Ciproxin施博善

Ciproxin

ciprofloxacin

Manufacturer:

Bayer

Distributor:

Zuellig
/
Four Star
Full Prescribing Info
Contents
Ciprofloxacin.
Description
Film-coated tablet: Each film-coated tablet contains 250 mg ciprofloxacin (as hydrochloride).
The tablets can be divided into equal doses.
Infusion: Each glass bottle with 100mL infusion solution contains 200mg ciprofloxacin. The sodium chloride content is 900 mg (15.4 mmol).
Each glass bottle with 200 mL infusion solution contains 400 mg ciprofloxacin. The sodium chloride content is 1800 mg (30.8 mmol).
The pH-value of the solution for infusion ranges from 3.9 to 4.5.
Excipients/Inactive Ingredients: Film-coated tablet: Tablet core: Cellulose microcrystalline, Crospovidone, Maize starch, Magnesium stearate, Silica colloidal anhydrous.
Film-coat: Hypromellose, Macrogol 4000, Titanium dioxide (E171).
Infusion: Lactic acid solution 20 %, Sodium chloride, Hydrochloric acid concentrated, Water for injections.
Action
Pharmacotherapeutic group: Fluoroquinolones. ATC code: J01MA02.
Pharmacology: Pharmacodynamics: Mechanism of action: As a fluoroquinolone antibacterial agent, the bactericidal action of ciprofloxacin results from the inhibition of both type II topoisomerase (DNA-gyrase) and topoisomerase IV, required for bacterial DNA replication, transcription, repair and recombination.
Pharmacokinetic/pharmacodynamic relationship: Efficacy mainly depends on the relation between the maximum concentration in serum (Cmax) and the minimum inhibitory concentration (MIC) of ciprofloxacin for a bacterial pathogen and the relation between the area under the curve (AUC) and the MIC.
Mechanism of resistance: In-vitro resistance to ciprofloxacin can be acquired through a stepwise process by target site mutations in both DNA gyrase and topoisomerase IV. The degree of cross-resistance between ciprofloxacin and other fluoroquinolones that results is variable. Single mutations may not result in clinical resistance, but multiple mutations generally result in clinical resistance to many or all active substances within the class. Impermeability and/or active substance efflux pump mechanisms of resistance may have a variable effect on susceptibility to fluoroquinolones, which depends on the physiochemical properties of the various active substances within the class and the affinity of transport systems for each active substance. All in-vitro mechanisms of resistance are commonly observed in clinical isolates. Resistance mechanisms that inactivate other antibiotics such as permeation barriers (common in Pseudomonas aeruginosa) and efflux mechanisms may affect susceptibility to ciprofloxacin.
Plasmid-mediated resistance encoded by qnr-genes has been reported.
Spectrum of antibacterial activity: Breakpoints separate susceptible strains from strains with intermediate susceptibility and the latter from resistant strains: EUCAST Recommendations: See Table 1.

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The prevalence of acquired resistance may vary geographically and with time for selected species and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.
Groupings of relevant species according to ciprofloxacin susceptibility (for Streptococcus species see Precautions). (See Table 2.)

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Pharmacokinetics: Absorption: Film-coated tablet: Following oral administration of single doses of 250 mg, 500 mg, and 750 mg of ciprofloxacin tablets, ciprofloxacin is absorbed rapidly and extensively, mainly from the small intestine, reaching maximum serum concentrations 1-2 hours later.
Single doses of 100-750 mg produced dose-dependent maximum serum concentrations (Cmax) between 0.56 and 3.7 mg/L. Serum concentrations increase proportionately with doses up to 1000 mg.
The absolute bioavailability is approximately 70-80%.
A 500 mg oral dose given every 12 hours has been shown to produce an area under the serum concentration-time curve (AUC) equivalent to that produced by an intravenous infusion of 400 mg ciprofloxacin given over 60 minutes every 12 hours.
Infusion: Following an intravenous infusion of ciprofloxacin the mean maximum serum concentrations were achieved at the end of infusion. Pharmacokinetics of ciprofloxacin were linear over the dose range up to 400 mg administered intravenously.
Comparison of the pharmacokinetic parameters for a twice a day and three times a day intravenous dose regimen indicated no evidence of drug accumulation for ciprofloxacin and its metabolites.
A 60-minute intravenous infusion of 200 mg ciprofloxacin or the oral administration of 250 mg ciprofloxacin, both given every 12 hours, produced an equivalent area under the serum concentration time curve (AUC).
A 60-minute intravenous infusion of 400 mg ciprofloxacin every 12 hours was bioequivalent to a 500 mg oral dose every 12 hours with regard to AUC.
The 400 mg intravenous dose administered over 60 minutes every 12 hours resulted in a Cmax similar to that observed with a 750 mg oral dose.
A 60-minute infusion of 400 mg ciprofloxacin every 8 hours is equivalent with respect to AUC to 750 mg oral regimen given every 12 hours.
Distribution: Protein binding of ciprofloxacin is low (20-30%). Ciprofloxacin is present in plasma largely in a non-ionised form and has a large steady state distribution volume of 2-3 L/kg body weight. Ciprofloxacin reaches high concentrations in a variety of tissues such as lung (epithelial fluid, alveolar macrophages, biopsy tissue), sinuses, inflamed lesions (cantharides blister fluid), and the urogenital tract (urine, prostate, endometrium) where total concentrations exceeding those of plasma concentrations are reached.
Biotransformation: Low concentrations of four metabolites have been reported, which were identified as: desethyleneciprofloxacin (M 1), sulphociprofloxacin (M 2), oxociprofloxacin (M 3) and formylciprofloxacin (M 4). The metabolites display in-vitro antimicrobial activity but to a lower degree than the parent compound.
Ciprofloxacin is known to be a moderate inhibitor of the CYP 450 1A2 iso-enzyme.
Elimination: Film-coated tablet: Ciprofloxacin is largely excreted unchanged both renally and, to a smaller extent, faecally. The serum elimination half-life in subjects with normal renal function is approximately 4-7 hours. (See Table 3.)

