Ecocylol - 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 pronounced morphological changes (incl.cell wall and membranes) and rapid death of a 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. Against the background of taking ciprofloxacin, there is no parallel development of resistance to other antibiotics that do not belong to the group of DNA-gyrase inhibitors, 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 are also sensitive to ciprofloxacin: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae).

It is active against Bacillus anthracis.

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 (mainly in the 12-finger and jejunum). Eating slows down absorption, but does not change the maximum concentration (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%. The time to reach the maximum concentration (TC_max) - 60-90 min, the maximum concentration linearly depends on the value of the accepted dose and is 1.2, 2.4, 4.3 and 5.4 μg / ml, respectively, at doses of 250, 500, 750 and 1000 mg. 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 (endometrium, fallopian tubes and ovaries, uterus), seminal fluid, prostate tissue, kidney and urinary organs, lung 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 chronic renal insufficiency up to 12 hours. It is excreted mainly by the kidneys through tubular filtration and tubular secretion in unchanged form (40-50%) and in the form of metabolites (15%), the rest - through the gastro- intestinal tract.A small amount is excreted in breast milk.

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

In chronic renal failure (creatinine clearance above 20 ml / min), the percentage of ciprofloxacin excreted through the kidneys decreases, but cumulation in the body does not occur due to a compensatory increase in the metabolism of ciprofloxacin excretion through the gastrointestinal tract.

Indications:

Infectious-inflammatory diseases caused by sensitive microorganisms:

diseases 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);
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);
infection against the background of immunodeficiency (arising in the treatment of immunosuppressive drugs or in patients with neutropenia);
prevention and treatment of pulmonary form of anthrax.

Children:

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, simultaneous administration with tizanidine (risk of pronounced reduction in blood pressure, drowsiness), age to 18 years (until completion of the skeletal process, 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 pulmonary form anthrax), pregnancy, lactation.

Carefully:Severe atherosclerosis of the cerebral vessels, cerebral circulation disorder, mental illness, epilepsy, lowering the threshold of convulsive readiness (or convulsive seizures in the anamnesis), severe renal and / or hepatic insufficiency, elderly age, tendon damage with prior quinolone treatment, increased risk of lengthening the interval QT or the development of arrhythmias such as "pirouette" (for example, the syndrome of congenital extension of the QT interval,heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia)), simultaneous use of drugs that extend the QT interval (including antiarrhythmic IA and III classes, tricyclic antidepressants, macrolides, neuroleptics ), simultaneous use with inhibitors of isoenzymes CYP4501A2, (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine), myasthenia gravis, deficiency of glucose-6-phosphate dehydrogenase.

Dosing and Administration:

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

For infections of the lower respiratory tract of mild and moderate degree - 500 mg 2 times a day.

For acute sinusitis, 500 mg twice a day. With infection of the skin and soft tissues of mild and moderate degree, 500 mg 2 times a day.

When infections of bones and joints - mild and moderate - 500 mg 2 times a day.

With infections of the urinary tract - acute, uncomplicated: 500 mg 2 times a day; cystitis in women (before menopause): 500 mg once a day; Complicated: 500 mg 2 times a day.

With chronic bacterial prostatitis - 500 mg 2 times.

With gonorrhea - 500 mg once a day.

Acute intestinal infections (salmonellosis, shigellosis, campylobacteriosis, etc.) - 500 mg 2 times.

With diarrhea: 500 mg 2 times a day.

With typhoid fever - 500 mg 2 times.

With complicated intra-abdominal infections - 500 mg every 12 hours.

For prevention and treatment of pulmonary form of anthrax - 500 mg 2 times a day.

Elderly patients should be prescribed lower doses of ciprofloxacin, depending on the severity of the disease and the creatinine clearance rate.

In patients with immunodeficiency treatment is prescribed depending on the severity of the infection and the type of pathogen. Antibiotic therapy is performed throughout the neutropenia period.

In pediatrics:

In the treatment of complications caused by Pseudomonas aeruginosa, in children with cystic fibrosis of the lungs from 5 to 17 lys - 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.

