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

Antimicrobial preparation of a broad spectrum of action from the group of fluoroquinolones. It is bactericidal. The drug inhibits the enzyme DNA-giperazu bacteria (topoisomerases II and IV, responsible for the process of supercoiling the chromosomal DNA around the nuclear RNA, which is necessary for reading the genetic information), violates the synthesis of DNA,growth and division of bacteria; causes significant morphological changes (including the cell wall and membranes) and the rapid death of the bacterial cell.

Ciprofloxacin acts bacteriocally on gram-negative organisms during rest and division (since it affects not only 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 DNA-gyrase inhibitors, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines.

Gram-negative aerobic bacteria are sensitive to ciprofloxacin: 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.), other 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., Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii.

Gram-positive aerobic bacteria are also sensitive to ciprofloxacin: Staphylococcus spp.(Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

Active with respect to Bacillus anthracis.

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).

The drug is resistant Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides.

The drug is not effective against Treponema pallidum.

Pharmacokinetics:

When taken orally ciprofloxacin quickly and quite fully absorbed from the gastrointestinal tract (mainly in the 12-finger and jejunum). Eating slows down absorption, but does not change the maximum concentration (C_max) and bioavailability. Bioavailability of the drug is 50-85%. Time to reach the maximum concentration (TC_max) - 60-90 min, C_max linearly depends on the value of the dose taken and is about 2.4 and 5.4 μg / ml at doses of 500 and 1000 mg, respectively. After 12 hours after ingestion of 500 mg, the concentration of the drug in the plasma is reduced to 0.2 μg / ml.

Ciprofloxacin is well distributed in tissues and body fluids. High concentrations of the drug are achieved in bile, lung, kidney, liver, gall bladder, uterus, seminal fluid, prostate tissue, tonsils, endometrium,fallopian tubes and ovaries. Concentration in tissues is 2-12 times higher than in plasma. Ciprofloxacin also penetrates well into the bones, eye fluid, bronchial secretion, saliva, skin, muscles, pleura, peritoneum, lymph, through the placenta. In the cerebrospinal fluid the drug penetrates in a small amount, where its concentration in the absence of inflammation of the meninges is 6-10% of that in the serum, and when inflamed - 14-37%. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in blood serum.

The volume of distribution in the body is 2-3.5 l / kg.

The degree of binding of ciprofloxacin to plasma proteins is 20-40%. Metabolised in the liver (15-30%) with the formation of low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxocycloploxacin, formyl ciprofloxacin).

The half-life period (T1 / 2) is about 4 hours, with chronic renal insufficiency up to 12 hours. It is mainly excreted by the kidneys by tubular filtration and tubular secretion unchanged (40-50%) and metabolites (15%), the rest part - 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 failure (creatinine clearance above 20 ml / min), the percentage of ciprofloxacin excreted through the kidneys decreases, but cumulation in the body does not occur due to a compensatory increase in the metabolism of ciprofloxacin and excretion through the gastrointestinal tract.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to the preparation:

- diseases of the lower respiratory tract (acute and chronic (at the stage of exacerbation) bronchitis, pneumonia, bronchiectatic disease, infectious complications of cystic fibrosis);

- infection of the ENT organs (acute sinusitis);

- infection of the kidneys and urinary tract (cystitis, pyelonephritis);

- complicated intra-abdominal infections (in combination with metronidazole);

- chronic bacterial prostatitis;

- uncomplicated gonorrhea;

- typhoid fever,

- infectious diarrhea, including campylobacteriosis, shigellosis, diarrhea of "travelers";

- 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.

Children:

- therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years.

- prevention and treatment of pulmonary form of anthrax (infection Bacillus anthracis).

Contraindications:

- increased sensitivity to ciprofloxacin or other drugs from the group of fluoroquinolones;

- children and adolescents up to the age of 18 (except for the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years; prevention and treatment of pulmonary form of anthrax),

- simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure, drowsiness)

- pregnancy;

- the period of breastfeeding;

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulation disorder, mental illness, epilepsy, severe renal and / or hepatic insufficiency, elderly age, tendon lesions with previous treatment with fluoroquinolones.

Dosing and Administration:

Inside.Tablets should be swallowed whole with a small amount of liquid after eating. When taking a tablet on an empty stomach, the active substance is absorbed more quickly.

The dose of ciprofloxacin and the duration of treatment depends on the severity of the disease, type of infection, age, weight of the patient and kidney function. Recommended doses are usually:

- For infections of the lower respiratory tract of mild and moderate degree - 500 mg 2 times a day. The course of treatment is 7-14 days.

- In acute sinusitis - 500 mg 2 times a day. The course of treatment is 10 days.

- With infection of the skin and soft tissues of mild and moderate degree - 500 mg 2 times a day. The course of treatment is 7-14 days.

