Ciprofloxacin, 500 mg 10 pcs

Pharmacotherapeutic group: Antimicrobial agent – fluoroquinolone

ATX code: JO1MA02

.Pharmacological properties

Pharmacodynamics

strong>Mechanism of Action

Cyprofloxacin has in vitro activity against a wide range of Gram-negative and Gram-positive microorganisms. Bactericidal action of ciprofloxacin is realized through inhibition of bacterial topoisomerases (topoisomerase II – DNA-gyrase and topoisomerase IV) which are necessary for replication, transcription, repair and recombination of bacterial DNA.

Ciprofloxacin acts on Gram-negative microorganisms during resting and dividing period, as it affects not only DNA-gyrase, but also causes lysis of cell wall, on Gram-positive microorganisms only during dividing. Low toxicity to macroorganism cells is explained by the absence of DNA-gyrase in them.

With ciprofloxacin there is no parallel development of resistance to other antibacterial drugs which do not belong to the group of gyrase inhibitors and this makes it highly effective against bacteria which are resistant to, for example, aminoglycosides, penicillins, cephalosporins, getracyclines and many other antibacterial drugs.

Resistance mechanisms

Resistance in vitro to ciprofloxacin is often caused by point mutations in bacterial topoisomerases and DNA gyrase and develops slowly through multistep mutations.

Single mutations can lead to rather reduced sensitivity, multiple mutations mainly lead to the development of clinical resistance to ciprofloxacin and to cross-resistance to quinolone-type drugs.

Resistance to ciprofloxacin can form as a result of decreased permeability of the bacterial cell wall and/or activation of ciprofloxacin excretion from the microbial cell. The development of resistance due to the Q_nr encoding gene localized on plasmids has been reported.

The resistance mechanisms that lead to inactivation of penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines probably do not impair the antibacterial activity of ciprofloxacin. Microorganisms resistant to these drugs may be sensitive to ciprofloxacin. The minimum bactericidal concentration (MBC) usually does not exceed the minimum inhibitory concentration (MIC) by more than 2-fold.

For certain strains, the spread of acquired resistance may vary by geographic region and over time.

In vitro <strongsensitivityto ciprofloxacin<

In vitro activity of ciprofloxacin against the following susceptible microbial strains has been demonstrated:

Aerobic Gram-positive microorganisms: Bacillus anthracis, Staphylococcus aureus (methicillin-sensitive), Staphylococcus saprophyticus, Streptococcus spp.

Aerobic Gram-negative microorganisms: Aeromonas spp., Moraxella catarrhalis, Brucella spp., Neisseria meningitidis, Citrobacter koseri, Pasteurella spp., Francisella tularensi, Salmonella spp., Haemophilus ducreyi, Shigella spp., Haemophilus influenzae, Vibrio spp., Legionella spp, Yersinia pestis.

Anaerobic microorganisms: Mobiluncus spp.

Other microorganisms: Chlamidia trachomatis, Chlamidia pneumoniae, Mycoplasma hominis, Mycoplasma pneumoniae.

Varying degrees of sensitivity to ciprofloxacin have been demonstrated for the following microorganisms: Acinetobacter baumann, Burkholderia. cepacian, Campylobacter spp., Enterococcus faecalis, Enterobacter aerogenes, Enterobacter <emcloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii</em/em>, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia marcescens, Streptococcus pneumoniae</em/em>, Peptostreptococcus spp., Propionibacterium acnes.

The natural resistance to ciprofloxacin is believed to be Staphylococcus aureus (methicillin-resistant), Stenotrophomonas maltophilia, Actinomyces spp., Enterococcus faecium, .Listeria monocytogenes, Mycoplasma genitalium, Ureaplasma urealitycum, anaerobic microorganisms (except Mobiluncus spp., Peptostreptococcus spp, Propionibacterium acnes).

Pharmacokinetics

absorption

. After oral administration, ciprofloxacin is rapidly absorbed from the gastrointestinal tract, mainly in the duodenum and jejunum. Maximal concentration (С_max) of ciprofloxacin in blood serum is reached after 1-2 hours and amounts to 1.2; 2.4; 4.3 and 5.4 mcg/ml, respectively in per oral administration of 250, 500, 700 and 1000 mg of preparation. Bioavailability is about 70-80%. The values of maximum plasma concentration and area under the curve “concentration-time” (AUC) increase in proportion to the dose. Food intake (except dairy products) slows absorption but does not change C_max and bioavailability.