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Infusion: Ciprofloxacin is largely excreted unchanged both renally and, to a smaller extent, faecally. (See Table 4.)

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Renal clearance is between 180-300 mL/kg/h and the total body clearance is between 480-600 mL/kg/h. Ciprofloxacin undergoes both glomerular filtration and tubular secretion. Severely impaired renal function leads to increased half lives of ciprofloxacin of up to 12 h.
Non-renal clearance of ciprofloxacin is mainly due to active trans-intestinal secretion and metabolism. 1% of the dose is excreted via the biliary route. Ciprofloxacin is present in the bile in high concentrations.
Paediatric patients: The pharmacokinetic data in paediatric patients are limited.
In a study in children Cmax and AUC were not age-dependent (above one year of age). No notable increase in Cmax and AUC upon multiple dosing (10 mg/kg three times daily) was observed.
In 10 children with severe sepsis Cmax was 6.1 mg/L (range 4.6-8.3 mg/L) after a 1-hour intravenous infusion of 10 mg/kg in children aged less than 1 year compared to 7.2 mg/L (range 4.7-11.8 mg/L) for children between 1 and 5 years of age. The AUC values were 17.4 mg*h/L (range 11.8-32.0 mg*h/L) and 16.5 mg*h/L (range 11.0-23.8 mg*h/L) in the respective age groups.
These values are within the range reported for adults at therapeutic doses. Based on population pharmacokinetic analysis of paediatric patients with various infections, the predicted mean half-life in children is approx. 4-5 hours and the bioavailability of the oral suspension ranges from 50 to 80%.
Toxicology: Preclinical safety data: Non-clinical data reveal no special hazards for humans based on conventional studies of single dose toxicity, repeated dose toxicity, carcinogenic potential, or toxicity to reproduction.
Like a number of other quinolones, ciprofloxacin is phototoxic in animals at clinically relevant exposure levels. Data on photomutagenicity/ photocarcinogenicity show a weak photomutagenic or phototumorigenic effect of ciprofloxacin in-vitro and in animal experiments. This effect was comparable to that of other gyrase inhibitors.
Articular tolerability: As reported for other gyrase inhibitors, ciprofloxacin causes damage to the large weight-bearing joints in immature animals. The extent of the cartilage damage varies according to age, species and dose; the damage can be reduced by taking the weight off the joints. Studies with mature animals (rat, dog) revealed no evidence of cartilage lesions. In a study in young beagle dogs, ciprofloxacin caused severe articular changes at therapeutic doses after two weeks of treatment, which were still observed after 5 months.
Indications/Uses
Ciproxin Tab 250 mg/Ciproxin Infusion IV 0.2% is indicated for the treatment of the following infections (see Precautions and Pharmacology: Pharmacodynamics under Actions).
Special attention should be paid to available information on resistance to ciprofloxacin before commencing therapy.
Consideration should be given to official guidance on the appropriate use of antibacterial agents.
Adults: Lower respiratory tract infections due to Gram-negative bacteria: exacerbation of chronic obstructive pulmonary disease - in exacerbation of chronic obstructive pulmonary disease Ciproxin Tab 250 mg/Ciproxin Infusion IV 0.2% should be used only when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the treatment of these infections; broncho-pulmonary infections in cystic fibrosis or in bronchiectasis; pneumonia.
Chronic suppurative otitis media.
Acute exacerbation of chronic sinusitis especially if these are caused by Gram-negative bacteria.
Urinary tract infections: Uncomplicated acute cystitis - in uncomplicated acute cystitis Ciproxin Tab 250 mg should be used only when it is considered inappropriate to use other antibacterial agents that are commonly recommended for the treatment of these infections; Acute pyelonephritis; Complicated urinary tract infections; Bacterial prostatitis.
Genital tract infections: gonococcal urethritis and cervicitis due to susceptible Neisseria gonorrhoeae (tab only); epididymo-orchitis including cases due to susceptible Neisseria gonorrhoeae; pelvic inflammatory disease including cases due to susceptible Neisseria gonorrhoeae.
Infections of the gastro-intestinal tract (e.g. travellers' diarrhoea).
Intra-abdominal infections.
Infections of the skin and soft tissue caused by Gram-negative bacteria.
Malignant external otitis.
Infections of the bones and joints.
Prophylaxis of invasive infections due to Neisseria meningitidis (tab only).
Inhalation anthrax (post-exposure prophylaxis and curative treatment).
Ciprofloxacin may be used in the management of neutropenic patients with fever that is suspected to be due to a bacterial infection.
Children and adolescents: Broncho-pulmonary infections due to Pseudomonas aeruginosa in patients with cystic fibrosis.
Complicated urinary tract infections and acute pyelonephritis.
Inhalation anthrax (post-exposure prophylaxis and curative treatment).
Ciprofloxacin may also be used to treat severe infections in children and adolescents when this is considered to be necessary.
Treatment should be initiated only by physicians who are experienced in the treatment of cystic fibrosis and/or severe infections in children and adolescents (see Precautions and Pharmacology: Pharmacodynamics under Actions).
Dosage/Direction for Use
Posology: The dosage is determined by the indication, the severity and the site of the infection, the susceptibility to ciprofloxacin of the causative organism(s), the renal function of the patient and, in children and adolescents the body weight.
The duration of treatment depends on the severity of the illness and on the clinical and bacteriological course.
After intravenous initiation of treatment, the treatment can be switched to oral treatment with tablet or suspension if clinically indicated at the discretion of the physician. IV treatment should be followed by oral route as soon as possible.
In severe cases or if the patient is unable to take tablets (e.g. patients on enteral nutrition), it is recommended to commence therapy with intravenous ciprofloxacin until a switch to oral administration is possible.
Treatment of infections due to certain bacteria (e.g. Pseudomonas aeruginosa, Acinetobacter or Staphylococci) may require higher ciprofloxacin doses and co-administration with other appropriate antibacterial agents.
Treatment of some infections (e.g. pelvic inflammatory disease, intra-abdominal infections, infections in neutropenic patients and infections of bones and joints) may require co-administration with other appropriate antibacterial agents depending on the pathogens involved.
Film-coated tablet: Adults: See Table 5.

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Paediatric population: See Table 6.

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Elderly patients: Elderly patients should receive a dose selected according to the severity of the infection and the patient's creatinine clearance.
Patients with renal and hepatic impairment: Recommended starting and maintenance doses for patients with impaired renal function: See Table 7.

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In patients with impaired liver function no dose adjustment is required.
Dosing in children with impaired renal and/or hepatic function has not been studied.
Infusion: Adults: See Table 8.

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Paediatric population: See Table 9.

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Elderly patients: Elderly patients should receive a dose selected according to the severity of the infection and the patient's creatinine clearance.
Patients with renal and hepatic impairment: Recommended starting and maintenance doses for patients with impaired renal function: See Table 10.

