Ciprofloxacin - instructions for use, dose, side effects, contraindications

Ciprofloxacin (in the form of ciprofloxacin hydrochloride monohydrate 291.50 mg) 250 mg. Excipients: microcrystalline cellulose, corn starch, sodium carboxymethyl starch, silicon dioxide colloid, magnesium stearate.

Composition of the film shell: hypromellose phthalate, titanium dioxide.

Ciprofloxacin 500 mg:

Active substance:

Ciprofloxacin (in the form of ciprofloxacin hydrochloride monohydrate 582.21) 500 mg. Excipients: microcrystalline cellulose, corn starch, sodium carboxymethyl starch, silicon dioxide colloid, magnesium stearate, propylene glycol.

Composition of the film shell: hypromellose phthalate, titanium dioxide.

Description:

250 mg tablets: Biconvex, round tablets of white color, film-coated, on one side, engraving "NP" on the background of wood.

Tablets 500 mg: Two-convex oval-shaped tablets of white color, film-coated, with a dividing strip on one side, on the other side an engraving "NP" on the background of a tree.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

A broad-spectrum antimicrobial agent, a derivative of fluoroquinolone, inhibits bacterial DNA gyrase (responsible for the process of supercoiling the chromosomal DNA around the nuclear RNA, which is necessary for reading out genetic information), disrupts DNA synthesis, growth and division of bacteria; causes significant morphological changes (including the cell wall and membranes) and the rapid death of the bacterial cell.

It acts bactericidal on gram-negative organisms during rest and division (because it affects not only the DNA-gyrase, but also causes lysis of the cell wall), gram-positive microorganisms - only during the fission period.

Low toxicity for macroorganism cells is explained by the absence of DNA-gyrase in them. Against the background of taking ciprofloxacin, there is no parallel development of resistance to other antibiotics that do not belong to the group of inhibitors of gyrase, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics.

Ciprofloxacin is sensitive to gram-negative aerobic bacteria - enterobacteria (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.), dR. gram-negative bacteria (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.), some intracellular pathogens - Legionella pneumophila, Brucella spp., Chlamydia trachomatis, 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).

The majority of staphylococci, resistant to methicillin, are resistant to ciprofloxacin. Sensitivity of bacteria Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) - moderate (to suppress them, high concentrations are required).

To the drug are resistant: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroids. He is effective against Treponema pallidum.

Resistance develops very slowly, since on the one hand, after the action of ciprofloxacin, there are practically no persistent microorganisms, and on the other hand bacterial cells do not have enzymes that inactivate it.

Pharmacokinetics:

When taken orally, it is quickly and sufficiently absorbed from the gastrointestinal tract (mainly in the duodenum and jejunum). Eating slows down absorption, but does not change the maximum concentration and bioavailability.Bioavailability is 50-85%, the volume of distribution is 2-3.5 l / kg, the connection with plasma proteins is 20-40%. The maximum oral concentration is 60-90 minutes, the maximum plasma concentration is linearly dependent on the dose taken and is 1.2, 2.4, 4.3 and 5.4 μg / ml at doses of 250, 500, 750 and 1000 mg, respectively. After 12 hours after ingestion of 250, 500 or 750 mg, the concentration of the drug in the plasma is reduced to 0.1, 0.2 and 0.4 μg / ml, respectively.

Well distributed in body tissues (excluding tissue, rich in fats, for example, nervous tissue). The content in the tissues is 2-12 times higher than in the plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gall bladder, bile, intestine, abdominal organs, pelvic organs (including uterus, endometrium, fallopian tubes and ovaries), seminal fluid, prostate tissue, kidney and urinary tract, pulmonary tissue, bronchial secretion, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. The cerebrospinal fluid penetrates in a small amount, where its concentration in non-inflamed meninges is 6-10 % from that in the blood serum, and when inflamed - 14-37%. Ciprofloxacin also well penetrates into the eye fluid, pleura, peritoneum, lymph, through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum.

Metabolised in the liver (15-30%) with the formation of low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxocycloploxacin, formyl ciprofloxacin).

The half-life is about 4 hours with the oral route of administration. It is excreted mainly by the kidneys through tubular filtration and tubular secretion in an unchanged form (40-50 %) and in the form of metabolites (15%), the rest - through the gastrointestinal tract. A small amount is excreted in breast milk.

Kidney clearance - 3-5 ml / min / kg; total clearance - 8-10 ml / min / kg.

