Ificipro

Ificipro

ciprofloxacin

Manufacturer:

Unique Pharma Lab

Distributor:

Unimed
Full Prescribing Info
Contents
Ciprofloxacin hydrochloride.
Description
FC tablet: Each film coated tablet contains: Ciprofloxacin Hydrochloride eq. to Ciprofloxacin 250 mg/500 mg.
Infusion soln: Each 100ml contains: Ciprofloxacin Hydrochloride equivalent to Ciprofloxacin 200 mg.
Action
Therapeutic Code: J01MA02: CIPROFLOXACIN.
Pharmacology: Pharmacodynamics:
Ciprofloxacin is from the quinolone group, these substances are also known as gyrase inhibitors.
Pharmacokinetics: FC tablet: Absorption of oral doses of ciprofloxacin tablet formulation occurs rapidly, mainly from the small intestine, the half-life of absorption being 2-15 minutes. Plasma levels are dose-related and peak 0.5-2.0 hours after dosing. The AUC also increases dose proportionately after administration of both single and repeated oral (tablet) and intravenous doses. The absolute bioavailability is reported to be 52-83% and ciprofloxacin is subject to only slight first pass metabolism. The oral bioavailability is approximately 70-80%.
The intake of food at the same time as administration of oral ciprofloxacin has a marginal but clinically not relevant effect on the pharmacokinetic parameters Cmax and AUC. No specific recommendations are necessary with regard to time of administration of oral ciprofloxacin relative to food intake.
Distribution of ciprofloxacin within tissues is wide and the volume of distribution high, though slightly lower in the elderly. Protein binding is low (between 19-40%). Only 10-20% of a single oral or intravenous dose is eliminated as metabolites (which exhibit lower activity than the parent drug). Four different antimicrobially active metabolites (which exhibit lower activity than the parent drug). Four different antimicrobially active metabolites have been reported, desethyleneciprofloxacin (M1), sulphociprofloxacin (M2), oxaciprofloxacin (M3) and formylciprofloxacin (M4). M2 and M3 account for one third each of metabolised substance and M1 is found in small amounts (1.3-2.6% of the dose). M4 has been found in very small quantities (<0.1% of the dose). M1-M3 have antimicrobial activity comparable to nalidixic acid and M4 found in the smallest quantity has antimicrobial activity similar to that of norfloxacin.
Elimination of ciprofloxacin and its metabolites occurs rapidly, primarily by the kidney. After single oral and intravenous doses of ciprofloxacin, 55% and 75% respectively are eliminated by the kidney and 39% and 14% in the faeces within 5 days. Renal elimination takes place mainly during the first 12 hours after dosing and renal clearance levels suggest that active secretion by the renal tubules occurs in addition to normal glomerular filtration. Renal clearance is between 0.18-0.3 l/h.kg and total body clearance between 0.48-0.60 l/h.kg. Approximately 1% of a ciprofloxacin dose is excreted via the biliary route. The elimination kinetics are linear and repeated dosing at 12 hourly intervals, no further accumulation is detected after the distribution equilibrium is attained (at 4-5 half-lives). The elimination half-life of unchanged ciprofloxacin over a period of 24-48 hours post-dose is 3.1-5.1 hours.
Some studies carried out with ciprofloxacin in severely renally impaired patients (serum creatinine >265 micromole/l or creatinine clearance <20ml/minute) demonstrated either a doubling of the elimination half-life, or fluctuations in half-life in comparison with healthy volunteers, whereas other studies showed no significant correlation between elimination half-life and creatinine clearance. However, it is recommended that in severely renally impaired patients, the total daily dose should be reduced by half, although monitoring of drug serum levels provides the most reliable basis for dose adjustment as necessary. Results of pharmacokinetic studies in paediatric cystic fibrosis patients have shown dosages of 20mg/kg orally twice daily or 10mg/kg iv three times daily are recommended to achieve plasma concentration/time profiles comparable to those achieved in the adult population at the currently recommended dosage regimen. Inhalation anthrax: Ciprofloxacin serum concentrations achieved in human serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for the recommended doses.
