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

Excipients:
Sodium chloride 865.0 mg
Lactic acid (90%) (corresponding to 63.2 mg of lactic acid in terms of 100% of the substance) - 71.1 mg
Disodium edetate dihydrate 10.0 mg
Citric acid monohydrate 12.0 mg
Sodium hydroxide 23.0 mg
1 M solution of hydrochloric acid or 1 M sodium hydroxide solution to pH 3.5-4.6
Water for injection - up to 100 ml

Theoretical osmolarity: 310 mOsm / l

Description:Transparent greenish-yellow solution.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

A broad-spectrum antimicrobial agent, a quinolone derivative, inhibits 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), violates the synthesis of DNA,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.

The 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: 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:

After an intravenous infusion of 200 mg, the time to reach the maximum concentration (TCmax) is 60 minutes, the maximum concentration (Cmax) is 2.1 μg / ml, the bond with plasma proteins is 20-40%.

It is well distributed in the tissues of the body. 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.In 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 blood plasma, 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 plasma.

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

The half-life period (T1 / 2) is 5-6 hours, with chronic renal failure (CRF) up to 12 hours. It is excreted mainly by the kidneys by tubular filtration and tubular secretion in unchanged form (50-70%) and in the form of metabolites (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 blood plasma, 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 released through the kidneys decreases, but no cumulation occurs in the body due to a compensatory increase in the metabolism of the drug and excretion through the gastrointestinal tract.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ciprofloxacin:

- diseases of the lower respiratory tract (exacerbation of chronic bronchitis, pneumonia, bronchiectasis, infectious complications of cystic fibrosis);

- infection of the ENT organs (acute sinusitis);

- infections 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;

- infectious diarrhea (including campylobacteriosis, shigellosis);

- infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);

- bones and joints (osteomyelitis, septic arthritis);

- septicemia;

- infection against the background of immunodeficiency (arising in the treatment of immunosuppressivedrugs or in patients with neutropenia);

- prevention and treatment of pulmonary form of anthrax.

Prevention of infections during surgical interventions.

Children:

- therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years;

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

Contraindications:

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

Carefully:

Severe atherosclerosis of the cerebral vessels, cerebral circulatory disorders, mental illness, epilepsy, renal and / or hepatic insufficiency, elderly age, tendon damage with prior quinolone treatment, congenital Q-T lengthening syndrome,heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), concomitant use of drugs that prolong the QT interval (including antiarrhythmic Ia and III classes), simultaneous use with inhibitors of CYP isoenzymes 450 1A2, (including theophylline, methylxanthine, caffeine, duloxetine, clozapine), mental illness.

Dosing and Administration:

Solution for infusion is administered intravenously drip. The duration of intravenous infusion of 200 mg (100 ml infusion solution) should be at least 30 minutes. 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.

In infections of the lower respiratory tract - 200-400 mg 2 times a day.

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

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

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

Especially severe infections (streptococcal pneumonia, infectious complications of cystic fibrosis, infections of bones and joints, septicemia, peritonitis), especially caused by Pseudomonas aeruginosa, Staphylococcus aureus - 400 mg 3 times a day.

Pulmonary form of anthrax (treatment and prophylaxis) - 400 mg 2 times a day.

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 taking ciprofloxacin is 60 days.

Use in patients with chronic renal failure

At a glomerular filtration rate (with a CK of 31-60 ml / min / 1.73 m2 or a plasma creatinine concentration of 1.4 to 1.9 mg / 100 ml), the maximum daily dose is 800 mg.At a glomerular filtration rate (with QC below 30 ml / min / 1.73 m2 or plasma creatinine concentration above 2 mg / 100 ml) and during hemodialysis, the maximum daily dose is 400 mg; in hemodialysis ciprofloxacin injected after a hemodialysis session.

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; during the whole period of the neutropenic phase - in patients with weakened protective forces of the body, 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.

Treatment should be carried out at least 3 days after the normalization of body temperature or the disappearance of clinical symptoms.

After intravenous administration, you can continue treatment orally.

Side effects:

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

From the nervous system: dizziness, head pain, increased fatigue, anxiety, tremor, insomnia, nightmarish dreams, peripheral paralysis (anomaly of perception of pain), increased intracranial pressure, confusion, depression, hallucinations, and other manifestations of psychotic reactions (occasionally progressing to conditions in which the patient can cause themselves harm), migraine, syncope, cerebral thrombosis, disorientation, dysesthesia, hypoesthesia, vertigo, impaired coordination of movements, peripheral neuropathy and polyneurop ment, psychomotor hyperactivity, agitation, sleep disturbances, gait abnormalities, seizures.

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

From the cardiovascular system: tachycardia, violations cardiac rhythm, lowering of arterial pressure, vasodilation, prolongation of Q-T interval.

From the hematopoiesis: leukopenia, granulocytopenia, neutropenia, agranulocytosis, anemia, thrombocytopenia, leukocytosis, thrombocytosis, hemolytic anemia, oppression of bone marrow hematopoiesis.

