. 40% to 50% is excreted in urine as unchanged drug. Approximately 15% of a single dose of ciprofloxacin is eliminated as metabolites. Elimination occurs primarily by the kidneys and mainly during the first 12 hours after dosing. Renal clearance is approximately 300 mL/minute. The elimination half-life of unchanged ciprofloxacin is 3-5 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 Infectionscaused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Pseudomonas aeruginosa, Haemophilus influenzaeand Haemophilus para-influenzae.
Urinary Tract Infectionscaused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Serratia marcescens, Proteus mirabilis, Providencia rettgeri, Morganella morganii, Citrobacter diversus, Citrobacter freundii, Pseudomonas aeruginosa, Staphylococcus epidermidisand Streptococcus faecalis.
Skin and Soft Tissue Infectionscaused by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Proteus mirabilis, Proteus vulgaris, Providencia stuartii, Morganella morganii, Citrobacter freundii, Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidisand Streptococcus pyogenes.
Gastro-intestinal Infections: Infective diarrhoea caused by E.coli, Campylobacter jejuni, Shigella flexneriand 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.
CIPROBAY 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.
CIPROBAY is contra-indicated in patients who have shown hypersensitivity to ciprofloxacin or any other quinolones.
WARNINGS:
CIPROBAY should be used with caution in patients with a history of convulsive disorders.
Crystalluria related to the use of CIPROBAY has been observed. Patients receiving CIPROBAY should be well hydrated and excessive alkalinity of the urine should be avoided.
DOSAGE AND DIRECTIONS FOR USE:
CIPROBAY TABLETS
CIPROBAY tablets should be swallowed whole with plenty of liquid and may be taken with or without meals.
CIPROBAY SUSPENSION
Always use the graduated measuring spoon to obtain the exact dose:
½ measuringspoonful (approx 2,5 mL) contains approx. 125 mg ciprofloxacin. 1 measuringspoonful (approx 5,0 mL) contains approx. 250 mg ciprofloxacin.
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 response 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 5-10 days with CIPROBAY tablets or suspension. 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; 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 4-6 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 or suspension, 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.
Instructions for use/handling:
Preparation of the ready-to-use suspension:
illustrated
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The small bottle contains the active substance, the large bottle contains the diluent liquid. |
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Shake the large bottle horizontallyfor about 15 seconds. |
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Open both bottles.
Childproof-cap: Press down on the cap and at the same time turn it to the left. |
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Empty the granules into the liquid by holding the large bottle at a slight angle and inserting the neck of the small bottle into the opening of the large bottle. |
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Then hold it vertically until all granules are in the large bottle.
Do not pour water into the suspension ! |
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Reclose the large bottle and shake it well horizontallyfor about 15 seconds. The correct mixture is now prepared, the suspension is ready to use. |
Taking the ready-to-use suspension:
Swallow the prescribed amount of suspension as quickly as possible. Do not chew the microcapsules present in the suspension, simply swallow them. A drink of water may be taken afterwards. Replace the cap on the bottle after use. It may be stored at room temperature up to 25°C. Do not store in refrigerator. The ready-to-use suspension is stable for 14 days. After treatment has been completed, it should not be re-used.
Shake well each time before use for approx. 15 seconds.
The graduated measuringspoon with the markings 1/2 is equivalent to 2,6 mL and contains 2,5 mL of final mixed suspension and 1/1 is equivalent to 5,2 mL and contains 5,0 mL of final mixed suspension. The graduated measuringspoon must be used for measuring the required prescribed amount of ciprofloxacin suspension.
Important incompatibilities:
No additions should be made to the mixed final suspension.
CIPROBAY IV
Dosage and Duration of Treatment:
The dosage of CIPROBAY 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. The usual dose is 100 mg - 200 mg IV every 12 hours. For severe and/or complicated infections 400 mg may be administered every 12 hours (i.e. bd). 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.
Cystic fibrosis:
In cystic fibrosis patients the normal dose is 200 mg IV twice daily. The low body mass of these patients should, however, be taken into consideration when determining dosage (5-10 mg/kg/day).
Directions for Intravenous Administration:
CIPROBAY IV should be administered by intravenous infusion over a period of 60 minutes. Slow infusion into a large vein will minimize patient discomfort and reduce the risk of venous irritation. The infusion solution can be infused either directly or after mixing with the other compatible infusion solutions.
The CIPROBAY IV infusion solution is compatible with physiological saline, Ringer solution and Ringer lactate solution, 5% and 10% glucose solutions, 10% fructose solution, and 5% glucose solution with 0,225% NaCl or 0,45% NaCl. When ciprofloxacin infusion solutions are mixed with compatible infusion solutions, for microbiological reasons and light sensitivity these solutions should be administered shortly after admixture.
Important incompatibilities:
Unless compatibility with other infusion solutions/drugs has been confirmed, the infusion solution must always be administered separately. The visual signs of incompatibility are e.g. precipitation, clouding and discolouration.
