Tsiprofloksatsin-FPO

General characteristics. Structure:

Active ingredient: 500 mg of ciprofloxacin (in the form of a hydrochloride) in 1 tablet.

Excipients: magnesium stearate, cellulose microcrystallic, кросповидон (коллидон CL), starch corn, silicon dioxide colloid (aerosil).

Excipients for a cover: gipromelloza (gidroksipropilmetil-cellulose), macrogoal 6000 (polyethyleneglycol 6000), titanium dioxide.

Pharmacological properties:

Pharmacodynamics. The antimicrobic broad-spectrum agent derivative of a ftorkhinolon, suppresses bacterial DNK-girazu (the topoisomerases II and IV responsible for process of superspiralling of chromosomal DNA around nuclear RNA that is necessary for reading of genetic information), breaks DNA synthesis, growth and division of bacteria; causes the expressed morphological changes (including a cell wall and membranes) and bystry death of a bacterial cell.

Affects bakteritsidno gram-negative organisms during a dormant period and divisions (since influences not only on DNK-girazu, but also causes a lysis of a cell wall), on gram-positive microorganisms - only during division. The hypotoxicity for cells of a macroorganism is explained by absence in them DNK-girazy. Against the background of reception of ciprofloxacin there is no parallel development of resistance to other aktibiotika which are not belonging to group of inhibitors of a giraza that does it highly effective in relation to bacteria which are steady, for example to aminoglycosides, penicillin, cephalosporins, tetracyclines and many other antibiotics.

Gram-negative aerobic bacteria are sensitive to ciprofloxacin: enterobakteriya (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus vulgaris, Serratia marcescens, Hafnia alvei, Edwardsiella tarda, Providencia spp., Morganella morganii, Vibrio spp., Yersinia spp.), other gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.), some intracellular activators - Legionella pneumophila, Brucella spp., Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium diphtheriae; gram-positive aerobic bacteria: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

The majority of the stafilokokk steady against Methicillinum, rezistentna and to ciprofloxacin. Sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) - moderated (for their suppression high concentration are required). To rezistentna drug: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. It is not effective concerning Treponema pallidum.

Resistance develops extremely slowly as, on the one hand, after effect of ciprofloxacin there is practically no persistent microorganism left, and with another - bacterial cells have no enzymes inactivating it.

Pharmacokinetics. At oral administration it is quickly and rather fully soaked up from the digestive tract (DT), it is preferential in 12-perstny and a jejunum. Meal slows down absorption, but does not change the maximum concentration in blood serum (Cmax) and bioavailability. Bioavailability - 50-85%, distribution volume - 2-3,5 l/kg, communication with proteins of plasma - 20-40%. Time of achievement of the maximum concentration in a blood plasma (TCmax) at oral administration - 60-90 min. Cmax linearly depends on the size of the accepted dose and makes at doses 250, 500, 750 both 1000 mg respectively 1,2, 2,4, 4,3 and 5,4 mkg/ml. In 12 h after intake of 250, 500 and 750 mg concentration of drug in plasma decreases to 0,1, 0,2 and 0,4 mkg/ml respectively.

It is well distributed in body tissues, excepting the fabric rich with fats, for example, nervous. Concentration in fabrics is 2-12 times higher, than in plasma. Therapeutic concentration are reached in saliva, almonds, a liver, a gall bladder, bile, intestines, abdominal organs and a small pelvis, a uterus, semen, prostate tissue, an endometria, fallopian pipes and ovaries, kidneys and urinary bodies, pulmonary fabric, a bronchial secret, a bone tissue, muscles, synovial fluid and joint cartilages, peritoneal liquid, skin. Gets into cerebrospinal fluid (SMZh) in a small amount where its concentration in the absence of an inflammation of a meninx makes 6-10% of that in blood serum, and at inflamed - 14-37%. Ciprofloxacin well gets also into eye liquid, a bronchial secret, a pleura, a peritoneum, a lymph, through a placenta. Concentration of ciprofloxacin in neutrophils of blood is 2-7 times higher, than in blood serum. Activity decreases at PH values less than 6 a little. It is metabolized in a liver (15-30%) with formation of low-active metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin).

Elimination half-life (T1/2) - about 4 h at a peroral way introduction, at the chronic renal failure (CRF) - to 12 h. It is removed generally by kidneys by canalicular filtering and canalicular secretion in not changed look (at intake - 40-50%) and in the form of metabolites (at intake - 15%), other part - through a GIT. A small amount is removed with breast milk. Renal clearance - 3-5 ml/min.; the general clearance - 8-10 ml/min.

At HPN (at the clearance of creatinine (CC) it is higher than 20 ml/min.) the percent of the drug removed through kidneys decreases, but cumulation in an organism does not happen owing to compensatory increase in metabolism of drug and removal with fecal masses.