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In patients with impaired liver function no dose adjustment is required.
Dosing in children with impaired renal and/or hepatic function has not been studied.
Method of administration: Film-coated tablet: Tablets are to be swallowed unchewed with fluid. They can be taken independent of mealtimes. If taken on an empty stomach, the active substance is absorbed more rapidly. Ciprofloxacin tablets should not be taken with dairy products (e.g. milk, yoghurt) or mineral-fortified fruit-juice (e.g. calcium-fortified orange juice) (see Interactions).
In severe cases or if the patient is unable to take tablets (e.g. patients on enteral nutrition), it is recommended to commence therapy with intravenous ciprofloxacin until a switch to oral administration is possible.
Infusion: Ciproxin Infusion IV 0.2% should be checked visually prior to use. It must not be used if cloudy.
Ciprofloxacin should be administered by intravenous infusion. For children, the infusion duration is 60 minutes.
In adult patients, infusion time is 60 minutes for 400 mg Ciproxin Infusion IV 0.2% and 30 minutes for 200 mg Ciproxin Infusion IV 0.2%. Slow infusion into a large vein will minimise 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 Special precautions for disposal and other handling under Cautions for Usage).
Overdosage
An overdose of 12 g has been reported to lead to mild symptoms of toxicity. An acute overdose of 16 g has been reported to cause acute renal failure.
Symptoms in overdose consist of dizziness, tremor, headache, tiredness, seizures, hallucinations, confusion, abdominal discomfort, renal and hepatic impairment as well as crystalluria and haematuria. Reversible renal toxicity has been reported.
Apart from routine emergency measures, e.g. ventricular emptying followed by medical carbon, it is recommended to monitor renal function, including urinary pH and acidify, if required, to prevent crystalluria. Patients should be kept well hydrated. Calcium or magnesium containing antacids may theoretically reduce the absorption of ciprofloxacin in overdoses.
Only a small quantity of ciprofloxacin (<10%) is eliminated by haemodialysis or peritoneal dialysis.
In the event of overdose, symptomatic treatment should be implemented. ECG monitoring should be undertaken, because of the possibility of QT interval prolongation.
Contraindications
Hypersensitivity to the active substance, to other quinolones or to any of the excipients listed in Description.
Concomitant administration of ciprofloxacin and tizanidine (see Interactions).
Special Precautions
The use of ciprofloxacin should be avoided in patients who have experienced serious adverse reactions in the past when using quinolone or fluoroquinolone containing products (see Adverse Reactions).
Treatment of these patients with Ciprofloxacin Bayer should only be initiated in the absence of alternative treatment options and after careful benefit/risk assessment (see also Contraindications).
Severe infections and mixed infections with Gram-positive and anaerobic pathogens: Ciprofloxacin monotherapy is not suited for treatment of severe infections and infections that might be due to Gram-positive or anaerobic pathogens. In such infections ciprofloxacin must be co-administered with other appropriate antibacterial agents.
Streptococcal Infections (including Streptococcus pneumoniae): Ciprofloxacin is not recommended for the treatment of streptococcal infections due to inadequate efficacy.
Genital tract infections: Gonococcal urethritis, cervicitis, epididymo-orchitis and pelvic inflammatory diseases may be caused by fluoroquinolone-resistant Neisseria gonorrhoeae isolates.
Therefore, ciprofloxacin should be administered for the treatment of gonococcal urethritis or cervicitis only if ciprofloxacin-resistant Neisseria gonorrhoeae can be excluded (tab only).
For epididymo-orchitis and pelvic inflammatory diseases, empirical ciprofloxacin should only be considered in combination with another appropriate antibacterial agent (e.g. a cephalosporin) unless ciprofloxacin-resistant Neisseria gonorrhoeae can be excluded. If clinical improvement is not achieved after 3 days of treatment, the therapy should be reconsidered.
Urinary tract infections: Resistance to fluoroquinolones of Escherichia coli - the most common pathogen involved in urinary tract infections - varies across the European Union. Prescribers are advised to take into account the local prevalence of resistance in Escherichia coli to fluoroquinolones.
Film-coated tablet: The single dose of ciprofloxacin, that may be used in uncomplicated cystitis in pre-menopausal women, is expected to be associated with lower efficacy than the longer treatment duration. This is all the more to be taken into account as regards the increasing resistance level of Escherichia coli to quinolones.
