TSiprolet - instructions for use, doses, side effects, contraindications

active substance: ciprofloxacin 200 mg; Excipients: sodium chloride 900 mg, disodium edetate 10 mg, lactic acid 75 mg, citric acid monohydrate 12 mg, sodium hydroxide 8 mg, hydrochloric acid 0.0231 ml, water for injection up to 100 ml.

Description:

Transparent colorless or light yellow liquid.

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 (since it affects not only DNA-gyrase, but also causes lysis of the cell wall), Gram-positive microorganisms are effective 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 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., 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).

It is active against Bacillus anthracis in vitro.

The majority of staphylococci, resistant to methicillin, are resistant to ciprofloxacin. Sensitivity Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) - moderate (to suppress them, high concentrations are required).

For drug resistant: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. 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:

After intravenous infusion of 200 or 400 mg of ciprofloxacin, the maximum concentration (C_max) is 2.1 and 4.6 μg / ml, respectively, the time to reach the maximum concentration (TC_max) - 60 min. The connection with plasma proteins is 20-40%. The volume of distribution is 2-3.5 l / kg

Well distributed in the tissues of the body (excluding the fat-rich tissue, for example, nerve 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 organs, pulmonary tissue, bronchial secretion , bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. In spinal fluid penetrates in a small amount, where the concentration, in the absence of inflammation of the meninges, is 6-10% of that in the blood serum, and in the presence of inflammation - 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 (oxo-, diethyl-, sulfo-, formylciprofloxacin).

The half-life period (T1) is about 5-6 hours, with chronic renal failure (CRF) up to 12 hours. It is mainly excreted by the kidneys through tubular filtration and tubular secretion in unchanged form (50-70%) and in the form of metabolites ( 10%), the rest - through the intestine. 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.

With 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 its excretion in the intestine.

Indications:

Adults

Bacterial infections caused by microorganisms that are sensitive to the drug:

- 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), including 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 on 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 Bacillus anthracis).

Contraindications:

Hypersensitivity to ciprofloxacin and other fluoroquinolone group preparations, as well as to auxiliary substances, pregnancy, lactation (breastfeeding), children's age (up 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; prevention and treatment of pulmonary form of anthrax), simultaneous administration with tizanidine (risk of pronounced reduction in blood pressure, drowsiness).

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulation disorder, mental illness, epilepsy, renal and / or hepatic insufficiency, elderly age, congenital QT prolongation syndrome, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (for example, hypokalemia, hypomagnesemia) simultaneous administration of drugs that extend the QT interval, (including antiarrhythmic IA and III classes), with simultaneous use with medications lysing isoenzymes CYP 450 1A2 (including, theophylline, methylxanthine, caffeine, duloxetine, clozapine); patients with a history of tendon damage associated with the use of quinolones.

Dosing and Administration:

Intravenously infuzionalno. The duration of the infusion is 30 minutes at a dose of 200 mg and 60 minutes at a dose of 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 of sodium chloride.

Adults

In infections of the lower respiratory tract - 200-400 mg 2 times a day, the course is 7-14 days. In severe pneumonia, including streptococcal, and infectious complications of cystic fibrosis - 400 mg 3 times a day, the course is 7-14 days;

With infections of the ENT organs - 200-400 mg 2 times a day, the course is 10 days;

With infections of the urinary tract: acute uncomplicated - 100 mg 2 times a day course 7-14 days; cystitis in women (before menopause) - once 100 mg; Complicated - 200 mg twice a day, the course is 7-14 days.

With chronic bacterial prostatitis - 400 mg 2 times a day, the course is 28 days;

With uncomplicated gonorrhea -100 mg once, with extragenital - 100 mg 2 times a day.

At typhoid fever - 400 mg 2 times a day, the course is 10 days;

With infectious diarrhea - 200 mg 2 times, the course of treatment - 5-7 days.

For mild and moderate infections of the skin and soft tissues, 400 mg 2 times a day, heavy - 400 mg 3 times a day, 7-14 days;

Particularly severe infections (infections of bones and joints, septicemia, peritonitis), especially caused Pseudomonas, Staphylococcus - 400 mg 3 times a day.

Pulmonary form of anthrax (treatment and prevention) - 400 mg 3 times a day, 60 days.

For the prevention of infections during surgical interventions - 200-400 mg for 0.5-1 h before surgery; When the duration of the operation is more than 4 hours, re-enter in the same dose. In other infections (depending on the severity of the flow) - 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 the use of ciprofloxacin is 60 days.

