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

Excipients: sodium chloride - 9 g, lactic acid in terms of 100% - 0.65 g, disodium edetate dihydrate (Trilon B) - 0.2 g, water for injection - up to 1 liter.

Description:

Transparent colorless or slightly yellowish 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 (deoxyribonucleic acid) and the synthesis of cellular bacterial proteins are violated.

It acts both on multiplying microorganisms, and on those in rest phase.

TO ciprofloxacin are sensitive 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: 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.

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 an intravenous infusion of 200 mg, the time to reach the maximum concentration (TC_max) - 60 min, the maximum concentration (C_max) - 2.1 μg / ml, the connection with plasma proteins - 20-40%.

Well distributed in body tissues (excluding tissue, rich in fats, for example, nervous tissue). The concentration in the tissues is 2-12 times higher than in the blood plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gall bladder, bile, intestine, abdominal organs and small pelvis (endometrium, fallopian tubes and ovaries, uterus),semen, prostate tissue, kidney and urinary organs, pulmonary 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%. Well penetrates into the eye fluid, pleura, peritoneum, lymph, through the placenta. Concentration 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 insufficiency 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 is 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 blood plasma, which significantly exceeds the minimum inhibitory concentration for most pathogens of urinary tract infections.

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

In chronic renal insufficiency (creatinine clearance (CC) above 20 ml / min), the percentage of the drug withdrawn through the kidneys decreases, but no cumulation in the body occurs due to a compensatory increase in the metabolism of the drug and excretion through the gastrointestinal tract.

Indications:

Bacterial infections caused by microorganisms sensitive to ciprofloxacin:

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), incl. peritonitis;
chronic bacterial prostatitis;
uncomplicated gonorrhea;
typhoid fever;
infectious diarrhea (including campylobacteriosis, shigellosis, diarrhea "travelers";
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 immunosuppressive drugs or in patients with neutropenia);
prevention and treatment of pulmonary form of anthrax.

Prevention of infections during surgical interventions.

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:

Increased sensitivity to ciprofloxacin or other drugs from the group of fluoroquinolones, as well as to auxiliary substances; simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure, drowsiness); children's age and adolescence under 18 years (except for the treatment of complications caused by Pseudomonas aeruginosa in children aged 5 to 17 years with cystic fibrosis of the lung, prevention and treatment of pulmonary form of anthrax).

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulation,mental illness, epilepsy, severe renal and / or hepatic insufficiency, elderly age, tendon damage in previous treatment with fluoroquinolones, congenital QT prolongation syndrome, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), simultaneous administration of drugs that extend the QT interval (including antiarrhythmic IA and III classes), simultaneous application with inhibitors of isoenzymes CYP450 1A2 (including theophylline, methylxanthine, caffeine, duloxetine, clozapine).

Pregnancy and lactation:

When pregnancy is contraindicated. If you need to use the drug during lactation at the time of treatment should stop breastfeeding.

Dosing and Administration:

Intravenously (intravenously) is drip.

The duration of intravenous infusion of 200 mg (100 ml infusion solution) should be at least 30 minutes. The infusion solution can be combined 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.

Application for adults. 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 a day, 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, Staphylococcus - 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.

Use in patients with chronic renal failure: at a glomerular filtration rate (CK 31-60 ml / min / 1.73 m2 or plasma creatinine concentration from 1.4 to 1.9 mg / 100 ml), the maximum daily dose is 800 mg .At a glomerular filtration rate (CC below 30 ml / min / 1.73 square meters or plasma 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.

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). Use in patients with hepatic insufficiency: dose selection is not required. 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 entire neutropenic phase - in patients with weakened protective forces of the body, but no more than 2 months - with osteomyelitis and 7-14 days - with all other infections. With streptococcal infections due to the danger of late complications, 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, the treatment can be continued orally.

Application for children. In the treatment of complications caused by Pseudomonas aeruginosa in children aged 5 to 17 years with cystic fibrosis of the lungs - 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.

The dosage regimen in children with renal failure was not studied.

Children with liver failure are not required to dose.

Side effects:

Allergic reactions: anaphylactic reactions, skin itching, urticaria, the formation of blisters accompanied by bleeding, and the appearance of small nodules forming scabs, drug fever, puncture of the face or larynx, dyspnea, eosinophilia, vasculitis, nodal erythema, multiforme exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome).