Distribution

The binding of ciprofloxacin to blood plasma proteins is 20-30%, the active substance is present in blood plasma mainly in the non-ionized form. Ciprofloxacin is freely distributed in tissues and body fluids. The volume of distribution in the body is 2-3 l/kg. Ciprofloxacin concentration in tissues is significantly (from 2 to 12 times) higher than in blood plasma. High concentrations of the drug are observed in bile, lung, kidney, liver, gallbladder, uterus, seminal fluid, prostate tissues, tonsils, endometrium, fallopian tubes and ovaries. It penetrates into cerebrospinal fluid at concentrations of 6-10% in non-inflamed cerebral membranes, 14-37% in inflamed ones – of the concentration in blood serum. It penetrates well into the intraocular fluid, bronchial secretion, pleura, peritoneum, lymph, breast milk, through the placenta.

Metabolism

Biotransformed in the liver (15-30%). Four metabolites of ciprofloxacin may be detected in the blood in low concentrations: diethylciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3), formylciprofloxacin (M4), three of which (M1-MZ) exhibit antibacterial activity in vitro, comparable with the antibacterial activity of nalidixic acid. The in vitro antibacterial activity of the M4 metabolite, which is present in smaller amounts, is more consistent with that of norfloxacin.

Elimation

Ciprofloxacin is excreted mainly by the kidneys through glomerular filtration and tubular secretion (50-70%); a small amount through the gastrointestinal tract (15-30 %).</Renal clearance is 3-5 ml/min/kg, total clearance about 8-10 ml/min/kg. About 1% of the administered dose is excreted with bile. In bile ciprofloxacin is present in high concentrations.

In patients with unchanged renal function the elimination half-life is usually 3-5 hours. In patients with impaired renal function the half-life is prolonged.

Indications

Uncomplicated and complicated infections caused by microorganisms sensitive 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. and staphylococci;

infections of the middle ear (otitis media), paranasal sinuses (sinusitis), especially caused by gram-negative microorganisms, including Pseudomonas aeruginosa or staphylococci;

eye infections;

infections of the genitourinary system (including cystitis, pyelonephritis, adnexitis, chronic bacterial prostatitis, orchitis, epididymitis, uncomplicated gonorrhea);

complicated intra-abdominal infections (in combination with metronidazole);

infections of the gallbladder and bile ducts;

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

infections of bones and joints (osteomyelitis, septic arthritis);

sepsis;

typhoid fever;

campylobacteriosis, shigellosis, traveler’s diarrhea;

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

selective intestinal decontamination in patients with reduced immunity;

prevention and treatment of pulmonary anthrax (infection with Bacillus anthracis);

prevention of invasive infections caused by Neisseria meningitidis.

Children

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

prevention and treatment of pulmonary anthrax (infection with Bacillus anthracis).

Pharmacological effect

Pharmacotherapeutic group: antimicrobial agent – fluoroquinolone

ATX code: JО1MA02

Pharmacological properties

Pharmacodynamics

Mechanism of action

Ciprofloxacin has in vitro activity against a wide range of gram-negative and gram-positive microorganisms. The bactericidal effect of ciprofloxacin is carried out through the inhibition of bacterial topoisomerases (topoisomerase II – DNA gyrase and topoisomerase IV), which are necessary for replication, transcription, repair and recombination of bacterial DNA.

Ciprofloxacin acts on gram-negative microorganisms during the dormant period and during the division period, since it affects not only DNA gyrase, but also causes lysis of the cell wall; on gram-positive microorganisms only during the division period. Low toxicity for the cells of the macroorganism is explained by the absence of DNA gyrase in them.

While taking ciprofloxacin, there is no parallel development of resistance to other antibacterial drugs 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, hetracyclines and many other antibacterial drugs.

Mechanisms of resistance

In vitro resistance to ciprofloxacin is often caused by point mutations in bacterial topoisomerases and DNA gyrase and develops slowly through multistep mutations.

Single mutations may lead to a decrease in sensitivity; multiple mutations mainly lead to the development of clinical resistance to ciprofloxacin and cross-resistance to quinolone drugs.

Resistance to ciprofloxacin can form as a result of decreased permeability of the bacterial cell wall and/or activation of the removal of ciprofloxacin from the microbial cell. The development of resistance caused by the Qnr coding gene localized on plasmids has been reported.

