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

A broad-spectrum antimicrobial agent, a quinolone derivative, suppresses bacterial DNA gyrase (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), 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.

The 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 actiobiotics 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.

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: 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 Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) - moderate (to suppress them, high concentrations are required). Ciprofloxacin is also sensitive Bacillus anthracis.

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

Resistance develops very slowly, because on the one hand, after the action of ciprofloxacin are left with persistent microorganisms, and on the other - the bacterial cells do not have the enzymes that inactivate it.

Pharmacokinetics:

After intravenous infusion of 200 mg or 400 mg, the time required to reach the maximum concentration (TCmax) - 60 min, the maximum concentration (Cmah) - 2,1 and 4,6 mkg / ml, respectively, the connection with plasma proteins - 20-40 % .

Well distributed in the tissues of the body (excluding tissue, rich in fats, for example, nervous tissue). Concentration in tissues is 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gall bladder, bile, intestine, abdominal and pelvic organs (endometrium, fallopian tubes and ovaries, uterus), seminal fluid, prostate tissue, kidney and urinary organs, lung tissue, bronchial secret,bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin; The cerebrospinal fluid 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%. Ciprofloxacin well penetrates also into the eye fluid, pleura, peritoneum, lymph, through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in blood serum.

The activity is somewhat reduced at pH values less than 6.

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

Half-life (T1 / 2) - 5-6 hours - with intravenous administration, with chronic renal failure - up to 12 hours. It is excreted mainly by the kidneys by tubular filtration and tubular secretion in unchanged form (50-70%) and in the form of metabolites ( 10%), the rest - through the gastrointestinal tract (GIT). A small amount is excreted in breast milk. After intravenous administration, the concentration in the urine during the first 2 hours after administration is almost 100 times greater,than in serum, which significantly exceeds the minimum inhibitory concentration for most pathogens of urinary tract infections.

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

In chronic renal failure (creatinine clearance (CC) above 20 ml / min), the percentage of the drug withdrawn 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.

Indications:

Bacterial infections caused by susceptible microorganisms:

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

infectionOP-organ (acute sinusitis);

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

Complicated intra-abdominal infections (in combination with metronidazole), incl. peritonitis;

chronic bacterial prostatitis; uncomplicated gonorrhea;

typhoid fever, campylobacteriosis, shigellosis, diarrhea of "travelers";

infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses,

phlegmon);

bones and joints (osteomyelitis, septic arthritis);

septicemia; infection on the background of immunodeficiency (arising in the treatment of immunosuppressive drugs or in patients with neutropenia); prevention of infections during surgical interventions; 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:

Hypersensitivity, simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure, drowsiness), children's age (up to 18 years - until the completion of the formation of the skeleton, in addition to 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), pregnancy, lactation.

Carefully:

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

Pregnancy and lactation:contraindicated

Dosing and Administration:

Intravenous infusion; the duration of the infusion is 30 minutes at a dose of 200 mg and 60 minutes at a dose of 400 mg. Infusion solutions ready for use can be mixed with 0.9% sodium chloride solution, Ringer's and Ringerlaktat solution, 5% and 10% dextrose solution, 10% fructose solution, and also a solution containing 5% dextrose solution with 0.225% or 0.45 % solution of sodium chloride.

With infections of the lower respiratory tract 200-400 mg 2 times a day.

With infections of the urinary tract: acute uncomplicated - 100 mg 2 times a day; cystitis in women (before menopause) - once 100 mg; Complicated - 200 mg 2 times a day.

With uncomplicated gonorrhea - 100 mg once, with extragenital - 100 mg 2 times a day.

Infectious diarrhea - 200 mg 2 times, the course of treatment - 5-7 days.

Particularly severe infections (streptococcal pneumonia, infectious complications of cystic fibrosis, infections of bones and joints, septicemia, peritonitis), especially caused Pseudomonas, Staphylococcus - 400 mg 3 times a day.

Pulmonary form of anthrax (treatment and prevention): 400 mg 2 times a day.

To prevent infections during surgical interventions - 200-400 mg for 0.5-1 h before the operation; When the duration of the operation is more than 4 hours, re-enter in the same dose.

With other infections (depending on the severity of the flow) - 200-400 mg 2 times a day.Older patients are prescribed lower doses, depending on the severity of the infection and the CC score.

In Pediatrics:

in the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years - 10 mg / kg 3 times a day (maximum dose of 1200 mg).

Duration of treatment is 10-14 days.

With a pulmonary form of anthrax (prevention and treatment) - 10 mg / kg 2 times a day. The maximum single dose is 400 mg, the daily dose is 800 mg. The total duration of taking ciprofloxacin is 60 days.

