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

Antimicrobial preparation of a broad spectrum of action from the group of fluoroquinolones. Inhibits bacterial DNA gyrase (topoisomerase II and IV, are responsible for the process of the chromosomal DNA supercoiling around nuclear RNA that is necessary for reading the genetic information) gives DNA synthesis, growth and division of bacteria is expressed morphological changes and rapid death of the bacterial cell. It acts bactericidal on gram-negative organisms during rest and division (because it affects not only the DNA-gyrase, but also causes lysis of the cell wall), gram-positive microorganisms - 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 not belonging to the group of inhibitors of gyrase, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines and other antibiotics. The effectiveness of ciprofloxacin depends to a large extent on the relationship between pharmacokinetic and pharmacodynamic parameters - between the maximum concentration in the serum (CMC) / minimum inhibitory concentration (MIC) and between the area under the concentration-time curve (AUC) / MIC. Resistance develops slowly and gradually ("multistage" type). There is no cross-resistance with other fluoroquinolones. The basis for the formation of resistance to ciprofloxacin are mutations of the gene (amino acid substitutions) in the region of the "quinolone pocket" - the site of the polypeptide chain of topoisomerases II and IV, in which their binding to ciprofloxacin should occur.Another possible mechanism of resistance is associated with mutations in the gene that encodes the membrane proteins involved in the active release (efflux) of ciprofloxacin from the cell and / or a decrease in the permeability of the cell membrane for ciprofloxacin. Usually, single mutations lead to an insignificant (2-4 times) increase in the MIC. A high level of resistance is usually associated with two or more mutations in one or more genes.

The natural resistance of microorganisms to ciprofloxacin depends on time and geographical factors. Therefore, it is desirable that this information is provided by local services to determine the sensitivity of microorganisms to antibiotics.

The most sensitive microorganisms

Gram-positive aerobic microorganisms: Bacillus anthracis, Staphylococcus aureus (methicillin-sensitive), Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus, Streptococcus pyogenes, Streptococcus agalactiae;Gram-negative aerobic microorganisms: Aeromonas spp., Brucella spp., Citrobacter koseri, Francisella tularensis, Haemophilus ducreyi, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycobacterium tuberculosis, Mycobacterium kansasil, Pasteurella multocida, Salmonella spp., Shigella spp., Vibrio spp., Yersinia pestis ; anaerobic microorganisms: Mobiluncus spp .; others microorganisms: Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma hominis, Mycoplasma pneumoniae.

Microorganisms with possible resistance

Gram-positive aerobic microorganisms: Enterococcus faecalis, Streptococcus pneumoniae; Gram-negative aerobic microorganisms: Acinetobacter baumannii, Burkholderia cepacia, Campylobacter jejuni, Citrobacter freundii, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Mycobacterium avium, Morganella morganii, Neisseria gonorrhoeae, Neisseria meningitides, Plesiomonas shigelloides, Proteus mirabilis, Proteus vulgaris, Providencia spp ., Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia marces cens; anaerobic microorganisms: Peptostreptococcus spp., Propionibacterium acnes.

Resistant microorganisms

Gram-positive aerobic microorganisms: Actinomyces spp., Enterococus faecium, Staphylococcus spp. (methicillin-resistant); Gram-negative aerobicmicroorganisms: Burkholderia cepacia, Nocardia asteroids, Stenotrophomonas maltophilia;anaerobic microorganisms not included in the lists above; other microorganisms:Bacteroides fragilis, Clostridium difficile, Listeria monocytogenes, Mycoplasma genitalium, Treponema pallidum, Ureaplasma urealyticum.

Pharmacokinetics:

Suction. With intravenous (iv) ciprofloxacin in doses of 200 and 400 mg, its serum concentration is 2.1 and 4.6 μg / ml, respectively. With IV infusion of 200 mg ciprofloxacin for 60 minutes every 12 hours and ingestion of 250 mg ciprofloxacin every 12 hours AUC are equivalent. With IV infusion of 400 mg of ciprofloxacin for 60 minutes every 12 hours and ingestion of 500 mg of ciprofloxacin every 12 hours the AUC is also equivalent. FROM_max with IV infusion 400 mg ciprofloxacin for 60 minutes every 12 hours is similar to C_max when ingested 750 mg ciprofloxacin every 12 hours.

