Ципринол®

General characteristics. Structure:

Active ingredient: 100 mg of ciprofloxacin on each 50 ml of solution.

Excipients: sodium a lactate, sodium chloride, Acidum hydrochloricum, water for injections.

Antimicrobic means of a wide range of atibakterialny action of group of ftorkhinolon for infusional introduction.

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 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. 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, 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, Mycobacterium avium (located intracellularly).        Also gram-positive  aerobic bacteria are sensitive to a tsiprofloksatsiy: 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., Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Effect of drug concerning Treponema pallidum is studied insufficiently. Both in vitro, and in vivo is also sensitive Bacillus anthracis to ciprofloxacin.

Pharmacokinetics. After intravenous (in/in) infusions of 200 mg or 400 mg, time of achievement of the maximum concentration (Tstakh) - 60 min., the maximum concentration (Stakh) - 2,1 mkg/ml and 4,6 mkg/ml respectively. Distribution volume in an organism varies from 1,74 to 5 l/kg, communication with proteins of plasma - 19 - 40%. It is well distributed in body tissues (excepting the fabric rich with fats, for example, nervous tissue). Content in fabrics is 2-12 times higher, than in plasma. 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%. Ciprofloxacin also well gets through a placenta. Concentration of ciprofloxacin in neutrophils of blood is 2-7 times higher, than in serum. It is metabolized  in  a liver  (15-30%)  with  formation  of low-active  metabolites (diethylciprofloxacin,  sulfociprofloxacin, oxociprofloxacin, formiltsiprofloksation).

At in introduction an elimination half-life (T1/2) - 3 - 5 h, at the chronic renal failure (CRF) -  to 12 h. It is removed generally by kidneys, by tubular filtering and canalicular secretion in an invariable look (at in introduction - 50-70%) and in the form of metabolites (at in introduction - 10%), other part - through a digestive tract.  A small amount is removed with breast milk.  Later in/in introductions concentration in urine during the first 2 h after introduction almost in 100 times more, than in serum that considerably surpasses the minimum overwhelming concentration (MOC) for the majority of causative agents of infections of urinary tract. Renal clearance - 3-5 ml/min.; the general clearance - 8-10 ml/min. At HPN (the clearance of creatinine (CC) - 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 through intestines.

Indications to use:

• The infectious and inflammatory diseases caused by microorganisms, sensitive to ciprofloxacin:
• respiratory tracts: pneumonia (except for pneumococcal pneumonia), an acute bronchitis and an exacerbation of chronic bronchitis, a bronchoectatic disease, a mucoviscidosis (if the activator are gram-negative bacteria, especially Pseudomonas aeruginosa);
• fish soup, throat and nose: acute average otitis, sinusitis, mastoiditis;
• kidneys and urinary tract: the uncomplicated and complicated infections of the lower and upper parts of an uric path (an urethritis, cystitis, pyelonephritis);
• bodies of a small pelvis and generative organs (epididymite, prostatitis, salpingitis, endometritis, oophoritis, tubular abscess and pelviperitonitis, gonorrhea, venereal ulcer, clamidiosis);
• abdominal organs: peritonitis, intraperitoneal abscess; cholecystitis, a cholangitis (in a combination with metronidazole or clindamycin), infectious diarrhea: salmonellosis, campilobacteriosis, иерсиниоз, shigellosis, cholera, typhoid;
• skin and soft tissues: the infected ulcers, contaminated wounds, abscesses, phlegmon, infections of outside acoustical pass infected burns;
• musculoskeletal system: osteomyelitis, septic arthritis;
• Sepsis, infections at patients with reduced immunity (against the background of therapy by immunodepressants or at patients with a neutropenia).
• Prevention of infections at surgical interventions (urological, on digestive tract (in a combination with metronidazole) and orthopedic).
• Prevention and treatment of a pulmonary form of a malignant anthrax.

Use in pediatrics. Ciprofloxacin is not recommended to be used at children up to 18 years for treatment of other infectious diseases, except:

• treatment and prevention of a malignant anthrax (after the assumed or proved Bacillus anthracis infection);
• therapy of the complications caused by Pseudomonas aeruginosa in children with a mucoviscidosis of easy from 5 to 17 years.

Route of administration and doses:

 It is appointed intravenously, it is possible to enter in/in struyno, but drop introduction within 30 minutes (200 mg) and 60 minutes (400 mg) is more preferable. The dose of ciprofloxacin  depends  on    disease severity,  type  of an infection, a condition of an organism, age, weight and function of kidneys at the patient.

The doses recommended usually:
for in/in maintaining a single dose - 200 mg (at heavy infections - 400 mg), frequency rate of introduction - 2 times a day. If necessary in/in treatments  of especially heavy,  life-threatening or recurrent infections caused by Pseudomonas spp., stafilokokkam or Streptococcus pneumoniae; sepsis, peritonitis, an infection of bones and joints the dose can be increased to 0,4 g with frequency rate of introduction to 3 times a day.

At acute uncomplicated gonorrhea - once, in/in 100 mg. For prevention of postoperative infections - in 30 - 60 minutes prior to operation in/in 200 - 400 mg; at long operation over 4 h are entered repeatedly in the same dose. Average duration of treatment:  1 day - at acute uncomplicated gonorrhea; up to 7  days - at infections of kidneys, mochevgvodyashchy ways 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. To elderly patients the dose is lowered by 30%. 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 - 800 mg. The patient with a heavy renal failure (KK is lower than 30 ml/min. / 1,73 of sq.m; concentration of creatinine are higher than 2 mg / 100 ml) it is necessary to appoint a half of a daily dose, the maximum daily dose - 400 mg.

