Ципринол® WEDNESDAY

General characteristics. Structure:

Active ingredient: 709 mg ципринол a semi-finished product granules (that corresponds to 500 mg of ciprofloxacin).

Excipients: magnesium stearate, silicon диок; ides colloid anhydrous, talc.

Cover: Opadray-U-1-7000 (structure of Opadray-U-1-7000: gipromeyaloza, titanium
dioxide and macrogoal 400).

Antimicrobic drug with broad antibacterial action.

Pharmacological properties:

Pharmacodynamics. Antimicrobic drug of a broad spectrum of activity from group of ftorkhinolon. Works bakteritsidno. Drug inhibits DNK-girazu enzyme of bacteria owing to what DNA replication and synthesis of cellular proteins of bacteria are broken. 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 ipynne of inhibitors of a giraza that does it highly effective in relation to bacteria which are steady, for example, against aminoglycosides, penicillin, cephalosporins, tetracyclines and many other antibiotics.

Ciprofloxacin affects both the breeding microorganisms, and on being in a resting phase. 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, Hafiiia alvei, Edwardsiella tarda, Providencia spp., Morganella morganii, Vibrio spp., Yersinia spp.), other gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeroironas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.); some intracellular activators: Legionella pneumophila, Brucella spp., Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Mycobacterium avium (located intracellularly).

Also grampolozhotelny aerobic bacteria are sensitive to ciprofloxacin: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae). The majority of the stafilokokk steady against Methicillinum are steady also against ciprofloxacin.

Sensitivity of bacteria of Streptococcus pneumoniae, Enterococcus faecalis moderate. To Corynebacterium spp rezistentna drug., Bacteroidcs fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridiiim difficile, Nocardia asteroides.

Study effect of drug concerning Treponema pallidum but insufficiently. Both in vitro, and in vivo is also sensitive Bacillus anthracis to ciprofloxacin.

Pharmacokinetics. At oral administration ciprofloxacin is quickly soaked up from digestive tract. The maximum plasma concentration (Smakh) is reached in 6 hours after intake and depends on a drug dose. In comparison with ciprofloxacin with the immediate release of the substance in a dose of 250 mg accepted twice a day, Smakh Tsiprinola by CP, accepted once a day, above; at the same time area indicators under a curve "concentration time" (AUC) are within a day equivalent.

Ciprofloxacin pharmacokinetics (tablets of the prolonged action, film coated).
	About a move (ng/ml)	AUCo-244 (¡úþ/ml)	Period to a poluvyva of a deniye (Тш) (h)	Time necessary for achievement of the maximum concentration (Tstakh) (h)
Ciprofloxacin of the prolonged action of 500 mg * 1 times/days	1264,7	7612,4	5	3,6

Bioavailability of drug makes 50-85%. The shopping center of elderly patients can be extended.

Ciprofloxacin contacts proteins of plasma for 20-40%. Distribution volume after oral administration of ciprofloxacin varies from 1,74 to 5 l/kg in an equilibrium state that demonstrates active penetration of ciprofloxacin into fabrics.

High concentration of drug are observed in bile, lungs, kidneys, a liver, a gall bladder, a uterus, semen, prostate gland tissue, almonds, an endometria, fallopian pipes and ovaries. Concentration of drug in these fabrics is higher, than in serum. Ciprofloxacin also well gets into bones, eye liquid, a bronchial secret, saliva, skin, muscles, a pleura, a peritoneum, a lymph. Gets into cerebrospinal fluid in a small amount where its concentration at an uninflammed meninx makes 6-10% of that in blood serum, and at inflamed - 14-37% (that exceeds minimum overwhelming concentration for the majority of enterobakteriya). Ciprofloxacin gets through a placenta.

Few active metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin) are metabolized in a liver (15-30%) with education.

Ciprofloxacin is removed preferential by kidneys: about 50% of nemetabolizirovanny drug and active metabolites, and also 11-12% of inactive metabolites. To 8% of metabolites are removed through intestines.