Indications to use:

- the bacterial infections caused by sensitive microorganisms: respiratory diseases - acute and chronic (in an aggravation stage) bronchitis, pneumonia, a bronchoectatic disease, a mucoviscidosis;

- infections of ENT organs - average otitis, antritis, a frontal sinusitis, sinusitis, a mastoiditis, tonsillitis, pharyngitis;

- infections of kidneys and urinary tract (MVP) - cystitis, pyelonephritis;

- infections of bodies of a small pelvis and generative organs - prostatitis, an adnexitis, a salpingitis, an oophoritis, an endometritis, tubular abscess, a pelviperitonitis, gonorrhea, a venereal ulcer, clamidiosis;

- infections of an abdominal cavity - bacterial infections of a GIT, bilious ways, peritonitis, intraperitoneal abscesses, salmonellosis, a typhoid, a campilobacteriosis, иерсиниоз, a shigellosis, cholera;

- infections of skin and soft tissues - the infected ulcers, wounds, burns, abscesses, phlegmon;

- infections of bones and joints - osteomyelitis, septic arthritis;

- sepsis; infections against the background of the immunodeficiency (arising at treatment by the immunodepressive medicines (M) or at patients with a neutropenia);

- prevention of infections at surgical interventions;

- prevention and treatment of a pulmonary form of a malignant anthrax.

Children:

- therapy of the complications caused by Pseudomonas aeruginosa in children with a mucoviscidosis of easy from 5 to 17 years;

- prevention and treatment of a pulmonary form of a malignant anthrax (Bacillus anthracis infection).

Route of administration and doses:

Inside, on 0,25 g 2-3 times a day, at the heavy course of infections – 0,5-0,75 g 2 times a day (each 12 h).

At MVP infections - on 0,25-0,5 g 2 times a day; a course of treatment - 7-10 days, at chronic prostatitis - 28 days.

At uncomplicated gonorrhea – 0,25-0,5 g once; at a combination of a gonococcal infection with Chlamidia and mycoplasmal – 0,75 g each 12 h within 7-10 days.

At a shankroida - on 0,5 g 2 times a day within several days.

At a meningococcal carriage in a nasopharynx - once, 0,5 or 0,75 g.

At a chronic carriage of salmonellas - inside, on 0,5 g 2 times; a course of treatment - to 4 weeks. If necessary the dosage can be increased to 0,75 g 2 times a day.

At pneumonia, osteomyelitis - inside, on 0,75 g 2 times a day. Duration of treatment of osteomyelitis can make up to 2 months.

At the infections of a GIT caused by Staphylococcus aureus - on 0,75 g each 12 h within 7-28 days.

It is necessary to continue treatment not less than 3 more days after normalization of body temperature or disappearance of clinical symptoms.

Children. At treatment of the complications caused by Pseudomonas aeruginosa in children with a mucoviscidosis of easy from 5 to 17 years - 20 mg/kg 2 times a day (the maximum dose of 1500 mg). Treatment duration - 10-14 days.

At a pulmonary form of a malignant anthrax (prevention and treatment) - 15 mg/kg 2 times a day. The maximum single dose - 500 mg, daily - 1000 mg. The general duration of reception of ciprofloxacin - 60 days.

At a glomerular filtration rate (KK of 31-60 ml/min. / 1.73 sq.m or serumal concentration of creatinine from 1,4 to 1,9 mg / 100 ml) the maximum daily dose - 1 g. At a glomerular filtration rate it is lower than 30 ml/min. / 1.73 of sq.m or serumal concentration of creatinine higher than 2 mg / 100 ml the maximum daily dose – 0,5 g.

If to the patient the hemodialysis or peritoneal dialysis – 0,25-0,5 g/days is carried out, but it is necessary to accept drug after the hemodialysis session.

At the heavy course of the infections (for example, at a recurrent mucoviscidosis, infections of an abdominal cavity, bones and joints) caused by Pseudomonas or stafilokokka at the acute pneumonias caused by Streptococcus pneumoniae and at chlamydial infections of urinogenital ways the dose has to be raised to 0,75 g each 12 h.

Tablets should be swallowed entirely with a small amount of liquid after meal. At reception of a tablet on an empty stomach active agent is soaked up quicker.

Average duration of treatment: 1 day - at acute uncomplicated gonorrhea and cystitis; up to 7 days - at infections of kidneys, MVP and an abdominal cavity, during the entire period of a neytropenichesky phase - at patients with the weakened protective forces of an organism, but no more than 2 months - at osteomyelitis and 7-14 days - at all other infections. At streptococcal infections in connection with danger of late complications, and also at chlamydial infections treatment has to continue not less than 10 days. At patients with an immunodeficiency treatment is carried out during the entire period of a neutropenia. Treatment it is necessary to spend not less than 3 more days after normalization of body temperature or disappearance of clinical symptoms.

Prevention and treatment of a pulmonary form of a malignant anthrax: on 500 mg 2 times a day. Administration of drug should be begun right after the assumed or confirmed infection. A course of treatment - 60 days.

Features of use:

Use at pregnancy and during breastfeeding: Contraindicated at pregnancy (safety and efficiency of use for women during pregnancy is not established). Ciprofloxacin passes through a placenta. Ciprofloxacin is excreted in breast milk therefore in the period of a lactation it is necessary to solve, to stop reception of ciprofloxacin or breastfeeding, based on degree of importance of use of HP for mother.