Intra-abdominal infections: There are limited data on the efficacy of ciprofloxacin in the treatment of post-surgical intra-abdominal infections.
Travellers' diarrhoea: The choice of ciprofloxacin should take into account information on resistance to ciprofloxacin in relevant pathogens in the countries visited.
Infections of the bones and joints: Ciprofloxacin should be used in combination with other antimicrobial agents depending on the results of the microbiological documentation.
Inhalational anthrax: Use in humans is based on in-vitro susceptibility data and on animal experimental data together with limited human data. Treating physicians should refer to national and/or international consensus documents regarding the treatment of anthrax.
Hypersensitivity: Hypersensitivity and allergic reactions, including anaphylaxis and anaphylactoid reactions, may occur following a single dose (see Adverse Reactions) and may be life-threatening. If such reaction occurs, ciprofloxacin should be discontinued and an adequate medical treatment is required.
Prolonged, disabling and potentially irreversible serious adverse drug reactions: Very rare cases of prolonged (continuing months or years), disabling and potentially irreversible serious adverse drug reactions affecting different, sometimes multiple, body systems (musculoskeletal, nervous, psychiatric and senses) have been reported in patients receiving quinolones and fluoroquinolones irrespective of their age and pre-existing risk factors. Ciprofloxacin Bayer should be discontinued immediately at the first signs or symptoms of any serious adverse reaction and patients should be advised to contact their prescriber for advice.
Tendinitis and tendon rupture: Ciprofloxacin should generally not be used in patients with a history of tendon disease/disorder related to quinolone treatment. Nevertheless, in very rare instances, after microbiological documentation of the causative organism and evaluation of the risk/benefit balance, ciprofloxacin may be prescribed to these patients for the treatment of certain severe infections, particularly in the event of failure of the standard therapy or bacterial resistance, where the microbiological data may justify the use of ciprofloxacin. Tendinitis and tendon rupture (especially but not limited to Achilles tendon), sometimes bilateral, may occur as early as within 48 hours of starting treatment with quinolones and fluoroquinolones and have been reported to occur even up to several months after discontinuation of treatment (see Adverse Reactions). The risk of tendinitis and tendon rupture is increased in older patients, patients with renal impairment, patients with solid organ transplants, and those treated concurrently with corticosteroids. Therefore, concomitant use of corticosteroids should be avoided.
At the first sign of tendinitis (e.g. painful swelling, inflammation) the treatment with Ciprofloxacin should be discontinued and alternative treatment should be considered. The affected limb(s) should be appropriately treated (e.g. immobilisation). Corticosteroids should not be used if signs of tendinopathy occur.
Patients with myasthenia gravis: Fluoroquinolones have neuromuscular blocking activity and may exacerbate muscle weakness in persons with myasthenia gravis. Postmarketing serious adverse events, including deaths and requirement for ventilator support, have been associated with fluoroquinolone use in persons with myasthenia gravis. Avoid fluoroquinolones in patients with known history of myasthenia gravis. (See Adverse Reactions.)
Vision disorders: If vision becomes impaired or any effects on the eyes are experienced, an eye specialist should be consulted immediately.
Photosensitivity: Ciprofloxacin has been shown to cause photosensitivity reactions. Patients taking ciprofloxacin should be advised to avoid direct exposure to either extensive sunlight or UV irradiation during treatment (see Adverse Reactions).
Seizures: Ciprofloxacin like other quinolones are known to trigger seizures or lower the seizure threshold. Cases of status epilepticus have been reported. Ciprofloxacin should be used with caution in patients with CNS disorders which may be predisposed to seizure. If seizures occur ciprofloxacin should be discontinued (see Adverse Reactions).
Peripheral neuropathy: Cases of sensory of sensorimotor polyneuropathy resulting in paraesthesia, hypaesthesia, dysesthesia, or weakness have been reported in patients receiving quinolones and fluoroquinolones. Patients under treatment with Ciprofloxacin should be advised to inform their doctor prior to continuing treatment if symptoms of neuropathy, such as pain, burning, tingling, numbness, or weakness develop in order to prevent the development of potentially irreversible condition (see Adverse Reactions).
