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

Active Ingredient: ciprofloxacin hydrochloride 297.07 mg, equivalent to ciprofloxacin 250 mg. Auxiliary Ingredients: microcrystalline cellulose 25.04 mg, corn starch 18.31 mg, magnesium stearate 3.74 mg, talc purified 2.28 mg, colloidal anhydrous silicon 4.68 mg, sodium starch glycolate 23.88 mg, purified water * q.s. Film sheath material: Opadine-OY-S58910 white 13.44 mg, talc purified 1.22 mg, talc purified q.s., purified water *.

* is lost in the production process.

Cyfran® 500 mg

Each film-coated tablet contains:

Active Ingredient: ciprofloxacin hydrochloride 594.14 mg, equivalent to ciprofloxacin 500 mg. Auxiliary Ingredients: microcrystalline cellulose 50.08 mg, corn starch 36.62 mg, magnesium stearate 7.48 mg, talc purified 4.56 mg, colloidal anhydrous silicon 9.36 mg, sodium starch glycolate 47.76 mg, purified water * q.s. Film sheath material: Opadine-OY-S58910 white 26.88 mg, talc purified 2.44 mg, talc purified q.s., purified water *.

* is lost in the production process.

Description:

Cyfran® 250 mg

White to almost white, round tablets covered with a film sheath, with bevelled edges, engraved with the inscription "CFT" on one side and "250" on the other side, with a diamond on both sides.

Cyfran® 500 mg

White to almost white, round tablets covered with a film sheath, with bevelled edges, engraved with the inscription "CFT" on one side and "500" on the other side, with a diamond on both sides.

Pharmacotherapeutic group:Antimicrobial agent, fluoroquinolone.

ATX: & nbsp

J.01.M.A.02 Ciprofloxacin

Pharmacodynamics:

Antimicrobial preparation of a broad spectrum of action from the group of fluoroquinolones. It is bactericidal. The drug inhibits the DNA enzyme enzyme of bacteria, as a result of which replication and synthesis of bacterial cell proteins are disturbed. Ciprofloxacin acts on gram-negative microorganisms, during rest and division (because it affects not only DNA-gyrase, but also causes lysis of the cell wall), gram-positive microorganisms - only in the period of division. Low toxicity for microorganism cells is explained by the absence of DNA-gyrase in them.Against the background of taking ciprofloxacin, there is no parallel development of resistance to other antibacterial drugs not belonging to the group of inhibitors of gyrase, which makes it highly effective against bacteria that are resistant, for example, to aminoglycosides, penicillins, cephalosporins, tetracyclines and many other antibacterial drugs.

Resistance to ciprofloxacin develops slowly and gradually. When using ciprofloxacin, no cases of plasmid resistance were observed, which often develops with beta-lactam antibiotics, aminoglycosides and tetracyclines. Bacteria containing plasmids are also highly sensitive to ciprofloxacin.

During the use of ciprofloxacin, there is no parallel resistance of pathogens to antibiotics of other groups: β-lactam antibiotics, aminoglycosides, tetracyclines, macrolides, sulfonamides, trimethoprim or nitrofuran derivatives. therefore ciprofloxacin is highly effective against bacteria resistant to the antibiotics of these groups.

Ciprofloxacin maintains efficacy against pathogens that are resistant to other gyrase inhibitors.

Due to its chemical structure ciprofloxacin is highly effective against strains producing β-lactamases.

Sensitivity testing in-vitro

The reproducible criteria for the study of susceptibility to ciprofloxacin approved by the European Committee for the Determination of Sensitivity to Antibiotics (EUCAST) are presented in the table below:

European Committee on the definition of sensitivity to antibiotics. Boundary MIC values (mg / ml) in clinical settings for ciprofloxacin.

