Axcel Ciprofloxacin

Axcel Ciprofloxacin

ciprofloxacin

Manufacturer:

Kotra Pharma

Distributor:

Kotra Pharma
Full Prescribing Info
Contents
Ciprofloxacin hydrochloride.
Description
Axcel Ciprofloxacin-250mg Tablet: Each tablet contains Ciprofloxacin Hydrochloride equivalent to Ciprofloxacin 250mg.
Axcel Ciprofloxacin-500mg Tablet: Each tablet contains Ciprofloxacin Hydrochloride equivalent to Ciprofloxacin 500mg.
Action
Pharmacology: Mechanism of Action: Ciprofloxacin is a synthetic broad spectrum quinolone antibacterial agent. Ciprofloxacin has in-vitro against virtually all gram-negative and gram-positive organisms. The bactericidal action of ciprofloxacin results from inhibition of bacterial type II topoisomerases (DNA gyrase and topoisomerase IV), which are required for bacterial DNA replication, transcription, repair and recombination.
Mechanism of resistance: In-vitro resistance to ciprofloxacin is commonly due to mutations in bacterial topoisomerases and develops slowly through multiple-step mutations. Ciprofloxacin resistance due to spontaneous mutations occurs at a frequency of between <10-9 to 10-6. Cross-resistance among fluoroquinolones may occur when resistance arises through mutations. Single mutations may result in reduced susceptibility rather than clinical resistance, but multiple mutations generally result in clinical resistance to ciprofloxacin and cross-resistance across the quinolone class. Bacterial impermeability and/or expression of efflux pumps may impact ciprofloxacin susceptibility. Plasmid-mediated resistance encoded by the qnr gene has been reported. Resistance mechanisms that inactive penicillins, cephalosporins, aminoglycosides, macrolides, and tetracyclines do not interfere with the antibacterial activity of ciprofloxacin and there is no known cross-resistance between ciprofloxacin and other classes of antimicrobials. Organisms resistant to these drugs may be susceptible to ciprofloxacin.
The minimal bactericidal concentration (MBC) generally does not exceed the minimal inhibitory concentration (MIC) by more than a factor of 2.
In vitro Susceptibility to Ciprofloxacin: The prevalence of acquired resistance may vary geographically and with time for selected species and local information of resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought where the local prevalence of resistance is such that utility of the agent, in at least some types of infections, is questionable.
Ciprofloxacin has been shown to be active in vitro against susceptible strains of the microorganisms listed as follows: Aerobic Gram-positive Microorganisms: Bacillus anthracis; Enterococcus faecalis (many strains are only moderately susceptible); Staphylococcus aureus (methicillin-susceptible); Staphylococcus; Saprophyticus; Streptococcus pneumoniae.
Aerobic Gram-negative Microorganisms: Burkholderia cepacia; Morganella morganii; Campylobacter spp.; Neisseria gonorrhoeae; Citrobacter freudii; Proteus mirabilis; Enterobacter aerogenes; Proteus vulgaris; Enterobacter clocae; Providencia spp.; Escherichia coli; Pseudomonas aeruginosa; Haemophilius influenza; Pseudomonas fluorescens; Klebsiella pneumonia; Serratia marcescens; Klebsiella oxytoca; Shigella spp.; Moraxella catarrhalis.
The following microorganisms show varying degrees of susceptibility to ciprofloxacin: Burkholderia cepacia, Campylobacter spp., Enterococcus faecalis, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia marcescens. The following microorganisms are considered inherently resistant to ciprofloxacin: Staphylococcus aureus (methicillin-resistant) and Stenotrophomonas maltophilia. Ciprofloxacin has been shown to be active against Bacillus anthracis both in vitro and by use of serum levels as a surrogate marker.
Inhalational anthrax-additional information: Ciprofloxacin serum concentrations achieved in humans serve as a surrogate endpoint reasonably likely to predict clinical benefit and provide the basis for this indication.