At peritonitis at the patients who are on out-patient peritoneal dialysis, perhaps intraperitoneal administration of ciprofloxacin in a dose of 50 mg 4 times a day on 1 l of dialyzate. Solution for infusion can be combined from 0,9% chloride sodium solution, Ringer's solution, 5% and 10% solution of a dextrose, 10% fructose solution, and also the solution containing 5% dextrose solution from 0,225% or 0,45% chloride sodium solution. Later in/in uses it is possible to continue treatment orally.

At a pulmonary form of a malignant anthrax (prevention and treatment): Adults: on 400 мт in / twice a day. Children (from 5 to 17 years): 10 mg/kg of body weight 2 times a day. It is not necessary to exceed the maximum single dose - 400 mg in/in (the maximum daily dose – 800 mg). Treatment should be begun right after the assumed or confirmed infection. The general duration of treatment by ciprofloxacin at a pulmonary form of a malignant anthrax makes 60 days. At  treatment  of the complications  caused    by Pseudomonas aeruginosa  at  children  with a mucoviscidosis of easy from 5 to 17 years the recommended dose of a piprofloksatsin makes  10  mg/kg  each  8  h  (    no more than 400  mg  in/in  each  8  h). Duration of treatment is 10-14 days.

Features of use:

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 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 of an inflammation (preferential at the elderly patients who are at the same time receiving  glucocorticosteroids) 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 treatment by ciprofloxacin it is necessary to avoid ultra-violet radiation (including contact with direct sunshine).  During therapy   increase in a prothrombin    ratio (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-phosphate-dehydrogenase   Tsiprinol's appointment can become the reason of development of hemolitic anemia. During treatment patients should not take alcohol. 1 ml  of solution for infusions Tsiprinol  contains 3,61 mg of sodium. Therefore patients for whom the diet with the low content of sodium is recommended need to be careful.

With care: the expressed atherosclerosis of vessels of a brain, disturbance of cerebral circulation, mental diseases, an epileptic syndrome, epilepsy, the expressed renal and/or liver failure, advanced age, deficit of a glyukozo-6-phosphate-dehydrogenase, therapy of glucocorticosteroids, patients for whom the diet with the low content of sodium is recommended.

The patients accepting ciprofloxacin should be careful during the driving of the car and occupations other potentially dangerous types of activity requiring special attention and speed psychomotor reaction (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  paralgeziya (anomaly of perception of feeling of pain), 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, unconscious states, thrombosis of cerebral arteries.

From sense bodys: disturbance 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, a lowering of arterial pressure (ABP), feeling of "inflows" of blood to face skin.

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

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.

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

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

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

Local: pain and burning in an injection site, phlebitis.

Interaction with other medicines:

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 (warfarin, etc.), promotes decrease in a prothrombin ratio (risk of development of bleedings).

Ciprofloxacin is raised by Stakh 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. 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.

The simultaneous nazanacheniye of ciprofloxacin and Phenytoinum can lead to increase or decrease in serumal concentration of Phenytoinum. 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 azlotsilliny and a ceftazidime at infections of the caused Pseudomonas spp.; with mezlotsilliny, azlotsilliny and others beta лактамными antibiotics - at streptococcal infections; from izoksazolilpenshchillina and vankomshchiny - at staphylococcal infections; with metronidazole and clindamycin - at mephitic gangrenes.

Infusion solution pharmaceutical is incompatible with all infusion solutions and medicines which physical and chemically are unstable in acid medium (рН infusion solution of ciprofloxacin - 3,5 - 4,6).

Contraindications:

• Hypersensitivity to ciprofloxacin or other drugs
from group of hinolon or to any other component of drug.
• Pregnancy and period of a lactation.
• Children's and teenage age up to 18 years (except therapy of the complications caused by Pseudomonas aeruginosa in children with a mucoviscidosis of lungs at children from 5 to 17 years; prevention and treatment of a pulmonary form of a malignant anthrax);
• A concomitant use with tizanidiny (risk of the expressed lowering of arterial pressure (ABP), drowsiness).

Overdose:

If the patient accepted  too large number of tablets   at one time, it is necessary  to call the doctor immediately.

Overdose symptoms: excessive decrease in the ABP up to development of a collapse, a myocardial infarction, an acute disorder of cerebral circulation or tromboembolic episodes, spasms, a stupor.

Treatment: the patient is transferred to horizontal position with a low headboard.

In mild cases the gastric lavage and intake of saline solution, in more serious cases – the actions directed to stabilization of the ABP in/in introduction of normal saline solution, plasma substitutes, if necessary – in/in administration of angiotensin II, a hemodialysis are shown (enalaprilat removal speed - 62 ml/min.). 

Storage conditions:

List B. To store in the place protected from light, at a temperature not above 30 °C. Not to freeze! To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Solution for infusions of 2 mg/ml. On 50 ml or 100 ml, or 200 ml of solution for infusions in the transparent bottle (glass type I) corked with a rubber cover with the teflon film which is rolled up by an aluminum cap and from above closed by a plastic cover on which the text of "flip off" is applied. The internal production code of drug is applied on an aluminum cap. On 1 bottle of 50 ml or 100 ml, or 200 ml place in a pack cardboard together with the application instruction.