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

Excipients: disodium edetate 0.1 mg. Lactic acid 0.64 mg, sodium chloride (0.9% w / v) 8.285 mg. sodium hydroxide 0.44 mg, hydrochloric acid 0.001 mg, water for injection q.s. up to 1 ml, sodium hydroxide * q.s., hydrochloric acid * q.s.

* Used only for pH adjustment.

Description:

Transparent, from colorless to light yellow liquid.

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. Ciprofloxacin It acts both on multiplying microorganisms, and on those in the resting phase. Ciprofloxacin is sensitive to Gram-negative aerobic bacteria: 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). The majority of staphylococci, resistant to methicillin, are resistant to ciprofloxacin.

Both in vitro and according to the study of the concentration of the drug in blood plasma (as a surrogate marker), ciclofloxacin is also sensitive to Bacillus anthracis. The sensitivity of bacteria Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium-intracellulare is moderate (high concentrations are required for their suppression).

To a drug resistant Corynebacterium spp., Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. The drug is not effective against Treponema pallidum.

Pharmacokinetics:

When intravenously administered 200 mg or 400 mg of ciprofloxacin 60 minutes after the start of infusion, the concentration of the active substance in the serum is 2.1 μg / ml or 4.6 μg / ml.

The volume of distribution in the equilibrium state is 2-3 l / kg. 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. Therapeutic concentrations are achieved in saliva, tonsils of the pharyngeal lymphadenoid ring, liver, gall bladder, bile, intestine, abdominal and pelvic organs, uterus,seminal fluid, prostate gland, endometrium, fallopian tubes and ovaries, kidney and urinary organs, pulmonary tissue, bronchial secretion, bone tissue, muscles, synovial fluid and articular cartilage, peritoneal fluid, skin. After intravenous administration, the concentration in the urine during the first two hours of intake is almost 100 times greater than in the serum. The spinal fluid penetrates in a small amount, where its concentration in non-inflamed brain

shells is 6-10% of that in the blood serum, and when inflamed - 14-37%. Ciprofloxacin also well penetrates into the eye fluid, pleura, peritoneum, lymph, through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum. The activity decreases slightly at acidic pH values. Metabolised in the liver (15-30%) with the formation of low-activity metabolites.

In patients with unchanged kidney function, the elimination half-life is usually 3-5 hours. If the kidney function is impaired, the elimination half-life increases.

The main way to remove ciprofloxacin from the body is the kidney. The kidneys deduce 50-70%.From 15 to 30% is excreted through the intestine.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ciprofloxacin:

respiratory tract;
ENT-organs;
kidney and urinary tract;
genital organs (including uncomplicated gonorrhea, prostatitis, adnexitis);
the abdominal cavity (bacterial infections of the gastrointestinal tract, gallbladder and bile ducts);
skin, mucous membranes and soft tissues;
musculoskeletal system;
prevention and treatment of pulmonary form of anthrax (infection with Bacillus anthracis).

Ciprofloxacin is indicated for treatment of peritonitis and sepsis, as well as for the prevention and treatment of infections in patients with reduced immunity (for immunosuppressive therapy, neutropenia).

When prescribing the drug, it should take into account the updates of official guidelines on the rules for the use of antibacterial agents.

Pediatric Use

Prevention and treatment of pulmonary form of anthrax (infection with Bacillus anthracis).

The use of ciprofloxacin in children under 18 years of age should be started only after assessing the benefit / risk relationship due to possible side effects on the joints and tendons.

Contraindications:

Hypersensitivity to ciprofloxacin or other drugs from the group of fluoroquinolones;
pregnancy;
lactation period (breastfeeding);
children and adolescents under 18;
simultaneous reception of tizanidine.

Carefully:

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

Dosing and Administration:

The drug should be injected as an intravenous infusion into a large vein for at least 60 minutes, which will prevent complications at the site of infusion.