Indications to use:

The infectious and inflammatory diseases caused by microorganisms, sensitive to ciprofloxacin:

1.dykhatelnykh ways: pneumonia (except for pneumococcal pneumonia), an acute bronchitis and an exacerbation of chronic bronchitis, a bronchoectatic disease, a mucoviscidosis (if the activator is gram-negative bacteria, especially Pseudomonas aeruginosa);
2.ukha, throat and nose: acute average otitis, sinusitis, mastoiditis;
3.pochek and urinary tract: the uncomplicated and complicated infections of the lower and upper parts of an uric path (an urethritis, cystitis, pyelonephritis);
4.organov small pelvis and generative organs (epididymite, prostatitis, salpingitis, endometritis, oophoritis, tubular abscess and pelviperitonitis, gonorrhea, venereal ulcer, clamidiosis);
5.organov abdominal cavity: intraperitoneal abscess; cholecystitis, a cholangitis (in a combination with metronidazole or clindamycin), infectious diarrhea: salmonellosis, campilobacteriosis, иерсиниоз, shigellosis, cholera, typhoid, diarrhea of travelers, Salmonella typhi bacteriocarrier.
6.kozhi and soft tissues: the infected ulcers, contaminated wounds, abscesses, phlegmon, infections of outside acoustical pass infected burns;
7.oporno-motive device: osteomyelitis, septic arthritis;

1. Infections at patients with reduced immunity (against the background of therapy by immunodepressants or at patients with a neutropenia).
2. Prevention of infections at surgical interventions (urological, on digestive tract (in a combination with metronidazole) and orthopedic).
3. Prevention and treatment of a pulmonary form of a malignant anthrax.

Route of administration and doses:

Inside, 1 time a day. It is necessary to take drug after food, to swallow a pill entirely, without chewing and washing down with enough liquid. The dose of ciprofloxacin depends on weight got sick, like an infection, a condition of an organism, age, weight and function of kidneys at the patient.
The recommended schemes of dosing:

Indication	Severity	Daily dose	Frequency rate of reception	Usual prodolzhiyotelnost of treatment *
Infectious and inflammatory diseases of an ear, throat and nose	Easy/moderate	1000 mg	1 time a day	10 days
Infectious and inflammatory diseases of lower parts of respiratory tracts: pneumonia (except for pneumococcal pneumonia), an acute bronchitis and an exacerbation of chronic bronchitis, bronchoectatic disease, mucoviscidosis (if the activator is gram-negative bacteria, especially Pseudomonas aeruginosa)	Easy/moderate Heavy / complicated	1000 mg 1500 mg	1 time in days of 1 times a day	7-14 days 7-14 days
Infections of kidneys and urinary tract	Acute uncomplicated cystitis Easy/moderate	500 mg 500 mg	1 time in days of 1 times a day	3 days 7-14 days
	Heavy / complicated	1000 mg	1 time a day	7-14 days
Chronic bacterial prostatitis	Easy/moderate	1000 mg	1 time a day	28 days
Infectious and inflammatory diseases of abdominal organs: intraperitoneal abscess,	Complicated	1000 mg	1 time a day	7-14 days
cholecystitis, cholangitis (in a combination with metronidazole or clindamycin)
Infections of skin and soft tissues	Easy/moderate Heavy / complicated	1000 mg 1500 mg	1 time a day 1 time a day	7-14 days 7-14 days
Infectious and inflammatory diseases of a musculoskeletal system: osteomyelitis, septic arthritis	Easy/moderate Heavy / complicated	1000 mg 1500 mg	1 time in days of 1 times a day	4-6 weeks 4-6 weeks
Infectious diarrhea	Easy / moderate/heavy	1000 mg	1 time a day	5-7 days
Typhoid	Easy/moderate	1000 mg	1 time a day	10 days
Gonorrhea	Complicated	500 mg	1 time a day	3-5 days

Treatment needs to be continued, at least, within 2 days after disappearance of symptoms and symptoms of an infection. At heavy infections treatment can be begun with parenteral forms of drug, further to pass to oral administration of drug.

