Ciprofloxacin

General characteristics. Structure:

Active agent: hydrochloride ciprofloxacin monohydrate in terms of ciprofloxacin — 250 mg;

Excipients (kernel): кросповидон — 7 mg, cellulose microcrystallic — 43,9 mg, povidone (polyvinylpirrolidone) — 16,3 mg, magnesium stearate — 3,7 mg, starch corn — 13,0 mg.

Excipients (cover): a gipromelloza — 8,5 mg, titanium dioxide — 4,5 mg, a macrogoal — 2,0 mg.

Pharmacological properties:

Pharmacodynamics. The Pragivomikrobny broad-spectrum agent derivative of a hinolon, 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 microorganisms 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 antibiotics which are not belonging to group of DNK-girazy inhibitors that does it highly effective in relation to bacteria which are steady, for example to kaminoglikozida, penicillin, cephalosporins, tetracyclines. Gram-negative aerobic bacteria are sensitive to ciprofloxacin: enterobakteriya (Escherichia coli, Salmonella spp., Shigella spp., Citrobacterspp., Klebsiella spp., Enterobacterspp., 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., Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii.
Gram-positive aerobic bacteria: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae). Bacillus anthracis is also sensitive to ciprofloxacin.
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. He is 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 digestive tract (preferential in 12-perstny and a jejunum). Meal slows down absorption, but does not change the maximum concentration (Stakh) 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 (Tsglakh) at oral administration — 60-90 min., Stakh 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 till 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 tissue). 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 (an endometria, fallopian pipes and ovaries, a uterus), semen, prostate gland tissue, 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 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 pleura, a peritoneum, a lymph, through a placenta. Concentration of ciprofloxacin in neutrophils of blood is 2-7 times higher, than in blood serum. 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 chronic renal failure — to 12 h. Other part — through digestive tract is removed generally by kidneys by canalicular filtering and canalicular secretion in not changed look (40-50%) and in the form of metabolites (15%). A small amount is removed with breast milk. Renal clearance — 3 — 5 ml/min.; the general clearance — 8-10 ml/min.
At a chronic renal failure (the clearance of creatinine (CC) is higher than 20 ml/min.) the percent of the ciprofloxacin removed through kidneys decreases, but cumulation in an organism does not happen owing to compensatory increase in metabolism of ciprofloxacin and removal through digestive tract.

Indications to use:

The infectious and inflammatory diseases caused by sensitive microorganisms:
- diseases of the lower respiratory tracts (acute and chronic (in an aggravation stage) bronchitis, pneumonia, a bronchoectatic disease, infectious complications of a mucoviscidosis);
- insrektion of ENT organs (acute sinusitis);
- insrektion of kidneys and urinary tract (cystitis, pyelonephritis);
- the complicated intraabdominal infections (in a combination with metronidazole);
- chronic bacterial prostatitis;
- uncomplicated gonorrhea;
- typhoid,
- inspection diarrhea, including campilobacteriosis, shigellosis, diarrhea of "travelers";
- the insrektion of skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);
- bones and joints (osteomyelitis, septic arthritis);
- insrektion against the background of the immunodeficiency (arising at treatment by immunodepressive medicines or at patients with a neutropenia);
- 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. Tablets should be swallowed entirely with a small amount of liquid after food. At reception of a tablet on an empty stomach active agent is soaked up quicker.
At lower respiratory tract infections of easy and average degree — 0.5 g 2 times a day, at a heavy current — 0.75 g 2 times. A course of treatment — 7-14 days.
At acute sinusitis — on 0.5 g 2 times a day. A course of treatment — 10 days.
At an infection of skin and soft tissues of easy and average degree — 0.5 g2 once a day, at a heavy current — 0.75 g 2 times. A course of treatment — 7-14 days.
At infections of bones and joints — easy and average degree — 0.5 g2 once a day, at a heavy current — 0.75 g 2 times. A course of treatment — to 4-6 weeks.
At infections of urinary tract — on 0.25-0.5 g 2 times a day; a course of treatment — 7-14 days, at uncomplicated cystitis at women — 3 days.
At chronic bacterial prostatitis — on 0.5 g 2 times, a course of treatment — 28 days.
At uncomplicated gonorrhea — 0.25-0.5 g once. Infectious diarrhea — on 0.5 g 2 times, a course of treatment — 5-7 days. At a typhoid — on 0.5 g 2 times; a course of treatment — 10 days. At the complicated intraabdominal inspections — on 0.5 g each 12 h within 7-14 days.
For prevention and treatment of a pulmonary srorma of a malignant anthrax — on 0.5 g 2 times a day within 60 days.
Other infections (see. "Indications to use") — on 0.5 g 2 times a day.
In pediatrics:
at treatment of the complications caused by Pseudomonas aeruginosa children with a mucoviscidosis of lungs have from 5 to 17 years — 20 mg/kg 2 times a day (the maximum dose of 1.5 g). Treatment duration — 10-14 days.
At a pulmonary form of a malignant anthrax (prevention and treatment) — 2 times pass 15 mg/kg.
The maximum single dose — 0.5 g, daily — 1 g. The general duration of reception of ciprofloxacin — 60 days. Chronic renal failure: at KK more than 50 ml/min. of dose adjustment are not required; at KK of 30-50 ml/min. — 0.25-0.5 each 12 h; at KK of 5-29 ml/min. — 0.25-0.5 g each 18 h. 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.

