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

Excipients: disodium edetate 0.050 mg, sodium hydroxide 0.200 mg, sodium chloride 8.641 mg, lactic acid (88% purity) 0.727 mg, equivalent to lactic acid 100% purity 0.640 mg, water for injection - sk. treb, up to 1 ml.

Description:

Transparent solution from colorless to light yellow color.

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. The drug inhibits the enzyme 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 DNA synthesis, growth and division of bacteria, causes marked morphological changes (incl. cell wall and membranes) and rapid death of a bacterial cell. It acts bactericides both on multiplying microorganisms, and on those in rest phase.Against the background of taking ciprofloxacin, there is no parallel development of resistance to other antibiotics that do not belong to the group of inhibitors of gyrase, which makes it highly effective. in relation to 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 .; Chlamydia trachomatis, 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 of bacteria Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium moderate.

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

He is effective against Treponema pallidum.

Pharmacokinetics:

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

Well distributed in body tissues (excluding tissue, rich in fats, for example, nervous tissue). Concentration in tissues is 2-12 times higher than in plasma. Therapeutic concentrations are achieved in saliva, tonsils, liver, gall bladder, bile, intestine, abdominal and pelvic organs, endometrium, fallopian tubes and ovaries, uterus, seminal fluid, prostate tissue, kidneys and urinary organs, pulmonary tissue; bone tissue, muscles, synovial fluid and articular cartilage; peritoneal fluid, skin. The cerebrospinal fluid penetrates in a small amount, where its concentration in the absence of inflammation of the meninges is 6-10% of that in the serum, and when inflamed - 14-37%.

Ciprofloxacin well penetrates also into the eye fluid, pleura, peritoneum, lymph, - through the placenta. The concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum.

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

With intravenous administration, the half-life is 5-6 hours, with chronic renal insufficiency up to 12 hours. It is mainly excreted by the kidneys by tubular filtration and tubular secretion in unchanged form (50-70%) and in the form of metabolites (10%), part - through the gastrointestinal tract. A small amount is excreted in breast milk. After intravenous administration, the concentration in the urineduring the first 2 hours after administration, it is almost 100 times greater than in serum, which significantly exceeds the minimum inhibitory concentration for the majoritypathogens of urinary tract infections.

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

In chronic renal insufficiency (creatinine clearance 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 excretion through the gastrointestinal tract.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ciprofloxacin.

Adults

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, campylobacteriosis, shigellosis;
infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);
infection of 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.

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 the pulmonary form of anthrax (infection with Bacillus anthracis).

Contraindications:

Hypersensitivity to ciprofloxacin or other drugs from the fluoroquinolones group, also to excipients;
simultaneous reception with tizanidine (risk of pronounced reduction in blood pressure, drowsiness);
pseudomembranous colitis;
children's age to 18 years (until the completion of the process of forming the skeleton,except therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis lung from 5 to 17 years, prevention and treatment of pulmonary anthrax);
pregnancy;
lactation period.

Carefully:

Expressed cerebral atherosclerosis, ischemic, congenital elongation syndrome QT interval, cardiac diseases (cardiac insufficiency, myocardial infarction, bradycardia), electrolyte imbalance (e.g., hypokalemia, hypomagnesemia), concomitant use of drugs, prolonging the interval QT (in including antiarrhythmic IA and III classes), simultaneous use with inhibitors of CYP450 1A2 enzymes, (including theophylline, methylxanthine, caffeine, duloxetine, clozapine), Patients with a history of guidance on the tendons of the disease associated with taking quinolones, mental illness, seizures, epilepsy, severe renal and / or hepatic insufficiency, elderly.

Pregnancy and lactation:

Ciprofloxacin is contraindicated during pregnancy and breastfeeding.

Dosing and Administration:

Intravenously, infusion.

The drug should be administered intravenously drip for 30 minutes at a dose of 200 mg and 60 minutes at a dose of 400 mg.The infusion solution 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.

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

with infections of the lower respiratory tract - 200-400 mg 2 times a day;
with uncomplicated gonorrhea - 100 mg once, with extragenital -100 mg 2 times a day;
with infections of the urinary tract: acute uncomplicated - 100 mg per day, complicated - 200 mg 2 times a day;
especially severe infections (streptococcal pneumonia, infectious complications, cystic fibrosis, infections of bones and joints, septicemia, peritonitis), especially caused by Pseudomonas, Staphylococcus - 400 mg 3 times a day;
for the prevention of postoperative infections - for 30-60 minutes before the operation 200-400 mg; if the duration of the operation is more than 4 hours, re-enter in the same dose;
pulmonary form of anthrax (treatment and prevention) - 400 mg 2 times a day;

In pediatric practice:

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). The duration of the course 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.

