Ciprinol tablets 500mg, No. 10

Uncomplicated and complicated infections caused by microorganisms susceptible to ciprofloxacin.

Adults

• Respiratory tract infections - pneumonia caused by Klebsiella spp., Enterobacter spp., Proteus spp., Escherichia coli, Pseudomonas aeruginosa, Haemophilus spp., Moraxella catarrhalis, Legionella spp., Staphylococcus spp .;

• middle ear infections (otitis media), especially if these infections are caused by Staphylococcus spp. and gram-negative microorganisms including Pseudomonas aeruginosa; eye infections;

• kidney infections and / or complicated urinary tract infections;

• genital infections, including adnexitis, gonorrhea, prostatitis;

• infections of the abdominal cavity (bacterial infections of the gastrointestinal tract, biliary tract, peritonitis);

• infections of the skin and soft tissues; infections of bones and joints;

• sepsis;

• infections or prevention of infections in immunocompromised patients (patients taking immunosuppressants or patients with neutropenia);

• selective bowel decontamination in immunocompromised patients; prevention and treatment of pulmonary anthrax (infection with Bacillus anthgasis).

• For the treatment of the following infectious and inflammatory diseases, ciprofloxacin can only be used as an alternative to other antimicrobial drugs: acute sinusitis; uncomplicated urinary tract infections.

  Children

  For oral administration - treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years old;

• prevention and treatment of pulmonary anthrax (infection with Bacillus anthracis) in children from 3 years of age. The use of ciprofloxacin in children should be started only after assessing the benefit / risk ratio due to possible side effects on the joints and periarticular tissues.

Inside for adults - 250-750 mg 2 times / day; children 15-20 mg / kg 2 times / day.

White film-coated tablets, oval, biconvex, with a notch on one side; view at the break: white rough mass with a white film shell.

1 tab.

ciprofloxacin hydrochloride monohydrate 582 mg,

which corresponds to the content of ciprofloxacin 500 mg

Excipients: microcrystalline cellulose, sodium carboxymethyl starch (type A), povidone K25, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate.

• Hypersensitivity to ciprofloxacin or other drugs from the fluoroquinolone group;

• the simultaneous use of ciprofloxacin and tizanidine due to clinically significant side effects (arterial hypotension, drowsiness) associated with an increase in the concentration of tizanidine in the blood plasma; pregnancy;

• period of breastfeeding.

• children up to age 3 years.

  Carefully

• Epilepsy, a decrease in the seizure threshold (or a history of seizures), severe atherosclerosis of the cerebral vessels, impaired cerebral circulation, organic brain damage or stroke; mental illness (depression, psychosis); severe renal and / or hepatic impairment; damage to the tendons with previous treatment with quinolones; increased risk of lengthening the QT interval or developing arrhythmias of the 'pirouette' type (for example, congenital lengthening of the QT interval, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (for example, with hypokalemia, hypomagnesemia); concomitant use of drugs that prolong QT interval (including antiarrhythmic classes IA and III, tricyclic antidepressants, macrolides, antipsychotics);simultaneous use with inhibitors of the isoenzyme CYP1A2 (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine, agomelatine); myasthenia gravis; use in elderly patients, in patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin.