Distribution. The volume of distribution (Vd) is 2-3 l / kg, the connection with plasma proteins is 20-40%. Large Vd is associated with good penetration of the drug into the tissue.The content in the tissues is 2-12 times higher than in the plasma. Therapeutic concentrations achieved in saliva, tonsil, liver, gallbladder, bile, intestine, abdominal and pelvic, uterine, semen, prostate tissue, endometrium, fallopian tubes and ovaries, kidneys and urinary organs, lung tissues, bronchial secretions, paranasal sinuses, bone, muscle, synovial fluid and articular cartilage, peritoneal fluid, skin. In small quantities it penetrates the cerebrospinal fluid, where its concentration at nevospalonnyh meninges is 6-10% of that in the serum, while inflamed - 14-37%. Ciprofloxacin also well penetrates 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 serum. The activity decreases somewhat in an acid medium.

Metabolism. Metabolised in the liver (15-30%) with the formation of low-activity metabolites (diethylciprofloxacin, sulfociprofloxacin, oxocycloploxacin, formyl ciprofloxacin). It is a moderate inhibitor of the isoenzyme CYP1A2.

Excretion. With iv introduction, the half-life (T1) is 5-6 hours, with chronic renal failure - up to 12 hours. It is excreted mainly by the kidneys by tubular filtration and tubular secretion in unchanged form (with i / in introduction - 61.5%). and in the form of metabolites (with intravenous administration - 9.5%), the rest - intestine (15.2% and 2.6% respectively). A small amount is excreted in breast milk. After intravenous administration, the concentration in the urine during the first 2 hours after injection is almost 100 times greater than in the serum, which is significantly superior to the MIC for most pathogens of urinary tract infections. Kidney clearance is 180-300 ml / min / kg, the total clearance is 480-600 ml / min / kg.

With moderate chronic renal failure (creatinine clearance more than 20 ml / min), the percentage of ciprofloxacin excreted through the kidneys is reduced, but cumulation in the body does not occur due to a compensatory increase in the metabolism of the drug and excretion by the intestine. In severe renal failure (CC less than 20 ml / min), T1 increases to 12 hours, so the daily dose of ciprofloxacin should be reduced by 2 times.

Indications:

Adults

- Infections of the lower respiratory tract caused by gram-negative microorganisms, including pneumonia, bronchopulmonary infections in cystic fibrosis.

- Infections of ENT organs (sinusitis, otitis media).

- Hearing organ infections, including chronic purulent otitis media, malignant external otitis media.

- Urinary tract infections, including cystitis, pyelonephritis.

- Infections of the genitourinary system and pelvic organs, including those caused by Neisseria gonorrhoeae.

- Gastrointestinal infections.

- Infections of the abdominal cavity, including peritonitis, intraperitoneal abscesses, cholecystitis, cholangitis.

- Infections of bones and joints.

- Infections of soft tissues and skin caused by gram-negative microorganisms.

- Infections against the background of immunodeficiency, which occurs in the treatment of immunosuppressive drugs or in patients with neutropenia.

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

Children aged 5-17 years

Therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs.

Contraindications:

Hypersensitivity to ciprofloxacin or any component of the drug, as well as to other antimicrobial drugs from the quinolone group; simultaneous application of ciprofloxacin and tizanidine; children under 18 years of age (before completion of the skeletal process, except for the treatment of complications caused by Pseudomonas aeruginosa, in children aged 5-17 years with cystic fibrosis); diseases of the tendons, including in the anamnesis; pregnancy; the period of breastfeeding.

Carefully:

Severe atherosclerosis of the cerebral vessels, cerebral circulation disorder, mental illness, epilepsy, epileptic syndrome, renal and / or hepatic impairment, increased risk of QT interval prolongation or pirouette-like arrhythmia (eg, QT syndrome, heart disease ( heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), severe gravis gravis, deficiency of glucose-6-phosphate dehydrogenase, age, simultaneous administration of drugs that extend the QT interval (including antiarrhythmic drugs of IA and III classes, tricyclic antidepressants, macrolides, neuroleptics), simultaneous use with inhibitors of isoenzymes CYP450 1A2 (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine), the defeat of the tendons in the previous treatment with quinolones.

Pregnancy and lactation:

Ciprofloxacin is contraindicated during pregnancy.

Because the ciprofloxacin is excreted in breast milk, it should not be prescribed to nursing mothers. If it is necessary to use ciprofloxacin in the mother during lactation, breastfeeding should be terminated before treatment begins.

