Ципринол®

General characteristics. Structure:

Acting veshchestvo:100 with ciprofloxacin mg.

Вспомогательні substances: lactic acid, dinatrium эдетат, Acidum hydrochloricum концентрированнаядо Ph = 3,4-3,6, water for injections

Antimicrobic means of a wide range of antibkterialny 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 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., 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 (TCmax) - 60 min., the maximum concentration (Cmax) - 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 (Т½) - 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 mochevgeodyashchy ways: 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.

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.

Before use 1 ampoule of a concentrate for preparation of solution for infusions needs to be parted with adequate amount of infusion solution: 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 up to the minimum volume of 50 ml.

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 introductions 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, urinary tract 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 mg 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 ciprofloxacin 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 simultaneous administration of ciprofloxacin and medicine constant control of the heart rate (HR), the ABP, an ECG is necessary for the general anesthesia from group of derivatives of barbituric acid.

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.

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 dangerous 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 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.

Achlergichesky 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, тендовагиннт, 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 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. The concomitant use with non-steroidal anti-inflammatory drugs (excepting acetylsalicylic acid) - increases risk of development of spasms. At simultaneous use of a tsiprofoksatsin of 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.

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; with izoksazolilpenitsillina and Vancomycinum  - 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);
• Concomitant use with tizanidiny (risk of the expressed lowering of arterial pressure (ABP), drowsiness).

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.

Overdose:

Symptoms: nausea, vomiting, diarrhea, a headache and dizziness, and in more hard cases confusion, a tremor, hallucinations and spasms.

Treatment:    symptomatic    to provide    sufficient    intake    of liquid. The specific antidote is unknown. The hemodialysis does not render clinical effect at intoxication.

Storage conditions:

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

Issue conditions:

According to the recipe

Packaging:

Concentrate for preparation of solution for infusions, 10 mg/ml. On 10 ml in ampoules from neutral transparent glass. The color point on site of a break is applied on an ampoule. On 5 ampoules in the blister or on 5 ampoules in a plastic planimetric strip packaging. 1 blister or 1 plastic planimetric strip packaging in a pack cardboard together with the application instruction.