In chronic renal insufficiency (creatinine clearance above 20 ml / min), the percentage of the drug released through the kidneys decreases, but cumulation in the body does not occur due to a compensatory increase in the metabolism of the drug and excretion through the gastrointestinal tract. Patients with severe renal insufficiency (CC below 20 ml / min / 1.73 m 2) should be prescribed half the daily dose.

Indications:

Infectious-inflammatory diseases caused by sensitive microorganisms: respiratory tract infections - acute and chronic (at the stage of exacerbation) bronchitis, pneumonia, bronchiectasis,cystic fibrosis; infection of ENT organs - otitis media, sinusitis, frontal sinitis, sinusitis, mastoiditis, tonsillitis, pharyngitis; infection of the kidneys and urinary tracts - cystitis, pyelonephritis; infections of the pelvic organs and genital organs - prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubular abscess, gonorrhea, chancroid, chlamydia; infection of the abdominal cavity - bacterial infections of the gastrointestinal tract, biliary tract, salmonellosis, abdominal. typhus, campylobacteriosis, yersiniosis, shigellosis, cholera; infections of the skin and soft tissues - infected ulcers, wounds, burns, abscesses, phlegmon; bones and joints - osteomyelitis, septic arthritis; infection against the background of immunodeficiency (arising in the treatment of immunosuppressive drugs or in patients with neutropenia); prevention and treatment of pulmonary form of anthrax.

Contraindications:

Hypersensitivity to ciprofloxacin and other fluoroquinolones, simultaneous reception with tizanidine (risk of pronounced decrease in blood pressure, drowsiness), pseudomembranous colitis, children under 18 years of age, pregnancy, lactation, deficiency of glucose-6-phosphate dehydrogenase.

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulation disorder, mental illness, epileptic syndrome, epilepsy, marked renal and / or hepatic insufficiency, elderly age.

Dosing and Administration:

Inside, 250 mg 2-3 times a day, with severe infections - 500-750 mg 2 times a day (every 12 hours). The drug should be taken on an empty stomach, washed down with a sufficient amount of liquid. The dose of ciprofloxacin depends on the severity of the disease, the type of infection, the condition of the body, the age, weight and function of the kidney in the patient, but treatment should always last at least three more days after the symptoms disappear. Usually the duration of treatment is 7-10 days.

Recommended doses are usually:

uncomplicated infections of the kidneys and urinary tracts - 250 mg twice a day, for 3-5 days, and in complicated cases - 500 mg twice a day, for 7-14 days;
uncomplicated infections of the lower respiratory tract - 250 mg, and in more severe cases, 500-750 mg 2 times a day, for 7-14 days;
with uncomplicated gonorrhea, a single administration of ciprofloxacin in a dose of 250-500 mg is recommended; when combined gonococcal infection with Chlamydia and Mycoplasma - 750 mg 2 times a day, for 7-14 days;
chronic prostatitis - 500 mg 2 times a day, for 28 days;
infection of bones and joints - 500 mg twice a day, with a heavy course of 750 mg 2 times a day for 4 to 6 weeks;
infectious diarrhea - 500 mg twice a day, for 5-7 days;
typhoid fever - 500 mg twice a day, for 10 days;
infections of the skin and soft tissues - 500 mg 2 times a day, with a heavy course of 750 mg 2 times a day, for 7-14 days;
pulmonary form of anthrax - 500 mg twice a day, for 60 days.

Table of recommended doses of the drug for patients with renal insufficiency:

Creatinine clearance, ml / min	Dose
>50	The usual dosing regimen
30-50	250-500 mg once every 12 hours
5-29	250-500 mg once every 18 hours
Patients on hemolytic or peritoneal dialysis	after dialysis 250-500 mg once every 24 hours

Elderly patients are reduced by 30%.

Side effects:

On the part of the gastrointestinal tract: nausea, diarrhea, vomiting, abdominal pain, flatulence, decreased appetite, cholestatic jaundice (especially in patients with liver disease), hepatitis, hepatonecrosis.

From the nervous system: dizziness, headache, fatigue, anxiety, tremor, insomnia, "nightmarish" dreams, peripheral paralysis (anomaly of perception of pain), sweating,increased intracranial pressure, anxiety, confusion, depression, hallucinations, as well as other manifestations of psychotic reactions (occasionally progressing to conditions in which the patient may be harmed), migraine, fainting, thrombosis of the cerebral arteries.

From the senses: a violation of taste and smell, visual impairment (diplopia, change in color perception), noise in the ears, hearing loss.

On the part of the cardiovascular system: tachycardia, heart rhythm disturbances, lowering blood pressure, "tides" of blood to the skin of the face.

From the hematopoietic system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia.