Dosing and Administration:

Dosing and Administration

Intravenously drip: the duration of the infusion is 30 minutes at a dose of 0.2 g and 60 minutes - at a dose of 0.4 g, the frequency of administration 2-3 times per day. Infusion solution should be injected slowly into a large vein, which helps prevent complications at the site of infusion. The infusion solution can be administered alone or together with other compatible infusion solutions.

Adults

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

Table 1. Recommended daily dose of the drug Ciprofloxacin Sandoz®, solution for infusions, adulthollow

Indications	Dosing regimen taking into account a single dose and multiplicity
Respiratory tract infections (depending on the severity of the infection and the patient's condition)	From 2 x 400 mg to 3 x 400 mg

Infections of the genitourinary system: - acute, uncomplicated - complicated - adnexitis, prostatitis, orchitis, epididymitis	From 2 x 200 mg to 2 x 400 mg From 2 x 400 mg to 3 x 400 mg From 2 x 400 mg to 3 x 400 mg
Diarrhea	2 x 400 mg
Other infections (see section "Indications for use")	2 x 400 mg
Particularly severe, representing a threat to life, including - recurrent infections in cystic fibrosis of the lungs - bones and joints - septicemia - peritonitis Especially when available Pseudomonas spp. or Staphylococcus spp.	3 x 400 mg
Pulmonary form of anthrax (treatment and prevention)	2 x 400 mg

Children and teens

Table 2. Recommended daily dose of the drug Ciprofloxacin Sandoz®, solution for infusions, in children and adolescents

Indication	Dosage regimen for children and adolescents with a single dose and multiplicity (ciprofloxacin, mg, intravenous administration)
Complications of cystic fibrosis of the lungs caused by Pseudomonas aeruginosa (in children from 5 to 17 years of age)	10 mg / kg of body weight x 3 times a day (maximum single dose of 400 mg)
Pulmonary form of anthrax (postcontact)	10 mg / kg body weight x 2 times a day (maximum dose of 400 mg)

Use in selected patient groups

Patients old age lower doses of ciprofloxacin should be given depending on the severity of the disease and the creatinine clearance rate (see also information on patients with impaired hepatic and / or renal function).

Dosage regimen for pulmonary form of anthrax (treatment and prevention) for adults and children

See information in Tables 1 and 2. Treatment should begin immediately after suspected or confirmed infection. The total duration of treatment with ciprofloxacin in pulmonary form of anthrax is 60 days.

Dosing regimen for violations of kidney and liver function in adults

Table 3. Recommended doses for patients with renal insufficiency

Creatinine clearance (ml / min 1.73 m²)	Serum creatinine (mg / 100 mL)	Total daily dose of the drug Ciprofloxacin Sandoz®, solution for infusions
30 to 60	1.4 to 1.9	Maximum 800 mg
Below 30	>2,0	Maximum 400 mg

Dosing regimen for renal dysfunction in patients on hemodialysis - with a clearance of creatinine from 30 to 60 ml / min / 1.73 m² or its concentration in the blood plasma from 1.4 to 1.9 mg / 100 ml, the maximum dose of the drug Ciprofloxacin Sandoz should be 800 mg per day; with a creatinine clearance of 30 ml / min / 1.73 m or less (severe renal failure) or a plasma concentration of 2 mg / 100 ml or more, the maximum dose of the drug Ciprofloxacin Sandoz® should be 400 mg per day on dialysis days after the procedure.

Dosing regimen in patients with renal failure with prolonged outpatient peritoneal dialysis (CAPD)

The drug Ciprofloxacin Sandoz is added to dialysate (intraperitoneally): 50 mg ciprofloxacin per liter dialysate is administered 4 times a day every 6 hours.

Dosing regimen in patients with hepatic insufficiency

Correction of the dose is not required.

Dosing regimen in patients with impaired renal and hepatic function

- with clearance of creatinine from 30 to 60 ml / min / 1.73 m² (moderate renal failure) or at a creatinine concentration in the blood plasma from 1.4 to 1.9 mg / 100 ml, the maximum dose of the drug Ciprofloxacin Sandoz® should be 800 mg;

with a creatinine clearance of 30 ml / min / 1.73 m or less (severe renal failure) or a plasma concentration of 2 mg / 100 ml or more, the maximum dose of the drug Ciprofloxacin Sandoz® should be 400 mg.