- When infections of bones and joints - mild and moderate - 500 mg 2 times a day. The course of treatment is up to 4-6 weeks.

- With infections of the urinary tract - 500 mg 2 times a day. The course of treatment - 7-14 days, with uncomplicated cystitis in women - 3 days.

- With chronic bacterial prostatitis - 500 mg 2 times a day. The course of treatment is 28 days.

- With uncomplicated gonorrhea - 500 mg g once.

- With typhoid fever, 500 mg twice a day. The course of treatment is 10 days.

- With infectious diarrhea - 500 mg 2 times a day. The course of treatment is 5-7 days.

- For complicated intra-abdominal infections, 500 mg every 12 hours for 7-14 days.

- Other infections (seesection "Indications for use") - 500 mg 2 times a day.

For the prevention and treatment of pulmonary form of anthrax - 500 mg twice a day for 60 days.

In pediatrics:

- in the treatment of complications caused by Pseudomonas aeruginosa, in children with cystic fibrosis of the lungs from 5 to 17 years - 20 mg / kg 2 times a day (maximum dose of 1500 mg). Duration of treatment is 10-14 days.

- With pulmonary form of anthrax (prevention and treatment) - 15 mg / kg 2 times a day. The maximum single dose is 500 mg, the daily dose is 1000 mg. The total duration of taking ciprofloxacin is 60 days.

Chronic kidney failure:

Table of recommended doses of the drug for patients with chronic renal failure:

Creatinine clearance ml / min	Dose
>50	The usual dosing regimen
30-50	500 mg once every 12 hours
5 - 29	500 mg once every 18 hours

Patients on hemo-or peritoneal dialysis - 500 mg once every 24 hours, but should take the drug after a hemodialysis session.

Side effects:

From the digestive system: 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), increased intracranial pressure, anxiety, confusion, depression, hallucinations, and other manifestations of psychotic reactions (occasionally progressing to conditions in which the patient can do harm to himself), migraine, fainting.

From the sense organs: violation of taste and smell, visual impairment (diplopia, change in color perception), tinnitus, hearing loss.

From the cardiovascular system: tachycardia, cardiac arrhythmias, lowering blood pressure, thrombosis of the cerebral arteries, "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.

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

Allergic reactions: itching, hives, blisters, accompanied by bleeding, and small nodules that form scabs, drug fever, petechial hemorrhages (petechiae), swelling of the face or throat, shortness of breath, eosinophilia, vasculitis, erythema nodosum, exudative erythema multiforme, Stevens-Johnson syndrome ( malignant exudative erythema), toxic epidermal necrolysis (Lyell's syndrome).

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

Other: general weakness, superinfection (candidiasis, pseudomembranous colitis), increased sensitivity to light, sweating.

Overdose:

Treatment: The specific antidote is unknown. It is necessary to carefully monitor the patient's condition, make gastric lavage, carry out usual 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 the decrease in the activity of microsomal oxidation in hepatocytes, it increases the concentration and prolongs the half-life of theophylline (and other xanthines, for example, caffeine), oral hypoglycemic drugs, indirect anticoagulants, and helps to reduce the prothrombin index.

When combined with other antimicrobial agents (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, leads to a decrease in the absorption of ciprofloxacin, so it should be prescribed 1-2 hours before or 4 hours after the administration of the above drugs.

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 ions of aluminum and magnesium. .

Metoclopramide accelerates absorption, which leads to a decrease in the time to reach its maximum concentration (C_max).

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

Increases the maximum concentration (C_max) in 7 times (from 4 to 21 times) and the area under the concentration / time curve (AUC) 10 times (from 6 to 24 times) of tizanidine, which increases the risk of pronounced decrease in blood pressure and drowsiness.

Special instructions:

Ciprofloxacin is not a drug of choice in suspected or established pneumonia caused by Streptococcus pneumoniae.

To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, adequate fluid intake and maintenance of acid urine reaction are also necessary.

Patients with epilepsy, seizures history of seizures, vascular diseases and organic brain lesions, because of the threat of adverse reactions in 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, avoid contact with UV rays, including direct sunlight.

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

Patients receiving ciprofloxacin, you should refrain from driving a car and practicing other potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated 500 mg.

Packaging:

For 10 tablets in a planar cell packaging made of polyvinylchloride film and aluminum foil printed lacquered.

1 or 2 contour squares, together with instructions for use, are placed in a pack of cardboard.

Storage conditions:

In a place protected from light and moisture at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LS-000424

Date of registration:24.05.2010

The owner of the registration certificate:VALENTA PHARM, PAO VALENTA PHARM, PAO Russia

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Information update date: & nbsp24.10.2015

Illustrated instructions

Instructions

Ciprofloxacin (Ciprofloxacin)