Tsifran AUDE

General characteristics. Structure:

Tablets, coated, the prolonged action, in 1 table.
ciprofloxacin of 500 mg, 1000 mg
in the blister of 5 pieces; in a pack cardboard 1 or 2 blisters.

Description. Tablets "Цифран® ODES of 500 Mg": an oval form, from white till almost white color, film coated, with a napechatka black food ink — "Cifran OD 500 mg".
Tablets "Цифран® ODES of 1000 Mg": an oval form, from white till almost white color, film coated, with a napechatka black food ink — "Cifran OD 1000 mg".

Pharmacological properties:

Pharmacodynamics. Absorption. After intake ciprofloxacin is quickly absorbed from digestive tract. Цифран® ODES of a tablet provide long, uniform release of ciprofloxacin, at the same time drug is accepted only once in day. One dose of Tsifran® of ODES of 500 mg and Tsifran® of ODES of 1000 mg are capable to maintain necessary concentration of ciprofloxacin which in other cases is provided with double use of usual ciprofloxacin 250 or 500 of mg respectively.
Distribution. after introduction of a single dose the maximum concentration in Cmax plasma are reached during 6 h and make (1,3±0,4) mkg/ml and (2,4±0,7) mkg/ml for Tsifran® of ODES of 500 mg and Tsifran® of ODES of 1000 mg respectively. The corresponding AUC0-t values — (8,3±2,1) and (18,9±4,6) mkg • ml/h. Binding by proteins of a blood plasma — 20–40%. Ciprofloxacin well gets into fabrics and fluid mediums of an organism: lungs, integuments, fatty tissue, muscles, cartilaginous and bone tissue, prostate; it is found in saliva, a secret of a mucous membrane of a nasal cavity and bronchial tubes, sperm, a lymph, peritoneal liquid and a secret of a prostate.
Metabolism. Ciprofloxacin is partially metabolized in a liver.
Removal. About 50% of the dose accepted inside are excreted by kidneys in not changed look and about 15% — in the form of active metabolites. The rest of the arrived dose is exposed to entero-gepatichesky circulation. T1/2 — about 3,5-4,5 p. T1/2 can be extended at the expressed renal failure and at elderly people.
Special groups of patients
 At an impaired renal function. At patients with an insignificant impaired renal function, T1/2 of ciprofloxacin can slightly increase. In this case carrying out correction of the mode of dosing is necessary (See. "Route of administration and doses").
At the broken function of a liver. In preliminary researches at patients with the stable course of cirrhosis any significant changes of pharmacokinetics of ciprofloxacin are noted. However researches on ciprofloxacin kinetics at patients with an acute liver failure were not conducted.

Pharmacokinetics. Bactericidal action of ftorkhinolon is caused by disturbance of effect of bacterial enzyme — topoisomerases II (DNK-girazy). Topoisomerase is necessary for normal replication of bacterial DNA. This ATP-dependent process in the absence of topoisomerase leads to uncontrollable replication of the damaged DNA and, therefore, to disturbance of synthesis of normal proteins in bacteria.
Has the expressed activity of in vitro concerning a wide range of gram-negative and gram-positive bacteria. It is active concerning the majority of strains of below-mentioned organisms:
— aerobic gram-positive:
Bacillus anthracis, Enterococcus faecalis (the majority of strains are rather sensitive), Listeria monocytogenes, Staphylococcus aureus (Methicillinum - sensitive iprodutsiruyushchy a penicillinase, partially Methicillinum - resistant strains), Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus pneumoniae, Streptococcus pyogenes;
— aerobic gram-negative:
Campylobacter jejuni, Citrobacter diversus, Citrobacter freundii, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Klebsiella pneumoniae, Moraxella catarrhalis, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia rettgeri, Pseudomonas aeruginosa, Salmonella typhi, Serratia marcescens, Shigella boydii, Shigella dysenteriae, Shigella flexneri, Shigella sonnei.
In the researches in vitro ciprofloxacin in MPK <1 mkg/ml is active concerning the majority (> 90%) strains of the given microorganisms, but the clinical importance of these data is still specified:
— aerobic gram-positive:
Staphylococcus haemophilus, Staphylococcus hominis;
— aerobic gram-negative:
Acinetobacter lwoffii, Aeromonas hydrophila, Brucella melitensis, Edwardsiella tarda, Legionella pneumophila, Salmonella enteritidis, Vibrio cholerae, Vibrio parahaemolyticus, Vibrio vulnificus, Klebsiella oxytoca, Yersinia enterocolitica;
— others:
Mycobacterium tuberculosis, Chlamydia trachomatis (are rather sensitive).
The majority of strains of Burkholderia cepacia and some strains of Stenotrophomonas maltophilia of a rezistentna to ciprofloxacin, as well as the majority of anaerobic bacteria, including Bacteroides fragilis and Clostridium difficile.