Dosage regimen for kidney and liver dysfunction in children

The dosage regimen in children with impaired renal and hepatic function has not been studied.

Compatibility with other solutions

Infusion solution of the drug Ciprofloxacin Sandoz® is compatible with 0.9% sodium chloride solution, Ringer's solution, Ringer's lactate solution, 5% and 10% dextrose solution, 10% fructose solution, and 5% dextrose solution with 0.225% NaCl or 0.45% NaCl.

The solution obtained after mixing ciprofloxacin with compatible infusion solutions should be used as soon as possible to maintain the sterility of the solution. If compatibility with another infusion solution / drug is not confirmed, the infusion solution of ciprofloxacin should be administered separately. Visible signs of incompatibility are precipitation, clouding or discoloration of the solution.

Incompatibility occurs with all solutions / preparations that are physically or chemically unstable at a value pH Ciprofloxacin infusion solution (eg, penicillins, heparin solution), and in particular with solutions that alter the value pH in the alkaline side {pH The infusion solution of ciprofloxacin is 3.9 - 4.5).

When storing the infusion solution of ciprofloxacin at low temperatures, a precipitate may form which dissolves at room temperature.Therefore, it is not recommended to store the infusion solution in the refrigerator and freeze.

Only clean clear solution should be used.

Duration of therapy

The duration of treatment depends on the severity, clinical course and cure of the disease. It is important to continue treatment for at least 3 days after the disappearance of fever or other clinical symptoms. Average duration 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 period of the neutropenic phase in patients with immunodeficiency;

- no more than 2 months with osteomyelitis;

- 7-14 days - with other infections.

In infections caused by Chlamydia spp., treatment should last at least 10 days.

Children and teens

for treatment of complications of cystic fibrosis of the lungs caused by Pseudomonas aeruginosa (in children from 5 to 17 years), the duration of therapy is 10-14 days.

Side effects:

According to the World Health Organization (WHO), unwanted effects are classified according to their frequency of development as follows: very often (> 1/10), often (> 1/100,<1/10) infrequently (> 1/1000 <1/100), rare (> 1/10000, <1/1000), very rare (<1/10000) unknown frequency (frequency can not be determined based on available data).

Infectious and parasitic diseases

infrequently: fungal superinfections; rarely: pseudomembranous colitis (in very rare cases with possible fatal outcome).

From the gastrointestinal tract

often: nausea, diarrhea; infrequently: dyspepsia, vomiting, abdominal pain, flatulence; rarely: pancreatitis.

From the liver and biliary tract

infrequently: increased activity of "hepatic" transaminases, increased bilirubin concentration; rarely: violations of the liver, cholestatic jaundice, hepatitis; rarely: necrosis of liver tissue (in extremely rare cases progressing to life-threatening liver failure).

From the nervous system

infrequently: dizziness, headache, sleep disturbance, taste disorder; rarely: tremor, convulsions (including epileptic seizures), vertigo, hypesthesia, paresthesia and dysesthesia; rarely: migraine, impaired motor coordination, impaired smell, gait disturbance, hypersensitivity, intracranial hypertension (benign); frequency is unknown: peripheral neuropathy and polyneuropathy.

Disorders of the psyche

infrequently: psychomotor hyperactivity / agitation; rarely: confusion and disorientation, anxiety, depression (potentially leading to suicidal behavior / thoughts or attempts at suicide and suicide), pathological dreams, hallucinations; rarely: psychotic reactions (potentially leading to suicidal behavior / thoughts or attempts at suicide and suicide).

From the side of the organ of vision

rarely: visual impairment; rarely: violation of color perception.

From the side of the hearing organ and labyrinthine disorders

rarely: tinnitus, hearing loss / hearing loss.

From the side of the cardiovascular system

rarely: tachycardia, vasodilation, lowering blood pressure, fainting, feeling of "tide" of blood to the face; rarely: vasculitis; frequency is unknown: prolongation of the QT interval, ventricular arrhythmias (including pirouette type), mainly in patients with risk factors for prolonging the QT interval.

On the part of the blood and lymphatic system

infrequently: eosinophilia; rarely: anemia, neutropenia, thrombocytopenia, leukocytosis, thrombocythemia, leukopenia; rarely: hemolytic anemia, pancytopenia (life threatening), agranulocytosis, oppression of bone marrow hematopoiesis (life threatening).