Microorganism	Sensitive (mg / L)	Resistant (mg / L)
Enterobacteriaceae	≤0,5	>1
Pseudomonas spp.	≤0,5	>1
Acinetobacter spp.	≤1	>1
Staphylococcus¹ ssp.	≤1	>1
Streptococcus pneumoniae²	≤0,125	>2
Haemophilus influenzae and Moraxella catarrhalis³	≤0,5	>0,5
Neisseria gonorrhoeae	≤0,03	>0,06
Neisseria meningitidis	≤0,03	>0,06
Boundary values, not	≤0,5	>1
associated with species
microorganisms⁴

Staphylococcus spp. - borderline values for ciprofloxacin and ofloxacin are associated with high-dosage therapy.
Streptococcus pneumoniae - wild type S. pneumoniae is not considered sensitive to ciprofloxacin and ofloxacin and thus belongs to the category of microorganisms with intermediate sensitivity.
Strains with a MIC value greater than the sensitive / moderately sensitive threshold are very rare, and so far there have been no reports of them. Tests for identification and antimicrobial sensitivity in the detection of such colonies must be repeated, and the results should be confirmed when analyzing the colonies in the reference laboratory.Until the evidence of a clinical response is obtained for strains with confirmed MIC values exceeding the current resistance threshold, they should be considered as resistant. Haemophilus spp./Moraxella spp.-Possible detection of strains of Haemophilus influenzae with low sensitivity to fluoroquinolones (MIC for ciprofloxacin - 0.125-0.5 mg / l). Evidence of the clinical significance of low resistance for respiratory infections caused by H. influenzae is not.
Boundary values not associated with microbial species were determined mainly on the basis of pharmacokinetics / pharmacodynamics data and are not dependent on MIC distribution for specific species. They are applicable only to species for which a sensitivity threshold specific to the species has not been determined, and not for those for which testing of sensitivity is not recommended. For certain strains, the spread of acquired resistance may vary depending on the geographical region and over time. In this regard, it is desirable to have local information on resistance, especially when treating local infections.

Data from the Institute of Clinical and Laboratory Standards for MIC boundary values (mg / ml) and diffusion testing using ciprofloxacin disks 5 μg.

Institute of Clinical and Laboratory Standards. Boundary values for MIC (mg / L) and for diffusion testing (mm) using discs.

Microorganism	Sensitive	Intermediate	Resistant
Enterobacteriaceae	<1^a	2^a	>4^a
Enterobacteriaceae	>21^b	16-20^b	<15^a
Pseudomonas aeruginosa and other bacteria, family-related Enterobacteriaceae	<1^a	2^a	>4^a
	>21^b	16-20^b	<15^b
Staphylococcus spp.	<1^a	2^a	>4^a
Staphylococcus spp.	>21^b	16-20^b	<15^b
Enterococcus spp.	<1^a	2^a	>4^a
Enterococcus spp.	>21^b	16-20^b	<15^b
Haemophilus spp.	<1^B	-	-
Haemophilus spp.	>21^g	-	-
Neisseria gonorrhoeae	<0,06^d	0,12-0,5^d	>1^d
Neisseria gonorrhoeae	>41^d	28-40^d	<27^d
Neisseria meningitidis	<0,03^e	0,06^e	>1,12^e
Neisseria meningitidis	>35^f	33-34^f	<32^f
Bacillus anthracis Yersinia pestis	<0,25^a	-	-
Francisella tularensi	<0,5^a

a. This reproducible standard is applicable only to dilutions with broth using cationic corrected Mueller-Hinton broth (SAMS) which is incubated with air access at a temperature of 35 ± 2 ° C for 16-20 hours for Enterobacteriaceae, Pseudomonas aeruginosa, other bacteria other than the Enterobacteriaceae family, Staphylococcus spp., Enterococcus spp., and Bacillus anthracis: 20-24 h for Acinetobacter spp., 24 h. For Y. pestis (with insufficient growth, incubate for another 24 h)

b. This reproducible standard is applicable only to diffusion tests using discs using air at a temperature of 35 ± 2 ° C for 16-18 hours.

at.This reproducible standard is applicable only to diffusion tests using sensitivity discs with Haemophilus influenzae and Haemophilus parainfluenzae using a bouillon test medium for Haemophilus spp. (NTM), which is inhibited with air access at a temperature of 35 ± 2 ° C for 20-24 hours.

d. This reproducible standard is applicable only to diffusion tests using discs using NTM, which is incubated in 5% CO₂ at a temperature of 35 ± 2 ° C for 16-18 hours.

etc. This reproducible standard is applicable only to sensitivity tests (diffusion tests using zone discs and agar agar for MIC) using gonococcal agar and 1% of the growth additive at a temperature of 36 ± 2 ° C (not exceeding 37 ° C) in 5 % CO₂ for 20-24 hours.

e. This reproducible standard applies only to dilutions with broth using cullon adjusted Mueller-Hinton broth (SAMS) with the addition of 5% sheep blood that is incubated in 5% CO₂ at 35 ± 2 ° C for 20-24 hours.

f. This reproducible standard is applicable only to dilutions with broth using cationic corrected Mueller-Hinton broth (SAMS) with the addition of a certain 2% growth additive,which is incubated with air access at 35 ± 2 ° C for 48 hours.