Psychiatric reactions: Psychiatric reactions may occur even after first administration of ciprofloxacin. In rare cases, depression or psychosis can progress to suicidal ideations/thoughts culminating in attempted suicide or completed suicide. In the occurrence of such cases, ciprofloxacin should be discontinued.
Cardiac disorders: Caution should be taken when using fluoroquinolones, including ciprofloxacin, in patients with known risk factors for prolongation of the QT interval such as, for example: congenital long QT syndrome; concomitant use of drugs that are known to prolong the QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics); uncorrected electrolyte imbalance (e.g. hypokalaemia, hypomagnesaemia); cardiac disease (e.g. heart failure, myocardial infarction, bradycardia).
Elderly patients and women may be more sensitive to QTc-prolonging medications. Therefore, caution should be taken when using fluoroquinolones, including ciprofloxacin, in these populations. (See Elderly patients under Dosage & Administration, Interactions, Adverse Reactions, Overdosage).
Dysglycaemia: As with all quinolones, disturbances in blood glucose, including both hypoglycaemia and hyperglycaemia have been reported (see Adverse Reactions), usually in elderly diabetic patients receiving concomitant treatment with an oral hypoglycaemic agent (e.g. glibenclamide) or with insulin. Cases of hypoglycaemic coma have been reported. In diabetic patients, careful monitoring of blood glucose is recommended.
Gastrointestinal System: The occurrence of severe and persistent diarrhoea during or after treatment (including several weeks after treatment) may indicate an antibiotic-associated colitis (life-threatening with possible fatal outcome), requiring immediate treatment (see Adverse Reactions). In such cases, ciprofloxacin should immediately be discontinued, and an appropriate therapy initiated. Anti-peristaltic drugs are contraindicated in this situation.
Renal and urinary system: Crystalluria related to the use of ciprofloxacin has been reported (see Adverse Reactions). Patients receiving ciprofloxacin should be well hydrated and excessive alkalinity of the urine should be avoided.
Impaired renal function: Since ciprofloxacin is largely excreted unchanged via renal pathway dose adjustment is needed in patients with impaired renal function as described in Dosage & Administration to avoid an increase in adverse drug reactions due to accumulation of ciprofloxacin.
Hepatobiliary system: Cases of hepatic necrosis and life-threatening hepatic failure have been reported with ciprofloxacin (see Adverse Reactions). In the event of any signs and symptoms of hepatic disease (such as anorexia, jaundice, dark urine, pruritus, or tender abdomen), treatment should be discontinued.
Glucose-6-phosphate dehydrogenase deficiency: Haemolytic reactions have been reported with ciprofloxacin in patients with glucose-6-phosphate dehydrogenase deficiency. Ciprofloxacin should be avoided in these patients unless the potential benefit is considered to outweigh the possible risk. In this case, potential occurrence of haemolysis should be monitored.
Resistance: During or following a course of treatment with ciprofloxacin bacteria that demonstrate resistance to ciprofloxacin may be isolated, with or without a clinically apparent superinfection. There may be a particular risk of selecting for ciprofloxacin-resistant bacteria during extended durations of treatment and when treating nosocomial infections and/or infections caused by Staphylococcus and Pseudomonas species.
Cytochrome P450: Ciprofloxacin inhibits CYP1A2 and thus may cause increased serum concentration of concomitantly administered substances metabolised by this enzyme (e.g. theophylline, clozapine, olanzapine, ropinirole, tizanidine, duloxetine, agomelatine). Therefore, patients taking these substances concomitantly with ciprofloxacin should be monitored closely for clinical signs of overdose, and determination of serum concentrations (e.g. of theophylline) may be necessary (see Interactions). Co-administration of ciprofloxacin and tizanidine is contraindicated.
Methotrexate: The concomitant use of ciprofloxacin with methotrexate is not recommended (see Interactions).
Interaction with tests: The in-vitro activity of ciprofloxacin against Mycobacterium tuberculosis might give false negative bacteriological test results in specimens from patients currently taking ciprofloxacin.
Aortic aneurysm and dissection: Epidemiologic studies report an increased risk of aortic aneurysm and dissection after intake of fluoroquinolones, particularly in the older population.