Resistance mechanisms that lead to inactivation of penicillins, cephalosporins, aminoglycosides, macrolides and tetracyclines do not likely interfere with the antibacterial activity of ciprofloxacin. Microorganisms resistant to these drugs may be sensitive to ciprofloxacin. The minimum bactericidal concentration (MBC) usually does not exceed the minimum inhibitory concentration (MIC) by more than 2 times.

For certain strains, the distribution of acquired resistance may vary across geographic regions and over time.

In vitro sensitivity to ciprofloxacin

In vitro activity of ciprofloxacin has been demonstrated against the following sensitive strains of microorganisms:

Aerobic gram-positive microorganisms: Bacillus anthracis, Staphylococcus aureus (methicillin-sensitive), Staphylococcus saprophyticus, Streptococcus spp.

Aerobic gram-negative microorganisms: Aeromonas spp., Moraxella catarrhalis, Brucella spp., Neisseria meningitidis, Citrobacter koseri, Pasteurella spp., Francisella tularensi, Salmonella spp., Haemophilus ducreyi, Shigella spp., Haemophilus influenzae, Vibrio spp., Legionella spp., Yersinia pestis.

Anaerobic microorganisms: Mobiluncus spp.

Other microorganisms: Chlamidia trachomatis, Chlamidia pneumoniae, Mycoplasma hominis, Mycoplasma pneumoniae.

Varying degrees of sensitivity to ciprofloxacin have been demonstrated for the following microorganisms: Acinetobacter baumann, Burkholderia cepacian, Campylobacter spp., Enterococcus faecalis, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Morganella morganii, Neisseria gonorrhoeae, Proteus mirabilis, Proteus vulgaris, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Serratia marcescens, Streptococcus pneumoniae, Peptostreptococcus spp., Propionibacterium acnes.

It is believed that Staphylococcus aureus (methicillin-resistant), Stenotrophomonas maltophilia, Actinomyces spp., Enterococcus faecium, Listeria monocytogenes, Mycoplasma genitalium, Ureaplasma urealitycum, anaerobic microorganisms (with the exception of Mobiluncus spp., Peptostreptococcus) have natural resistance to ciprofloxacin spp., Propionibacterium acnes).

Pharmacokinetics

Suction

After oral administration, ciprofloxacin is rapidly absorbed from the gastrointestinal tract, mainly in the duodenum and jejunum. The maximum concentration (Cmax) of ciprofloxacin in the blood serum is achieved after 1-2 hours and is 250, 500, 700 and 1000 mg of the drug 1.2 when taken orally; 2.4; 4.3 and 5.4 μg/ml, respectively. Bioavailability is about 70-80%. The values ​​of the maximum plasma concentration and the area under the concentration-time curve (AUC) increase in proportion to the dose. Eating (with the exception of dairy products) slows absorption, but does not change Cmax and bioavailability.

Distribution

The binding of ciprofloxacin to plasma proteins is 20-30%; the active substance is present in the blood plasma mainly in non-ionized form. Ciprofloxacin is freely distributed in tissues and body fluids. The volume of distribution in the body is 2-3 l/kg. The concentration of ciprofloxacin in tissues is significantly (from 2 to 12 times) higher than the concentration in blood plasma. High concentrations of the drug are observed in bile, lungs, kidneys, liver, gall bladder, uterus, seminal fluid, prostate tissue, tonsils, endometrium, fallopian tubes and ovaries. Penetrates into the cerebrospinal fluid in concentrations of 6-10% for non-inflamed meninges, 14-37% for inflamed ones – from the concentration in the blood serum. Penetrates well into the intraocular fluid, bronchial secretions, pleura, peritoneum, lymph, breast milk, through the placenta.

Metabolism

Biotransformed in the liver (15-30%). Four metabolites of ciprofloxacin can be detected in the blood in small concentrations: diethylciprofloxacin (M1), sulfociprofloxacin (M2), oxociprofloxacin (M3), formylciprofloxacin (M4), three of which (M1-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 smaller quantities, is more consistent with the activity of norfloxacin.

Removal

Ciprofloxacin is excreted from the body primarily by the kidneys by glomerular filtration and tubular secretion (50-70%); a small amount – through the gastrointestinal tract (15-30%). Renal clearance is 3-5 ml/min/kg, total clearance is about 8-10 ml/min/kg. Approximately 1% of the administered dose is excreted in bile. Ciprofloxacin is present in bile in high concentrations.