Infusion soln: The pharmacokinetics of ciprofloxacin are linear over the dose range of 200 to 400 mg administered intravenously. The serum elimination half-life is approximately 5-6 hours and the total clearance is around 35 L/hr. Comparison of the pharmacokinetic parameters following the 1st and 5th I.V. dose on a q 12 h regimen indicates no evidence of drug accumulation.
After intravenous administration, approximately 50% to 70% of the dose is excreted in the urine as unchanged drug. Following a 200-mg I.V. dose, concentrations in the urine exceed 200 μg/mL 0-2 hours after dosing and are usually greater than 30 μg/mL 8-12 hours after dosing. Following a 400-mg I.V dose, urine concentrations generally exceed 400 μg/mL 0-2 hours after dosing and are usually greater than 30 μg/mL 8-12 hours after dosing. The renal clearance is approximately 22 L/hr. The urinary excretion of ciprofloxacin is virtually complete by 24 hours after dosing.
The serum concentrations of ciprofloxacin and metronidazole were not altered when these two drugs were given concomitantly.
Co-administration of probenecid with ciprofloxacin results in about 50% reduction in the ciprofloxacin renal clearance and a 50% increase in its concentration in the systemic circulation. Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after intravenous dosing, only a small amount of the administered dose (<1%) is recovered from the bile as unchanged drug. Approximately 15% of an I.V. dose is recovered from the feces within 5 days after dosing.
After I.V. administration, three metabolites of ciprofloxacin have been identified in human urine which together account for approximately 10% of the intravenous dose. Pharmacokinetic studies of the oral (single dose) and intravenous (single and multiple dose) forms of ciprofloxacin indicate that plasma concentrations of ciprofloxacin are higher in elderly subjects (>65 years) as compared to young adults. Although the Cmax is increased 16-40%, the increase in mean AUC is approximately 30%, and can be at least partially attributed to decreased renal clearance in the elderly. Elimination half-life is only slightly (~20%) prolonged in the elderly. These differences are not considered clinically significant.
In patients with reduced renal funciton, the half-life of ciprofloxacin is slightly prolonged and dosage adjustments may be required. In preliminary studies in patients with stable chronic liver cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. However, the kinetics of ciprofloxacin in patients with acute hepatic insufficiency have not been fully elucidated.
Following infusion of 400 mg I.V. ciprofloxacin every eight hours in combination with 50 mg/kg I.V. piperacillin sodium every 4 hours, mean serum ciprofloxacin concentrations were 3.02 μg/mL ½ hour and 1.18 μg/mL between 6-8 hours after the end of infusion.
The binding of ciprofloxacin to serum proteins is 20 to 40%. After intravenous administration, ciprofloxacin is present in saliva, nasal and bronchial secretions, sputum, skin blister fluid, lymph, peritoneal fluid, bile, and prostatic secretions. It has also been detected in the lung, skin, fat, muscle, cartilage, and bone.
Although the drug diffuses intro cerebrospinal (CSF), CSF concentrations are generally less than 10% of peak serum concentrations. Levels of the drug in the aqueous and vitreous chambers of the eye are lower than in serum.
Microbiology: Gram-Negative Organisms: Enterobacteriaceae including E.coli, Salmonella species, Klebsiella species, Shigella, Proteus mirabilis, Proteus vulgaris, K. oxytoca, Yersinia enterocolitica, Enterobacter, Citrobacter, Morganella morganii, Pseudomonas aeruginosa, Haemophilus Influenzae, Acinetobacter, Campylobacter, Brucella melitensis, Pasteurella multocida, Eikenella corrodenus, Flavobacterium, Moraxella, Gardenerella Vaginalis, Legionella species, Vibrio cholerae and Vibrio parahemolyticus, Neisseria meningitidis and Neisseria gonorrhoeae including β-lactomase producing strains.
