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

active substance: ciprofloxacin hydrochloride (in terms of ciprofloxacin) 0.25 g; Excipients: starch 1500 (pregelatinized), lactose (sugar milk), povidone (Kollidon 25), talc, silicon dioxide colloid (aerosil), calcium stearate; Opadrai II (series 85): polyvinyl alcohol, macrogol, titanium dioxide E171, talc.

Description:

The tablets covered with a film membrane of white color round biconcave. At the break - white.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

The broad-spectrum antimicrobial agent, a derivative of fluoroquinolone, 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), 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.

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 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.

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., 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. The sensitivity of Streptococcus pneumoniae, Enterococcus faecalis,

Mycobacterium avium (located intracellularly) - moderate (to suppress them, high concentrations are required).

Both in vitro and in vivo, ciprofloxacin is sensitive to Bacillus anthracis.

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

When taken orally, it is quickly and sufficiently absorbed from the gastrointestinal tract (mainly in the 12-finger and jejunum). Eating slows down absorption, but does not change the maximum concentration in the blood plasma and bioavailability. Bioavailability - 50-85%, volume of distribution - 2-3.5 l / kg, communication with plasma proteins - 20-40%. The time to reach the maximum concentration for oral administration is 60-90 min, the maximum concentration in the blood plasma depends linearly on the value of the dose taken and is 1.2, 2.4, 4.3 and 5, respectively, at doses of 250, 500, 750 and 1000 mg, respectively , 4 μg / ml.After 12 hours after ingestion of 250, 500 and 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). 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, uterus, seminal fluid, prostate tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary tracts, 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 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.

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, with chronic renal failure - up to 12 hours. It is mainly excreted by the kidneys by tubular filtration and tubular secretion in unchanged form - 40-50%, and in the form of metabolites 15%, the rest - through gastrointestinal tract. A small amount is excreted in breast milk. 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:

respiratory tract diseases - 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 field organs - prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubular abscess, pelvioperitonitis, gonorrhea, chancroid, chlamydia;
infection of the abdominal cavity - bacterial infections of the gastrointestinal tract, biliary tract, intraperitoneal abscesses, salmonellosis, typhoid fever, campylobacteriosis, iersiniosis, shigellosis, cholera;
infections of the skin and soft tissues - infected ulcers, wounds, burns, abscesses, phlegmon;
infection of 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 of infections during surgical interventions;
prevention and treatment of pulmonary form of anthrax.

Pediatric use: 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 (infection with Bacillus anthracis).

Contraindications:Hypersensitivity to the components of the drug and other fluoroquinolones, simultaneous administration with tizanidine (risk of pronounced reduction in blood pressure, drowsiness), children under 18 years of age (before the completion of the skeletal process, in addition to the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis 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, epileptic syndrome, renal and / or hepatic insufficiency, elderly age.

Dosing and Administration:

Inside, 0.25 g 2-3 times a day, with severe infections - 0.5-0.75 g 2 times a day (every 12 hours).

With infections of the urinary tract - 0.25-0.5 g 2 times a day, the course of treatment - 7-10 days.

With chronic prostatitis - 0.5 g 2 times a day, the course of treatment 28 days.

With uncomplicated gonorrhea - 0.25-0.5 g once; when combined gonococcal infection with Chlamydia and Mycoplasma - 0.75 g every 12 hours for 7-10 days.

With chancroid, 0.5 g 2 times a day for several days.

When meningococcal carriage in the nasopharynx - once, 0.5 or 0.75 g.

With chronic carrier of salmonella - 0.5 g 2 times; course of treatment - up to 4 weeks. If necessary, the dosage can be increased to 0.75 g 2 times a day.

In severe infections (for example, with recurrent cystic fibrosis, infections of the abdominal cavity, bones and joints) caused by Pseudomonas or staphylococci, in acute pneumonia caused by Streptococcus pneumoniae and in chlamydial infections of the urogenital tract, the dose should be increased to 0.75 g every 12 h.The duration of treatment of osteomyelitis can be up to 2 months.

For gastrointestinal infections caused by Staphylococcus aureus, 0.75 g every 12 hours for 7-28 days.

Treatment should continue for at least 3 days after the normalization of body temperature or the disappearance of clinical symptoms.

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): children - 15 mg / kg 2 times a day, adults - 500 mg 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. The drug should be taken immediately after a suspected or confirmed infection.

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 1 g. At a glomerular filtration rate (CC below 30 ml / min / 1.73 m2 or a serum creatinine concentration above 2 mg / 100 ml), the maximum daily dose is 0.5 g.

If the patient is undergoing hemodialysis or peritoneal dialysis - 0.25-0.5 g / day, then the drug should be taken after a hemodialysis session.

Elderly patients are reduced by 30%.

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 sweating, increased intracranial pressure, confusion, depression, hallucinations, and 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.

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

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

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

Other: increased sensitivity to light, fatigue, superinfection (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 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 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.

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

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 dinanosine-containing ions of aluminum and magnesium ions. Metoclopramide accelerates absorption, which leads to a decrease in the time to reach its maximum concentration in the blood plasma.

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 the maximum concentration in blood plasma by 7 times (from 4 to 21 times) and bioavailability by 10 times (from 6up to 24 times) of tizanidine, which increases the risk of a marked decrease in blood pressure and drowsiness.

Special instructions:

To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, adequate fluid intake (under the control of diuresis) and maintaining an acidic 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 contact with UV-irradiation (including 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:

Tablets, film-coated 250 mg.

Packaging:

10 tablets per contour cell packaging made of polyvinylchloride film, aluminum foil printed lacquered.

1 circuit cell pack together with instructions for use in the pack.

Storage conditions:

In dry, dark place 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.

Terms of leave from pharmacies:On prescription

Registration number:P N003258 / 01

Date of registration:15.12.2008

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

Manufacturer: & nbsp

VALENTA PHARMACEUTICS, JSC Russia

Information update date: & nbsp21.10.2015

Illustrated instructions

Instructions

Ciprofloxacin (Ciprofloxacin)