Indications to use:

Treatment of the infectious and inflammatory diseases caused by sensitive microorganisms:
● acute sinusitis;
● infectious and inflammatory diseases of the lower respiratory tracts, including pneumonia, an exacerbation of chronic bronchitis and infectious complications of a mucoviscidosis;
● pyelonephritis, cystitis (including complicated);
● chronic bacterial prostatitis;
● gonorrhea;
● the complicated intra belly infections (it is applied in a combination with metronidazole);
● cholecystitis, cholangitis;
● infectious diseases of integuments;
● infectious diseases of bones and joints (including acute and chronic osteomyelitis);
● diarrhea of infectious genesis;
● typhus fever.

Route of administration and doses:

Inside, after food, entirely (without breaking and without chewing a tablet), washing down with enough water.
Use of ciprofloxacin has to continue, at least, 2 more days after total disappearance of symptoms of a disease. The recommended doses for adults:
Acute sinusitis easy/average degree of 1000 mg each 24 h 10 days
 Infectious and inflammatory diseases of the lower respiratory tracts easy/average degree of 1000 mg each 24 h 7-14 days,
 heavy / each 24 h 7-14 days complicated by 1500 mg
 Infections of urinary tract acute uncomplicated 500 mg each 24 h 3 days, easy/average 500 m each 24 h 7-14 days, heavy / each 24 h 7-14 days complicated by 1000 mg
 Chronic bacterial prostatitis easy/average degree of 1000 mg each 24 h 28 days
 Intra belly infections * each 24 h 7-14 days complicated by 1000 mg
 Infectious diseases of integuments easy/average degree of 1000 mg each 24 h 7-14 days, heavy / each 24 h 7-14 days complicated by 1500 mg
 Infectious diseases of bones and joints easy/average степеь 1000 mg each 24 h> 4–6 weeks, heavy / each 24 h complicated by 1500 mg> 4–6 weeks
 Diarrhea of infectious genesis of easy/average/heavy 1000 m of each 24 h 5-7 days
 Typhoid easy/average degree of 1000 mg each 24 h 10 days
 The gonorrhea of acute uncomplicated 500 mg once 1 day complicated 500 Each 24 h 3-5 days
* It is applied in a combination with metronidazole.
Correction of the modes of dosing at a renal failure
 At an impaired renal function the following mode of dosing for adults is recommended:
Clearance of creatinine, ml/min. Dose
> 50 Usual dosage
30–50 500–1000 mg/days
5–29 Use Tsifrana AUDE is not recommended
 Patients on a hemodialysis or peritoneal dialysis 
If only concentration of creatinine in a blood plasma is known, the following formula for definition of Cl of creatinine is recommended:
men: Cl of creatinine (ml/min.) = Weight (kg) x (140−vozrast)/72 x concentration of creatinine of serum (mg/dl);
women: Cl of creatinine (ml/min.) = 0,85 x the indicator calculated for men.
Use for elderly patients. At use of ftorkhinolon for patients of this group it is necessary to pay attention to possible depression of function of kidneys, dependent on age, therefore carrying out correction of the mode of dosing is necessary. (See. "Route of administration and doses").