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

In the absence of other prescriptions, the following dosing regimen should be followed:

respiratory tract infections - 400 mg 2 times / day, with severe infections - 3 times / day;
infections of the genitourinary system:
acute, uncomplicated (gonorrhea) - from 200 mg to 400 mg 2 times / day;
Complicated (prostatitis, adnexitis) - 400 mg 2 times / day or 3 times / day;
especially severe, threatening life, incl. peritonitis, sepsis, infections of bones and joints - 400 mg 3 times / day;
pulmonary form of anthrax: adults - 400 mg 2 times / day; children - 10 mg / kg body weight 2 times / day. Do not exceed the maximum single dose of 400 mg (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.
other infections (see "Indications for use") - 400 mg 2 times / day (for severe infections - 3 times / day), the duration of treatment depends on the severity of the disease - 1-2 weeks, if necessary and more.

Dosage regimen for renal dysfunction

With a clearance of creatinine from 30 to 60 ml / min / 1.73 m² or a serum creatinine concentration of 1.4 to 1.9 mg / 100 ml, the maximum dose of ciprofloxacin for intravenous administration should be 800 mg per day.

With a creatinine clearance of 30 ml / min / 1.73 m² or less, or a serum creatinine concentration of 2.0 mg / 100 ml or more, the maximum dose of ciprofloxacin for intravenous administration should be 400 mg per day.

Duration of application

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:

Adults

1 day with acute uncomplicated ambulation;
up to 7 days with infections of the kidneys, urinary tract, abdominal organs;
the entire neutropenia period in immunocompromised patients;
no more than 2 months with osteomyelitis;
from 7 to 14 days with other infections.

In infections caused by streptococci, due to the risk of late complications, treatment should last at least 10 days.

With infections caused by chlamydia, treatment should also continue for at least 10 days.

Side effects:

From the gastrointestinal tract: nausea, vomiting, diarrhea, abdominal pain, flatulence, decreased appetite, cholestatic jaundice (especially in patients with liver disease), hepatitis, hepatonecrosis, pseudomembranous colitis, pancreatitis, hepatic insufficiency.

From the central nervous system: headache, dizziness, fatigue, anxiety, tremors, sleep disorders, "nightmarish" dream, hallucination, peripheral paralgeziya (anomaly perception of feeling pain), sweating, increased intracranial pressure, confusion, depression, manifestations of psychotic reactions (sometimes progressing to states , in which the patient can do harm to himself), migraine, fainting, cerebral artery thrombosis, agitation, disorientation, paresthesia, dysesthesia, hypoesthesia, convulsions, impaired coordination of movements, perif Neuropathy and polyneuropathy.

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

From the side of the urinary system, impaired renal function,crystalluria (especially in alkaline urine and low diuresis), glomerulonephritis, dysuria, polyuria, hematuria, urinary retention, albuminuria, urethral bleeding, decreased renal nitrogen function, interstitial nephritis, renal insufficiency.

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

On the part of the hematopoiesis system: leukopenia, granulocytopenia, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia, agranulocytosis, neutropenia, pancytopenia, oppression of bone marrow hematopoiesis.

From the cardiovascular system: tachycardia, cardiac arrhythmias, lowering of blood pressure, "tides" of blood to the skin of the face, vasodilation, prolongation of the QT interval, ventricular arrhythmias (including pirouettes, mostly observed in patients at increased risk of prolonging the QT interval).

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

Allergic reactions: dermal itching, urticaria, the formation of blisters accompanied by bleeding, and the appearance of small nodules forming scabs, drug fever, pinpoint hemorrhages (petechiae), edema of the face or larynx, dyspnea, eosinophilia, vasculitis, erythema nodosum, exudative erythema multiforme, Stevens-Johnson syndrome (malignant exudative erythema), toxic epidermal necrolysis (Lyell's syndrome), anaphylactic reactions, anaphylactic shock, serum sickness.

From the musculoskeletal system: arthralgia. swelling in the joint area, arthritis, tendovaginitis, tendon ruptures (predominantly achilles), myalgia, increased muscle tone, muscle weakness, worsening of myasthenia symptoms, gait disturbance.

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

Other: superinfection (candidiasis), general weakness, increased photosensitivity, increased sweating, asthenia, chest pain.

Overdose:

The specific antidote is unknown. It is necessary to carefully monitor the patient's condition, to carry out usual measures of emergency care, symptomatic therapy, to ensure sufficient supply of fluid.With the help of hemo- or peritoneal dialysis, only a small amount (less than 10%) of the drug can be excreted. ECG monitoring should be started because of the possible prolongation of the QT interval.

