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

Excipients: Lactic acid 43.00 mg, Disodium edetate 1.00 mg, Hydrochloric acid concentrated q.s. up to pH = 3.4 - 3.6, Water for injection q.s. up to 10,00 ml.

Description:

Transparent, colorless or slightly yellowish-greenish solution.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

Antimicrobial preparation of a broad spectrum of action from the group of fluoroquinolones. It is bactericidal. The drug inhibits the DNA enzyme enzyme of bacteria, as a result of which DNA replication and the synthesis of bacterial cell proteins are disturbed. 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. Ciprofloxacin It acts both on multiplying microorganisms, and on those in the resting phase. 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, Mycobacterium avium (located intracellularly).

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.

The sensitivity of bacteria Streptococcus pneumoniae, Enterococcus faecalis is moderate. To a drug resistant Corynebacterium spp., Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. The effect of the drug against Treponema pallidum has not been adequately studied.

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

Pharmacokinetics:

After intravenous (iv) infusion of 200 mg or 400 mg, the time to reach the maximum concentration (TC_max) - 60 min, the maximum concentration (C_max) Were 2.1 μg / ml and 4.6 μg / ml, respectively. The volume of distribution in the body varies from 1.74 to 5 l / kg, the connection with plasma proteins - 19 - 40%.

Well distributed in body tissues (excluding tissue, rich in fats, for example, nervous tissue). The content in the tissues is 2-12 times higher than in the plasma.

High concentrations of the drug are observed in bile, lungs, kidneys, liver, gall bladder, uterus, seminal fluid, prostate tissue, tonsils, endometrium, fallopian tubes and ovaries. The concentration of the drug in these tissues is higher than in the serum. Ciprofloxacin also penetrates well into the bones, eye fluid, bronchial secretion, saliva, skin, muscles, pleura, peritoneum, lymph. The cerebrospinal fluid penetrates in a small amount, where its concentration in uninflated cerebral membranes is 6-10% of that in the serum, and when inflamed - 14-37%. Ciprofloxacin also penetrates well through the placenta.

The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum.

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

With IV introduction, the half-life (T1) is 3-5 hours, with chronic renal failure (CRF) up to 12 hours.It is excreted mainly by the kidneys, by the tubular filtration and tubular secretion in the unchanged form (with iv introduction - 50-70%) and in the form of metabolites (with iv introduction - 10%), the rest - 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 (MIC) for most pathogens of urinary tract infections.

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

When CRF (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 intestine.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ciprofloxacin:

respiratory tract: pneumonia (with the exception of pneumococcal pneumonia), acute bronchitis and exacerbation of chronic bronchitis, bronchiectasis, cystic fibrosis (if the pathogen is Gram-negative bacteria, especially Pseudomonas aeruginosa);
ear, nose and throat: acute otitis media, sinusitis, mastoiditis;
kidney and urinary tract: uncomplicated and complicated infections of the lower and upper urinary tract (urethritis, cystitis, pyelonephritis);
pelvic and genital organs (epididymitis, prostatitis, salpingitis, endometritis, oophoritis, tubular abscess and pelvic inflammation, gonorrhea, chancroid, chlamydia);
abdominal cavity organs: peritonitis, intraperitoneal abscess; cholecystitis, cholangitis (in combination with metronidazole or clindamycin), infectious diarrhea: salmonellosis, campylobacteriosis, yersiniosis, shigellosis, cholera, typhoid fever;
skin and soft tissues: infected ulcers, infected wounds, abscesses, phlegmon, infections of the external auditory canal, infected burns;
musculoskeletal system: osteomyelitis, septic arthritis;

Sepsis, infection in patients with reduced immunity (against immunosuppressant therapy or in patients with neutropenia).
Prevention of infections during surgical interventions (urological, on the gastrointestinal tract (in combination with metronidazole) and orthopedic).
Prevention and treatment of pulmonary form of anthrax.

Pediatric Use

Ciprofloxacin is not recommended for use in children under 18 years of age for the treatment of other infectious diseases, except:

treatment and prevention of anthrax (after suspected or proven infection with Bacillus anthracis);
therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years.

Contraindications:

Hypersensitivity to ciprofloxacin or other drugs from the quinolone group or any other component of the drug.
Pregnancy and lactation.
Children and adolescents under 18 years (except for the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs in children aged 5 to 17 years, prevention and treatment of pulmonary form of anthrax);
Simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure (BP), drowsiness).