Features of use:

At some patients receiving ftorkhinolona photosensitivity reactions were observed. It is necessary to avoid excessive influence of direct sunshine and UF of radiation. At emergence of reaction of photosensitivity it is recommended to stop drug use. As Tsifran® of ODES is drug with possible reversible toxic impact on kidneys, it is not recommended to apply it at patients with an impaired renal function, with creatinine Cl <30 ml/min. or at the patients who are on a hemodialysis or peritoneal dialysis.
At use practically of all antimicrobic drugs, including Tsifran® of ODES, development of the pseudomembranous colitis varying on weight from a lung to life-threatening is possible. At emergence in time or after treatment of heavy and long diarrhea it is necessary to exclude the diagnosis of pseudomembranous colitis which demands immediate drug withdrawal and purpose of the corresponding treatment.
In order to avoid development of a crystalluria exceeding of the recommended daily dose is inadmissible, sufficient consumption of liquid and maintenance of acid reaction of urine is also necessary.
The patient with epilepsy, attacks of spasms in the anamnesis, vascular diseases and organic lesions of a brain, in connection with threat of development of adverse reactions from TsNS, it is necessary to appoint Tsifran® of ODES only according to vital indications.
At emergence of pains in sinews or at emergence of the first symptoms of a tendovaginitis treatment should be stopped (separate cases of an inflammation and even a rupture of sinews are described during treatment of a ftorkhinolonama).
During treatment it is necessary to avoid contact with direct sunshine.
During treatment it is necessary to abstain from occupations potentially dangerous types of activity requiring special attention and speed of mental and motor reactions.

Side effects:

From the alimentary system: nausea, vomiting, diarrhea, an abdominal pain, a meteorism, anorexia, cholestatic jaundice (especially at patients with the postponed liver diseases), hepatitis, гепатонекроз.
From a nervous system: dizziness, a photophobia, sleeplessness, paresthesias, irritability, a headache, increased fatigue, uneasiness, a tremor, dreadful dreams, a peripheral paralgeziya (anomaly of perception of feeling of pain), increase in intracranial pressure, confusion of consciousness, a depression, hallucinations, and also other manifestations of the psychotic reactions (which are occasionally progressing to states in which the patient can do himself harm), migraine, a faint, thrombosis of cerebral arteries.
From sense bodys: disturbances of taste and sense of smell, vision disorder (diplopia, change of color perception), sonitus, decrease in hearing.
From cardiovascular system: tachycardia, disturbances of a cordial rhythm, decrease in the ABP, rushes of blood to face skin.
From the hemopoietic system: eosinophilia, leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolitic anemia.
Laboratory indicators: prothrombinopenia, increase in activity of hepatic transaminases, giperkreatininemiya, hyperbilirubinemia, hyperglycemia, increase in activity of ShchF and lactate dehydrogenase.
From an urinary system: a hamaturia, a crystalluria (first of all at alkali reaction of urine and a hypouresis), acute intersticial nephrite (with possible development of an acute renal failure), a glomerulonephritis, a dysuria, a polyuria, an ischuria, an albuminuria, urethral bleedings, decrease in azotovydelitelny function of kidneys.
Allergic reactions: a skin itch, a small tortoiseshell, blistering, followed by bleedings, and emergence of the small small knots forming crusts, medicinal fever, dot hemorrhages on skin (petechia), a face edema or throats, an asthma, a vasculitis, a knotty erythema, a mnogoformny exudative erythema, a malignant exudative erythema (Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease).
From a musculoskeletal system: arthralgia, arthritis, tendovaginitis, ruptures of sinews, mialgiya.
Others: the increased perspiration, photosensitivity, the general weakness, superinfections (candidiasis, pseudomembranous colitis).