In-Vitro sensitivity to ciprofloxacin

For certain strains, the spread of acquired resistance may vary depending on the geographical region and over time. In this regard, when testing the sensitivity of a strain, it is desirable to have local information on resistance, especially when treating severe infections. If the local prevalence of resistance is such that the use of the drug, at least for several types of infections, is questionable - it is necessary to consult a specialist.

In-vitro demonstrated the activity of ciprofloxacin 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:

Chlamydia trachomatis, Chlamydia pneumoniae, Mycoplasma hominis, Mycoplasma pneumoniae.

A varying degree of sensitivity to ciprofloxacin for the following microorganisms was demonstrated:

Acinetobacter baumann, Burkholderia cepacia, Campylobacter spp., Citrobacter freundii, 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 the natural resistance to ciprofloxacin possess 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 spp., Propionibacterium acnes).

Pharmacokinetics:

After oral administration, it is rapidly absorbed from the gastrointestinal tract (mainly in the small intestine). The maximum concentration of the drug in the blood serum of healthy volunteers with oral intake (before meals) of 250, 500, 700 and 1000 mg of the drug is achieved in 1-2 hours and is 1.2; 2.4; 4.3 and 5.4 μg / ml, respectively.

Bioavailability is about 70-80%.

Orally taken ciprofloxacin distributed in tissues and body fluids. High concentrations of the drug are observed in bile, lung, kidney, liver, gall bladder, uterus, seminal fluid, prostate tissue, tonsils, endometrium, fallopian tubes and ovaries. The concentration of the drug in these tissues is higher than in the serum. Ciprofloxacin also penetrates well into the bones, eye fluid, bronchial secretion, saliva, skin, muscles, pleura, peritoneum, lymph.The accumulating concentration of ciprofloxacin in blood neutrophils is 2-7 times higher than in serum.

Ciprofloxacin is distributed freely in tissues and body fluids. The volume of distribution in the body is 20-30%. In the cerebrospinal fluid the drug penetrates in a small amount, where its concentration is 6-10% of that in serum.

The degree of binding of ciprofloxacin to plasma proteins is 20-30%, the active substance is present in the plasma mainly in non-ionized form. Biotransformatsya in the liver. In the blood, four metabolites of ciprofloxacin can be detected in small concentrations. All of them have antibacterial activity.

In patients with unchanged renal function, the elimination period is usually 3-5 hours. If the kidney function is impaired, the elimination half-life increases. The main way of excretion from the body - the kidney (by glomerular filtration and tubular secretion) is 50-70%. An insignificant amount is excreted through the gastrointestinal tract (from 15 to 30%)

Approximately 1% of the administered dose is excreted with bile. In the bile ciprofloxacin is present in high concentrations.

Indications:

Infectious-inflammatory diseases caused by microorganisms sensitive to ciprofloxacin:

Diseases of the lower respiratory tract (acute and chronic (at the stage of exacerbation) bronchitis, pneumonia, bronchiectatic disease, infectious complications of cystic fibrosis);
infection of the ENT organs (otitis media, acute sinusitis);
infection of the kidneys and urinary tract (cystitis, pyelonephritis)
Eye infections
complicated intra-abdominal infections (in combination with metronidazole);
Infections of the genital organs, including adnexitis, chronic bacterial prostatitis;
Infections of the gallbladder and biliary tract
Sepsis
uncomplicated gonorrhea;
typhoid fever,
Campylobacteriosis, shigellosis, diarrhea "travelers";
infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon);
infection of bones and joints (osteomyelitis, septic arthritis);
infection against the background of immunodeficiency (arising in the treatment of immunosuppressive drugs or in patients with neutropenia);
selective decontamination of the intestine in patients with reduced immunity;
Prevention of infections during surgical interventions.
prevention and treatment of pulmonary form of anthrax.