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulation disorder, mental illness, epileptic syndrome, epilepsy, severe renal and / or hepatic insufficiency, elderly age, deficiency of glucose-6-phosphate dehydrogenase, glucocorticosteroid therapy.

Pregnancy and lactation:

During pregnancy and lactation it is not possible to prescribe a drug.

Dosing and Administration:

It is administered intravenously, it can be injected intravenously, but more preferably a drip for 30 minutes (200 mg) and 60 minutes (400 mg).

Before using 1 ampoule concentrate for the preparation of solution for infusion, it is necessary to dilute with an adequate amount of infusion solution: 0.9% solution of sodium chloride, Ringer's solution, 5% and 10% dextrose solution, 10% fructose solution, and also solution containing 5% dextrose solution with 0.225% or 0.45% sodium chloride solution to a minimum volume of 50 ml.

The dose of ciprofloxacin depends on the severity of the disease, the type of infection, the body's condition, age, weight and kidney function in the patient.

Recommended doses are usually: for intravenous administration, a single dose of 200 mg (in severe infections - 400 mg), the frequency of administration - 2 times a day.

If necessary, in / in the treatment of especially severe, life-threatening or recurrent infections caused by Pseudomonas spp., Staphylococci or Streptococcus pneumoniae; sepsis, peritonitis, infections of bones and joints, the dose may be increased to 0.4 g with a multiplicity of administration up to 3 times a day.

In acute uncomplicated gonorrhea - once, in / in 100 mg.

For the prevention of postoperative infections - 30 to 60 minutes before the IV / 200-400 mg operation; with prolonged operation for more than 4 hours, re-administered in the same dose.

Average duration of treatment: 1 day - with acute uncomplicated gonorrhea; 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, 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.

Elderly patients are reduced by 30%.

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.

Patients with severe renal insufficiency (CC below 30 ml / min / 1.73 sq. M, creatinine concentration above 2 mg / 100 ml) should be prescribed half the daily dose, the maximum daily dose - 400 mg.With peritonitis in patients on ambulatory peritoneal dialysis, intraperitoneal administration of ciprofloxacin is possible at a dose of 50 mg 4 times per day per liter of dialysate.

The infusion solution can be combined with 0.9% sodium chloride solution, Ringer's solution, 5% and 10% dextrose solution, 10% fructose solution, and also a solution containing 5% dextrose solution with 0.225% or 0.45% sodium chloride solution . After IV application, you can continue treatment orally.

With pulmonary form of anthrax (prevention and treatment):

Adults: 400 mg IV twice a day

Children (5 to 17 years): 10 mg / kg body weight 2 times a day. Do not exceed the maximum single dose - 400 mg IV (the maximum daily dose is 800 mg).

Treatment should begin immediately after suspected or confirmed infection. The total duration of treatment with ciprofloxacin in pulmonary form of anthrax is 60 days.

In the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years, the recommended dose of ciprofloxacin is 10 mg / kg every 8 hours (not more than 400 mg IV every 8 hours). Duration of treatment is 10-14 days.

Side effects:

From the digestive system: nausea, diarrhea, vomiting, abdominal pain, flatulence, anorexia, cholestatic jaundice (especially in patients with liver disease), hepatitis, hepatonecrosis, pseudomembranous colitis.

From the central and peripheral nervous system: dizziness, headache, fatigue, agitation, convulsions, anxiety, tremor, insomnia, nightmarish dreams, peripheral paralysis (anomaly of perception of pain), 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, with suicidal tendencies), 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 of blood pressure (BP), sensation of "tides" of blood to the skin of the face.

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

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, exanthema, nodular erythema, exudative erythema multiforme, Stevens-Johnson syndrome (malignant erythema), toxic epidermal necrolysis (Lyell's syndrome), anaphylactic shock.

From the musculoskeletal system: arthralgia, arthritis, tendonitis, tendon rupture, myalgia, swelling in the joint.

Other: general weakness, sweating, superinfections (candidiasis), increased photosensitivity

From the laboratory indicators: hypoprothrombinemia, increased activity of "liver" transaminases and alkaline phosphatase, hypercreatininaemia, hyperbilirubinemia, hyperuricemia, hyperglycemia.

Local: pain and burning at the injection site, phlebitis.