Positioning in special cases

Patients with impaired renal function

With SC 31-60 ml / min / 1.73 m2 or serum creatinine concentration of 1.4 to 1.9 mg / 100 ml), the maximum daily dose is 800 mg. With QC 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. With hemodialysis ciprofloxacin injected after a hemodialysis session.

Patients on hemodialysis or peritoneal dialysis

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; 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, 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 intravenous administration of ciprofloxacin, treatment can be continued with oral administration of the drug.

Side effects:

Depending on the frequency of occurrence, the following groups of side effects are distinguished: frequent - more than 1%, infrequent - 0,1-1%, rare - 0,01-0,1%, very rare - less than 0,01%.

From the central and peripheral nervous system: infrequently - dizziness, headache, increased fatigue; rarely - insomnia, tremor; very rarely - anxiety, 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 to hurt themselves), migraine, syncope, cerebral artery thrombosis, agitation, disorientation, paresthesia and dysesthesia, hypesthesia, convulsions, vertigo, impaired coordination of movements, gait, hyperesthesia, peripheral neuropathy and polyneuropathy.

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

From the side of the cardiovascular system: in very rare cases - tachycardia, other disorders of the heart rhythm, prolongation of the Q-T interval, ventricular arrhythmias (including pirouette type), vasodilation, lowering of blood pressure.

From the side of the digestive system, infrequently - nausea, vomiting, diarrhea, abdominal pain, flatulence, decreased appetite; rarely - cholestatic jaundice (especially in patients with liver disease), pancreatitis; very rarely - hepatitis, hepatonecrosis.

On the part of the hematopoiesis system: infrequently - leukopenia, granulocytopenia, thrombocytopenia, anemia; Very rarely - leukocytosis, thrombocytosis, hemolytic anemia, neutropenia, agranulocytosis, pancytopenia, oppression of bone marrow hematopoiesis, serum sickness.

From the urinary system: rarely - hematuria, crystalluria (especially with alkaline urine and low diuresis), dysuria, polyuria, urinary retention, albuminuria, renal insufficiency; very rarely - glomerulonephritis urethral bleeding, hematuria, decreased renal nitrogen function, interstitial nephritis.

On the part of the respiratory system: violation of breathing (including bronchospasm).

From the musculoskeletal system: rarely - arthralgia, arthritis, tendovaginitis; very rarely - tendon ruptures, asthenia, myalgia, increased muscle tone, muscle weakness, exacerbation of myasthenia gravis symptoms.

Allergic reactions: rarely - 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 (petechiae); rarely -, swelling of the face or larynx, dyspnea, eosinophilia, increased photosensitivity; very rarely - vasculitis, erythema nodosum, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell syndrome) anaphylactic reactions, anaphylactic shock.

Changes in laboratory indicators: hypoprothrombinemia, increased activity of "hepatic" transaminases, alkaline phosphatase, and amylases, hypercreatininemia, hyperbilirubinemia, hyperglycemia.

Local reactions: edema, pain at the injection site.

Other: infrequently - the "tides" of blood to the face; very rarely - superinfection (candidiasis, pseudomembranous colitis).

Overdose:

Symptoms: nausea, vomiting, confusion, mental agitation.

Treatment: a specific antidote is unknown. It is necessary to carefully monitor the patient's condition, carry out symptomatic therapy, and 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 lengthens T1 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 nefrotoksicheskoe action of cyclosporine, there is an increase in serum creatinine, these patients need to monitor this indicator twice a week.

With simultaneous application increases the effect of indirect anticoagulants.

It is often necessary to monitor the international normalized ratio (INR) during co-administration with ciprofloxacin and for a short time after completion of the combination therapy.

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

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

Increases the maximum concentration of tizanidine by 7 times (from 4 to 21) and the area under the pharmacokinetic curve "concentration-time" by 10 times (from 6 to 24), which increases the risk of pronounced decrease in blood pressure and drowsiness.

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physico-chemically unstable in an acidic medium (the pH of the infusion solution of ciprofloxacin- 3.9-4.5). Do not mix the intravenous solution with solutions that have a pH of more than 7.

With the simultaneous use of Q-T (antiarrhythmic IA and III classes) with Q-T prolongations, prolongation of the Q-T interval is possible. With the simultaneous use of ciprofloxacin and omeprazole, there may be a slight decrease in the maximum plasma concentration in the plasma, and a decrease in the area under the concentration-time curve. The simultaneous use of probenecid and ciprofloxacin increases the concentration of ciprofloxacin in the blood plasma (probenecid slows the rate of excretion of ciprofloxacin by the kidneys). With the simultaneous use of ciprofloxacin, renal metabolism of methotrexate may be slowed, which may be accompanied by an increase in the concentration of methotrexate in the blood plasma (the probability of side effects of methotrexate increases).