In order to avoid development of a crystalluria exceeding of the recommended daily dose is inadmissible, also sufficient consumption of liquid and maintenance of acid reaction of urine is necessary.

During treatment it is necessary to abstain from occupations potentially dangerous types of activity requiring special attention and speed of mental and motor reactions.

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 side reactions from the central nervous system it is necessary to appoint ciprofloxacin only according to vital indications.

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.

At emergence of pains in sinews or 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.

Side effects:

From the alimentary system: nausea, diarrhea, vomiting, an abdominal pain, a meteorism, a loss of appetite, cholestatic jaundice (especially at patients with the postponed liver diseases), hepatitis, гепатонекроз.

From a nervous system: dizziness, a headache, increased fatigue, uneasiness, a tremor, sleeplessness, "dreadful" dreams, a peripheral paralgeziya (anomaly of perception of feeling of pain), the increased sweating, 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, unconscious states, 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.

From the hemopoietic system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolitic anemia.

From laboratory indicators: prothrombinopenia, increase in activity of "hepatic" transaminases and alkaline phosphatase, lactate dehydrogenase, increase in concentration of urea, giperkreatininemiya, hyperbilirubinemia, hyperglycemia.

From an urinary system: a hamaturia, a crystalluria (first of all at alkalinuria and a hypouresis), a glomerulonephritis, a dysuria, a polyuria, an ischuria, an albuminuria, urethral bleedings, decrease in azotvydelitelny function of kidneys, intersticial nephrite.

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, an eosinophilia, the raised photosensitivity, a vasculitis, a nodal erythema, a multiformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease).

Others: an arthralgia, arthritis, a tendovaginitis, ruptures of sinews, an adynamy, a mialgiya, superinfections (candidiasis, pseudomembranous colitis), "inflows" of blood to the person.

Interaction with other medicines:

Owing to decrease of the activity of processes of a microsomal oxidation in hepatocytes increases concentration in a blood plasma and extends T1/2 of theophylline and other xanthines, (for example, caffeine) and promotes increase of risk of development of the toxic action connected with theophylline, peroral hypoglycemic HP, indirect anticoagulants, promotes decrease in a prothrombin ratio and lengthening of a bleeding time.

At a combination to other antimicrobic HP (beta лактамными antibiotics, aminoglycosides, clindamycin, metronidazole) usually observe a synergism; it can successfully be applied in a combination with azlotsilliny and a ceftazidime at the infections caused by Pseudomonas 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.

At a concomitant use strengthens effect of indirect anticoagulants.

Oral administration together with ferriferous HP, sukralfaty and the antiacid drugs containing ions of magnesium, calcium and aluminum leads to decrease in absorption of ciprofloxacin. Bioavailability of ciprofloxacin in the presence of antiacid drugs made 9,5%. Antiulcerous drug сукралфат, consisting of a complex of a hydroxide of aluminum and the sulphated sukroza had similar effect on absorption of ftorkhinolon. Interaction is explained with formation of the insoluble and badly soaking up chelate complexes between ftorkhinolona and cations of aluminum and magnesium. Therefore it is necessary to appoint it for 1-2 h to or in 4 h after reception of the above-stated HP.

Non-steroidal anti-inflammatory drugs (excepting acetylsalicylic acid) increase risk of development of spasms.

At simultaneous use of ciprofloxacin with didanoziny absorption of ciprofloxacin decreases owing to formation of complexes of ciprofloxacin with the ions of aluminum and magnesium which are contained in the didanozena.

Metoclopramidum accelerates ciprofloxacin absorption that leads to reduction of its TCmax.

Joint purpose of uricosuric HP leads to removal delay (up to 50%) and increase in plasma concentration of ciprofloxacin.

Raises Cmax by 7 times (from 4 to 21 times) and AUC by 10 times (from 6 to 24 times) of a tizanidin that increases risk of the expressed decrease in the ABP and drowsiness.

Contraindications:

Hypersensitivity, concomitant use with tizanidiny (risk of the expressed lowering of arterial pressure (ABP), drowsiness), children's age (up to 18 years - before completion of process of formation of a skeleton, except therapy of the complications caused by Pseudomonas aeruginosa in children with a mucoviscidosis of easy from 5 to 17 years; prevention and treatment of a pulmonary form of a malignant anthrax), pregnancy, lactation period.

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

Overdose:

The specific antidote is unknown. It is necessary to control carefully a condition of the patient, to make a gastric lavage, to carry out usual measures of acute management, to provide sufficient intake of liquid. By means of haemo - or peritoneal dialysis the amount of drug can be removed only insignificant (less than 10%).

Storage conditions:

In the dry, protected from light place at a temperature not over 25 ºС. To store in the place, unavailable to children. A period of validity - 2 years. Not to use after the period of validity specified on packaging.

Issue conditions:

According to the recipe

Packaging:

Tablets film coated 500 mg. On 10, 15, 20, 30 tablets in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 1, 2 or 3 blister strip packagings together with the application instruction in a pack from a cardboard.