pharmachologic effect

ѕротивомикробное средство широкого спектра действи¤, производное фторхинолона. ѕодавл¤ет бактериальную ?Ќ -гиразу (топоизомеразы II и IV, ответственные за процесс суперспирализации хромосомной ?Ќ  вокруг ¤дерной –Ќ , что необходимо дл¤ считывани¤ генетической информации), нарушает синтез ?Ќ , рост и деление бактерий; вызывает выраженные морфологические изменени¤ (в т.ч. клеточной стенки и мембран) и быструю гибель бактериальной клетки. ?ействует бактерицидно на грамотрицательные организмы в период поко¤ и делени¤ (т.к.вли¤ет не только на ?Ќ -гиразу, но и вызывает лизис клеточной стенки), на грамположительные микроорганизмы - только в период делени¤. Ќизка¤ токсичность дл¤ клеток макроорганизма объ¤сн¤етс¤ отсутствием в них ?Ќ - гиразы. Ќа фоне приема ципрофлоксацина не происходит параллельной выработки устойчивости к другим антибиотикам, не принадлежащим к группе ингибиторов гиразы, что делает его высокоэффективным по отношению к бактери¤м, которые устойчивы, например, к аминогликозидам, пенициллинам, цефалоспоринам, тетрациклинам и многим другим антибиотикам.   ципрофлоксацину чувствительны грамотрицательные аэробные бактерии: энтеробактерии (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.), другие грамотрицательные бактерии (Haemophilus spp., Pseudomonas aeruginosa, Moraxella catarrhalis, Aeromonas spp., Pasteurella multocida, Plesiomonas shigelloides, Campylobacter jejuni, Neisseria spp.), некоторые внутриклеточные возбудители (Legionella pneumophila, Brucella spp., Chlamydia trachomatis, Listeria monocytogenes, Mycobacterium tuberculosis, Mycobacterium kansasii, Corynebacterium diphtheriae); грамположительные аэробные бактерии: Staphylococcus spp. (Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus hominis, Staphylococcus saprophyticus), Streptococcus spp. (Streptococcus pyogenes, Streptococcus agalactiae). Ѕольшинство стафилококков, устойчивых к метициллину, резистентны и к ципрофлоксацину. „увствительность Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (расположенных внутриклеточно) - умеренна¤ (дл¤ их подавлени¤ требуютс¤ высокие концентрации).   препарату резистентны: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia, Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides. Ќеэффективен в отношении Treponema pallidum. –езистентность развиваетс¤ крайне медленно, поскольку с одной стороны, после действи¤ ципрофлоксацина практически не остаетс¤ персистирующих микроорганизмов, а с другой - у бактериальных клеток нет ферментов, инактивирующих его.

Pharmacokinetics

After oral administration, ciprofloxacin is rapidly absorbed mainly from the small intestine. Cmax in blood plasma is achieved after 1-2 hours. Bioavailability is about 70-80%. The values ??of Cmax in blood plasma and AUC increase in proportion to the dose. The binding of ciprofloxacin to blood plasma proteins is 20-30%; the active substance is present in blood plasma mainly in a non-ionized form. Ciprofloxacin is freely distributed in tissues and body fluids. Vd in the body is 2-3 l / kg. The concentration of ciprofloxacin in the tissues is significantly higher than the concentration in the blood serum. It is metabolized in the liver. Four metabolites of ciprofloxacin can be found in the blood at low concentrations: diethylcyprofloxacin (Ml), sulfocyprofloxacin (M2), oxocyprofloxacin (M3), formylcyprofloxacin (M4),three of which (Ml-M3) exhibit antibacterial activity in vitro comparable to the antibacterial activity of nalidixic acid. The in vitro antibacterial activity of the M4 metabolite, present in a smaller amount, is more consistent with the activity of norfloxacin. Ciprofloxacin is excreted mainly by the kidneys by glomerular filtration and tubular secretion; a small amount - through the digestive tract. Renal clearance is 0.18-0.3 l / h / kg, total clearance is 0.48-0.60 l / h / kg. Approximately 1% of the administered dose is excreted in the bile. In bile, ciprofloxacin is present in high concentrations. In patients with unchanged renal function, T1 / 2 is usually 3-5 hours. With impaired renal function, T1 / 2 increases.The in vitro antibacterial activity of the M4 metabolite, present in a smaller amount, is more consistent with the activity of norfloxacin. Ciprofloxacin is excreted mainly by the kidneys by glomerular filtration and tubular secretion; a small amount - through the digestive tract. Renal clearance is 0.18-0.3 l / h / kg, total clearance is 0.48-0.60 l / h / kg. Approximately 1% of the administered dose is excreted in the bile. In bile, ciprofloxacin is present in high concentrations. In patients with unchanged renal function, T1 / 2 is usually 3-5 hours. With impaired renal function, T1 / 2 increases.The in vitro antibacterial activity of the M4 metabolite, present in a smaller amount, is more consistent with the activity of norfloxacin. Ciprofloxacin is excreted mainly by the kidneys by glomerular filtration and tubular secretion; a small amount - through the digestive tract. Renal clearance is 0.18-0.3 l / h / kg, total clearance is 0.48-0.60 l / h / kg. Approximately 1% of the administered dose is excreted in the bile. In bile, ciprofloxacin is present in high concentrations. In patients with unchanged renal function, T1 / 2 is usually 3-5 hours. With impaired renal function, T1 / 2 increases.a small amount - through the digestive tract. Renal clearance is 0.18-0.3 l / h / kg, total clearance is 0.48-0.60 l / h / kg. Approximately 1% of the administered dose is excreted in the bile. In bile, ciprofloxacin is present in high concentrations. In patients with unchanged renal function, T1 / 2 is usually 3-5 hours. With impaired renal function, T1 / 2 increases.a small amount - through the digestive tract. Renal clearance is 0.18-0.3 l / h / kg, total clearance is 0.48-0.60 l / h / kg. Approximately 1% of the administered dose is excreted in the bile. In bile, ciprofloxacin is present in high concentrations. In patients with unchanged renal function, T1 / 2 is usually 3-5 hours. With impaired renal function, T1 / 2 increases.