Interaction with other medicines:

Theophylline. At combined use with ciprofloxacin increase in concentration of theophylline in a blood plasma is observed. If it is impossible to exclude combined use of these drugs, it is necessary to control the content of theophylline in a blood plasma
 The antiacid drugs containing magnesium hydroxide or aluminum hydroxide. At presence of these antacids ciprofloxacin absorption decreases, thus, the concomitant use of these drugs has to be excluded.
Probenetsid and other drugs blocking canalicular secretion. At combined use with probenitsidy renal excretion of ciprofloxacin decreases.
Antineoplastic and immunosuppressive drugs. Absorption of ciprofloxacin after use inside decreases after performing cytotoxic therapy.
Analgetics. Combined use with NPVP, strengthens side effects of ciprofloxacin on TsNS.
Phenytoinum. At the patients receiving therapy using ciprofloxacin and Phenytoinum variability (decrease and increase) of Phenytoinum levels in a blood plasma is noted.
Sukralfat. In a stomach сукральфат releases aluminum ions therefore absorption of ciprofloxacin decreases.
Peroral anticoagulants. Derivatives of hinolon strengthen effect of peroral anticoagulants, such as warfarin and its derivatives. At combined use with these drugs, it is necessary to conduct researches of coagulant system of blood regularly.
Antagonists of N2-of receptors. Antagonists of H2 receptors of a histamine do not exert significant impact on bioavailability of ciprofloxacin.
Glyburidum. In rare instances combined use with ciprofloxacin can lead to the expressed hypoglycemia.
Metronidazole. At combined use of ciprofloxacin and metronidazole any changes of their concentration in plasma are not revealed.
Owing to decrease of the activity of processes of a microsomal oxidation in hepatocytes increases concentration and extends T1/2 of xanthines (for example, caffeine), peroral hypoglycemic drugs.
Didanozin reduces absorption of ciprofloxacin owing to formation of complexes with it with the aluminum and magnesian salts which are contained in the didanozena.
Metoclopramidum accelerates absorption that leads to reduction of time of achievement of its Cmax.
Joint purpose of uricosuric drugs leads to removal delay (up to 50%) and increase in plasma concentration of ciprofloxacin.
At a combination to other antimicrobic drugs (beta lactams, aminoglycosides, clindamycin, metronidazole) a synergism is usually observed; it can successfully be applied in a combination with azlotsilliny and a ceftazidime — at infections, vyzvannykhpseudomonas spp.; with mezlotsilliny, azlotsilliny and others beta лактамными antibiotics — at streptococcal infections; with izoksazolpenitsillina and Vancomycinum — at staphylococcal infections; with metronidazole and clindamycin — at mephitic gangrenes.
Strengthens nephrotoxic effect of cyclosporine, increase in serumal creatinine is noted, at such patients control of this indicator 2 times a week is necessary. If use of theophylline is necessary during therapy by ciprofloxacin, it is necessary to control concentration of theophylline, if necessary to make the corresponding correction of the mode of dosing.

Contraindications:

● hypersensitivity to ciprofloxacin or other drugs from group of ftorkhinolon;
● pseudomembranous colitis;
● children's age up to 18 years (before completion of process of formation of a skeleton);
● pregnancy;
● lactation period.

With care:
● the expressed atherosclerosis of vessels of a brain;
● disturbance of cerebral circulation;
● mental diseases;
● epileptic syndrome;
● epilepsy;
● the expressed liver and/or renal failure;
● advanced age.

USE AT PREGNANCY AND FEEDING by the BREAST.  Примененять during pregnancy it is not recommended.
Ciprofloxacin is excreted in breast milk, therefore in the period of a lactation if use of the drug Tsifran® ODES is necessary, then, based on degree of importance of its use for mother, it is necessary to solve, whether to stop administration of drug or breastfeeding.

Overdose:

Perhaps reversible toxic impact on kidneys.
There is no specific antidote therefore therapy has to be symptomatic. It is necessary:
- to cause vomiting or to carry out a gastric lavage;
- to carry out measures for adequate hydration of an organism (infusional therapy);
- maintenance therapy.
Only insignificant amounts of ciprofloxacin (<10%) can be removed by means of haemo - and peritoneal dialysis.

Storage conditions:

List B. In the place protected from moisture, at a temperature not above 25 °C. To store in the place, unavailable to children. A period of validity - 2 years.

Issue conditions:

According to the recipe