In patients with unchanged renal function, the half-life is usually 3-5 hours. If renal function is impaired, the half-life increases.

Special instructions

When treating severe infections, staphylococcal infections and infections caused by anaerobic bacteria, ciprofloxacin should be used in combination with appropriate antibacterial agents.

The drug Ciprofloxacin is not the drug of choice for the treatment of infections caused by Streptococcus pneumoniae due to its limited effectiveness against the pathogen.

For genital infections suspected of being caused by strains of Neisseria gonorrhoeae resistant to fluoroquinolones, information about local resistance to ciprofloxacin should be taken into account and the sensitivity of the pathogen should be confirmed by laboratory tests.

Ciprofloxacin has an effect on prolongation of the QT interval (see section “Side effects”). Given that women have a longer average QT interval compared to men, they are more sensitive to drugs that cause QT prolongation. Elderly patients also have increased sensitivity to the effects of drugs that prolong the QT interval. Ciprofloxacin should be used with caution in combination with drugs that prolong the QT interval (for example, class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics) (see section “Interaction with other drugs”) in patients with an increased risk of prolongation of the QT interval or the development of torsade de pointes (for example, congenital long QT syndrome, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia)).

Sometimes, after taking the first dose of ciprofloxacin, hypersensitivity to the drug may develop (see section “Side effects”), including allergic reactions, which should be reported to your doctor immediately. In rare cases, after the first use, anaphylactic reactions up to anaphylactic shock may occur. In these cases, use of the drug ciprofloxacin should be stopped immediately and appropriate treatment should be 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 a day). In this situation, the use of drugs that suppress intestinal motility is contraindicated.

Cases of liver necrosis and life-threatening liver failure have been reported with the use of ciprofloxacin; in the presence of symptoms of liver disease, such as anorexia, jaundice, dark urine, itching, abdominal tenderness, the use of ciprofloxacin should be discontinued.

Patients taking the drug ciprofloxacin and who have had liver disease may experience a temporary increase in the activity of liver transaminases and alkaline phosphatase or cholestatic jaundice.

In patients with myasthenia gravis gravis, ciprofloxacin should be used with caution as it may worsen symptoms.

When using ciprofloxacin, cases of tendinitis and tendon rupture (mainly the Achilles tendon), sometimes bilateral, may occur within the first 48 hours after the start of therapy. Inflammation and rupture of the tendon may occur even several months after stopping treatment with ciprofloxacin. Elderly patients and patients with tendon diseases who are simultaneously treated with glucocorticosteroids have an increased risk of tendinopathy. Cases of status epilepticus have been reported with the use of ciprofloxacin. Ciprofloxacin, like other fluoroquinolones, can provoke convulsions and lower the seizure threshold; if convulsions occur, use of the drug should be discontinued. Psychiatric reactions may occur even after the first use of fluoroquinolones, including ciprofloxacin; in rare cases, depression or psychotic reactions may progress to suicidal thoughts and self-injurious behavior, such as suicide attempts, including completed suicide; if the patient develops one of these reactions, the drug should be discontinued and the doctor should be informed. In patients with epilepsy and a history of central nervous system diseases (for example, a decrease in the seizure threshold, a history of seizures, cerebrovascular accidents, organic brain lesions or stroke) due to the risk of developing adverse reactions from the central nervous system, ciprofloxacin should be used only in cases where the expected clinical effect outweighs the possible risk of developing side effects of the drug.

When taking fluoroquinolones, cases of sensory or sensorimotor polyneuropathy, hypoesthesia, dysesthesia, and weakness have been reported. If symptoms such as pain, burning, tingling, numbness, weakness occur, you should not continue to use the drug until consulting your doctor.

Since photosensitivity reactions may occur when taking the drug, patients should avoid contact with direct sunlight and ultraviolet light. If symptoms of photosensitivity appear, treatment should be discontinued.

Caution should be exercised when simultaneous use of ciprofloxacin and drugs metabolized by CYP450 1A2 isoenzymes (such as theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine).

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 may 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 the drug.

Long-term and repeated use of ciprofloxacin may lead to superinfection with resistant bacteria or fungal infections.

Children

Based on an analysis of data on the safety of the use of ciprofloxacin in children under 18 years of age, despite the lack of a proven connection between damage to cartilage or joints and taking the drug, it is not recommended to use ciprofloxacin in children for the treatment of diseases other than the treatment of complications of cystic fibrosis of the lungs (in children 5-17 years old) associated with Pseudomonas aeruginosa, and for the treatment and prevention of pulmonary anthrax (after suspected or proven infection with Bacillus anthracis).

