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

Excipients: corn starch, microcrystalline cellulose, crospovidone, silicon dioxide colloid (aerosil), magnesium stearate. Shell: hypromellose (hydroxypropylmethylcellulose), titanium dioxide, polyethylene glycol 6000.

Description:The tablets covered with a cover of white color, round, biconcave form.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

A 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 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. While receiving ciprofloxacin occurs parallel generating resistance to other antibiotics, does not belong to the group of gyrase inhibitors, which makes it highly effective against bacteria which are resistant, such as 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, Corynebacterium diphtheriae; 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 Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) - moderate (high concentrations are required to repress). For drug resistant: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Not 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 fairly fully absorbed from the gastrointestinal tract (GIT), mainly in the 12-finger and jejunum. Eating slows down absorption, but does not change the maximum concentration in serum (C_max) and bioavailability. Bioavailability is 50-85%, the volume of distribution is 2-3.5 l / kg, the connection with plasma proteins is 20-40%. Time to reach the maximum concentration in the blood plasma (TC_max) with oral administration - 60-90 minutes. C_max linearly depends on the value of the dose taken and is 1.2, 2.4, 4.3 and 5.4 μg / ml, respectively, at doses of 250, 500, 750 and 1000 mg, respectively. 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 the tissues of the body, excluding tissue, rich in fats, for example, nervous. 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, kidney and urinary organs, pulmonary tissue, bronchial secretion, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. In cerebrospinal fluid (CSF) 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. The activity decreases slightly at pH values below 6. Metabolized in the liver (15-30%) with the formation of low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxocycloploxacin, formyl ciprofloxacin).

The half-life (T_1/2) - about 4 hours with the oral route of administration, with chronic renal failure (CRF) - up to 12 hours. It is mainly excreted by the kidneys by tubular filtration and tubular secretion unchanged (with oral administration - 40-50%) and in the form of metabolites ( when ingested - 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. When CRF (with creatinine clearance (CC) above 20 ml / min), the percentage of the drug output through the kidneys decreases, but no cumulation in the body occurs due to a compensatory increase in the metabolism of the drug and excretion with calves.

Indications:

- bacterial infections caused by sensitive microorganisms: respiratory tract diseases - acute and chronic (in the acute stage) bronchitis, pneumonia, bronchiectasis, cystic fibrosis;

- ENT organs infection - otitis media, sinusitis, frontal sinitis, sinusitis, mastoiditis, tonsillitis, pharyngitis;

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

- infections of the pelvic organs and genital organs - prostatitis, adnexitis, salpingitis, oophoritis, endometritis, tubular abscess, pelvioperitonitis, gonorrhea, chancroid, chlamydia;

- infections of the abdominal cavity - bacterial infections of the gastrointestinal tract, biliary tract, peritonitis, intraperitoneal abscesses, salmonellosis, typhoid fever, campylobacteriosis, iersiniosis, shigellosis, cholera;

- skin and soft tissue infections - infected ulcers, wounds, burns, abscesses, phlegmon;

- infections of bones and joints - osteomyelitis, septic arthritis;

- sepsis; infection against the background of immunodeficiency (arising in the treatment of immunosuppressive drugs (LS) 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:

Hypersensitivity, simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure (BP), 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, epileptic syndrome, renal and / or hepatic insufficiency, elderly age.

Pregnancy and lactation:

Contraindicated in pregnancy (safety and efficacy in women during pregnancy is not established). Ciprofloxacin passes through the placenta. Ciprofloxacin is excreted into breast milk, therefore during lactation it is necessary to decide whether to stop taking ciprofloxacin or breastfeeding, based on the importance of the use of drugs for the mother.

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 MVP - 0.25-0.5 g 2 times a day; course of treatment - 7-10 days, with chronic prostatitis - 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 - inside, 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.

With pneumonia, osteomyelitis - inside, at 0.75 g 2 times a day. 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.

Children. 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.

At a 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 below 30 ml / min /1.73 square meters or a serum creatinine concentration above 2 mg / 100 ml, the maximum daily dose is 0.5 g.

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

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.

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

Average duration of treatment: 1 day - with acute uncomplicated gonorrhea and cystitis; up to 7 days - with infections of the kidneys, MVP and abdominal cavity, during the entire 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, as well as in chlamydial infections, 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.

Prevention and treatment of pulmonary form of anthrax: 500 mg 2 times a day. The drug should be taken immediately after a suspected or confirmed infection. The course of treatment is 60 days.

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	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

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, 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.

From the laboratory indicators: hypoprothrombinemia, increased activity of "liver" transaminases and alkaline phosphatase, lactate dehydrogenase, increased urea concentration, 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.

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, increased sensitivity, vasculitis, nodular erythema multiforme erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

Other: arthralgia, arthritis, tendonitis, tendon rupture, fatigue, myalgia, superinfection (candidiasis, pseudomembranous colitis), "tides" of blood to the face.

Overdose:

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 a decrease in the activity of microsomal oxidation in hepatocytes, it increases the concentration in the blood plasma and lengthens T_1/2theophylline and other xanthines, (for example,caffeine) and contributes to an increased risk of toxic effects associated with theophylline, oral hypoglycemic drugs, indirect anticoagulants, helps to reduce the prothrombin index and prolong the bleeding time.

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 isoxazole penicillins 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 reception together with iron-containing drugs, sucralfate and antacid preparations containing magnesium, calcium and aluminum ions,leads to a decrease in the absorption of ciprofloxacin. Bioavailability of ciprofloxacin in the presence of antacid preparations was 9.5%. A similar effect on the absorption of fluoroquinolones was provided by an antiulcer drug sucralfate, consisting of a complex of aluminum hydroxide and sulfated sucrose. Interaction is explained by the formation of insoluble and poorly absorbed chelate complexes between fluoroquinolones and aluminum and magnesium cations. Therefore, it should be prescribed 1-2 hours before or 4 hours after taking the above medicines.

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

With the simultaneous use of ciprofloxacin with didanosine, ciprofloxacin absorption decreases due to the formation of ciprofloxacin complexes with didanosine-containing ions of aluminum and magnesium.

Metoclopramide accelerates the absorption of ciprofloxacin, which leads to a decrease in its TC_max.

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

Increases C_max 7 times (4 to 21 times) and AUC by 10 times (from 6 to 24 times) tizanidine, which increases the risk of significant decrease in blood pressure and sleepiness.

Special instructions:

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, episodes of seizures in history, vascular diseases and organic brain damage due to the threat of development of adverse reactions from the central nervous system ciprofloxacin should be prescribed only for life 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 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:

The tablets covered with a cover, 250 mg.

Packaging:

For 10 and 20 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 1 or 2 contour packagings together with the instructions for use are placed in a pack of cardboard.

Storage conditions:

Store in a dry, dark place at a temperature of no higher than 25 ° C. 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:P N001625 / 01

Date of registration:01.07.2008

The owner of the registration certificate:OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Manufacturer: & nbsp

OBOLENSKOE PHARMACEUTICAL ENTERPRISE, CJSC Russia

Information update date: & nbsp09.10.2015

Illustrated instructions

Instructions

Ciprofloxacin-FPO (Ciprofloxacin-FPO)