Gram-Positive Organisms: Staphylococcus aureus including β-lactamase producing and methicillin-resistant strains, streptococcus pneumoniae group A B-hemolytic streptococci, group B streptococci and other streptococci, Enterococci including Enterococcus faecalis, Corynebacterium and Listeria monocytogenes.
Other microorganisms: Anaerobic bacteria including actinomyces, Bifidobacterium, Peptococcus, Clostridium perfringens, Eubacterium, Propionibacterium acnes, Veiilonella and some strains of Bacteroides, Chlamydia, Mycoplasma and Mycobacterium. Ificipro is effective against organisms resistant to nalidixic acid. Since cross-resistance is unlikely, Ificipro may be used to treat infections caused by organism resistant to other class of antibacterials such as aminoglycosides, penicillins, sulfonamides, tetracyclines and cephalosporins.
Indications/Uses
Ificipro is indicated for the treatment of the following infections caused by sensitive Pathogens: Infections of the respiratory tract: In the treatment of outpatients with pneumonia due to Pneumococcus, ciprofloxacin should not be used as a first choice of drug. Ciprofloxacin can be regarded as an advisable treatment for pneumonias caused by Klebsiella, Enterobacter, Proteus, E.Coli, Pseudomonas, Haemophilus, Branhamella, Legionella and Staphylococcus.
Infections of the middle ear (Otitis media), of the Paranasal sinuses (sinusitis), especially if these are caused by gram-negative organisms including Pseudomonas or by Staphylococcus.
Infections of the kidneys and / or the efferent urinary tract.
Infections of the genital organs, including adnexitis, gonorrhoea, prostatis.
Infections of the abdominal cavity (eg, infections of the gastrointestinal tract or of the biliary tract, peritonitis).
Infections of the skin and soft tissue.
Infections of the eyes.
Infections of the bones and joints.
Sepsis.
Infections or imminent risk of infection (prophylaxis) in patients whose immune system has been weakened (eg patients on immunosuppressants or have neutropenia).
Selective intestinal decontamination in immunosuppressed patients.
According to in vitro investigations, the following pathogens can be regarded as sensitive: E.Coli, Shigella, Salmonella, Citrobacter, Klebsiella, Enterobacter, Serratia, Hafnia, Edwardsiella, Proteus (indole-positive and indole-negative), Providencia, Morganella, Yersinia, Vibrio, Aeromonas, Plesiomonas, Pasteurella, Haemophilus, Campylobacter, Pseudomonas, Legionella, Neisseria, Moraxella, Acinetobacter, Brucella; Staphylococcus, Listeria, Corynebacterium, Chlamydia.
The following show varying degrees of sensitivity: Gardnerella, Flavobacterium, Alcaligenes, Streptococcus agalactiae, Enterococcus faecalis, Streptococcus pyogenes, Streptococcus pneumoniae, Viridans group streptococci, mycoplasma hominis, Mycobacterium tuberculosis and Mycobacterium fortuitum.
The following are usually resistant: Enterococcus faecium, Ureaplasma urealyticum, Nocardia asteroids. With a few exceptions, anaerobes are moderately sensitive eg. Peptococcus, peptostreptococcus to resistant eg, bacteroides. Ciprofloxacin is ineffective against Treponema pallidum.
Dosage/Direction for Use
FC tablet: General dosage recommendations: The dosage of Ificipro tablets is determined by the severity and type of infection, the sensitivity of the causative organism(s) and the age, weight and renal function of the patient. Ificipro tablets should be swallowed whole with an adequate amount of liquid.
If Ificipro Tablets are taken on an empty stomach, the active substance is absorbed more rapidly. In this case, the tablets should not be taken concurrently with dairy products or with mineral fortified drinks alone (e.g. milk, yoghurt, and calcium fortified orange juice). However, a normal diet that will contain small amounts of calcium, does not significantly affect ciprofloxacin absorption.
If the patient is unable to take tablets, because of the severity of the illness or for other reasons, it is recommended to commence the therapy with an intravenous form of ciprofloxacin. (See Table 1.)