Side effect

Infectious and parasitic diseases: infrequently - mycotic superinfection; rarely - pseudomembranous colitis (in very rare cases with a possible fatal outcome).

From the hematopoietic system: infrequently - eosinophilia; rarely - leukopenia, anemia, neutropenia, leukocytosis, thrombocytopenia, thrombocythemia. Very rare: hemolytic anemia, agranulocytosis, pancytopenia (life-threatening), bone marrow suppression (life-threatening).

Allergic reactions: infrequently - urticaria; rarely - allergic edema / angioedema; very rarely - anaphylactic reactions, anaphylactic shock (life-threatening), serum sickness.

From the endocrine system: the frequency is unknown - the syndrome of inappropriate secretion of ADH.

From the side of metabolism: infrequently - decreased appetite and the amount of food taken; rarely - hyperglycemia, hypoglycemia; the frequency is unknown - severe hypoglycemia, up to the development of hypoglycemic coma, especially in elderly patients, patients with diabetes mellitus, taking oral hypoglycemic drugs or insulin. Mental disorders: infrequently - psychomotor hyperactivity / agitation; rarely - confusion and disorientation, anxiety, disturbed dreams (nightmares), depression (increased behavior for the purpose of self-harm, such as suicidal acts / thoughts, as well as attempted suicide or successful suicide), hallucinations; very rarely - psychotic reactions (increased behavior for the purpose of self-harm, such as suicidal acts / thoughts, as well as attempted suicide or successful suicide);the frequency is unknown - impaired attention, nervousness, memory impairment, delirium.

From the nervous system: infrequently - headache, dizziness, sleep disturbances, taste disturbances; rarely - paresthesia and dysesthesia, hypesthesia, tremor, convulsions (including seizures of epilepsy), vertigo; very rarely - migraine, impaired coordination of movements, impaired sense of smell, hyperesthesia, intracranial hypertension (cerebral pseudotumor symptoms); frequency unknown - peripheral neuropathy and polyneuropathy.

From the side of the organ of vision: rarely - visual disturbances; very rarely - a violation of color perception.

On the part of the organ of hearing and labyrinth disorders: rarely - tinnitus, hearing loss; very rarely - hearing impairment.

From the side of the cardiovascular system: rarely - tachycardia, vasodilation, decreased blood pressure, fainting; very rarely - vasculitis; the frequency is unknown - prolongation of the QT interval, ventricular arrhythmias (including the 'pirouette' type, more often in patients with a predisposition to the development of prolongation of the QT interval). From the respiratory system: rarely - breathing disorders (including bronchospasm).

From the digestive system: often - nausea, diarrhea; infrequently - vomiting, abdominal pain, dyspepsia, flatulence; very rarely - pancreatitis.

From the liver and biliary tract: infrequently - an increase in the activity of hepatic transaminases, an increase in the concentration of bilirubin; rarely - liver dysfunction, jaundice, hepatitis (non-infectious); very rarely - liver tissue necrosis (in extremely rare cases, progressing to life-threatening liver failure).

On the part of the skin and subcutaneous tissues: infrequently - rash, itching, urticaria; rarely - photosensitivity, blistering; very rarely - petechiae, erythema multiforme of small forms, erythema nodosum, Stevens-Johnson syndrome (malignant exudative erythema), incl. potentially life threatening; Lyell's syndrome (toxic epidermal necrolysis), incl. potentially life threatening; frequency unknown - acute generalized pustular exanthema.