From the side of the kidneys and urinary tract

infrequently: impaired renal function; rarely: renal failure, hematuria, crystalluria, tubulointerstitial nephritis.

From the immune system

rarely: allergic reactions, allergic edema / angioedema; rarely: anaphylactic reactions, anaphylactic shock (life threatening), serum sickness.

From the skin and subcutaneous tissues

infrequently: itching, rashes, urticaria; rarely: Photosensitivity reactions; rarely: petechiae, erythema multiforme, erythema nodosum, Stevens-Johnson syndrome (potentially life-threatening), toxic epidermal necrolysis (Lyell's syndrome), potentially life-threatening; frequency unknown: acute generalized exentematous pustulosis (OGEEP).

From the side of metabolism and nutrition

infrequently: anorexia, decreased appetite and intake of food; rarely: hyperglycemia, hypoglycemia.

From the respiratory system

rarely: violation of breathing (including bronchospasm).

From the musculoskeletal and connective tissue

infrequently: arthralgia, musculoskeletal pain (including pain in the limbs, back pain, chest pain); rarely: myalgia, arthritis, increased muscle tone, muscle cramps; rarely: muscle weakness, tendonitis, rupture of tendons (mainly Achilles), exacerbation of myasthenia gravis symptoms.

General violations and violations at the site of introduction

often: reactions at the injection site (pain, burning, redness, phlebitis); infrequently: general weakness, fever; rarely: swelling, increased sweating.

Laboratory indicators

infrequently: increased activity of alkaline phosphatase in the blood; rarely: a change in the concentration of prothrombin (including hypoprothrombinemia), an increase in the activity of amylase; frequency unknown: an increase in the international normalized relationship (INR) (in patients taking vitamin K antagonists).

The frequency of development of the following side effects with intravenous administration and with the use of stepwise therapy of ciprofloxacin (with intravenous administration of the drug with subsequent ingestion) is higher than with oral administration:

often: vomiting, transient increase in the activity of "liver" transaminases, rash infrequently: thrombocytopenia, thrombocytopenia, confusion and disorientation, hallucinations, paresthesia and dysesthesia, convulsions, vertigo, visual impairment, hearing loss, tachycardia, vasodilation, lowering of blood pressure, reversible liver function disorders, cholestatic jaundice, renal failure, swelling rarely: pancytopenia, bone marrow suppression, anaphylactic shock, psychotic reactions, migraine, impaired sense of smell, hearing impairment, vasculitis, pancreatitis, necrosis of liver tissue, petechia, tendon rupture.

Children: children often reported on the development of arthropathies.

Overdose:

Symptoms: dizziness, tremor, headache, increased fatigue, convulsions, hallucinations, impaired consciousness, dyspepsia, abdominal pain, renal and hepatic insufficiency, as well as crystalluria and hematuria.

Reversible nephrotoxicity was reported.

Treatment: symptomatic, specific antidote is unknown. It is necessary to carefully monitor the patient's condition, to ensure a 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 carried out because of the possibility of extending the QT interval. In order to prevent the development of crystallaria, it is recommended to monitor renal function, including pH and acidity of urine.

Interaction:

Due to a decrease in the activity of microsomal oxidation in hepatocytes, it increases the concentration and prolongs the half-life theophylline (and etc. xanthines, eg, caffeine). Simultaneous use of ciprofloxacin and phenytoin may cause an increase or decrease in the concentration of phenytoin in the blood plasma, so it is recommended to monitor the concentrations of the corresponding drugs.

Simultaneous application ciprofloxacin and vitamin K antagonists (eg, warfarin, acenocoumarol, fenprocumone, fluindone) can enhance their anticoagulant effect.

The severity of this effect may vary depending on the concomitant infections, age and general condition of the patient, so the degree of effect of ciprofloxacin on increasing INR is difficult to assess.It is often enough to monitor INR during the combined use of ciprofloxacin with antagonists of vitamin K, and also for a short time after the completion of the combination therapy.

In studies involving healthy volunteers, it was shown that simultaneous application of preparations containing lidocaine, and ciprofloxacin, a moderate inhibitor of the isoenzyme CYP450 1A2, reduces the clearance lidocaine for intravenous use by 22%. Despite good tolerability lidocaine, with joint application, there may be an increase in side effects due to interaction. With the simultaneous use of ciprofloxacin and oral hypoglycemic drugs, mainly sulfonylureas (for example, glibenclamide, glimepiride), may enhance the effect of the latter. Simultaneous use of the intravenous drug Ciprofloxacin Sandoz and indirect anticoagulants promotes an increase in prothrombin time.