Overdose:

Symptoms: nausea, vomiting, diarrhea, headache and dizziness, and in more severe cases confusion, tremors, hallucinations and convulsions.

Treatment: symptomatic, ensure a sufficient supply of fluid.

The specific antidote is unknown. Hemodialysis does not have a clinical effect with intoxication.

Interaction:

Due to a decrease in the activity of microsomal oxidation in hepatocytes, it increases the concentration and lengthens the half-life theophylline and / or caffeine (and other xanthines), oral hypoglycemic drugs (glibenclamide - which can lead to hypoglycemia), indirect anticoagulants (warfarin and etc.), helps reduce the prothrombin index (risk of bleeding).

Ciprofloxacin increases C_max in 7 times (from 4 to 21 times) and AUC in 10 times (from 6 to 24 times)tizanidine, which increases the risk of a marked decrease in blood pressure and drowsiness.

Simultaneous reception with nonsteroidal anti-inflammatory drugs (excluding acetylsalicylic acid) - increases the risk of seizures.

With the simultaneous use of ciprofloxacin and cyclosporine the nephrotoxic effect of cyclosporine is increased (control of the level of the creatinine of the blood 2 times a week is necessary).

Simultaneous reception of ciprofloxacin and glucocorticosteroids may increase the risk of rupture of tendons.

Simultaneous appointment ciprofloxacin and phenytoin may lead to an increase or decrease in serum concentration of phenytoin.

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

When combined with other antimicrobial agents (beta-lactams, aminoglycosides, clindamycin, metronidazole) synergy is usually observed: the drug can be successfully used in combination with azlocillin and ceftazidime for infections caused by Pseudomonas spp .; from mezlocillin, azlocillin and others beta-lactam antibiotics - with streptococcal infections; from isoxazolylpenicillins and vancomycin - with staphylococcal infections; from metronidazole and clindamycin - atanaerobic infections.

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physico-chemically unstable in an acid medium (the pH of the infusion solution of ciprofloxacin is 3.5-4.6).

Special instructions:

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 with ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment.

If pain occurs in the tendons or when the first signs of tendovaginitis appear, treatment should be discontinued due to the fact that individual cases of inflammation (mainly in elderly patients receiving glucocorticosteroids) and even tendon rupture during treatment with fluoroquinolones are described.

During therapy with ciprofloxacin it is recommended to avoid excessive physical exertion.

During the treatment with ciprofloxacin, in order to avoid the development of crystalluria, it is inadmissible to exceed the recommended daily dose. It is also necessary to ensure the intake of a sufficient amount of fluid (under the control of diuresis) to maintain normal diuresis and maintain an acidic urine reaction.

During the treatment with ciprofloxacin, ultraviolet irradiation should be avoided (including contact with direct sunlight).

During the period of therapy, an increase in the prothrombin index is possible (during surgical interventions it is necessary to monitor the state of the blood coagulation system).

In patients with deficiency of glucose-6-phosphate dehydrogenase, the appointment of Ciprinol may cause the development of hemolytic anemia.

During treatment, patients should not consume alcohol.

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

Patients receiving ciprofloxacin, you should be careful when driving a car and doing other potentially hazardous activities,requiring increased attention and speed of psychomotor reactions (especially with simultaneous use of alcohol).

Form release / dosage:

Concentrate for solution for infusion, 10 mg / ml.

Packaging:

For 10 ml in ampoules of neutral clear glass. The ampoule has a colored dot on the fault site. 5 ampoules in a blister or 5 ampoules in a plastic contour-cell package. 1 blister or 1 plastic contour-cell packaging in a pack of cardboard along with instructions for use.

Storage conditions:

Store in a dark place at a temperature of no higher than 25 ° C. Do not freeze! Keep out of the reach of children.

Shelf life:

5 years.

Do not use after expiry date.

Terms of leave from pharmacies:On prescription

Registration number:П N014323 / 02

Date of registration:22.07.2008

The owner of the registration certificate:KRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Manufacturer: & nbsp

KRKA, dd, Novo mesto, AO Slovenia

KRKA-RUS, LLC Russia

VECTOR-MEDICA, CJSC Russia

Representation: & nbspKRKA, dd, Novo mesto, AOKRKA, dd, Novo mesto, AO

Information update date: & nbsp24.10.2015

Illustrated instructions

Instructions

Cyprinol® (Ciprinol®)