Dosing regimen for patients with renal failure: with creatinine clearance from 30 to 60 ml / min / 1.73 m² or its concentration in blood plasma from 1.4 to 1.9 mg / 100 ml, the maximum daily dose of ciprofloxacin is 1000 mg; when the creatinine clearance is less than 30 ml / min / 1.73 m² or its concentration in blood plasma from 2 mg / 100 ml or more, the maximum daily dose of ciprofloxacin is 500 mg; patients with renal insufficiency on hemodialysis: with a clearance of creatinine from 30 to 60 ml / min / 1.73 m² or its concentration in blood plasma from 1.4 to 1.9 mg / 100 ml maximum daily dose of ciprofloxacin - 1000 mg; when the creatinine clearance is less than 30 ml / min / 1.73 m² or its concentration in blood plasma from 2 mg / 100 ml or more, the maximum daily dose of ciprofloxacin is 500 mg.

In days of hemodialysis ciprofloxacin take after the procedure.

Ambulatory patients with renal failure who are on continuous peritoneal dialysis: the maximum daily dose of ciprofloxacin is 500 mg.

Patients with hepatic impairment: dose adjustment is not required.

The dosage regimen in children with impaired liver and kidney function has not been studied. The duration of treatment depends on the severity of the disease, clinical and bacteriological control. It is important to continue treatment systematically, at least 3 days after the disappearance of fever or other clinical symptoms. Average duration of treatment: 1 day with acute uncomplicated gonorrhea and cystitis; up to 7 days with infections of the kidneys, urinary tract,intra-abdominal infections; the entire neutropenia period in immunocompromised patients; no more than 2 months with osteomyelitis; from 7 to 14 days with other infections. For infections caused by Streptococcus spp., Due to the risk of late complications, treatment should last at least 10 days; for infections caused by Chlamydia spp., treatment should also be continued for at least 10 days.

Side effects:

From the digestive system: nausea, diarrhea, vomiting, abdominal pain, flatulence, decreased appetite and intake, anorexia, cholestatic jaundice (especially in patients with liver disease), hepatitis, pancreatitis, hepatonecrosis.

From the central nervous system: dizziness, headache, fatigue, anxiety, tremor, insomnia, nightmarish dreams, paresthesia and dysesthesia, hypesthesia, hyperesthesia, convulsions, vertigo, impaired coordination of movements, sweating, psychomotor hyperactivity / agitation, disorientation, confusion, hallucinations , psychotic reactions (which can lead to self-damaging behavior,such as suicidal behavior / thoughts, as well as attempted suicide or suicide), depression (which can lead to self-damaging behavior such as suicidal behavior / thoughts, as well as attempted suicide or suicide), epileptic seizures, benign intracranial hypertension, migraine, peripheral neuropathy and polyneuropathy.

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

From the side of the cardiovascular system: tachycardia, lowering of arterial pressure, prolongation of QT interval, ventricular arrhythmias (including "pirouette" type, vasodilation.

From the side of the circulatory system: neutropenia, leukopenia, granulocytopenia, agranulocytosis, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia, pancreatitis (life threatening).

Laboratory indicators: increased activity of "hepatic" transaminases and alkaline phosphatase, hypercreatininemia, hyperbilirubinemia, hypoglycemia, hyperglycemia, an increase in the international normalized relationship (in patients,receiving antagonists of vitamin K), a change in the content of prothrombin, an increase in the activity of amylase.

From the urinary system: hematuria, crystalluria (primarily with alkaline urine and low diuresis), impaired renal function, renal failure, interstitial nephritis.

Allergic reactions: skin itching, urticaria, rash, the formation of blisters accompanied by bleeding, and the appearance of small nodules forming scabs, drug fever, pinpoint hemorrhages on the skin (petechiae), swelling of the face or larynx, dyspnea, eosinophilia, vasculitis, erythema nodosum, exudative erythema multiforme , acute generalized pustular exanthema, Stevens-Johnson syndrome (malignant exudative erythema), toxic epidermal necrolysis (Lyell's syndrome), angioedema, anaphylactic reactions, anaphylaxis Actic shock (life threatening), serum sickness.

From the side of the musculoskeletal system: arthralgia, arthritis, tendovaginitis, tendon ruptures, myalgia, increased muscle tone, muscle cramps, muscle weakness, exacerbation of myasthenia symptoms, gait disturbance.

Other: violation of breathing (including bronchospasm), general weakness, increased photosensitivity, superinfections (candidiasis, pseudomembranous colitis), "tides" of blood to the face.

Overdose:

Symptoms: nausea, vomiting,

dizziness, tremor, headache, confusion, fatigue, convulsive seizures, hallucinations, mental arousal, prolongation of the QTc interval, abnormalities of the gastrointestinal tract, impaired liver and kidney function, crystalluria, hematuria.