From the musculoskeletal system: infrequently - arthralgia; rarely - myalgia, arthritis, increased muscle tone, muscle cramps; very rarely - muscle weakness, tendonitis, rupture of tendons (mainly Achilles), exacerbation of symptoms of myasthenia gravis.

From the side of the kidneys and urinary tract: infrequently - impaired renal function; rarely - renal failure, hematuria, crystalluria, tubulointerstitial nephritis.

General reactions: infrequently - pain syndrome of nonspecific etiology, general malaise, fever; rarely - edema, hyperhidrosis; very rarely - gait disturbance.

Laboratory indicators: infrequently - increased ALP activity; rarely - a change in prothrombin content, an increase in amylase activity; frequency unknown - increased INR (in patients receiving vitamin K antagonists). The incidence of the following adverse reactions with intravenous administration and with the use of stepwise therapy with ciprofloxacin (with intravenous administration followed by oral administration) is higher than when taken orally: often - vomiting, increased activity of hepatic transaminases, rash; infrequently - thrombocytopenia, thrombocythemia, confusion and disorientation, hallucinations, paresthesia and dysesthesia, convulsions, vertigo, visual impairment, hearing loss, tachycardia, vasodilation, decreased blood pressure, reversible liver dysfunction, jaundice, renal failure, edema; rarely - pancytopenia, bone marrow depression, anaphylactic shock,psychotic reactions, migraine, impaired smell, hearing impairment, vasculitis, pancreatitis, liver tissue necrosis, petechiae, tendon rupture. Children often have arthropathies. The frequency of arthropathy (arthralgia, arthritis) indicated above is based on clinical studies in adult patients.

Application during pregnancy and lactation

Use during pregnancy and breastfeeding is contraindicated.

Application for violations of liver function

Use with caution in severe hepatic impairment.

Application for impaired renal function

Patients with impaired renal function require a dosage adjustment.

Application in children

IV injection is contraindicated - until the age of 18 - until the process of skeletal formation is completed for all indications (except for the treatment of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs under 5 years of age; prevention and treatment of pulmonary anthrax); for oral administration - children under 3 years of age.

Use in elderly patients

In elderly patients, ciprofloxacin should be used in lower doses, depending on the severity of the disease and CC.