Impact on the ability to drive vehicles and operate machinery

Ciprofloxacin may impair the ability of patients to drive a car and engage in other potentially hazardous activities that require increased attention and speed of psychomotor reactions due to its effect on the central nervous system. The potential for side effects such as dizziness, vertigo, confusion and drowsiness should be taken into account. If the described adverse events occur, you should refrain from performing these activities.

Active ingredient

Ciprofloxacin

Composition

Active ingredient: ciprofloxacin hydrochloride (monohydrate) 582.2 mg, equivalent to ciprofloxacin 500.0 mg;

excipients: microcrystalline cellulose 78.0 mg, corn starch 52.4 mg, povidone-K30 40.0 mg, magnesium stearate 7.6 mg;
shell: film coating (polyvinyl alcohol 8,800 mg, titanium dioxide 5,500 mg, macrogol 4,444 mg, talc 3,256 mg) – 22.0 mg.

Pregnancy

Ciprofloxacin is contraindicated during pregnancy and breastfeeding.
If it is necessary to use ciprofloxacin in a mother during breastfeeding, breastfeeding should be stopped before starting treatment.

Contraindications

Hypersensitivity to ciprofloxacin or other drugs from the fluoroquinolone group, as well as to other components of the drug;
simultaneous use of ciprofloxacin and tizanidine (see section “Interaction with other drugs”);
children under 18 years of age (until the process of skeletal formation is completed, except for the indications specified in the section “Indications for use”, children);
pregnancy;
breastfeeding period.
With caution
Severe cerebral atherosclerosis, cerebrovascular accidents, organic brain lesions or stroke, mental illness (depression, psychosis), epilepsy, decreased seizure threshold (or history of seizures), severe renal and/or liver failure, advanced age, tendon damage during previous treatment with quinolones, increased risk of prolongation of the QT interval or the development of arrhythmia type “pirouette” (for example, congenital long QT syndrome, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (for example, with hypokalemia, hypomagnesemia), simultaneous use of drugs that prolong the QT interval (including class IA and III antiarrhythmics, tricyclic antidepressants, macrolides, antipsychotics), simultaneous use with inhibitors CYP450 1A2 isoenzymes (including theophylline, methylxanthine, caffeine, duloxetine, clozapine, ropinirole, olanzapine), mental illness, myasthenia gravis, glucose-6-phosphate dehydrogenase deficiency.

Side Effects

The following adverse reactions were classified as follows: “very common” (≥ 10), “common” (≥ 1/100, < 1/10), “uncommon” (≥ 1/1000, < 1/100), “rare” (≥ 1/10,000, < 1/1000), “very rare” (≤ 10,000), “frequency unknown.”

From the gastrointestinal tract

often – nausea, diarrhea; uncommon – vomiting, abdominal pain, dyspepsia, flatulence, decreased appetite and amount of food taken, anorexia; rarely – dysphagia, cholestatic jaundice (especially in patients with previous liver diseases), hepatitis (non-infectious), oral candidiasis; very rarely – pancreatitis, antibiotic-associated pseudomembranous colitis, liver tissue necrosis (in extremely rare cases, progressing to life-threatening liver failure).

From the hematopoietic system

uncommon – eosinophilia, rare – leukopenia (granulocytopenia), anemia, neutropenia, leukocytosis, thrombocytopenia, very rare – hemolytic anemia, agranulocytosis, pancytopenia (life-threatening), bone marrow depression (life-threatening).

Allergic reactions

uncommon – skin rash; itching, urticaria, macular nodular rash; rarely – allergic reactions, allergic edema/angioedema, photosensitivity, erythema multiforme, erythema nodosum; very rarely – anaphylactic reactions, anaphylactic shock (life-threatening), serum sickness, Stevens-Johnson syndrome, Lyell’s syndrome, pinpoint hemorrhages on the skin, frequency unknown – acute generalized pustular exanthema.