Therefore, fluoroquinolones should only be used after careful benefit-risk assessment and after consideration of other therapeutic options in patients with positive family history of aneurysm disease, or in patients diagnosed with pre-existing aortic aneurysm and/or aortic dissection, or in presence of other risk factors or conditions predisposing for aortic aneurysm and dissection (e.g., Marfan syndrome, vascular Ehlers-Danlos syndrome, Takayasu arteritis, giant cell arteritis, Behcet's disease, hypertension, known atherosclerosis).
In case of sudden abdominal, chest or back pain, patients should be advised to immediately consult a physician in an emergency department.
Effects on ability to drive and use machines: Due to its neurological effects, ciprofloxacin may affect reaction time. Thus, the ability to drive or to operate machinery may be impaired.
Use in Children: The use of ciprofloxacin in children and adolescents should follow available official guidance. Ciprofloxacin treatment should be initiated only by physicians who are experienced in the treatment of cystic fibrosis and/or severe infections in children and adolescents.
Ciprofloxacin has been shown to cause arthropathy in weight-bearing joints of immature animals. Safety data from a randomised double-blind study on ciprofloxacin use in children (ciprofloxacin: n=335, mean age = 6.3 years; comparators: n=349, mean age = 6.2 years; age range = 1 to 17 years) revealed an incidence of suspected drug-related arthropathy (discerned from joint-related clinical signs and symptoms) by Day +42 of 7.2% and 4.6%. Respectively, an incidence of drug-related arthropathy by 1-year follow-up was 9.0% and 5.7%. The increase of suspected drug-related arthropathy cases over time was not statistically significant between groups. Treatment should be initiated only after a careful benefit/risk evaluation, due to possible adverse events related to joints and/or surrounding tissue (see Adverse Reactions).
Broncho-pulmonary infections in cystic fibrosis: Clinical trials have included children and adolescents aged 5-17 years. More limited experience is available in treating children between 1 and 5 years of age.
Complicated urinary tract infections and pyelonephritis: Ciprofloxacin treatment of urinary tract infections should be considered when other treatments cannot be used, and should be based on the results of the microbiological documentation.
Clinical trials have included children and adolescents aged 1-17 years.
Other specific severe infections: Other severe infections in accordance with official guidance, or after careful benefit-risk evaluation when other treatments cannot be used, or after failure to conventional therapy and when the microbiological documentation can justify a ciprofloxacin use.
The use of ciprofloxacin for specific severe infections other than those mentioned above has not been evaluated in clinical trials and the clinical experience is limited. Consequently, caution is advised when treating patients with these infections.
Infusion: Injection Site Reaction: Local intravenous site reactions have been reported with the intravenous administration of ciprofloxacin. These reactions are more frequent if the infusion time is 30 minutes or less. 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.
NaCl Load: In patients for whom sodium intake is of medical concern (patients with congestive heart failure, renal failure, nephrotic syndrome, etc.), the additional sodium load should be taken into account (for sodium chloride content, see Description).
Use In Pregnancy & Lactation
Pregnancy: The data that are available on administration of ciprofloxacin to pregnant women indicates no malformative or feto/neonatal toxicity of ciprofloxacin. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. In juvenile and prenatal animals exposed to quinolones, effects on immature cartilage have been observed, thus, it cannot be excluded that the drug could cause damage to articular cartilage in the human immature organism / foetus (see Toxicology: Preclinical safety data under Actions). As a precautionary measure, it is preferable to avoid the use of ciprofloxacin during pregnancy.
Breast-feeding: Ciprofloxacin is excreted in breast milk. Due to the potential risk of articular damage, ciprofloxacin should not be used during breast-feeding.
Adverse Reactions
The most commonly reported adverse drug reactions (ADRs) are nausea, diarrhoea, vomiting, transient increase in transaminases, rash, and injection and infusion site reactions.
ADRs derived from clinical studies and post-marketing surveillance with Ciproxin (oral, intravenous and sequential therapy) sorted by categories of frequency are listed as follows. The frequency analysis takes into account data from both oral and intravenous administration of ciprofloxacin. (See Table 11.)