special instructions

When treating severe infections, staphylococcal infections and infections caused by anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents. Ciprofloxacin is not recommended for the treatment of Streptococcus pneumoniae infections due to its limited efficacy against the pathogen. For genital infections suspected to be caused by fluoroquinolone-resistant strains of Neisseria gonorrhoeae, information on local resistance to ciprofloxacin should be considered and the susceptibility of the pathogen confirmed by laboratory tests. Resistance to fluoroquinolones of Escherichia coli, the most common pathogenic microorganism causing urinary tract infections, varies by region of the Russian Federation.When prescribing, it is recommended to take into account the local prevalence of Escherichia coli resistance to fluoroquinolones. Ciprofloxacin has an effect on the prolongation of the QT interval. Given that women have a longer average QT interval compared to men, they are more sensitive to drugs that cause QT interval prolongation. Elderly patients also have an increased sensitivity to the action of drugs that cause prolongation of the QT interval. Caution should be exercised when using ciprofloxacin in combination with drugs that prolong the QT interval (eg, class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, and antipsychotics) or in patients at increased risk of QT prolongation or pirouette-type arrhythmias(for example, with congenital long QT syndrome, corrected electrolyte imbalances such as hypokalemia or hypomagnesemia, as well as heart diseases such as heart failure, myocardial infarction, bradycardia). Sometimes, after taking the first dose of ciprofloxacin, hypersensitivity reactions may develop, incl. allergic reactions. In rare cases, after the first use, anaphylactic reactions may occur, up to anaphylactic shock. In these cases, the use of ciprofloxacin should be stopped immediately and appropriate treatment carried out. If 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 (vancomycin orally at a dose of 250 mg 4 times / day). In this situation, the use of drugs that suppress intestinal motility is contraindicated. When using ciprofloxacin, there have been cases of liver necrosis and life-threatening liver failure. If you have the following signs of liver disease, such as anorexia, jaundice, dark urine, itching, painful abdomen, ciprofloxacin should be discontinued. In patients taking ciprofloxacin and having had liver disease, there may be a temporary increase in the activity of hepatic transaminases and alkaline phosphatase or cholestatic jaundice. Ciprofloxacin should be used with caution in patients with severe myasthenia gravis. exacerbation of symptoms is possible.At the first signs of tendinitis (painful swelling in the joint area, inflammation), the use of ciprofloxacin should be discontinued, physical activity should be excluded, because there is a risk of tendon rupture, and consult a doctor. When taking ciprofloxacin, there may be cases of tendonitis and tendon rupture (mainly the Achilles tendon), sometimes bilaterally, already within the first 48 hours after the start of therapy. Inflammation and rupture of the tendon may occur even several months after stopping ciprofloxacin treatment. Elderly patients, patients with renal insufficiency, patients after organ transplantation, while receiving treatment with corticosteroids, there is an increased risk of tendinopathy. Ciprofloxacin should be used with caution in patientswith a history of indications of tendon diseases associated with the intake of quinolones. Ciprofloxacin, like other fluoroquinolones, can induce seizures and lower the seizure threshold. For patients with epilepsy and previous CNS diseases (for example, a decrease in the seizure threshold, a history of seizures, cerebrovascular accident, organic brain damage or stroke) due to the threat of CNS side reactions, ciprofloxacin should be used only in cases where when the expected clinical effect outweighs the possible risk of side effects. If seizures occur, the use of ciprofloxacin should be discontinued. Mental reactions can occur even after the first use of fluoroquinolones, including ciprofloxacin.In rare cases, depression or psychotic reactions can progress to suicidal thoughts and suicidal attempts, incl. completed. In case of development of any side effects from the central nervous system, including mental disorders, it is necessary to immediately discontinue ciprofloxacin and begin appropriate therapy. In these cases, it is recommended to switch to therapy with an antibiotic other than fluoroquinolones, if possible. Cases of sensory or sensorimotor polyneuropathy, hypoesthesia, dysesthesia, or weakness have been reported in patients taking fluoroquinolones, including ciprofloxacin. If symptoms such as pain, burning, tingling, numbness, weakness occur, patients should inform the doctor before continuing to use the drug. When taking ciprofloxacin, a photosensitization reaction may occur,therefore, patients should avoid contact with direct sunlight and UV light. Treatment should be discontinued if symptoms of photosensitivity are observed (for example, skin changes resemble sunburn). Ciprofloxacin is known to be a moderate inhibitor of CYP1A2 isoenzymes. Care should be taken with the simultaneous use of ciprofloxacin and drugs metabolized by these enzymes, such as theophylline, methylxanthine, caffeine, duloxetine, ropinirole, clozapine, olanzapine, agomelatine. an increase in the concentration of these drugs in serum, due to inhibition of their metabolism by ciprofloxacin, can cause specific adverse reactions. The simultaneous use of ciprofloxacin and tizanidine is contraindicated.In order to avoid the development of crystalluria, it is unacceptable to exceed the recommended daily dose; it is also necessary to have sufficient fluid intake and maintain an acidic urine reaction. In vitro, ciprofloxacin can interfere with the bacteriological study of Mycobacterium tuberculosis, inhibiting its growth, which can lead to false negative results when diagnosing this pathogen in patients taking ciprofloxacin. As with other fluoroquinolones, the use of ciprofloxacin may change the concentration of glucose in the blood, including hypo- and hyperglycemia. Against the background of therapy with ciprofloxacin, dysglycemia may more often occur in elderly patients and patients with diabetes mellitus receiving concomitant therapy with oral hypoglycemic drugs (for example, sulfonylureas) or insulin.When using ciprofloxacin in such patients, the risk of developing hypoglycemia, up to hypoglycemic coma, increases. It is necessary to inform patients about the symptoms of hypoglycemia (confusion, dizziness, increased appetite, headache, nervousness, palpitations or increased heart rate, pallor of the skin, perspiration, trembling, weakness). If a patient develops hypoglycemia, treatment with ciprofloxacin should be discontinued immediately and appropriate therapy initiated. In these cases, it is recommended to switch to therapy with an antibiotic other than fluoroquinolones, if possible. When treating with ciprofloxacin in elderly patients, in patients with diabetes mellitus, careful monitoring of blood glucose concentration is recommended.According to epidemiological studies, an increased risk of aortic aneurysm and aortic dissection has been reported after taking fluoroquinolones, especially in elderly patients. Therefore, fluoroquinolones should only be used after careful assessment of the benefit / risk ratio and consideration of other treatment options in patients with a family history of aortic aneurysm or in patients with a diagnosis of aortic aneurysm and / or aortic dissection or other risk factors or conditions predisposing to the development of aortic aneurysm or aortic dissection (for example, Marfan syndrome, Ehlers-Danlos syndrome of the vascular type, Takayasu arteritis, giant cell arteritis, Behcet's disease, arterial hypertension, atherosclerosis). In case of sudden abdominal pain,chest or back patients should seek immediate medical attention in the emergency department.