At elderly people the dose of drug is reduced depending on clearance of creatinine, character and severity of an infectious disease.

Dosing for patients with renal failures:

Clearance of creatinine	Serum creatinine	Dose
> 50 ml/min.	<120 µmol (<1,4 mg / 100 ml)	Usual dose
30-50 ml/min.	120-179 µmol (1,4-1,9 mg / 100 ml)	500-1000 mg/days

Features of use:

At emergence in time or after treatment by ciprofloxacin 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. When developing pains in sinews or at emergence of the first symptoms of a tendovaginitis treatment should be stopped because separate cases (preferential at the elderly patients who are at the same time receiving glucocorticosteroids) an inflammation and even a rupture of sinews are described during treatment of a ftorkhinolonama. During therapy ciprofloxacin recommends to avoid excessive exercise stresses.

During treatment by ciprofloxacin, in order to avoid development of a crystalluria, exceeding of the recommended daily dose is inadmissible. It is also necessary to provide reception of enough liquid (under control of a diuresis) for observance of a normal diuresis and maintenance of acid reaction of urine.

During the period, treatments by ciprofloxacin it is necessary to avoid ultra-violet radiation (including contact with direct sunshine).

During therapy increase протромбиновсго an index (when carrying out surgical interventions it is necessary to control a condition of system of a blood coagulation) is possible.

At patients with deficit of a glyukozo-6-dehydrogenase purpose of ciprofloxacin can become the reason of development of hemolitic anemia.

During treatment patients should not take alcohol.

At pregnancy and in the period of a lactation it is impossible to appoint drug. 

The patients accepting ciprofloxacin should be careful during the driving of the car and occupations other potentially olasny types of activity requiring special attention and speed of psychomotor reactions (especially at simultaneous alcohol intake).

Side effects:

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

From the central and peripheral nervous system: dizziness, a headache, increased fatigue, excitement, spasms, uneasiness, a tremor, sleeplessness, "dreadful" dreams, a peripheral mialgeziya (anomaly of perception of feeling of pain), a hyperesthesia, giposteziya, perspiration, increase in intracranial pressure, confusion of consciousness, a depression, hallucinations, and also other manifestations of psychotic reactions (which are occasionally progressing to states in which the patient can do himself harm, with suicide tendencies), migraine.

From sense bodys: disturbance of taste and sense of smell, taste loss (tranzitorny), vision disorders (a diplopia, change tsvetovospriyatit), a sonitus, decrease in hearing, tranzitorny deafness (especially for high frequencies).

From warmly vascular system: tachycardia, disturbances of a cordial rhythm, a lowering of arterial pressure (ABP), a syncope, feeling of "inflows" of blood to face skin, thrombosis of cerebral arteries, peripheral hypostases.

From the hemopoietic system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolitic anemia, pancytopenia, agranulocytosis, oppression of a marrowy hemopoiesis.

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 azotovydelitelny function of kidneys, intersticial nephrite.

Allergic reactions: a skin itch, a small tortoiseshell, blistering, followed by bleedings and small small knots forming crusts, medicinal fever, dot hemorrhages (petechias), a face edema or throats, short wind, an eosinophilia, a vasculitis, a dieback, a nodal erythema, an exudative multiformny erythema, Stevensa-Johnson's syndrome (a malignant exudative erythema), a toxic epidermal necrolysis (Lyell's disease), an acute anaphylaxis, a serum disease.

From a musculoskeletal system: an arthralgia, arthritis, a tendovaginitis, ruptures of sinews, a mialgiya, hypostasis in a joint.

Others: the general weakness, superinfections (candidiasis, псевдомембранозньй colitis), the raised photosensitivity.

