Ciprofloxacin tablets 500mg, No. 10

Infectious and inflammatory diseases caused by microorganisms sensitive to the drug:

- kidney and urinary tract;

- genitals (including gonorrhea, prostatitis);

- respiratory tract;

- musculoskeletal system;

- sepsis;

- peritonitis;

- ear, throat and nose;

- gynecological (including adnexitis) and postpartum infections;

- the digestive system (including the oral cavity, teeth, jaws);

- gallbladder and biliary tract;

- skin, mucous membranes and soft tissues;

Prevention and treatment of infections in patients with reduced immunity (during therapy with immunosuppressants).

Individual, depending on indications, clinical situation and patient's age

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

Film-coated tablets

1 tab. ciprofloxacin

Care should be taken to prescribe the drug for severe atherosclerosis of the vessels of the brain, cerebrovascular accident, mental illness, convulsive syndrome, epilepsy, severe renal and / or hepatic failure, elderly patients.

- children under 18 years of age (until the completion of the skeleton formation process);

- pregnancy;

- lactation period (breastfeeding);

- deficiency of glucose-6-phosphate dehydrogenase;

- pseudomembranous colitis;

- hypersensitivity to Ciprofloxacin or other drugs from the fluoroquinolone group.

pharmachologic effect

A broad-spectrum antimicrobial agent, a fluoroquinolone derivative. Suppresses bacterial DNA gyrase (topoisomerases II and IV, responsible for the process of supercoiling of chromosomal DNA around nuclear RNA, which is necessary for reading genetic information), disrupts DNA synthesis, growth and division of bacteria; causes pronounced morphological changes (including the cell wall and membranes) and rapid death of the bacterial cell. It has a bactericidal effect on gram-negative organisms during dormancy and division (because it affects not only DNA gyrase, but also causes lysis of the cell wall), on gram-positive microorganisms - only during the period of division. Low toxicity for cells of a macroorganism is explained by the absence of DNA gyrase in them.

While taking ciprofloxacin, there is no parallel development of resistance to other antibiotics that do not belong to the group of gyrase inhibitors, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibiotics. Gram-negative aerobic bacteria are susceptible to ciprofloxacin: enterobacteria (Escherichia coli, Salmonella spp., Shigella spp., Citrobacter spp., Klebsiella spp., Enterobacter spp., Proteus mirabilis, Proteus alwards. , 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). Most methicillin-resistant staphylococci are also resistant to ciprofloxacin. The sensitivity of Streptococcus pneumoniae, Enterococcus faecalis, Mycobacterium avium (located intracellularly) is moderate (high concentrations are required to suppress them). Resistant to the drug: Bacteroides fragilis, Pseudomonas cepacia, Pseudomonas maltophilia,Ureaplasma urealyticum, Clostridium difficile, Nocardia asteroides.

Ineffective against Treponema pallidum.

Resistance develops extremely slowly, because on the one hand, after the action of ciprofloxacin, there are practically no persistent microorganisms, and on the other hand, bacterial cells do not have enzymes that inactivate it.

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.