Influence on the ability to drive vehicles and mechanisms

Fluoroquinolones, including ciprofloxacin, can interfere with the ability of patients to drive and engage in other potentially hazardous activities that require increased attention and speed of psychomotor reactions due to the effect on the central nervous system.

Drug interactions

—ледует соблюдать осторожность при одновременном применении ципрофлоксацина, как и других фторхинолонов, пациентам, получающим лекарственные препараты, вызывающие удлинение интервала QT (например, антиаритмические препараты класса I ј или класса III, трициклические антидепрессанты, макролиды, антипсихотические препараты). ќдновременный прием ципрофлоксацина внутрь и катионсодержащих препаратов, минеральных добавок, содержащих кальций, магний, алюминий, железо, сукральфата, антацидов, полимерных фосфатных соединений (таких как севеламер, карбонат лантана) и препаратов с большой буферной емкостью (таких как таблетки диданозина), содержащих магний, алюминий или кальций, снижает всасывание ципрофлоксацина. ¬ таких случа¤х ципрофлоксацин следует принимать либо за 1-2 ч до, либо через 4 ч посл еприема этих препаратов. Ёто ограничение не относитс¤ к лекарственным блокаторам гистминовых Ќ2-рецепторов. ћетоклопрамид ускор¤ет всасывание ципрофлоксацина (при приеме внутрь), что приводит к более короткому времени достижени¤ Cmax ципрофлоксацина в плазме. ¬ли¤ни¤ на биодоступность ципрофлоксацина обнаружено не было. ѕри одновременном применении ципрофлоксацина и омепразола, может отмечатьс¤ незначительное снижение Cmax в плазме и уменьшение AUC. ќдновременное применение ципрофлоксацина и теофиллина может вызвать нежелательное повышение концентрации теофиллина в плазме крови и, соответственно, возникновение теофиллин-индуцированных неблагопри¤тных ¤влений; в очень редких случа¤х эти неблагопри¤тные ¤влени¤ могут быть угрожающими дл¤ жизни пациента. ?сли одновременное применение этих двух препаратов неизбежно, то рекомендуетс¤ проводить посто¤нный контроль концентрации теофиллина в плазме крови и, если необходимо, снизить дозу теофиллина. ќдновременное применение ципрофлоксацина и кофеина или пентоксифиллина (окспентифиллин) может приводить к увеличению концентрации производных ксантина в сыворотке крови. —очетание очень высоких доз хинолонов (ингибиторов ?Ќ -гиразы) и некоторых Ќѕ¬— (исключа¤ ацетилсалициловую кислоту) может провоцировать судороги. ѕри одновременном применении ципрофлоксацина и препаратов, содержащих циклоспорин, наблюдалось кратковременное преход¤щее повышение концентрации креатинина в плазме крови. ¬ таких случа¤х необходимо 2 раза в неделю определ¤ть концентрацию креатинина в крови. ѕри одновременном применении ципрофлоксацина и пероральных гипогликемических средств, главным образом, производных сульфонилмочевины (например, глибенкламида, глимепирида), развитие гипогликемии предположительно обусловлено усилением действи¤ пероральных гипогликемических средств (см. раздел Ђѕобочное действиеї). ѕробенецид замедл¤ет скорость выведени¤ ципрофлоксацина почками. ќдновременное применение ципрофлоксацина и препаратов, содержащих пробенецид, приводит к повышению концентрации ципрофлоксацина в плазме крови. ѕри одновременном применении ципрофлоксацина и фенитоина наблюдалось изменение (повышение или понижение) содержани¤ фенитоина в плазме крови. ¬о избежание ослаблени¤ противосудорожного эффекта фенитоина вследствие снижени¤ его концентрации, а также дл¤ предотвращени¤ нежелательных ¤влений, св¤занных с передозировкой фенитоином при прекращении приема ципрофлоксацина, рекомендуетс¤ осуществл¤ть контроль за терапией фенитоином у пациентов, принимающих оба препарата, включа¤ определение содержани¤ фенитоина в плазме крови в течение всего периода одновременного применени¤ обоих препаратов и непродолжительное врем¤ после завершени¤ комбинированной терапии. ѕри одновременном применении метотрексата и ципрофлоксацина может замедл¤тьс¤ почечно-канальцевый транспорт метотрексата, что может сопровождатьс¤ повышением концентрации метотрексата в плазме крови. ѕри этом может увеличиватьс¤ веро¤тность развити¤ побочных эффектов метотрексата. ¬ св¤зи с этим за пациентами, получающими одновременную терапию метотрексатом и ципрофлоксацином, должно быть установлено тщательное наблюдение. ѕри одновременном применении ципрофлоксацина и тизанидина наблюдалось увеличение концентрации тизанидина в сыворотке крови: увеличение —max в 7 раз (от 4 до 21 раза), увеличение AUC в 10 раз (от 6 до 24 раз). ”величение концентрации тизанидина в сыворотке крови может вызвать снижение ј? и сонливость. “аким образом, одновременное применение ципрофлоксацина и препаратов, содержащих тизанидин, противопоказано. ¬ ходе проведени¤ клинических исследований было показано, что одновременное применение дулоксетина и мощных ингибиторов изофермента CYP1ј2 (таких как флувоксамин), может привести к увеличению AUC и —mах дулоксетина. Ќесмотр¤ на отсутствие клинических данных о возможном взаимодействии с ципрофлоксацином, можно предвидеть веро¤тность подобного взаимодействи¤ при одновременном применении ципрофлоксацина и дулоксетина. ќдновременное применение ропинирола и ципрофлоксацина, умеренного ингибитора изофермента CYP1ј2, приводит к увеличению —mах и AUC ропинирола на 60% и 84% соответственно. —ледует контролировать неблагопри¤тные эффекты ропинирола во врем¤ его совместного применени¤ с ципрофлоксацином и в течение короткого времени после завершени¤ комбинированной терапии. ¬ исследовании на здоровых добровольцах было установлено, что одновременное применение препаратов, содержащих лидокаин, и ципрофлоксацина, умеренного ингибитора изофермента CYP1ј2, приводит к снижению клиренса лидокаина на 22% при его в/в введении. Ќесмотр¤ на хорошую переносимость лидокаина при одновременном применении с ципрофлоксацином, возможно усиление побочных эффектов вследствие взаимодействи¤. ѕри одновременном применении клозапина и ципрофлоксацина в дозе 250 мг в течение 7 дней, наблюдалось увеличение сывороточных концентраций клозапина и N-десметилклозапина на 29% и 31% соответственно. —ледует контролировать состо¤ние пациента и при необходимости проводить коррекцию режима дозировани¤ клозапина во врем¤ его совместного применени¤ с ципрофлоксацином и в течение короткого времени после завершени¤ комбинированной терапии. ѕри одновременном применении у здоровых добровольцев ципрофлоксацина в дозе 500 мг и силденафила в дозе 50 мг, отмечалось увеличение —mах и AUC силденафила в 2 раза. ¬ св¤зи с этим применение данной комбинации возможно только после оценки соотношени¤ польза/риск. ѕри одновременном приеме агомелатина и ципрофлоксацина можно ожидать аналогичных эффектов. ѕри одновременном применении золпидема и ципрофлоксацина возможно повышение концентрации золпидема в плазме крови. ќдновременное применение препаратов, содержащих данные вещества, не рекомендуетс¤. —овместное применение ципрофлоксацина и антагонистов витамина   (например, варфарина,