Incompatibility appears with all infusion solutions/drugs that are physically or chemically unstable at the pH of the solution (e.g. penicillins, heparin solutions), especially on combination with solutions adjusted to an alkaline pH (pH of the ciprofloxacin infusion solutions: 3,9-4,5).
Any remaining solution should be discarded.
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/1,73m2 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 (intraperitoneal): 50 mg ciprofloxacin/litre dialysate administered 4 times a day.
2.2 Oral administration of either ciprofloxacin film coated tablet as 500 mg tablet or 2 x 250 mg tablets or ciprofloxacin suspension 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 dose 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 gastrointestinal tract:
Nausea, diarrhoea, vomiting, dyspepsia, abdominal pain, flatulence, anorexia, oral moniliasis. 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 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, serum-sickness like reactions.
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, 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. Very rarely: general feeling of weakness, muscular pains (which may be of special importance in patients with myaesthenia gravis), 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.
- Local reactions:
Phlebitis or thrombophlebitis, local irritation and pain at the site of injection have been reported with intravenous administration of ciprofloxacin. 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 hand are used. These may appear as local skin reactions which resolve rapidly upon completion of the infusion. Subsequent intravenous administration is not contraindicated unless the reactions recur or worsen.
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 CIPROBAY 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.
CIPROBAY tablets or suspension 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 CIPROBAY and warfarin may intensify the action of warfarin.
In particular cases, concurrent administration of CIPROBAY and glibenclamide can intensify the action of glibenclamide (hypoglycaemia).
Probenecid interferes with renal secretion of CIPROBAY. Co-administration of probenecid and CIPROBAY increases the CIPROBAY serum concentrations.
Metoclopramide accelerates the absorption of CIPROBAY, resulting in a shorter time to reach maximum plasma concentrations. No effect was seen on the bioavailability of CIPROBAY.
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:
CIPROBAY 250 tablets: Round, scored, convex, slightly yellowish, film-coated tablet with CIP 250 imprinted on the upper side and the Bayer cross on the lower side.
CIPROBAY 500 tablets: Oblong, scored, convex, slightly yellowish, film-coated tablet with CIP 500 imprinted on the upper side and Bayer on the lower side.
CIPROBAY 750 tablets: Oblong, scored, convex, slightly yellowish, film-coated tablet with CIP 750 imprinted on the upper side and Bayer on the lower side.
CIPROBAY IV: Clear pale yellow solution.
CIBROBAY
Suspension 5%:
microcapsules White to slightly yellowish granules for reconstitution.
diluent: White to slightly yellowish, oily suspension with strawberry odour, occasionally may contain yellow-orange droplets and globular particles.
When reconstituted as directed, the final mixed suspension is white to slightly yellowish with a strawberry odour, occasionally may contain yellow-orange droplets and globular particles.
PRESENTATION:
CIPROBAY tablets: Blister packs of 10 tablets. 250 mg tablets also available in packs of 6.
CIPROBAY IV: 50 mL, 100 mL and 200 mL glass infusion bottles.
CIPROBAY
Suspension 5%: Each trade package carton comprises:
1 brown glass bottle containing microcapsules for reconstitution.
1 white plastic bottle with suspension diluent to prepare the final mixed suspension.
1 graduated measuringspoon.
STORAGE INSTRUCTIONS:
CIPROBAY tablets: Store below 25°C. Keep out of reach of children.
CIPROBAY IV: Store below 25°C. Keep out of reach of children.
CIPROBAY IV: After infusion of the required dose, any remaining solution should be discarded. CIPROBAY IV is light-sensitive and should always be stored in the cardboard outer carton. No special precautions are, however, required during the 60 minute infusion period. In daylight conditions, efficacy is guaranteed for a period of 3 days.
CIPROBAY Suspension: The individual components viz. microcapsules and suspension diluent should not be used after the expiration dates have been reached.
microcapsules: Store below 25°C. Keep out of reach of children.
diluent: Store below 25°C. Protect from freezing. Store in upright position.
Keep out of reach of children.
When reconstituted as directed utilizing the individual components, the final mixed ready-to-use suspension is stable at room temperature (up to 25°C) for 14 days. After this time the final mixed suspension should not be taken.
Keep out of reach of children.
REGISTRATION NO:
CIPROBAY 250: U/20.1.1/126
CIPROBAY 500: U/20.1.1/127
CIPROBAY 750: U/20.1.1/128
CIPROBAY IV: Y/20.1.1/311
CIPROBAY Suspension 5%: 31/20.1.1/0111
Diluent for Ciprobay
Suspension 5%: 31/34/0113
ZIMBABWE:
PP Ciprobay 250: 94/7.2.5/2873
PP Ciprobay 500: 94/7.2.5/2874
NAME AND BUSINESS ADDRESS OF THE APPLICANT:
Bayer (Pty) Ltd
Registration No. 68/11192/07
Wrench Road Isando 1600
DATE OF PUBLICATION OF THIS PACKAGE INSERT:
4 August 2000
® = Registered trade mark of Bayer AG, Germany |
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