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

Ciprofloxacin is a synthetic antimicrobial agent of a broad spectrum of action of a group of fluoroquinolones. The main mechanism of action is the suppression of the bacterial DNA-gyrase enzyme, as a result of which the replication of deoxyribonucleic acid and the synthesis of bacterial cell proteins are violated. The drug has a bactericidal effect on gram-negative microorganisms during rest and division and on Gram-positive microorganisms during the fission period.

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). The majority of staphylococci, resistant to methicillin, are resistant to ciprofloxacin.

Both in vitro and in vivo, ciprofloxacin is also sensitive to Bacillus anthracis. The sensitivity of bacteria Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) is moderate (their suppression requires high concentrations). The drug is resistant to Corynebacterium spp., Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroids. The effect of the drug against Treponema pallidum has not been adequately studied.

Pharmacokinetics:

After intravenous infusion of 200 mg or 400 mg the time to reach the maximum concentration of the drug in the blood (T_sweeps) - 60 min, the maximum concentration of the drug in the blood (C_max) - 2.1 and 4.6 μg / ml, respectively, the connection with plasma proteins - 20-40%.

Well distributed in body tissues (excluding tissue, rich in fats, for example, nervous tissue).Concentration in tissues is 2-12 times higher than in plasma. Therapeutic concentrations achieved in saliva, tonsil, liver, gallbladder, bile, intestine, abdominal and pelvic (endometrium, fallopian tubes and ovaries, uterus), semen, prostate tissue, kidney and urinary organs, lung tissues, bronchial secretions , 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, bronchial secretion, pleura, peritoneum, lymph, through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in blood serum.

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

T1 / 2 - 5-6 hours - with intravenous administration, with chronic renal failure - up to 12 hours. It is mainly excreted by the kidneys by tubular filtration and tubular secretion in unchanged form (50-70%) and in the form of metabolites (10%), the rest is through the gastrointestinal tract.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 the 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 insufficiency (creatinine clearance 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:

Infectious-inflammatory diseases caused by sensitive microorganisms: infections 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), 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 against 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 with Bacillus anthracis).

Contraindications:

pregnancy;
lactation period (breastfeeding);
childhood and adolescence (up to 18 years - until the completion of the skeletal formation, except for the treatment of complications caused by Pseudomonas aeruginosa in children with Cystic fibrosis of the lungs from 5 to 17 years old, prevention and treatment of the pulmonary form of anthrax);
increased sensitivity to ciprofloxacin or other drugs from the group of fluoroquinolones;
simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure, drowsiness)

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulation disorder, mental illness, epilepsy, epileptic syndrome, marked honor and / or liver failure, elderly age.

Dosing and Administration:

The drug is administered intravenously drip for 30 minutes (200 mg) and 60 minutes (400 mg). Infusion solutions ready for use can be mixed with 0.9% sodium chloride solution, Ringer's and Ringer's lactate solution, 5 and 10% dextrose solution, 10% fructose solution, and also a solution containing 5% dextrose solution with 0.225-0.45% solution sodium chloride.

In 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.

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

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

To prevent infections during surgical interventions - 0.2-0.4 g for 0.5-1 h before surgery; When the duration of the operation is more than 4 hours, re-enter in the same dose.

For other infections (depending on the severity of the course) - 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: at a glomerular filtration rate (CK 31-60 ml / min / 1.73 square meters or serum creatinine concentration from 1.4 to 1.9 mg / 100 ml), the maximum daily dose is 800 mg. At a 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 dialysate (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 entire neutropenic phase - in patients with weakened body defenses, but no more than 2 months - with osteomyelitis and 7-14 days - with all other infections. When (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 IV application, you can continue treatment orally.

Side effects:

On the part of 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" dream, peripheral paralgeziya (anomaly perception of feeling pain), increased sweating, increased intracranial pressure, confusion, depression, hallucinations, and others . manifestations of psychotic reactions (sometimes progressing to the states in which the patient may self-harm), migraine, syncope, cerebral artery thrombosis.

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

Cardio-vascular system: tachycardia, cardiac arrhythmias, lowering blood pressure.

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

From the laboratory parameters: hypoprothrombinemia, increased activity of "liver" transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

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

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 (petechia), swelling of the face or larynx, dyspnea, eosinophilia, increased photosensitivity, vasculitis, erythema nodosum, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

Other: arthralgia, arthritis, tendovaginitis, tendon ruptures, asthenia, myalgia, superinfections (candidiasis, pseudomembranous colitis), "tides" of blood to the face.

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 the reduced activity of microsomal oxidation process increases the concentration in hepatocytes and lengthens T1 / 2 of theophylline (et al. Xanthines, e.g., caffeine), oral hypoglycemic drugs, anticoagulants, thereby reducing 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 C_max7 times (4 to 21 times) and AUC 10 times (6 to 24 times) of tizanidine, which increases the risk of pronounced reduction 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 3.9-4.5). 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 pneumoniae.

With simultaneous intravenous administration of ciprofloxacin and medicines for general anesthesia from the group of barbituric acid derivatives, continuous monitoring of the heart rate, blood pressure, and ECG 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 ultraviolet radiation, 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:

To 100 ml in a polyethylene bottle, packed in a transparent polypropylene bag. The bottle together with the instruction for use is placed in a cardboard box.

For hospitals: 20, 24, 50 or 100 vials together with instructions for use in a cardboard box.

Storage conditions:

In a dry, protected from light place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the time specified on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N012707 / 01

Date of registration:06.11.2009

The owner of the registration certificate:Aquarium EnterpriseAquarium Enterprise India

Manufacturer: & nbsp

AQUARIUS ENTERPRISES India

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Ciprofloxacin (Ciprofloxacin)