Pharmacokinetics: Ciprofloxacin is suitable for oral and intravenous administration. Owing to its excellent antibacterial activity and its good pharmacokinetics properties, ciprofloxacin can be given orally for injections which previously could only be treated intravenously with, say, penicillins, cephalosporins or aminoglycosides. For acute life-threatening infections or patients unable to take tablets it is advisable to commence treatment with the intravenous form of ciprofloxacin. Following an initial intravenous dose (short-term 30 minute infusion), treatment can be continued with oral ciprofloxacin, which is a distinct advantage, especially from the patient's point of view.
Absorption and bioavailability: After oral administration ciprofloxacin is largely absorbed from the small intestine. A specific study with C14-labelled ciprofloxacin showed that 73% of the dose was absorbed intestinally. Absorption is rapid, leading to peak serum levels after 60-90 minutes. Absolute bioavailability has been shown to be 70-80% in various studies by a direct comparison between the oral and intravenous forms of ciprofloxacin.
Distribution volume: The distribution volume of ciprofloxacin in steady state is 2-3 liters/kg. This unusually high figure, more than 10 times that of beta-lactam antibiotics and aminoglycosides, is an indication that ciprofloxacin reaches higher concentrations in tissue and body fluids than in serum. Concentrations were in fact measured in a number of tissue and fluid samples that were several times higher than the corresponding serum levels.
Concentrations in body fluids and tissues/protein binding: The pharmacokinetics properties of ciprofloxacin suggest good tissue penetration, with distribution volume as a good indicator of the high tissue concentrations one may expect to find. The rate of protein binding and degree of ionisation are decisive factors in the diffusion of a substance from the intra to the extravascular space. It is reasonable to assume that only the proportion of the substance not bound to serum proteins and not ionized is able to diffuse into the extravascular space. Protein binding by ciprofloxacin is low (approx. 20-30%) and the substance is mostly found in a non-ionised form in the plasma. Therefore virtually the entire dose administered is free to diffuse into the extravascular space.
In addition, sub-cellular structures and certain physiological factors (e.g. pH in body fluids and tissues) may bring about a relative intracellular concentration of ciprofloxacin. This is how the concentrations in certain body fluids and tissues far surpass the corresponding serum levels.
Indications/Uses
Uncomplicated and complicated infections caused by ciprofloxacin 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 eyes; Infections of the kidneys and/or the efferent urinary tract; Infections of the genital organs, including adnexitis, gonorrhoea, and prostatitis; Infections of the abdominal cavity (e.g. infections of gastrointestinal tract or of the biliary tract, peritonitis); Infections of the skin and soft tissues; Infections of the bones and joints; Sepsis; Infections or imminent risk of infection (prophylaxis) in patients whose immune system has been weakened (e.g. patients on immunosuppressants or have neutropenia); Selective intestinal decontamination in immunocompromised patients.
Inhalation anthrax (post-exposure) in adults and in children: To reduce the incidence or progression of disease following exposure to aerosolised Bacillus anthracis.
Dosage/Direction for Use
To be taken orally, independent of mealtime. If the tablets are taken on an empty stomach, the active substance is absorbed more rapidly. In this case, 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, dietary calcium as part of a meal does not significantly affect the absorption of ciprofloxacin. 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. After intravenous administration the treatment can be continued orally.
Adults: Unless otherwise prescribed, the following guideline doses are recommended; (See Table 1.)