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The following undesirable effects have a higher frequency category in the subgroups of patients receiving intravenous or sequential (intravenous to oral) treatment: See Table 12.

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Paediatric population: The incidence of arthropathy (arthralgia, arthritis), mentioned previously, is referring to data collected in studies with adults. In children, arthropathy is reported to occur commonly (see Precautions).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.
Drug Interactions
Effects of other products on ciprofloxacin: Drugs known to prolong QT interval: Ciprofloxacin, like other fluoroquinolones, should be used with caution in patients receiving drugs known to prolong QT interval (e.g. Class IA and III anti-arrhythmics, tricyclic antidepressants, macrolides, antipsychotics) (see Precautions).
Probenecid: Probenecid interferes with renal secretion of ciprofloxacin. Co-administration of probenecid and ciprofloxacin increases ciprofloxacin serum concentrations.
Film-coated tablet: Chelation Complex Formation: 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 or lanthanum carbonate), sucralfate or antacids, and highly buffered drugs (e.g. didanosine tablets) containing magnesium, aluminium, or calcium reduces 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 receptor blockers.
Food and Dairy Products: Dietary calcium as part of a meal does not significantly affect absorption. However, the concurrent administration of dairy products or mineral-fortified drinks alone (e.g. milk, yoghurt, calcium-fortified orange juice) with ciprofloxacin should be avoided because absorption of ciprofloxacin may be reduced.
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.
Omeprazole: Concomitant administration of ciprofloxacin and omeprazole containing medicinal products results in a slight reduction of Cmax and AUC of ciprofloxacin.
Effects of ciprofloxacin on other medicinal products: Tizanidine: Tizanidine must not be administered together with ciprofloxacin (see Contraindications). In a clinical study with healthy subjects, there was an increase in serum tizanidine concentration (Cmax increase: 7-fold, range: 4 to 21-fold; AUC increase: 10-fold, range: 6 to 24-fold) when given concomitantly with ciprofloxacin. Increased serum tizanidine concentration is associated with a potentiated hypotensive and sedative effect.
Methotrexate: Renal tubular transport of methotrexate may be inhibited by concomitant administration of ciprofloxacin, potentially leading to increased plasma levels of methotrexate and increased risk of methotrexate-associated toxic reactions. The concomitant use is not recommended (see Precautions).
Theophylline: Concurrent administration of ciprofloxacin and theophylline can cause an undesirable increase in serum theophylline concentration. This can lead to theophylline-induced side effects that may rarely be life threatening or fatal. During the combination, serum theophylline concentrations should be checked and the theophylline dose reduced as necessary (see Precautions).
Other xanthine derivatives: On concurrent administration of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline), raised serum concentrations of these xanthine derivatives were reported.
Phenytoin: Simultaneous administration of ciprofloxacin and phenytoin may result in increased or reduced serum levels of phenytoin such that monitoring of drug levels is recommended.
Cyclosporin: A transient rise in the concentration of serum creatinine was observed when ciprofloxacin and cyclosporin containing medicinal products were administered simultaneously. Therefore, it is frequently (twice a week) necessary to control the serum creatinine concentrations in these patients.
Vitamin K antagonists: Simultaneous administration of ciprofloxacin with a vitamin K antagonist may augment its anti-coagulant effects. The risk may vary with the underlying infection, age and general status of the patient so that the contribution of ciprofloxacin to the increase in INR (international normalised ratio) is difficult to assess.
The INR should be monitored frequently during and shortly after co-administration of ciprofloxacin with a vitamin K antagonist (e.g., warfarin, acenocoumarol, phenprocoumon, or fluindione).