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

Caution should be exercised with the simultaneous use of ciprofloxacin, like other fluoroquinolones, in patients receiving drugs that cause prolongation of the QT interval (for example, class I A or class III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotic drugs). Concomitant oral administration of ciprofloxacin and cation-containing drugs, mineral supplements containing calcium, magnesium, aluminum, iron, sucralfate, antacids, polymeric phosphate compounds (such as sevelamer, lanthanum carbonate) and drugs with a large buffer capacity (such as didanosine tablets) containing magnesium , aluminum or calcium, reduces the absorption of ciprofloxacin. In such cases, ciprofloxacin should be taken either 1Ц2 hours before or 4 hours after taking these drugs.This limitation does not apply to histamine H2 receptor drug blockers. Metoclopramide accelerates the absorption of ciprofloxacin (when taken orally), which leads to a shorter time to reach the Cmax of ciprofloxacin in plasma. No effect on the bioavailability of ciprofloxacin was found. With the simultaneous use of ciprofloxacin and omeprazole, there may be a slight decrease in Cmax in plasma and a decrease in AUC. The simultaneous use of ciprofloxacin and theophylline can cause an undesirable increase in the concentration of theophylline in the blood plasma and, accordingly, the occurrence of theophylline-induced adverse events; in very rare cases, these adverse events can be life-threatening for the patient. If the simultaneous use of these two drugs is unavoidable,it is recommended to continuously monitor the concentration of theophylline in the blood plasma and, if necessary, reduce the dose of theophylline. The simultaneous use of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline) can lead to an increase in the concentration of xanthine derivatives in the blood serum. The combination of very high doses of quinolones (DNA gyrase inhibitors) and some NSAIDs (excluding acetylsalicylic acid) can provoke seizures. With the simultaneous use of ciprofloxacin and preparations containing cyclosporine, a short-term transient increase in the concentration of creatinine in the blood plasma was observed. In such cases, it is necessary to determine the concentration of creatinine in the blood 2 times a week. With the simultaneous use of ciprofloxacin and oral hypoglycemic agents, mainly sulfonylurea derivatives (for example,glibenclamide, glimepiride), the development of hypoglycemia is presumably due to an increase in the action of oral hypoglycemic agents (see section 'Side effects'). Probenecid slows down the rate of excretion of ciprofloxacin by the kidneys. The simultaneous use of ciprofloxacin and preparations containing probenecid leads to an increase in the concentration of ciprofloxacin in the blood plasma. With the simultaneous use of ciprofloxacin and phenytoin, a change (increase or decrease) in the content of phenytoin in the blood plasma was observed. In order to avoid a weakening of the anticonvulsant effect of phenytoin due to a decrease in its concentration, as well as to prevent adverse events associated with an overdose of phenytoin when ciprofloxacin is discontinued, it is recommended to monitor phenytoin therapy in patients taking both drugs.including the determination of the content of phenytoin in blood plasma during the entire period of simultaneous use of both drugs and for a short time after the completion of combination therapy. With the simultaneous use of methotrexate and ciprofloxacin, the renal tubular transport of methotrexate may slow down, which may be accompanied by an increase in the concentration of methotrexate in the blood plasma. This may increase the likelihood of developing side effects of methotrexate. In this regard, patients receiving concomitant therapy with methotrexate and ciprofloxacin should be closely monitored. With the simultaneous use of ciprofloxacin and tizanidine, an increase in the concentration of tizanidine in the blood serum was observed: an increase in Cmax by 7 times (from 4 to 21 times), an increase in AUC by 10 times (from 6 to 24 times).An increase in serum tizanidine concentration can cause a decrease in blood pressure and drowsiness. Thus, the simultaneous use of ciprofloxacin and preparations containing tizanidine is contraindicated. In the course of clinical studies, it has been shown that the simultaneous use of duloxetine and powerful inhibitors of the isoenzyme CYP1A2 (such as fluvoxamine) can lead to an increase in AUC and Cmax of duloxetine. Despite the lack of clinical data on a possible interaction with ciprofloxacin, the likelihood of such an interaction can be predicted with the simultaneous use of ciprofloxacin and duloxetine. The simultaneous use of ropinirole and ciprofloxacin, a moderate inhibitor of the isoenzyme CYP1A2, leads to an increase in Cmax and AUC of ropinirole by 60% and 84%, respectively.The adverse effects of ropinirole should be monitored during its combined use with ciprofloxacin and for a short time after the completion of combination therapy. In a study on healthy volunteers, it was found that the simultaneous use of drugs containing lidocaine and ciprofloxacin, a moderate inhibitor of the isoenzyme CYP1A2, leads to a 22% decrease in the clearance of lidocaine when administered intravenously. Despite the good tolerance of lidocaine when used simultaneously with ciprofloxacin, it is possible that side effects may increase due to interaction. With the simultaneous use of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, there was an increase in serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively.The patient's condition should be monitored and, if necessary, the dosage regimen of clozapine should be adjusted during its joint use with ciprofloxacin and within a short time after the completion of combination therapy. With the simultaneous use in healthy volunteers of ciprofloxacin at a dose of 500 mg and sildenafil at a dose of 50 mg, there was an increase in Cmax and AUC of sildenafil by 2 times. In this regard, the use of this combination is possible only after assessing the benefit / risk ratio. With the simultaneous administration of agomelatine and ciprofloxacin, similar effects can be expected. With the simultaneous use of zolpidem and ciprofloxacin, an increase in the concentration of zolpidem in the blood plasma is possible. The simultaneous use of preparations containing these substances is not recommended.The combined use of ciprofloxacin and vitamin K antagonists (for example, warfarin, acenocoumarol, phenprocoumon) can lead to an increase in their anticoagulant effect. The magnitude of this effect may vary depending on concomitant infections, age and general condition of the patient, so it is difficult to assess the effect of ciprofloxacin on increasing INR. INR should be monitored quite often during the combined use of ciprofloxacin and vitamin K antagonists, as well as for a short time after the completion of combination therapy. Avoid the simultaneous use of ciprofloxacin and dairy products or beverages fortified with minerals (for example, milk, yogurt, calcium-fortified orange juice), as this may reduce the absorption of ciprofloxacin. However, calcium,included in other food products, does not significantly affect the absorption of ciprofloxacin.