From the central nervous system

uncommon – headache, dizziness, fatigue, sleep disturbance, anxiety, psychomotor hyperactivity/agitation, taste disturbance; rarely – paresthesia and dysesthesia, hypoesthesia, tremor, convulsions, epileptic seizures, vertigo, confusion, anxiety; very rarely – migraine, impaired motor coordination, impaired sense of smell, hyperesthesia, benign intracranial hypertension, dream disturbance (nightmares), psychotic reactions (which can lead to self-harmful behavior such as suicidal acts/thoughts, as well as attempted or successful suicide), depression (which can lead to self-harmful behavior such as suicidal actions/thoughts, as well as attempted suicide or successful suicide), hallucinations; frequency unknown – peripheral neuropathy and polyneuropathy.

From the side of the organ of vision

very rarely – visual disturbances, diplopia, impaired color perception.

From the side of the hearing organ

very rarely – tinnitus, temporary hearing loss.

From the cardiovascular system

infrequently – palpitations; rarely – tachycardia, a feeling of a “rush” of blood to the face, vasodilation, fainting, decreased blood pressure; very rarely – vasculitis; frequency unknown – QT interval prolongation, ventricular arrhythmias (including pirouette type, more often in patients with a predisposition to developing QT interval prolongation).

From the respiratory system

rarely – dyspnea, laryngeal edema, pulmonary edema, respiratory failure (including bronchospasm).

From the musculoskeletal system

infrequently – arthralgia; rarely – myalgia, joint swelling; very rarely – arthritis, increased muscle tone, muscle cramps, muscle weakness, tendonitis (mainly Achilles tendons), tendon rupture, exacerbation of myasthenia gravis symptoms.

From the urinary system

rarely – acute renal failure, hematuria, crystalluria, interstitial nephritis.

Others

uncommon – general malaise, fever, fungal superinfection; rarely – pain syndrome of nonspecific etiology, peripheral edema, sweating (hyperhidrosis); very rarely – gait disturbance.

Laboratory indicators

uncommon – increased alkaline phosphatase activity in the blood, urea concentration in the blood, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity, hyperbilirubinemia; rarely – an increase or decrease in prothrombin, increased amylase activity, hyperglycemia, hypoglycemia; frequency unknown – increase in international normalized ratio (INR) (in patients receiving vitamin K antagonists).

Children

often – reversible arthropathy.

Interaction

Drugs that cause QT prolongation

Caution should be exercised when simultaneous use of ciprofloxacin (as well as other fluoroquinolones) in patients receiving drugs that cause prolongation of the QT interval (for example, class IA and III antiarrhythmic drugs, tricyclic antidepressants, macrolides, antipsychotics, see section “Special Instructions”).

Theophylline

The simultaneous use of ciprofloxacin and drugs containing theophylline may 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 constantly monitor the concentration of theophylline in the blood plasma and, if necessary, reduce the dose of theophylline (see section “Special instructions”, cytochrome P450).

Other xanthine derivatives

The simultaneous use of ciprofloxacin and caffeine or pentoxifylline (oxpentifylline) may lead to an increase in the concentration of xanthine derivatives in the blood serum.

Tizanidine

With the simultaneous use of ciprofloxacin and drugs containing tizanidine, an increase in the concentration of tizanidine in the blood serum was detected: an increase in the maximum concentration (Cmax) by 7 (from 4 to 21) times, an increase in the AUC (area under the pharmacokinetic concentration-time curve) by an average of 10 (from 6 to 24) times. Since an increase in the concentration of tizanidine in the blood serum can cause clinically significant side effects: decreased blood pressure and drowsiness, the simultaneous use of ciprofloxacin and drugs containing tizanidine is contraindicated.

Nonsteroidal anti-inflammatory drugs

The combination of very high doses of quinolones (DNA gyrase inhibitors) and some non-steroidal anti-inflammatory drugs (except acetylsalicylic acid) can provoke seizures.

Cyclosporine

With the simultaneous use of ciprofloxacin and drugs containing cyclosporine, a short-term transient increase in plasma creatinine concentration was observed. In cases of combined use of ciprofloxacin and cyclosporine, it is necessary to determine the concentration of creatinine in the blood twice a week.

Oral hypoglycemic agents (glibenclamide, glimepiride) and insulin

With the simultaneous use of ciprofloxacin and oral hypoglycemic agents, mainly sulfonylureas or insulin, the development of hypoglycemia is presumably due to an increased effect of the hypoglycemic agents (see section “Side Effects”). Careful monitoring of blood glucose levels is necessary.

Probenecid

Probenecid slows down the rate of excretion of ciprofloxacin by the kidneys. The simultaneous use of ciprofloxacin and drugs containing probenecid leads to an increase in the concentration of ciprofloxacin in the blood plasma.