The special 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.

In order to prevent the development of crystallaria, it is recommended to monitor renal function, including pH and acidity of urine.

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.At simultaneous admission with theophylline it is recommended to conduct a constant control of the concentration of theophylline in the blood plasma and, if necessary, reduce the dose of theophylline.

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, etc. 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 admission with indirect anticoagulants, it is often necessary to monitor the international normalized relationship, as well as within a short time after the completion of the combination therapy. Oral reception together with iron-containing drugs,sucralfate and antacid medicines containing magnesium, calcium and aluminum salts, 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.

The simultaneous use of ciprofloxacin and dairy products or beverages enriched with minerals (eg milk, yogurt, calcium-fortified orange juice) should be avoided, since the absorption of ciprofloxacin may decrease. However, calcium, which is part of other foods, does not significantly affect the absorption of ciprofloxacin.

Non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid) increase the risk of seizures. Fluoroquinolones form chelate compounds with magnesium and aluminum ions of the didanosine dosage form buffer system, which drastically reduces the absorption of antibiotics, therefore ciprofloxacin take 2 hours before taking didanosine or 2 hours after taking this medication.

Metoclopramide accelerates absorption, which leads to a decrease in the time to reach its maximum concentration.

Ciprofloxacin, due to a decrease in the activity of microsomal oxidation in hepatocytes, increases the plasma concentration and extends T1 / 2 glibenclamide, which can lead to hypoglycemia, in rare cases, severe. Simultaneous use of ciprofloxacin with glibenclamide can enhance the effect of the latter.

With the simultaneous use of ciprofloxacin and phenytoin, there was a change (increase or decrease) in the content of phenytoin in the blood plasma. In order to avoid weakening of the anticonvulsant effect of phenytoin due to a decrease in its concentration, and also to prevent undesirable phenomena associated with a phenytoin overdose when ciprofloxacin is discontinued, it is recommended to monitor phenytoin therapy in patients taking both drugs. including the determination of the content of phenytoin in the blood plasma during the entire period of simultaneous application of both drugs and for a short time after the completion of the combination therapy. Caution should be exercised while using ciprofloxacin, as well as other fluoroquinolones, in patients receiving drugs that cause prolongation of the QT interval (for example, antiarrhythmic drugs of Class 1A or Class III.tricyclic antidepressants, macrolides, antipsychotics) (see section "Special instructions").

The combined use of uricosuric drugs leads to slower elimination (50%) and increase plasma concentration of ciprofloxacin. Increases in the maximum concentration of 7 times (4 to 21 times) and the area under the curve "concentration-time" 10 times (from 6 to 24 times) tizanidine, which exceeds the risk of significant decrease in blood pressure and sleepiness.

With simultaneous use with omeprazole, there may be a slight decrease in the maximum plasma concentration in the plasma and a decrease in AUC.

Probenecid inhibits the excretion of ciprofloxacin by the kidneys, leading to an increase in the concentration of ciprofloxacin.

In a study on healthy volunteers, it was found that the simultaneous use of drugs containing lidocaineAnd ciprofloxacin, a moderate inhibitor of isozyme CYP1A2 reduces the lidocaine clearance by 22% when administered intravenously. In spite of the good tolerability of lidocaine, simultaneous application with ciprofloxacin may increase the side affects due to the interaction.

With the simultaneous use of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, there was an increase in serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively. It is necessary to monitor the patient's condition and, if necessary, adjust the dosage regimen of clozapine during its simultaneous use with ciprofloxacin and for a short time after the completion of the combination therapy.

With the simultaneous use of ciprofloxacin and methotrexate, the renal tubular methotrexate transport slows, potentially leading to increased plasma concentrations of methotrexate, which may increase the risk of toxic reactions associated with methotrexate. Therefore, it is necessary to monitor the condition of patients in the treatment of methotrexate and simultaneous administration of ciprofloxacin.

Clinical studies have shown that the simultaneous use of duloxetine and potent inhibitors of the CYP1A2 isoenzyme (such as fluvoxamine) can lead to an increase in AUC and C_max duloxetine. Despite the lack of clinical data on the possible interaction with ciprofloxacin,it is possible to predict the likelihood of such interaction with the simultaneous use of ciprofloxacin and duloxetine.