The simultaneous use of duloxetine and potent inhibitors of the isoenzyme CYP450 1A2 (such as fluvoxamine) may lead to an increase in BMD and C_max duloxetine. Despite the lack of clinical data on the possible interaction with ciprofloxacin, it is possible to foresee the likelihood of such interaction with the simultaneous use of ciprofloxacin and duloxetine.

The simultaneous use of ropinirole and ciprofloxacin, a moderate inhibitor of the isoenzyme CYP450 1A2, leads to an increase in C_max and MIC of ropinirole at 60 and 84%, respectively. It is necessary to monitor the side effects of ropinirole during its combined use with ciprofloxacin and for a short time after completion of the combination therapy. Simultaneous use of lidocaine and ciprofloxacin, leads to a decrease in lidocaine clearance by 22% with its intravenous administration (it is possible to increase the side effects of lidocaine.) In simultaneous application of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, an increase in serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively (correction of the dosage regimen of clozapine during its simultaneous use with ciprofloxacin is necessary and for a short time after the completion of the combined In 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_max and MIC of sildenafil in 2 times (application of this combination is possible only after the evaluation of the ratio of benefit/risk).

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, 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.

With simultaneous intravenous administration of ciprofloxacin and drugs for general anesthesia from the barbituric acid derivative group, continuous monitoring of cardiac activity (heart rate, heart rate, arterial pressure, ECG monitoring) is necessary.

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 exposure to sunlight and ultraviolet radiation sources.

In severe infections, staphylococcal infections and infections caused by gram-positive and anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents. Ciprofloxacin It is not a drug of choice in suspected or established pneumonia caused by Streptococcus pneumoniae. In genital infections presumably caused by strains Neisseria gonorrhoeae, resistant to fluoroquinolones, local information on resistance to ciprofloxacin should be taken into account and the susceptibility of the pathogen in laboratory tests should be confirmed. In the case of anaphylactic reactions up to anaphylactic shock, ciprofloxacin should be discontinued immediately and treated accordingly.

In elderly patients with tendon diseases, or previously treated with glucocorticosteroids, there may be cases of rupture of tendons (mainly Achilles tendon).

Side effects from the CNS can occur after the first use of the drug.In very rare cases, psychosis may manifest as suicidal attempts. In these cases, ciprofloxacin should be discontinued immediately and reported to the doctor.

Ciprofloxacin is a moderate inhibitor of CYP 450 1A2 isoenzymes. Caution should be exercised with the simultaneous use of ciprofloxacin and drugs metabolized by these enzymes (including theophylline, methylxanthine, caffeine, duloxetine, clozapine), since an increase in the concentration of these drugs in the blood serum, due to inhibition of their metabolism by ciprofloxacin, can cause specific undesirable reactions.

Local reaction (inflammatory reaction) of the skin at the site of administration of the drug: edema, occurs more often if the infusion time is 30 minutes or less. The reaction quickly passes after the end of the infusion and is not a contraindication for the subsequent administration of the drug, unless its course becomes complicated.

In vitro in laboratory tests ciprofloxacin suppresses the growth of Mycobacterium spp., which can lead to false-negative results in the diagnosis of this pathogen in patients taking ciprofloxacin.

It is necessary to take into account the content of sodium chloride in the solution of ciprofloxacin, in the treatment of patients in whom sodium consumption is limited (heart failure, renal failure, nephrotic syndrome).

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

During the treatment period, care must be taken when driving vehicles and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:Solution for infusions 2 mg / ml.

Packaging:

To 100 ml in a translucent bottle of low density polyethylene, equipped with a dust cap, with a loop at the bottom, with a calibration scale and an internal packing code on the side of the bottle.

On 1 bottle together with the instruction on application place in a pack a cardboard. On the cardboard package valve, a sticker with the company logo is allowed to control the first opening.

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 expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N008395

Date of registration:01.08.2011

The owner of the registration certificate:Dr. Reddy's Laboratories Ltd.Dr. Reddy's Laboratories Ltd. India

Manufacturer: & nbsp

DR. REDDY`S LABORATORIES, LTD. India

Representation: & nbspDr. Reddy`c Laboratoris Ltd.Dr. Reddy`c Laboratoris Ltd.

Information update date: & nbsp22.10.2015

Illustrated instructions

Instructions

Ciprolet® (Ciprolet®)