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Additional information on special patient population: Children and adolescents: Cystic Fibrosis: Clinical and pharmacokinetic data support the use of Ciprofloxacin in pediatric cystic fibrosis patients (aged 5-17 years) with broncho-pulmonary infections associated with Pseudomonas aeruginosa infection, at a dose of 20mg/kg body weight oral twice daily with a maximum of 750mg per dose or 10mg/kg body weight intravenous three times daily with a maximum of 400mg per dose.
Complicated Urinary Tract Infections and Pyelonephritis: For complicated urinary tract infections or pyelonephritis the dose is 10mg/kg body weight oral twice daily to 20mg/kg body weight oral twice daily with a maximum of 750mg per dose or 6mg/kg body weight intravenous three times daily to 10mg/kg body weight intravenous three times daily with a maximum of 400mg per dose.
Geriatric patients (> 65 years): Elderly patients should receive a dose as low as possible depending on the severity of their illness and the creatinine clearance.
Patients with renal and hepatic impairment: Adults: Impaired renal function: Patients with creatinine clearance between 30 and 60mL/min/1.73m2 (moderate renal impairment) or serum creatinine concentration between 1.4 and 1.9mg/100mL, the maximum daily dose should be 1000mg for oral administration or 800mg for an intravenous regimen.
Patients with creatinine clearance less than 30mL/min/1.73m2 (severe renal impairment) or serum creatinine concentration equal or higher than 2.0mg/100mL, the maximum daily dose should be 500mg for oral administration (all formulations) or 400mg for an intravenous regimen.
Impaired renal function and hemodialysis: Patients with creatinine clearance between 30 and 60mL/min/1.73m2 (moderate renal impairment) or serum creatinine concentration between 1.4 and 1.9mg/100mL, the maximum daily dose should be 1000mg for oral administration (all formulations) or 800mg for an intravenous regimen.
Patients with creatinine clearance less than 30mL/min/1.73m2 (severe renal impairment) or serum creatinine concentration equal or higher than 2.0mg/100mL, the maximum daily dose should be 500mg for oral administration (all formulations) or 400mg for an intravenous regimen on dialysis days after dialysis.
Impaired renal function and continuous ambulatory peritoneal dialysis (CAPD): Addition of ciprofloxacin infusion solution to the dialysate (intraperitoneal): 50mg ciprofloxacin/liter dialysate administered 4 times a day every 6 hours.
Administration of ciprofloxacin film-coated tablets (oral) as 1 x 500mg film-coated tablet (or 2 x 250mg film-coated tablets).
Impaired liver function: No dose adjustment is required.
Impaired renal and liver function: Patients with creatinine clearance between 30 and 60 mL/min/1.73m2 (moderate renal impairment) or serum creatinine concentration between 1.4 and 1.9mg/100mL, the maximum daily dose should be 1000mg for oral administration (all formulations) or 800mg for an intravenous regimen.
Patients with creatinine clearance less than 30mL/min/1.73m2 (severe renal impairment) or serum creatinine concentration equal or higher than 2.0mg/100mL, the maximum daily dose should be 500mg for oral administration (all formulations) or 400mg for an intravenous regimen.
Children and adolescents: Dosing in children with impaired renal and or hepatic function has not been studied.
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; and 7-14 days in all other infections.
In streptococcal infections, the treatment must last at least ten days because of the risk of late complications. Infections caused by Chlamydia should also be treated for a minimum of ten days.
Children and adolescents: Cystic Fibrosis: For broncho-pulmonary infections of cystic fibrosis associated with Pseudomonas aeruginosa infection in pediatric patients (aged 5-17 years), the duration of treatment is 10-14 days.
Complicated Urinary Tract Infections and Pyelonephritis: For complicated urinary tract infections or pyelonephritis due to Escherichia coli, the duration of treatment is 10-21 days.
Inhalational Anthrax (Post-exposure) in Adults and Children Adults: Oral administration: 500mg twice daily.
Children: Oral administration: 15mg/kg twice daily. The maximum of 500mg per dose should not be exceeded (maximum daily dose of 1000mg).
60 days from the confirmation of Bacillus anthracis exposure.
Overdosage
In the event of acute, excessive oral over dosage, reversible renal toxicity has been reported in some cases. Therefore, apart from routine emergency measures, it is recommended to monitor renal function and to administer Magnesium or Calcium 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.
Contraindications
Ciprofloxacin must not be used in cases of hypersensitivity to ciprofloxacin or other quinolone chemotherapeutics or any of the excipients. Concurrent administration of ciprofloxacin and tizanidine is contraindicated since an undesirable increase in the serum tizanidine concentrations associated with clinically relevant tizanidine-induced side effects (hypotension, somnolence, and drowsiness) can occur.
Special Precautions