With the simultaneous use of ropinirole with ciprofloxacin, there is a possibility of an increase in the concentration of ropinirole, which may be accompanied by an increased risk of unwanted reactions. In case of simultaneous application it is necessary to control the adverse effects of ropinirole during its simultaneous application with ciprofloxacin and for a short time after completion of the combination therapy.

With the simultaneous use of ciprofloxacin in a dose of 500 mg and sildenafil at a dose of 50 mg, there was an increase in C_maxand AUC sildenafil in 2 times. The use of this combination is only possible after an evaluation of the benefit / risk ratio.

Special instructions:

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

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,cardiovascular diseases and organic lesions of the brain 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 with ciprofloxacin, the diagnosis of pseudomembranous colitis should be excluded, which requires immediate discontinuation of the drug and the appointment of appropriate treatment. Contraindicated in the use of drugs that suppress the intestinal peristalsis.

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

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

Given that women have a larger average duration of the QT interval than men, they are more sensitive to drugs that cause prolongation of the QT interval. Ciprofloxacin should be used with caution in combination with drugs,(eg, antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, macrolides, antipsychotics), in patients with an increased risk of prolonging the QT interval or developing pirouette-type arrhythmias (eg, QT syndrome, heart disease (heart failure) , myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia)).

When ciprofloxacin was used, cases of liver necrosis and life-threatening liver failure were noted. In the presence of symptoms of liver disease, such as anorexia, jaundice, darkening of the urine, itching, abdominal tenderness, the use of ciprofloxacin should be discontinued. Patients with severe myasthenia gravis ciprofloxacin should be used with caution, as possible exacerbation of symptoms.

With the use of ciprofloxacin, tendonitis and tendon rupture (predominantly Achilles tendon) can occur, sometimes bilateral, within the first 48 hours after the initiation of therapy, inflammation and rupture of the tendon may occur even several months after discontinuation of ciprofloxacin treatment.In elderly patients and patients with diseases of the tendons, simultaneously receiving treatment with glucocorticosteroids, there is an increased risk of tendonopathy.

When ciprofloxacin was used, cases of epileptic status were reported, ciprofloxacin, like other fluoroquinolones, can provoke cramps and reduce the threshold of convulsive readiness. If seizures occur, the drug should be discontinued, mental reactions may occur even after the first use of fluoroquinolones, including ciprofloxacin.

In patients who use fluoroquinolones, including ciprofloxacin, cases of sensory and sensorimotor axonal polyneuropathy affecting small and (or) large axons are recorded, leading to paresthesia, hyposthenia, dysesthesia and weakness. Symptoms may appear soon after the onset of use and be irreversible. If the patient develops symptoms of neuropathy, including pain, burning, tingling, numbness, and / or weakness or other sensitivity disorders, including tactile, pain, temperature, vibration sensitivity and a sense of position, the use of the drug ciprofloxacin must be discontinued immediately.

In rare cases, depression or psychotic reactions can progress to suicidal thoughts and self-damaging behavior, such as suicide attempts, including those that have occurred. If a patient develops one of these reactions, stop taking the medication and tell the doctor about it; caution should be exercised when using ciprofloxacin and preparations metabolized by CYP4501A2 isoenzymes, such as ropinirole, olanzapine, theophylline, methylxanthine, caffeine, duloxetine, clozapine.

Sometimes, after taking the first dose of ciprofloxacin, hypersensitivity to the drug may develop, including allergic reactions, which should be reported immediately to the treating doctor. In extremely rare cases, after the first application, anaphylactic reactions may occur up to anaphylactic shock. In these cases, the use of ciprofloxacin should be stopped immediately and appropriate treatment should be carried out.

Because the ciprofloxacin has some activity against Mycobacterium tuberculosis, when taking samples during treatment with ciprofloxacin, false negative results of culture testing can be obtained.

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

During treatment, one should refrain from driving vehicles and practicing potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Tablets, film-coated 500 mg.

Packaging:

5 tablets per contour pack of cellulose polyvinylchloride and aluminum foil lacquered.

For 10 tablets in a plastic bottle with a screw cap or a polymer can with a screw cap. 2 contour squares or 1 bottle or 1 jar along with instructions for use are placed in a pack of cardboard.

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:PL-000467

Date of registration:01.03.2011 / 27.05.2016

Expiration Date:Unlimited

The owner of the registration certificate:AVVA RUS, OJSC AVVA RUS, OJSC Russia

Manufacturer: & nbsp

AVVA RUS, OJSC Russia

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Ecocylol® (Ecociphol®)