When combined with other antimicrobial drugs (beta-lactam antibiotics, aminoglycosides, clindamycin, metronidazole) synergy is usually observed; can be successfully applied in combination with azlocillin and ceftazidime with infectionscaused by Pseudomonas spp. with mezlocillin, azlocillin, etc. beta-lactam antibiotics - with streptococcal infections; from isoxazolylpenicillin and vancomycin - with staphylococcal infections; from metronidazole and clindamycin - with anaerobic infections.

Ciprofloxacin increases nephrotoxicity cyclosporine, there is an increase in the concentration of creatinine in the blood serum; these patients need control of the kidney function (serum creatinine concentration) 2 times a week. When used simultaneously with non-steroidal anti-inflammatory drugs (excluding acetylsalicylic acid) the risk of seizures increases. Joint application uricosuric medicines leads to a delay in excretion (up to 50%) and an increase in the plasma concentration of ciprofloxacin.

Increases the maximum concentration (C_max) tizanidine in plasma of 7 times (from 4 to 21 times), and also increases the area under the pharmacokinetic curve "concentration-time" (AUC) by 10 times (from 6 to 24 times), which increases the risk of pronounced decrease in blood pressure and drowsiness .Thus, the simultaneous use of ciprofloxacin and preparations containing tizanidine, it is contraindicated.

Infusion solution of the drug Ciprofloxacin Sandoz® is pharmaceutically incompatible with all infusion solutions and drugs that are physico-chemically unstable in an acidic environment (the pH of the infusion solution of ciprofloxacin is 3.9 to 4.5). Do not mix intravenous solution with solutions that have pH more than 7. Caution should be exercised while using ciprofloxacin, as well as other fluoroquinolones, in patients receiving medications, lengthening interval QT (antiarrhythmic drugs IA and III classes, tricyclic antidepressants, macrolides and antipsychotics).

With the simultaneous use of ciprofloxacin and omeprazole there may be a slight decrease in the maximum concentration of the drug in the plasma and a decrease in the area under the concentration-time curve.

Simultaneous application 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 may be slowed down methotrexate, which can accompanied by an increase in concentration methotrexate in blood plasma (the probability of side effects increases methotrexate). Simultaneous application with eotrexate not recommended.

Simultaneous application duloxetine and potent inhibitors of the isoenzyme CYP450 1A2 (such as fluvoxamine) can lead to an increase in AUC 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.

Simultaneous application ropinirole and ciprofloxacin, a moderate inhibitor of the isoenzyme CYP450 1A2, leads to an increase in C_max and AUC ropinirole by 60% and 84%, respectively; Side effects should be monitored ropinirole during its simultaneous use with ciprofloxacin and for a short time after completion of the combination therapy.

With simultaneous application clozapine and ciprofloxacin at a dose of 250 mg for 7 days, an increase in serum concentrations clozapine and N-desmethylclozapine by 29% and 31%, respectively (correction of the dosing regimen is necessary 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 in a dose of 50 mg there was an increase in C_max and AUC of sildenafil in 2 times (application of this combination is possible only after evaluation of the benefit / risk ratio). Metoclopramide accelerates absorption, which leads to a decrease in the time to reach its C_max.

Special instructions:

Before prescribing the drug, it is necessary to make sure that strains of microorganisms causing an infectious disease are sensitive to ciprofloxacin. Ciprofloxacin It is not recommended to use for the treatment of infections caused by Streptococcus pneumoniae, because of insufficient effectiveness against the pathogen.

During prolonged therapy with ciprofloxacin it is recommended to conduct regular general blood tests and kidney and liver function.

With the simultaneous intravenous administration of ciprofloxacin and medications for general anesthesia, the barbituric acid derivative group requires constant monitoring of heart rate, blood pressure, and electrocardiogram (ECG).

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. Mental reactions may occur even after the first use of the drug; in rare cases, depression or psychotic reactions can progress to suicidal thoughts and self-damaging behavior, such as suicide attempts, including those that have occurred, in which case you should immediately stop taking ciprofloxacin and inform the doctor about it. Patients with epilepsy, episodes of seizures in history, vascular diseases and organic brain damage, in connection with the threat of the development of adverse reactions from the central nervous system, Ciprofloxacin Sandoz should be prescribed only for "vital" indications.