Older patients are prescribed lower doses, depending on the severity of the infection and the creatinine clearance rate.

In chronic renal failure: at a glomerular filtration rate (creatinine clearance 31-60 ml / min / 1.73 square meters or serum creatinine concentration from 1.4 to 1.9 mg / 100 ml), the maximum daily dose is 800 mg. At the glomerular filtration rate (creatinine clearance below 30 ml / min / 1.73 kv / m or serum 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 the dialysate (intraperitoneally) at a dose of 50 mg per 1 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, throughout the neutropenic phase in patients with weakened body defenses, 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, it is possible to continue treatment orally.

Side effects:

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

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

From the side of the cardiovascular system, tachycardia, cardiac rhythm disturbances, vasodilation, lowering of arterial pressure, prolongation of Q-T interval, ventricular arrhythmias, including "pirouette" type.

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

Co side of laboratory indicators: hypoprothrombinemia, increased activity of amylase, "liver" transaminases and alkaline phosphatase, hypercreatininaemia, hyperbilirubinemia; hyperglycemia.

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

From the musculoskeletal system: arthralgia, arthritis, tendovaginitis, tendon ruptures (mainly Achilles), myalgia, increased muscle tone, muscle cramps, muscle weakness, worsening of myasthenia symptoms, gait disturbance.

Allergic reactions: 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), swelling of the face or larynx, dyspnea, respiratory failure (including bronchospasm), serum sickness, eosinophilia, increased photosensitivity , vasculitis, erythema nodosum, exudative erythema multiforme, (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), anaphylactic reactions; anaphylactic shock.

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

Other: "tides" of blood to the face, superinfection (candidiasis, pseudomembranous colitis).

Overdose:Specific symptoms of an overdose are not present, therefore it is necessary to carefully monitor the patient's condition and carry out all activities aimed at maintaining vital body functions. With the help of hemo- or peritoneal dialysis, only a small amount (less than 10%) of the drug can be excreted. There is no specific antidote.

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, and decreases the prothrombin index.

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

Joint use with 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 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), so these patients need to monitor this indicator 2 times a week.

With simultaneous application increases the effect of indirect anticoagulants, therefore 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.

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

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 omeprazole cana 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 simultaneous use with 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_maxduloxetine.

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 IPC 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 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%, respectively (correction of the regimen is necessarydosing of clozapine during its simultaneous use with ciprofloxacin and for a short time after completion of the combination therapy).

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

The infusion solution is pharmaceutically incompatible with all infusion solutions and drugs whose physico-chemical properties are unstable under acidic conditions.Do not mix the intravenous solution with solutions that have a pH of more than 7.

Special instructions:

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

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, including anaphylactic shock. In these cases, the use of ciprofloxacin should be stopped immediately and appropriate treatment should be given.

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

Adverse reactions from the central nervous system may occurafter 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 CYP 450 1A2 isoenzymes. Caution should be exercised while using 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 may cause specific undesirable ones. reaction.

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 intake is limited (heart failure, kidney failure, nephrotic syndrome).

With simultaneous intravenous administration of ciprofloxacin and drugsfor general anesthesia from the barbituric acid derivative group, constant monitoring of heart rate, blood pressure, and electrocardiogram is necessary.

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 the tendons or when the first signs of tendovaginitis appear, ciprofloxacin treatment should be discontinued.

To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, it is also necessary to ensure the intake of a sufficient amount of liquid and the maintenance of an acidic urine reaction.

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.

During treatment with ciprofloxacin, avoid direct exposure to sunlight and UV irradiation in the solarium.

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 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 per bottle of low density polyethylene.

One bottle in a cellophane wrap is placed in a cardboard box along with instructions for use.

Storage conditions:

At a temperature of no higher than 30 ° C in a dark place. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:П N011675 / 02

Date of registration:25.07.2011 / 25.02.2013

Expiration Date:Unlimited

The owner of the registration certificate:Unik Pharmaceutical Laboratories Unik Pharmaceutical Laboratories India

Manufacturer: & nbsp

UNIQUE PHARMACEUTICAL Laboratories India

Representation: & nbsp"UNIC PHARMACEUTICAL LABORATORY (branch of the company" JB Chemicals and Pharmaceuticals Ltd. ")""UNIC PHARMACEUTICAL LABORATORY (branch of the company" JB Chemicals and Pharmaceuticals Ltd. ")"India

Information update date: & nbsp28.11.2017

Illustrated instructions

Instructions

Isfipro® (Ificipro®)