Laboratory indicators: hypoprothrombinemia, increased activity of "liver" transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

On the part of the urinary system: hematuria, crystalluria (primarily in alkaline urine and low diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, decreased renal nitrogen function, interstitial nephritis.

From the musculoskeletal system: arthralgia, arthritis, tendovaginitis, tendon ruptures, myalgia.

Allergic reactions: skin itching, urticaria, the formation of blisters accompanied by bleeding, and the appearance of small nodules that form scabs, drug fever, pinpoint hemorrhages on the skin (petechiae), edema of the face or larynx, dyspnea, eosinophilia, vasculitis, nodal erythema, exudative erythema multiforme , Stevens-Johnson syndrome (malignant exudative erythema), toxic epidermal necrolysis (Lyell's syndrome).

Other: increased photosensitivity, asthenia, superinfections (candidiasis, pseudomembranous colitis).

Overdose:

Treatment: a specific antidote is unknown. It is necessary to carefully monitor the patient's condition, perform gastric lavage and other emergency measures, ensure sufficient fluid intake. With the help of hemo- or peritoneal dialysis, only a small amount (less than 10%) of the drug can be excreted.

Interaction:

Due to a decrease in the activity of microsomal oxidation in hepatocytes, it increases the concentration and lengthens the half-life of theophylline (et al.xanthines, for example, caffeine), oral hypoglycemic drugs, indirect anticoagulants, helps to reduce the prothrombin index.

When combined with other antimicrobial drugs (beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole) synergy is usually observed; can be successfully used in combination with azlocillin and ceftazidime in infections caused by Pseudomonas spp .; with mezlocillin, azlocillin, etc. beta-lactam antibiotics - with streptococcal infections; with isoxazolylpenicillins and vancomycin - with staphylococcal infections; with metronidazole and clindamycin - with anaerobic infections.

Increases the nephrotoxic effect of cyclosporine, there is an increase in serum creatinine, in such patients monitoring of this indicator is required 2 times a week.

With simultaneous reception increases the effect of indirect anticoagulants.

Oral administration together with iron-containing preparations, sucralfate and antacid preparations containing magnesium, calcium and aluminum ions, leads to a decrease in absorption of ciprofloxacin, therefore it should be prescribed 1-2 hours before or 4 hours after the administration of the above-mentioned agents.

Non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid) increase the risk of seizures.

Didanosine reduces the absorption of ciprofloxacin due to the formation of complexes with didanosine containing aluminum and magnesium salts. Metoclopramide accelerates absorption, which leads to a decrease in the time to reach its maximum concentration in the plasma.

Joint appointment of uricosuric drugs leads to a delay in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

Increases C_max (maximum concentration in plasma) 7-fold (4 to 21 times) and AUC (area under the "active substance concentration-time" curve) by 10 times (6 to 24 times) of tizanidine, which increases the risk of a marked decrease in blood pressure and drowsiness.

Special instructions:

In order to avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, adequate fluid intake is also necessary if normal diuresis is observed and urine acid reaction is maintained.

Patients with epilepsy, seizures in the anamnesis, vascular diseases and organic brain lesions,in connection with the threat of development of adverse reactions from the central nervous system ciprofloxacin should be prescribed only for "vital" indications.

If a severe and prolonged diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be deleted, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

When pain occurs in the tendons or the first signs of tendovaginitis treatment should be discontinued (individual cases of inflammation and even rupture of tendons during treatment with fluoroquinolones are described).

During the treatment period one should avoid contact with direct sunlight and artificial ultraviolet irradiation.

Effect on the ability to drive transp. cf. and fur:

During treatment, one should refrain from engaging in potentially dangerous activities that require increased attention and speed of mental and motor reactions.

Form release / dosage:

Tablets, film-coated 250 mg and 500 mg.

Packaging:By 10, 12, 14,20 tablets in a blister of PVC /Al. For 1, 2, 3, 4, 5 blisters in a cardboard box with instructions for use.

Storage conditions:

At a temperature of no higher than 25 ° C, in a dry, protected from light place.

Keep out of the reach of children!

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014453 / 01

Date of registration:05.02.2009

Date of cancellation:2017-03-02

The owner of the registration certificate:Natur Product Europe BVNatur Product Europe BV Netherlands

Manufacturer: & nbsp

NATUR PRODUKT EUROPE, B.V. Netherlands

Representation: & nbspNatur Product International Inc.Natur Product International Inc.Russia

Information update date: & nbsp02.03.2017

Illustrated instructions

Instructions

Ciprofloxacin (Ciprofloxacin)