In patients taking fluoroquinolones, including ciprofloxacin, there were cases of sensory or sensorimotor polyneuropathy, hypesthesia, dysesthesia, or weakness. If symptoms such as pain, burning, tingling, numbness, weakness occur, patients should be informed before proceeding with the drug.

When ciprofloxacin was used, cases of epileptic status were reported.

Ciprofloxacin, like other fluoroquinolones, can provoke convulsions and reduce the threshold of convulsive readiness. In case of seizures, the drug should be discontinued.

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 ciprofloxacin was used, cases of liver necrosis and life-threatening liver failure were noted. In the presence of signs of liver disease, such as anorexia, jaundice, darkening of the urine, itching, abdominal tenderness, taking ciprofloxacin should be discontinued.

In patients receiving ciprofloxacin and those suffering liver disease, there may be a temporary increase in activity of "liver" transaminases, alkaline phosphatase or cholestatic jaundice.Patients with severe gravis myasthenia gravis should use Ciprofloxacin Sandoz with caution, as possible exacerbation of symptoms.

When taking ciprofloxacin, there may be cases of tendinitis and rupture of tendons (mainly Achilles tendon), sometimes bilateral, within the first 48 hours after the initiation of therapy. Inflammation and rupture of the tendon can occur even a few months after cessation of ciprofloxacin treatment. In elderly patients and patients with diseases of the tendons, simultaneously receiving treatment with glucocorticosteroids, there is an increased risk of tendonopathy.

At the first signs of tendonitis (painful swelling in the joint area, inflammation), ciprofloxacin should be discontinued, physical activity should be avoided, there is a risk of rupture of the tendon, as well as consult a doctor. Ciprofloxacin should be used with caution in patients with a history of indications of tendon diseases associated with the administration of quinolones.

During the treatment period, avoid contact with direct sunlight and other sources of ultraviolet radiation.

In the treatment of severe infections, staphylococcal infections and infections caused by anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents; in 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. Ciprofloxacin has an effect on the elongation of the QT interval. Given that women have a larger average duration of the QT interval than men, they are more sensitive to drugs that cause prolongation of the QT interval. In elderly patients, there is also increased sensitivity to the action of drugs that cause prolongation of the QT interval. Therefore, caution should be applied to the drug Ciprofloxacin Sandoz with drugs that extend the interval QT (eg, antiarrhythmic drugs of classes IA and III, tricyclic antidepressants, macrolides and antipsychotics), or in patients with an increased risk of prolonging the QT interval or developing pirouette-type arrhythmias (for example,with congenital syndrome of QT interval elongation, unadjusted electrolyte imbalance, such as hypokalemia and hypomagnesemia, as well as heart diseases such as heart failure, myocardial infarction, bradycardia).

In rare cases, after the first use of the drug, 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.

With intravenous administration of ciprofloxacin, a local reaction may occur at the site of administration (edema, pain). This reaction is more common 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 is complicated.

Ciprofloxacin is a moderate inhibitor of the isoenzyme CYP450 1A2; caution should be exercised with the simultaneous use of ciprofloxacin and drugs metabolized by the enzyme (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine), 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 growth Mycobacterium spp., which can lead to false-negative results in the diagnosis of this pathogen in patients who are injected ciprofloxacin.

In patients with a deficiency of glucose-6-phosphate dehydrogenase, ciprofloxacin, hemolytic reactions were noted. The appointment of ciprofloxacin in this category of patients is possible only if the potential benefit of the application exceeds the possible risk. Patient monitoring is necessary.

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).

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:

Infusion packs of 50 ml in packs cardboard.

Storage conditions:

Store at a temperature not exceeding 30 ° C. Do not freeze. Keep out of the reach of children.

Shelf life:

4 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001738

Date of registration:02.07.2012

Date of cancellation:2017-02-10

The owner of the registration certificate:Sandoz d.Sandoz d. Slovenia

Manufacturer: & nbsp

SALUTAS PHARMA, GmbH Germany

Representation: & nbspSANDOZ SANDOZ Switzerland

Information update date: & nbsp10.02.2017

Illustrated instructions

Instructions

Ciprofloxacin Sandoz® (Ciprofloxacin Sandoz®)