Phenytoin

With the simultaneous use of ciprofloxacin and phenytoin, a change (increase or decrease) in the content of phenytoin in the blood plasma was observed. To avoid weakening of the anticonvulsant effect of phenytoin due to a decrease in its concentration, as well as to prevent adverse events associated with phenytoin overdose when discontinuing ciprofloxacin, it is recommended to monitor phenytoin therapy in patients, including determination of phenytoin levels in the blood plasma during the entire period of simultaneous use of both drugs and for a short time after completion of combination therapy.

Methotrexate

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 and the likelihood of developing side effects of methotrexate. In this regard, patients receiving concomitant therapy with methotrexate and ciprofloxacin should be closely monitored.

Omeprazole

With the combined use of ciprofloxacin and drugs containing omeprazole, a slight decrease in the maximum concentration of ciprofloxacin in plasma and a decrease in the area under the concentration-time pharmacokinetic curve may be observed.

Duloxetine

The simultaneous use of duloxetine and fluvoxamine, a potent inhibitor of the CYP450 1A2 isoenzyme, may lead to an increase in the AUC and Cmax of duloxetine. The likelihood of such an interaction can be anticipated when ciprofloxacin and duloxetine are used concomitantly.

Ropinirole

The simultaneous use of ropinirole and ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, leads to an increase in the Cmax and AUC of ropinirole by 60 and 84%, respectively. Monitor for adverse effects of ropinirole during co-administration with ciprofloxacin and for a short time after completion of combination therapy.

Lidocaine

The simultaneous use of drugs containing lidocaine and ciprofloxacin, a moderate inhibitor of the CYP450 1A2 isoenzyme, can lead to a decrease in the clearance of lidocaine by 22% when administered intravenously. When used simultaneously with ciprofloxacin, side effects may increase due to interaction (see section “Special Instructions”, cytochrome P450).

Clozapine

Concomitant use of clozapine and ciprofloxacin may increase serum concentrations of clozapine and N-desmethylclozapine. The patient’s condition should be monitored and, if necessary, the dosage regimen of clozapine should be adjusted during its combined use with ciprofloxacin and for a short time after completion of combination therapy (see section “Special Instructions”, cytochrome P450).

Sildenafil

With the simultaneous use of ciprofloxacin and sildenafil, it is possible to increase the 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.

Vitamin K antagonists (warfarin, acenocoumarol, phenprocoumon, fluindon)

The combined use of ciprofloxacin and vitamin K antagonists may 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. The INR should be monitored during concomitant use of ciprofloxacin and vitamin K antagonists, as well as for a short time after completion of combination therapy.

Cation-containing drugs

Simultaneous use of ciprofloxacin and cation-containing drugs; mineral supplements containing calcium, magnesium, aluminum, iron; sucralfate, antacids, polymeric phosphate compounds (for example, sevelamer, lanthanum carbonate) and drugs with a large buffer capacity (for example, didanosine tablets) containing magnesium, aluminum or calcium, reduce the absorption of ciprofloxacin. In such cases, ciprofloxacin should be taken either 1-2 hours before or 4 hours after taking these drugs.

Eating food and dairy products

The simultaneous use of ciprofloxacin and dairy products or drinks fortified with minerals (for example, milk, yogurt, calcium-fortified juices) should be avoided as the absorption of ciprofloxacin may be reduced. Calcium contained in regular food does not significantly affect the absorption of ciprofloxacin.

Overdose

Symptoms: dizziness, tremor, headache, fatigue, seizures, hallucinations, prolongation of the QT interval, gastrointestinal (GIT) disorders, liver and kidney dysfunction, crystalluria, hematuria.
Treatment: specific antidote is unknown. Gastric lavage, taking activated charcoal, antacids containing calcium and magnesium to reduce the absorption of ciprofloxacin. To prevent the development of crystalluria, it is recommended to monitor renal function, including urine pH and acidity. Symptomatic therapy. Carefully monitor the patient’s condition, ensuring sufficient fluid intake. Using hemo- or peritoneal dialysis, only a small (less than 10%) amount of the drug can be removed.

Storage conditions

In a dry place, protected from light, at a temperature not exceeding 25 ° C.
Keep out of the reach of children.

Shelf life

2 years. Do not use after expiration date.

Manufacturer

Rapharma JSC, Russia