Interaction:

Simultaneous use of ciprofloxacin and theophylline may lead to an increase in the concentration of theophylline in the blood plasma, due to competitive inhibition in the binding sites of cytochrome P₄₅₀, which leads to an increase in the half-life of theophylline and an increased risk of toxic action associated with theophylline.

In some cases, the simultaneous use of ciprofloxacin and glibenclamide can enhance the effect of glibenclamide (hypoglycemia).

The simultaneous use of ciprofloxacin and warfarin, can enhance the effect of the latter.

With the simultaneous use of ciprofloxacin and cyclosporine, the nephrotoxic effect of the latter is enhanced.

With simultaneous use of ciprofloxacin and anticoagulants, bleeding time is prolonged.

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

Metoclopramide accelerates the absorption of ciprofloxacin, which leads to a decrease in the time to reach its maximum concentration (C_max).

Simultaneous use of 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; 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 in 7 times the maximum concentration of tizanidine, which increases the risk of pronounced reduction in blood pressure and drowsiness.

When used simultaneously with drugs that extend the QT interval (antiarrhythmic IA and III classes), the QT interval can be extended. 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 the "area under the concentration-time curve" (AUC) 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 PPC of ropinirole at 60 and 84%, respectively. It is necessary to monitor the side effects of ropinirole with simultaneous use with ciprofloxacin and for a short time after the completion of combination therapy.Simultaneous use of lidocaine and ciprofloxacin, leads to a decrease in clearance of lidocaine by 22% with its intravenous administration (possibly increasing side effects of lidocaine). With the simultaneous use of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, an increase in the serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively (correction of the dosage regimen of clozapine with simultaneous application with ciprofloxacin and for a short time after the completion of 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_max and PPC sildenafil in 2 times (the application of this combination is possible only after assessing the benefit / risk ratio).

With the simultaneous use of ciprofloxacin or phenytoin, both an increase and decrease in the concentration of phenytoin in the plasma is possible, so it is recommended to monitor its concentration.

Simultaneous use of ciprofloxacin and olanzapine leads to an increase in plasma olanzapine, and a lower initial dose of olanzapine should be considered.

Pharmaceutical interaction

The solution of ciprofloxacin is incompatible with solutions or medicines with a pH of 3-4 that are physically or chemically unstable. Do not mix the intravenous solution with solutions that have a pH of more than 7.

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 .

Special instructions:

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 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.

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 "vital" indications.

During the treatment with ciprofloxacin it is necessary to provide a sufficient amount of fluid while observing a normal diuresis.

During treatment with ciprofloxacin, avoid direct exposure to sunlight and UV irradiation in the solarium. In the treatment of severe infections, staphylococcal infections and infections caused by 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. For genital infections presumably caused by strains of Neisseria gonorrhoeae resistant to fluoroquinolones, local information on ciprofloxacin resistance should be taken into account and the susceptibility of the causative agent in laboratory tests should be confirmed. In 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 given.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, immediately stop taking ciprofloxacin and inform the doctor about it. Ciprofloxacin is a moderate inhibitor of the CYP 450 1A2 isoenzyme. Caution should be exercised when using ciprofloxacin and preparations metabolized by the enzyme, such as theophylline, methylxanthine, caffeine, duloxetine, clozapine, t. an increase in the concentration of these drugs in the blood serum, caused by the inhibition of their metabolism by ciprofloxacin, can cause specific undesirable reactions.

An inflammatory reaction of the skin at the injection site (swelling, pain) is possible, which 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).

Older patients, as well as women, may be more sensitive to drugs that extend the QTc interval. Therefore, fluoroquinolones, including ciprofloxacin, should be used in such patients with caution.

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

Patients receiving ciprofloxacin, care should be taken when driving a car and engaging in other potentially hazardous activities requiring increased attention and speed of psychomotor reactions.

Form release / dosage:

Solution for infusions 2 mg / ml.

Packaging:100 ml solution for infusion in a sterile sealed polyethylene bottle (type FFS) with a cap and holder ring; Each vial is packed in a sealed plastic bag and together with theapplication is placed in a cardboard box.

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:

2 years.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N014412 / 01-2002

Date of registration:20.05.2009

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

RANBAXY LABORATORIES, Ltd. India

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp19.10.2015

Illustrated instructions

Instructions

Cyphran® (Cifran®)