Laboratory indicators: hypoprothrombinemia, rise activity "hepatic" transaminases and alkaline phosphatase, hypercreatininaemia, hyperbilirubinemia, hyperglycemia.

From the urinary system: hematuria, crystalluria (formerly Total with alkaline urine reaction and low diuresis), glomerulonephritis, dysuria, polyuria, urinary retention, albuminuria, urethral bleeding, decreased renal nitrogen function, interstitial nephritis.

Allergic reactions: rash, cutaneous itching, hives, education blisters accompanied by bleeding, and the appearance of small nodules that form scabs, drug fever, puncture of the face or larynx, dyspnea, eosinophilia, vasculitis, erythema nodosum, multiforme exudative erythema (including Stevens-Johnson syndrome) ,toxic epidermal necrolysis (Lyell's syndrome), angioedema, serum sickness.

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

Local reactions: phlebitis, tenderness at the injection site.

Other: asthenia, superinfection (candidiasis, pseudomembranous colitis), increased sweating, "flushes" of blood to the face, increased photosensitivity, respiratory failure (including bronchospasm), anorexia.

Overdose:

Symptoms: nausea, vomiting, confusion, mental agitation.

Treatment: the specific antidote is unknown. It is necessary to carefully monitor the patient's condition, carry out other emergency measures, ensure sufficient fluid intake. With the help of hemo- or peritoneal dialysis, only a small amount (less than 10%) of the drug can be excreted.

Interaction:

When used simultaneously with drugs that extend the Q-T interval (antiarrhythmic Ia and III classes), the Q-T interval can be extended.With the simultaneous use of ciprofloxacin and methotrexate, there has been an increase in plasma methotrexate concentration. This may increase the likelihood of side effects of methotrexate, which requires careful monitoring of patients receiving co-therapy.

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).

The simultaneous use of duloxetine and potent inhibitors of the isoenzyme CYP450 1A2 (such as fluvoxamine) can lead to an increase in the area under the concentration-time curve (AUC) and Cmax of 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, increases the AUC and Cmax of ropinirole by 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 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 serum concentrations of clozapine and N-desmethylclozapine is possible by 29% and 31%, respectively (correction of the dosage regimen of clozapine during its simultaneous use with ciprofloxacin and for a short time after completion of combination therapy).

With the simultaneous use of ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg, AUC and Cmax sildenafil increased by a factor of 2 (this combination is possible only after the benefit / risk ratio).

Due to the decrease in the activity of microsomal oxidation in hepatocytes, it increases the concentration and lengthens the half-life of theophylline and other xanthines (eg, caffeine),oral hypoglycemic drugs, indirect anticoagulants (increased action), contributes to a decrease in 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 the nephrotoxic effect of cyclosporine, there is an increase in the serum creatinine concentration, in such patients monitoring of this indicator is required 2 times a week.

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

The joint administration of uricosuric medicines leads to a delay in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.Increases Cmax 7-fold (4 to 21 times) and AUC 10-fold (6 to 24 times) of tizanidine, which increases the risk of pronounced reduction in blood pressure and drowsiness. The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs that are physico-chemically unstable under acidic conditions (the pH of the infusion solution of ciprofloxacin is 3.5-4.6). Do not mix the intravenous solution with solutions that have a pH of more than 7.

Special instructions:

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

In the treatment of severe infections, staphylococcal infections and infections caused by anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents. For infections suspected to be caused by Neisseria gonorrhoeae resistant to fluoroquinolones, local information on ciprofloxacin resistance should be taken into account and the sensitivity 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. 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.

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.

With simultaneous intravenous administration of ciprofloxacin and drugs for general anesthesia from the group of barbituric acid derivatives, continuous monitoring of the heart rate, blood pressure, and electrocardiogram is necessary.

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.

Adverse reactions from the central nervous system may 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. Patients with epilepsy, seizures in the anamnesis, vascular diseases and organic brain lesions, 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, 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). In elderly patients with tendon diseases, or previously treated with glucocorticosteroids, there may be cases of rupture of tendons (mainly Achilles tendon).

During the treatment should avoid contact with direct sunlight, artificial UV-irradiation.

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

Patients receiving ciprofloxacin, you should refrain from driving a car and taking other potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:

Solution for infusions 2 mg / ml.

Packaging:

100 ml of solution in polyethylene bottles. One bottle together with the instruction for use is placed in a cardboard box. 10, 15, 24, 36, 40, 42, 48, 72, 80, 84, 96 bottles in packs are placed in a cardboard box.

10, 15, 24, 36, 40, 42, 48, 72, 80, 84, 96 bottles in bags or without packages with an equal number of instructions for use are placed in a cardboard box (for hospitals).

Storage conditions:

In a dry, dark place at a temperature of 2 to 30 ° C.

Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001972

Date of registration:18.01.2013

The owner of the registration certificate:EAST-PHARM, LLCEAST-PHARM, LLC

Manufacturer: & nbsp

EAST-PHARM, LLC

Information update date: & nbsp23.10.2015

Illustrated instructions

Instructions

Ciprofloxacin (Ciprofloxacin)