Hypersensitivity: In some instances, the hypersensitivity and allergic reactions already occurred after the first administration and the doctor should be informed immediately. Anaphylactic/anaphylactoid reactions in very rare instances can progress to a life threatening shock, in some instances after the first administration. In these cases Ciprofloxacin has to be discontinued, medical treatment (e.g. treatment for shock) is required.
Cytochrome P450: Ciprofloxacin is known to be moderate inhibitor of the CYP 450 1A2 enzymes. Care should be taken when other drugs are administered concomitantly which are metabolized via the same enzymatic pathway (e.g theophylline, methylxantines, caffeins, duloxetine, clozapine). Increased plasma concentrations associated with drug specific side effects may be observed due to inhibitions of their metabolic clearance by ciprofloxacin.
Gastrointestinal system: 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 (life threatening pseudomembranous colitis with possible fatal outcome), requiring immediate treatment. In such cases Ciprofloxacin must be discontinued and appropriate therapy initiated (e.g. vancomycin, orally, 4 x 250mg / day). Drugs that inhibit peristalsis are contraindicated. There can be a temporary increases in transaminases, alkaline phosphatase or cholestatic jaundice, especially in patients with previous liver damage.
Nervous system: In epileptics and in patients who have suffered from previous CNS-disorders (e.g lowered convulsion threshold, previous history of convulsion, reduced cerebral blood flow, altered brain structure/stroke), ciprofloxacin should only be used where the benefits of treatment exceed the risks, since these patients are endangered because of possible central-nervous side effects. In some instances the CNS reactions occurred after the first administration of Ciprofloxacin already. In rare cases depression or psychosis can progress to self-endangering behavior. In these cases Ciprofloxacin has to be discontinued and the doctor should be informed immediately.
Musculo-skeletal system: The risk of developing fluroquinolone-associated tendonitis and tendon rupture is further increased in people older than 60, in those taking corticosteroid drugs, and in kidney, heart, and lung transplant recipients. Patients experiencing pain, swelling, inflammation of a tendon or tendon rupture should be advised to stop taking their fluoroquinolone medication (to specify the active ingredient) and to contact their health care professional promptly about changing their antimicrobial therapy. Patients should also avoid exercise and using the affected area at the first sign of tendon pain, swelling or inflammation.
Skin and appendages: Ciprofloxacin has been shown to produce photosensitivity reactions. Patients taking Ciprofloxacin should avoid direct exposure to excessive sunlight or UV-light. Therapy should be discontinued if photosensitation (i.e. sunburn-like skin reactions) occurs.
Exacerbation of myasthenia gravis: Fluoroquinolones have neuromuscular blocking activity and may exacerbate muscle weakness in person with myasthenia gravis. Post marketing serious adverse events, including deaths and requirement for ventilator support have been associated with fluoraquinolones use in persons with myasthenia gravis. Avoid fluoroquinolones in patients with known history of myasthenia gravis.
Effects on ability to drive and use machines: Even when the drug is taken exactly as prescribed, it can affect the speed of reaction to such as extent that the ability to drive or to operate machinery is impaired. This applies particularly in combination with alcohol.
Use in Pregnancy and Lactation: Ciprofloxacin must not be prescribed for pregnant women or nursing mothers, since there is no experience on the drug's safety in these patient groups and since, on the basis of animal studies, it is not entirely improbable that the drug could cause damage to articular cartilage in the immature organism. Animal studies have not shown any evidence of teratogenic effects (malformations).
Use in Children: As with drugs in its class, ciprofloxacin has been shown to cause arthropathy in weight-bearing joints of immature animals. The analysis of available safety data from ciprofloxacin use in patients less than 18 years of age, the majority of whom had cystic fibrosis, did not disclose any evidence of drug related cartilage or articular damage. The use of ciprofloxacin for indications other than for the use in inhalational anthrax (post-exposure) is not recommended. For other indications clinical experience is limited. For the indication of inhalational anthrax (post-exposure), the risk-benefit assessment indicates that administration of ciprofloxacin to pediatric patients is appropriate.
Use In Pregnancy & Lactation
Ciprofloxacin must not be prescribed for pregnant women or nursing mothers, since there is no experience on the drug's safety in these patient groups and since, on the basis of animal studies, it is not entirely improbable that the drug could cause damage to articular cartilage in the immature organism. Animal studies have not shown any evidence of teratogenic effects (malformations).
Side Effects
(See Table 2.)