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Infusion soln: Ciprofloxacin should be administered by IV infusion over a period of 60 min. 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 other compatible infusion solutions. (See Table 2.)

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Incompatibilities: The ciprofloxacin 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% Sodium chloride or 0.45% Sodium Chloride. When ciprofloxacin infusion solutions are mixed with compatible infusion solutions, for microbiological reasons and light sensitivity these solutions should be administered shortly after admixture.
Unless compatibility with other infusion solutions/drugs have been confirmed, the infusion solution must always be administered separately. The visual signs of incompatibility are eg., precipitation, clouding and discoloration.
Incompatibility appears with all infusion solutions/drugs that are physically or chemically unstable at the pH of the solution (eg. penicillins, heparin solutions), especially on combination with solutions adjusted to an alkaline pH (pH of the ciprofloxacin infusion solutions: 3.9-4.5).
Duration of Treatment: The duration of treatment depends on the severity of the illness and on the clinical and bacteriological course. It is essential to continue therapy for at least 3 days after disappearance of the fever or of the clinical symptoms.
Mean duration of treatment: 1 day for acute uncomplicated gonorrhea and cystitis: up to 7 days for infections of the kidneys, urinary tract and abdominal cavity; over the entire period of the neutropenic phase in patients with weakened body defenses; a maximum of 2 months in osteomyelitis; 7-14 days in all other infections.
In streptococcal infections the treatment must last at least 10 days because of the risk of late complications.
Infections caused by Chlamydia should also be treated for a minimum of 10 days.
Elderly: Elderly patients should receive a dose as low as possible depending on the severity of their illness and the creatinine clearance.
Renal and Hepatic impairment: Impaired Renal Function: FC tablet: where creatinine clearance is between 31 and 60ml/min/1.73m2 or where the serum creatinine concentration is between 1.4 and 1.9mg/100ml. The maximum daily dose should be 1000mg per day for oral administration.
Where creatinine clearance is equal or less than 30ml/min/1.73m2 or where the serum creatinine concentration is equal or higher than 2mg/100ml the maximum daily dose should be 500mg/day for oral administration.
Infusion soln: where creatinine clearance is between 31 and 60ml/min/1.73m2 or where the serum creatinine concentration is between 1.4 and 1.9mg/100ml. The maximum daily dose should be 800mg/day for an IV regimen.
Where creatinine clearance is ≤ 30ml/min/1.7373m2 or where the serum creatinine concentration is 3 2mg/100ml the maximum daily dose should be 400mg/day for an IV regimen.
Impaired renal function+Haemodialysis: Dose as in 1.2; on dialysis days after dialysis.
Impaired renal function + CAPD: FC tablet: Administration of ciprofloxacin film coated tablets a 1x500mg film coated tablets or 2x250mg film coated tablets.
Infusion soln: Addition of ciprofloxacin infusion solution to the dialysate (intraperitoneal): 50mg ciprofloxacin/L dialysate administered 4 times a day every 6 hrs.
Impaired Renal function: No dose adjustment is required.
Impaired Renal and Liver function: Dose adjustment as in 1.1 and 1.2.
RECOMMENDED STARTING AND MAINTENANCE DOSES FOR PATIENTS WITH IMPAIRED RENAL FUNCTION: FC tablet: (See Table 3.)

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Mode of Administration: FC tablet: Tablet for oral consumption.
Infusion soln: Intravenous.
Overdosage
Based on the limited information available in two cases of ingestion of over 18g of ciprofloxacin, reversible renal toxicity has occurred. Therefore, apart from routine emergency measures, it is recommended to monitor renal function, including urinary pH and acidify, if required, to prevent crystalluria. Patients must be kept well hydrated, and in the case of renal damage resulting in prolonged oliguria, dialysis should be initiated. Serum levels of ciprofloxacin are reduced by dialysis.
Contraindications
Ificipro is contraindicated in individuals with a history of hypersensitivity to Ciprofloxacin or any other quinolone derivative. Its use is not recommended in children below the age of 12 years.
Special Precautions
Warning: The onset of tendon pain calls for immediate withdrawal of this drug.
Precautions: As Ificipro may cause CNS stimulation. It should be used with caution in patients with CNS disorders such as severe cerebral arteriosclerosis or epilepsy. Patients receiving this drugs should be well hydrated to prevent crystalluria. Excessive alkalinization of urine should be avoided. The dosage should be reduced in patients with renal impairment. Reproduction studies in animals at doses upto 6 times the usual daily human dose have not revealed any evidence of impaired fertility of teratogenecity due to Ificipro. However, information from well-controlled studies in pregnant women is not available. Since Ificipro causes arthropathy in immature animals, It should not be used in pregnant and nursing women.
Use In Pregnancy & Lactation
The safety and efficacy of ciprofloxacin in children, adolescents, pregnant women and lactating women have not been established.
Side Effects
Ificipro (Ciprofloxacin) is generally well tolerated. During clinical trials in a large number of patients, adverse effects related to drug occurred infrequently and were commonly reported as diarrhoea, vomiting,abdominal pain, headache, restlessness and rash. Other side effects which have been reported very rarely include arthralgia and increases in serum transaminases levels.
Drug Interactions
Serum concentrations and elimination half-life of theophylline may be increased when it is used concurrently with Ificipro it is recommended that patients be monitored for the signs of theophylline toxicity during concurrent use and dosage adjustments made as appropriate. Probenecid delays excretion of Ificipro.
Storage
Store at temperature not exceeding 30°C. Protect from light. Do not freeze.
Shelf-Life: 3 years from the month of manufacture.
MIMS Class
ATC Classification
J01MA02 - ciprofloxacin ; Belongs to the class of fluoroquinolones. Used in the systemic treatment of infections.
Presentation/Packing
FC tab 250 mg (white to yellowish white, round biconvex) x 10 x 10's. 500 mg (white to off-white capsule shaped with break line on one side) x 10 x 10's. Infusion soln 200 mg/100 mL (a clear, colourless to pale yellow liquid) x 1's.
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