medicalmeds.eu Medicines Antimicrobic means, фторхинолон. Ципринол®

Ципринол®

Producer: Krka Slovenia

Code of automatic telephone exchange: J01MA02

Release form: Firm dosage forms. Tablets.

Indications to use: Pneumonia. Acute bronchitis. Chronic bronchitis. Bronchoectatic disease. Mucoviscidosis. Average otitis. Sinusitis. Mastoiditis. Urethritis. Cystitis. Pyelonephritis. Epididymite. Prostatitis. Salpingitis. Endometritis. Oophoritis. Pelviperitonitis. Gonorrhea. Venereal ulcer. Clamidiosis. Intra belly abscesses. Salmonellosis. Cholera. Typhoid. Diarrhea of travelers. Campilobacteriosis. Iyersinioz. Dysentery (shigellosis). Contaminated wounds. Phlegmon. The infected burns. Osteomyelitis. Septic arthritis. Malignant anthrax. Prevention of a malignant anthrax.

General characteristics. Structure:

Active ingredient: 291 mg, 582 mg or 873 mg of ciprofloxacin in the form of monohydrate hydrochloride ciprofloxacin (that corresponds to ciprofloxacin - 250 mg, 500 mg and 750 mg).

Excipients: cellulose microcrystallic, sodium carboxymethylstarch (type A), povidone, croscarmellose sodium, silicon dioxide colloid anhydrous, magnesium stearate.

Cover: gipromelloza, talc, titanium dioxide, E171, propylene glycol.

Antimicrobic drug of broad antibacterial action of group of ftorkhinolon.

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. At oral administration ciprofloxacin is quickly soaked up from digestive tract. Meal slows down absorption, but does not change the maximum concentration and bioavailability. Bioavailability of drug makes 50-85%. The maximum concentration of drug in blood serum of healthy volunteers at oral administration (to food) 250, 500, 750 and 1000 mg of drug, is reached in 1-1,5 hours and makes 1,2; 2,4; 4,3 and 5,4 mkg/ml respectively.

Orally accepted ciprofloxacin well is distributed in fabrics and liquids of an organism. High concentration of drug are observed in bile, lungs, kidneys, a liver, a gall bladder, a uterus, semen, prostate 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. Distribution volume in an organism makes 2-3,5 l/kg. Extent of linkng of ciprofloxacin with proteins of plasma makes 30%.

It is metabolized in a liver (15-30%) with formation of low-active metabolites (diethylciprofloxacin, sulfociprofloxacin, oxociprofloxacin, formylciprofloxacin).

The main way of removal of ciprofloxacin from an organism - a kidney (50-70%). From 15 to 30% are removed through intestines. At patients with not changed function of kidneys the elimination half-life makes usually 3-5 hours. At a chronic renal failure increases to 12 h. A small amount is removed with breast milk.

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 is 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: 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.
• skin and soft tissues: the infected ulcers, contaminated wounds, abscesses, phlegmon, infections of outside acoustical pass infected burns;
• musculoskeletal system: osteomyelitis, septic arthritis;

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:

Inside, on 0,25 g 2-3 times a day, at the heavy course of an infection - 0,5-0,75 g 2 times a day (each 12 h). Drug should be accepted on an empty stomach, to swallow tablets entirely, washing down with enough liquid. 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 recommended schemes of dosing:

• uncomplicated infections of kidneys and urinary tract: on 250 mg, and at the complicated infections - on 500 mg 2 times a day; a course of treatment of uncomplicated infections of lower parts of urinary tract - 3 days; the complicated infections of urinary tract - 7-10 days;

• chronic prostatitis: on 500 mg 2 times a day, duration of treatment is-28 days;

• infectious and inflammatory diseases of lower parts of moderately severe respiratory tracts - on 250 mg - 500 mg, and in more hard cases on 750 mg, 2 times a day;

• acute gonorrhea: a single dose of ciprofloxacin in a dose of 250 mg - 500 mg; at a combination of a gonococcal infection with Chlamidia and mycoplasmal - to 750 mg there are each 12 hours within 7-10 days;

• шанкроид: on 0,5 g 2 times a day within several days;

• S.typhi bacteriocarrier: on 250 mg 2 times a day; a course of treatment up to 4 weeks. If necessary the single dose can be increased to 500 mg or 750 mg;

• heavy infections (osteomyelitis, infections of an abdominal cavity) - on 750 mg 2 times a day. Duration of therapy of osteomyelitis can make up to 2 months;

• the GIT infections caused by Staphylococcus aureus - on 750 mg each 12 hours within 7-28 days;

• treatment diarrhea of travelers: 500 mg 2 times a day, duration are from 5 to 7 days, in certain cases — up to 14 days;

• infections of an ear, throat and nose: moderate severity of 250-500 mg 2 times a day, heavy degree of 500-750 mg 2 times a day;

• 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 20 mg/kg of weight 2 times a day (the maximum dose of 1500 mg). Duration of treatment is 10-14 days;

• prevention of infections at surgical interventions: from 500 to 750 mg
Tsiprinola is appointed in 1-1,5 hours prior to operation;

• treatment and prevention of a malignant anthrax at patients: 2 times a day adults and 15 mg on kg of body weight of Tsiprinol have 500 mg of Tsiprinol at children 2 times a day. Administration of drug should be begun right after the assumed or confirmed infection. In an initiation of treatment use of parenteral forms is recommended. The general duration of therapy is 60 days.

Duration of treatment depends on disease severity, but treatment always has to continue at least three more days after normalization of temperature. Usually duration of treatment makes 7-10 days.
Patients with the expressed renal failures should appoint a half dose of drug.

Dosing at CRF (chronic renal failure):
Clearance of creatinine of ml/min.	Dose
> 50	usual mode of dosing
30-50	250-500 mg of 1 times at 12 o'clock
5-29	250-500 mg of 1 times at 18 o'clock
the patients who are on a hemodialysis or peritoneal dialysis	250-500 mg of 1 times at 24 o'clock

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 treatment by ciprofloxacin it is necessary to avoid UF - 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-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.

From the central and peripheral nervous system: dizziness, a headache, the increased fatigues, 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.

From sense bodys: disturbance of taste and sense of smell, vision disorder (diplopia, change of color perception), sonitus, decrease in hearing.

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

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, superinfections (candidiasis, pseudomembranous 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 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. The concomitant use of antacids, a sukralfata, and also the drugs containing ions of aluminum, zinc, calcium, iron or magnesium can cause decrease in absorption of ciprofloxacin therefore the interval between purpose of these drugs has to be not less than 4 h.

At simultaneous use of ciprofloxacin 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 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.

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).

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-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, 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.