Features of use:

Ciprofloxacin is not choice drug at the suspect or the established pneumonia caused by Streptococcus pneumoniae. 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 UF-radiation (including 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, faints, 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, lowering of arterial pressure.
- From the hemopoietic system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolitic anemia.
- Laboratory indicators: prothrombinopenia, increase in activity of "hepatic" transaminases and alkaline phosphatase, giperkreatininemiya, hyperbilirubinemia, hyperglycemia.
- From mochevshchelitelny 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 azotovydelitelny 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, short wind, an eosinophilia, a vasculitis, a knotty erythema, a muptiformny exudative erythema (including Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease).
- From a musculoskeletal system: arthralgia, arthritis, tendovaginitis, ruptures of sinews, mialgiya.
- Other: an adynamy, the raised photosensitivity, 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 and extends theophylline T1/2 (and other xanthines, for example, caffeine), peroral hypoglycemic medicines, indirect anticoagulants, promotes decrease in a prothrombin ratio. At a combination to other antimicrobic medicines (beta лактамные antibiotics, aminoglycosides, clindamycin, metronidazole) a synergism is usually observed; it can successfully be applied in a combination with azlotsilliny and tsesrtazidimy at the infections caused by Pseudomonas spp.; with mezlotsilliny, azlotsilliny and others beta лактамными antibiotics — at streptococcal infections; with izoksazolilpenitsillina and Vancomycinum — at staphylococcal infections; with metronidazole and clindamycin — at anaerobic inspections.
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 medicines, sukralfaty and the antiacid medicines containing ions of magnesium, calcium, aluminum leads to decrease in absorption of ciprofloxacin therefore it is necessary to appoint it for 1-2 h to or in 4 h after reception of the above-stated medicines.
Non-steroidal anti-inflammatory drugs (excepting acetylsalicylic acid) increase risk of development of spasms. Didanozin reduces absorption of ciprofloxacin owing to formation of complexes with it with the calcium ions which are contained in the didanozena, iron and magnesium.
Metoclopramidum accelerates absorption that his Stakh leads to reduction of time of achievement.
Combined use of uricosuric medicines leads to removal delay (up to 50%) and increase in plasma concentration of ciprofloxacin.
Stakh by 7 times (from 4 to 21 times) and the area under a pharmacological curve "concentration time" (AUC) by 10 times (from 6 to 24 times) of a tizanidin raises that increases risk of the expressed lowering of arterial pressure and drowsiness.

Contraindications:

Hypersensitivity, concomitant use with tizanidiny (risk of the expressed lowering of arterial pressure, drowsiness), age up to 18 years (before completion of process of a sformirovaniye 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, the expressed renal and/or liver failure, damage of sinews at earlier carried out baking of a ftorkhinolonama, advanced age.

Overdose:

Treatment: the specific antidote is unknown. I sew a gastric lavage and other measures of acute management, careful control of a state haemo - or peritoneal dialysis the amount of drug can be removed only insignificant (less than 10%).

Storage conditions:

To store in the dry, protected from light place at a temperature not above 25 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated 250 mg. On 10 tablets place in a blister strip packaging from a film of the polyvinyl chloride and printing aluminum foil varnished. On 20, 30, 40, 50, 60 or 100 tablets place in a container polymeric for medicines. 1 container or 1, 2, 3, 4 or 5 blister strip packagings together with the application instruction place in a pack from a cardboard.