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

Interaction with other medicines:

At simultaneous use of ciprofloxacin with didanoziny absorption of ciprofloxacin decreases owing to formation of complexes of ciprofloxacin with the aluminum and magnesian salts which are contained in the didanozena. Owing to decrease of the activity of processes of a microsomal oxidation in hepatocytes, increases concentration and extends an elimination half-life of theophylline and/or caffeine (etc. xanthines), peroral hypoglycemic drugs (Glibenclamidum - that can lead to a hypoglycemia), indirect anticoagulants, promotes decrease in a prothrombin ratio.

Ciprofloxacin is raised by Smakh 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. The concomitant use with non-steroidal anti-inflammatory drugs (excepting acetylsalicylic acid) - increases risk of development of spasms. The concomitant use of antacids, a sukraljfata, and also the drugs containing ions of aluminum, zinc, calcium, iron or magnesium can cause decrease in absorption of ciprofloxacin therefore Tsiprinol CP it is necessary to accept in 2 hours prior to reception of antacids or 6 hours later after their reception.

At simultaneous use of a tsiprofoksatsin and cyclosporine nephrotoxic effect of cyclosporine amplifies (control of level of creatinine of blood 2 times a week is necessary).

The concomitant use of ciprofloxacin and glucocorticosteroids can increase risk of emergence of a rupture of sinews.

 Co-administration of ciprofloxacin and Phenytoinum can lead to increase or decrease in serumal concentration of Phenytoinum.

Metoclopramidum accelerates ciprofloxacin absorption that leads to reduction of time of achievement of its maximum concentration in a blood plasma.

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: drug can successfully be used in a combination with azlotsipliny and a ceftazidime at infections of the caused 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 mephitic gangrenes.

Simultaneous use of a probenetsid and ciprofloxacin reduces renal clearance of ciprofloxacin, increasing its concentration in a ptazma.

Simultaneous administration of ciprofloxacin and meksiletin can lead to increase in concentration of a meksiletin.

At simultaneous use with ciprofloxacin tubular transport of a methotrexate decreases that can potentially lead to increase in its plasma concentration. At the same time the risk of toxic action of a methotrexate increases. The patients receiving therapy by a methotrexate need to be under careful medical observation during treatment by ciprofloxacin.

Contraindications:

1. Hypersensitivity to ciprofloxacin or other drugs from group of hinolon or to any other component of drug.
2. Pregnancy and period of a lactation.
3. Children's and teenage age up to 18 years.
4. A concomitant use with tizanidiny (risk of the expressed lowering of arterial pressure (ABP), drowsiness).
5. Pseudomembranous colitis;
6. Expressed renal (the clearance of creatinine (CC) <30 ml/min.) and/or a liver failure;
7. Diseases of the central nervous system (epilepsy, a reduced threshold of convulsive readiness, a convulsive syndrome in the anamnesis, disturbance of cerebral circulation, mental diseases).

With care: the expressed atherosclerosis of vessels of a brain, a renal and/or liver failure, advanced age, deficit of a glyukozo-6-dehydrogenase (risk of development of hemolitic anemia), therapy by glucocorticosteroids.

Overdose:

Symptoms: nausea, vomiting, diarrhea, a headache and dizziness, disturbances from a liver and kidneys, a crystalluria and a hamaturia, in more hard cases confusion, a tremor, hallucinations and spasms.

Treatment: symptomatic, gastric lavage, purpose of absorbent carbon and laxatives; to provide sufficient intake of liquid. The specific antidote is unknown. The hemodialysis does not render clinical effect at intoxication.

Storage conditions:

List B. To store at a temperature not above 30 °C. To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets of the prolonged action, film coated, 500 mg. 5 or 7 tablets in a blister strip packaging. 1 blister strip packaging on 7 tablets or 2 blister strip packagings on 5 tablets together with the application instruction is placed in a pack cardboard.