Chronic renal failure (CRF): at the glomerular filtration rate (CK 31 -60 ml / min / 1.73 m2 or serum creatinine concentration from 1.4 to 1.9 mg / 100 ml), the maximum daily dose is 800 mg. At the glomerular filtration rate (CC below 30 ml / min / 1.73 m2 or serum creatinine concentration above 2 mg / 100 ml) and during hemodialysis the maximum daily dose is 400 mg; in hemodialysis ciprofloxacin injected after a hemodialysis session.

With peritoneal dialysis the infusion solution is added to the dialysis (intraperitoneally) at a dose of 50 mg per liter of dialysate 4 times a day (every 6 hours).

The average course of treatment: 1 day - with acute uncomplicated gonorrhea and cystitis; up to 7 days - with infections of the kidneys,urinary tract and abdominal cavity; during the whole period of the neutropenic phase - in patients with weakened protective forces of the body, but no more than 2 months - with osteomyelitis and 7-14 days - with all other infections. With streptococcal infections due to the danger of late complications, treatment should last at least 10 days. In patients with immunodeficiency treatment is carried out throughout the neutropenia period.

Treatment should be carried out at least 3 days after the normalization of body temperature or the disappearance of clinical symptoms.

After intravenous administration, you can continue treatment orally.

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, increased

fatigue, anxiety, tremor, insomnia, nightmarish dreams, peripheral paralysis (anomaly of perception of pain), increased sweating, increased intracranial pressure, confusion, depression, gallusination, as well as other manifestations of psychotic reactions (occasionally progressing to conditions in which the patient can do harm to himself), migraine, fainting, thrombosis of the cerebral arteries.

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

From the cardiovascular system: tachycardia, heart rhythm disturbances, lowering blood pressure.

From the hematopoietic system: leukopenia, granulocytopenia, anemia,

thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia.

Laboratory indicators: hypoprothrombinemia, increased activity of "hepatic" transaminases and alkaline phosphatases, hypercreatininaemia, hyperbilirubinemia, hyperglycemia.

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

Allergic reactions: skin itching, urticaria, blistering,

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, multiforme exudative erythema (including Stevens-Johnson syndrome) , toxic epidermal necrolysis (Lyell's syndrome).

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

Other: asthenia, superinfection (candidiasis, pseudomembranous colitis), "tides" of blood to the face, increased photosensitivity.

Overdose:

Treatment: a specific antidote is unknown. It is necessary to carefully monitor the patient's condition, to ensure a sufficient supply of fluid. With hemo - or peritoneal dialysis, only a small (less than 10%) amount 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 T1 / 2 theophylline (and other 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 and other 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.

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

The joint administration of uricosuric medicines leads to a delay in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.. ......Increases Stakh 7 times (from 4 to 21 times) and the area under the curve "concentration - time" by 10 times (from 6up to 24 times) of tizanidine, which increases the risk of a marked decrease in blood pressure and drowsiness. The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physico-chemically unstable under acidic conditions (the pH of the infusion solution of ciprofloxacin is 3.9 to 4.5). Do not mix the intravenous solution with solutions that have a pH of more than 7.

Special instructions:

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

With simultaneous intravenous administration of ciprofloxacin and drugs for general anesthesia from the group of barbituric acid derivatives, continuous monitoring of the number of heartbeats, arterial pressure, and electrocardiograms is necessary.

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 in the anamnesis, vascular diseases and organic brain damage, 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 should avoid UV-irradiation (including contact with direct sunlight).

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:

Solution for infusions 2 mg / ml

Packaging:

Solution for infusions 2 mg / ml to 100 ml in bottles of orange or colorless glass with a capacity of 100 ml or 100 ml in bottles of orange or colorless glass with a capacity of 100 ml.

1 bottle or bottle is placed in a pack of cardboard with instructions for use and suspension polymer or without suspension.

35 bottles or bottles are placed in a box of corrugated cardboard with an equal number of instructions for use and polymer suspensions or without suspensions for delivery to hospitals.

Storage conditions:

In the dark place at a temperature of 5 to 25 ° C. Freezing is not allowed.

Keep out of the reach of children.

Shelf life:

2 of the year. Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:P N003684 / 01

Date of registration:04.06.2009

The owner of the registration certificate:SYNTHESIS, OJSC SYNTHESIS, OJSC Russia

Manufacturer: & nbsp

SYNTHESIS, OJSC Russia

Information update date: & nbsp12.12.2012

Illustrated instructions

Instructions

Ciprofloxacin (Ciprofloxacin)