Duloxetine: In clinical studies, it was demonstrated that concomitant use of duloxetine with strong inhibitors of the CYP450 1A2 isozyme 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 (see Precautions).
Ropinirole: It was shown in a clinical study that concomitant use of ropinirole with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isozyme, results in an increase of Cmax and AUC of ropinirole by 60% and 84%, respectively. Monitoring of ropinirole-related side effects and dose adjustment as appropriate is recommended during and shortly after co-administration with ciprofloxacin (see Precautions).
Lidocaine: It was demonstrated in healthy subjects that concomitant use of lidocaine containing medicinal products with ciprofloxacin, a moderate inhibitor of CYP450 1A2 isozyme, 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 250 mg ciprofloxacin with clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Clinical surveillance and appropriate adjustment of clozapine dosage during and shortly after co-administration with ciprofloxacin are advised (see Precautions).
Sildenafil: Cmax and AUC of sildenafil were increased approximately twofold in healthy subjects after an oral dose of 50 mg given concomitantly with 500 mg ciprofloxacin. Therefore, caution should be used prescribing ciprofloxacin concomitantly with sildenafil taking into consideration the risks and the benefits.
Agomelatine: Clinical studies have shown that fluvoxamine, a potent inhibitor of the CYP450 1A2 isoenzyme, markedly inhibits agomelatine metabolism. This leads to a 60-fold increase in agomelatine exposure. There are no clinical data concerning the interaction with ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme. However, co-administration is expected to produce similar effects (see Precautions).
Zolpidem: Co-administration of ciprofloxacin and zolpidem can lead to increased blood zolpidem levels. Co-administration is therefore not recommended.
Caution For Usage
Film-coated tablet: Incompatibilities: Not applicable.
Infusion: Special precautions for disposal and other handling: The ciprofloxacin infusion solution is compatible with Ringer solution, Ringer lactate solution, 5 % and 10 % glucose solutions, and 5 % and 10 % fructose solutions. When ciprofloxacin infusion solutions are mixed with compatible infusion solutions, for microbial reasons and light sensitivity these solutions must be administered shortly after admixture.
As the infusion solution is sensitive to light, only remove the bottles from the folding box for use. In daylight the full efficacy of the solution is guaranteed over a period of 3 days.
For single use only.
At cool temperatures precipitation may occur, which will re-dissolve at room temperature (15 °C - 25 °C).
For ease of use the infusion vial stopper should be penetrated in the central ring. Penetration of the outer ring may result in damage to the vial stopper.
Any unused solution should be disposed off.
Incompatibilities: This medicinal product must not be mixed with other medicinal products except those mentioned previously in Special precautions for disposal and other handling.
Unless compatibility with other solutions/drugs has been confirmed, the infusion solution must always be administered separately. The visual signs of incompatibility are e.g. precipitation, clouding, and discoloration.
Incompatibility appears with all infusion solutions/drugs that are physically or chemically unstable at the pH of the solutions (e.g. penicillins, heparin solutions), especially in combination with solutions adjusted to an alkaline pH (pH of ciprofloxacin solutions: 3.9 - 4.5).
Storage
Film-coated tablet: This medicinal product does not require any special storage conditions.
Infusion: Keep in the outer carton in order to protect from light. Do not refrigerate or freeze.
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, nearly white to slightly yellowish, marked with "CIP score 250" on one side and a Bayer cross on the reverse side) x 100's. Infusion (clear, nearly colourless to slightly yellowish solution) 200 mg/100 mL x 1's. 400 mg/200 mL x 1's.
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