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The undesirable effects as follows have a higher frequency category in the subgroups of patients receiving intravenous or sequential (intravenous to oral) treatment: (See Table 3.)

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Drug Interactions
Chelation Complex Formulation: The simultaneous administration of ciprofloxacin (oral) and multivalent cation-containing drugs and mineral supplements (e.g. calcium, magnesium, aluminium, iron), polymeric phosphate binders (e.g. sevelamer), sucralfate or antacids and highly buffered drugs (e.g. didanosine tablets), containing magnesium, aluminium or calcium reduce the absorption of ciprofloxacin. Consequently, ciprofloxacin should be administered either 1-2 hours before or at least 4 hours after these preparations. The restriction does not apply to antacids belonging to the class of H2 receptors blockers.
Food and Dairy Products: The concurrent administration of dairy products or mineral fortified drinks alone (e.g. milk, yoghurt, calcium fortified orange juice) and ciprofloxacin should be avoided because absorption of ciprofloxacin may be reduced. Dietary calcium as part of a meal, however, does not significantly affect absorption.
Omeprazole: Concomitant administration of ciprofloxacin and omeprazole results in a slight reduction of Cmax and AUC of ciprofloxacin.
Theophylline: Concurrent administration of ciprofloxacin and theophylline can cause an undesirable increase in the serum theophylline concentration. This can lead to theophylline-induced side effects in very rare cases these side effects can be life threatening or fatal. If concurrent use of the two products is unavoidable, the serum theophylline concentration should therefore be checked and theophylline dose appropriately reduced.
NSAIDs: Animal studies have shown that the combination of very high doses of quinolones (gyrase inhibitors) and certain non-steroidal anti-inflammatory agents (but not acetylsalicylic acid) can provoke convulsions.
Cyclosporin: A transient rise in the concentration of serum creatinine was observed when ciprofloxacin and cyclosporine were administered simultaneously. Therefore, it is necessary to control the serum creatinine concentrations in these patients frequently (twice a week).
Warfarin: The simultaneous administration of ciprofloxacin and warfarin may intensify the action of warfarin.
Glibenclamide: In particular cases, concurrent administration of ciprofloxacin and glibenclamide can intensify the action of glibenclamide (hypoglycaemia).
Probenecid: Probenecid interferes with renal secretion. Co-administration of probenecid and ciprofloxacin increases the ciprofloxacin serum concentrations.
Methotrexate: Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin potentially leading to increased plasma levels of methotrexate. This might increase the risk of methotrexate associated toxic reactions, therefore the concomitant use is not recommended.
Metoclopramide: Metoclopramide accelerates the absorption of ciprofloxacin (oral) resulting in a shorter time to reach maximum plasma concentrations. No effect was seen on the bioavailability of ciprofloxacin.
Tizanidine: In a clinical study in healthy subjects there was an increase in tizanidine serum concentrations (Cmax increase: 7-fold, range: 4 to 21-fold; AUC increase: 10-fold, range: 6 to 24-fold) when given concomitantly with ciprofloxacin. Associated with the increased serum concentrations was a potentiated hypotensive and sedative effects. Tizanidine must not be administered together with ciprofloxacin.
Duloxetine: In clinical studies it was demonstrated that the concomitant use of duloxetine with strong inhibitors of the CYP450 1A2 isoeyme such as fluvoxamine, may result in an increase of AUC and Cmax of duloxetine. Although no clinical data are available on a possible interaction with ciprofloxacin, similar effects can be expected upon concomitant administration.
Ropinirole: In a clinical study it was shown that concomitant use of ropinirole with ciprofloxacin, a medium inhibitor of the CYP450 1A2 isozyme, resulted in increases in the Cmax and AUC of ropinirole of 60 and 84% respectively. Although ropinirole treatment was well tolerated, case reports that a possible interaction with ciprofloxacin associated with side effects may occur upon concomitant administration.
Lidocaine: It was demonstrated in healthy subjects that concomitant use of lidocaine with ciprofloxacin, a moderate inhibitor of CYP450 1A2 isoeyme, reduces clearance of intravenous lidocaine by 22%. Although lidocaine treatment was well tolerated, a possible interaction with ciprofloxacin associated with side effects may occur upon concomitant administration.
Clozapine: Following concomitant administration of 250mg Ciprofloxacin for 7 days, serum concentration of clozapine and N-desmethylclozapnie were increased by 29% and 31%, respectively.
Storage
Store below 30°C. Protect from light.
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 (round, white, embossed with the word '
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'on one side and score line on the reverse line) x 10 x 10's. 500 mg (white, capsule shaped, embossed with the word '
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' on one side and score line on the reverse line) x 10 x 10's.
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