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

From the central nervous system (CNS): dizziness (vertigo), headache, fatigue, anxiety, tremor, insomnia, nightmarish dreams, peripheral paralysis (anomaly of perception of pain), paresthesia and dysesthesia, hypesthesia, convulsions, impaired coordination of movements, hyperesthesia, peripheral neuropathy and polyneuropathy, increased intracranial pressure, confusion, depression, hallucinations, agitation, disorientation, as well as other manifestations of psychotic reactions (occasionally progressing to conditions in which the patient can cause yourself harm), migraine, fainting, thrombosis of the cerebral arteries.

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, heart rhythm disturbances, lowering of arterial pressure, prolongation of the Q-T interval, ventricular arrhythmias (including "pirouette" type).

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

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

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

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

From the musculoskeletal system: arthralgia, arthritis, tendovaginitis, tendon ruptures (mainly Achilles), myalgia.

Local reactions: phlebitis, tenderness at the injection site, edema at the injection site.

Other: asthenia, superinfection (candidiasis, pseudomembranous colitis), increased sweating, "flushes" of blood to the face,increased photosensitivity, exacerbation of myasthenia gravis, increased muscle tone, muscle cramps, muscle weakness, gait disturbance.

If any of the side effects listed in the manual are aggravated, or if you notice any other side effects not listed in the instructions, tell your doctor.

Overdose:

Symptoms: there are no specific symptoms.

Treatment: the specific antidote is unknown. It is necessary to carefully monitor the patient's condition, perform gastric lavage and 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:

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 (increased action), and decreases the prothrombin index. It is often enough to monitor the international normalized attitude (INR) during a jointuse with ciprofloxacin and for a short time after the completion of combination therapy.

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 serum creatinine, 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 combined use of uricosuric drugs leads to slower elimination (50%) and increase plasma concentration of ciprofloxacin.

Increases C_max 7 times (4 to 21 times) and the area under the concentration-time curve (AUC) is 10 times (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.

When used simultaneously with drugs that extend the Q-T interval (antiarrhythmic AI and III classes), the Q-T 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) can lead to an increase in the minimum inhibitory concentration (MIC) 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 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 by 29% and 31% is possible,respectively (correction of the dosage regimen of clozapine during its simultaneous use with ciprofloxacin is necessary 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_max and IPC sildenafil in 2 times (the application of this combination is possible only after the evaluation of the benefit / risk ratio).

If you are taking other drugs, consult a doctor.

Special instructions:

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

With simultaneous intravenous administration with drugs for general anesthesia, the group of barbituric acid derivatives requires constant monitoring of the number of cardiac contractions, arterial pressure, and electrocardiograms. To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, sufficient fluid intake and maintenance of acid urine reaction is 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.

If a severe and prolonged diarrhea occurs during or after treatment, the diagnosis of pseudomembranous colitis should be ruled out, which requires immediate discontinuation of the drug and the 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 should avoid contact with direct sunlight, artificial UV-irradiation.

In the treatment of severe infections, staphylococcal infections and infections caused by gram-positive and anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents. When infections of the genital organs, presumably caused by Neisseria gonorrhoeae strains resistant to fluoroquinolones, local information on resistance to ciprofloxacin should be taken into account and the sensitivity of the pathogen 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 CYP450 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.

A local reaction (an inflammatory reaction of the skin at the injection site) swelling 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 should be taken into account the content of sodium chloride in the solution of ciprofloxacin, in the treatment of patients in whom sodium intake is limited (heart failure, renal insufficiency, "nephrotic syndrome").

After the expiry date of the drug, unused bottles should be carefully opened, the contents drained into the sewerage system.

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

During treatment, one should refrain from engaging in potentially dangerous activities that require increased attention and speed of mental and motor reactions.

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

Packaging:

100 ml in bottles of glass. Bottle with instructions for use in a pack of cardboard.

For hospitals:

48 bottles without bundles with an equal number of instructions for use in a box of corrugated cardboard;
1 bottle with instructions for use (from 1 to 48 bottles with an equal number of instructions for use) without a bundle in a box of corrugated cardboard.

Storage conditions:

In the 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:LS-000036

Date of registration:12.01.2010

The owner of the registration certificate:KRASFARMA, JSC KRASFARMA, JSC Russia

Manufacturer: & nbsp

KRASFARMA, JSC Russia

Information update date: & nbsp20.10.2015

Illustrated instructions

Instructions

Ciprofloxacin (Ciprofloxacin)