Children:

Therapy of complications caused by Pseudomonas aeruginosa in children with cystic fibrosis of the lungs from 5 to 17 years.
Prevention and treatment of pulmonary form of anthrax (infection with Bacillus anthracis).

Contraindications:

Pregnancy.
Breastfeeding period.
Children and adolescence under 18 years. Ciprofloxacin It is not recommended to use in children under 18 years old for the treatment of other infectious diseases, except for treatment of complications of cystic fibrosis of the lungs (in children from 5 to 17 years) caused by Pseudomonas aeruginosa, and for treatment and prevention of pulmonary form of anthrax (after presumed or proven infection with Bacillus anthracis ).
Hypersensitivity to ciprofloxacin or other drugs from the group of fluoroquinolones.
Pseudomembranous colitis.
Simultaneous use of ciprofloxacin and tizanidine due to clinically significant side effects (risk of pronounced reduction in blood pressure, drowsiness) associated with an increase in the concentration of tizanidine in blood plasma;
Hypersensitivity to other components of the drug.

Carefully:

Severe atherosclerosis of cerebral vessels, cerebral circulatory disorders, organic brain lesions or stroke,mental illness (depression, psychosis), epilepsy, lowering the threshold of convulsive readiness (or convulsions in the anamnesis), marked renal and / or hepatic insufficiency, elderly age, congenital QT interval prolongation syndrome, heart disease (heart failure, myocardial infarction, bradycardia), electrolyte imbalance (eg, hypokalemia, hypomagnesemia), simultaneous administration of drugs that extend the QT interval (including antiarrhythmic IA and III classes), simultaneous use with inhibitors of isoenzymes CYP 450 IA2, (including theophylline, methylxanthine, caffeine, duloxetine, clozapine), patients who have a history of indications of tendon diseases associated with the administration of quinolones.

Pregnancy and lactation:

The use of the drug during pregnancy and during breastfeeding is contraindicated.

Dosing and Administration:

Inside on an empty stomach, not liquid, squeezed a small amount of liquid. Can be taken regardless of food intake. If the drug is used on an empty stomach, the active substance is absorbed more quickly. In this case, the tablets should not be washed down with dairy products or calcium fortified (for example, milk, yogurt, juices with high calcium content).Calcium, contained in normal foods, does not affect the absorption of ciprofloxacin.

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

Adults:

Infections of the lower respiratory tract (acute and chronic bronchitis, pneumonia, bronchiectatic disease, infectious complications of cystic fibrosis) of mild and moderate severity are 500 mg twice a day, in severe cases 750 mg twice a day. The course of treatment is 7-14 days.
Infections of the ENT organs (otitis media, acute sinusitis) - 500 mg 2 times a day, treatment course 10 days.
Infections of bones and joints (osteomyelitis, septic arthritis) - mild and moderate severity - 500 mg 2 times a day, in severe cases 750 mg 2 times. The course of treatment is up to 4-6 weeks.
Infections of the skin and soft tissues (infected ulcers, wounds, burns, abscesses, phlegmon) of mild and moderate severity are 500 mg twice a day, in severe cases 750 mg twice a day. The course of treatment is 7-14 days.
Campylobacteriosis, shigellosis, diarrhea "travelers" - 500 mg 2 times a day, treatment course 5-7 days.
Typhoid fever is 500 mg twice a day for 10 days.
Complicated intra-abdominal infections (in combination with metronidazole) are 500 mg twice a day for 7-14 days.
Infections of the kidneys and urinary tract (cystitis, pyelonephritis) - 250 mg, complicated - 500 mg 2 times a day. The course of treatment is 7-14 days old. Uncomplicated cystitis in women - 250 mg 2 times a day for 3 days.
Uncomplicated gonorrhea - 250-500 mg once.
Chronic bacterial prostatitis - 500 mg 2 times a day, treatment course - 28 days.
Other infections (see section "Indications") - 500 mg 2 times a day. Septicemia, peritonitis (especially when infected with Pseudomonas, Staphylococcus or Streptococcus) - 750 mg 2 times a day.
Prevention and treatment of pulmonary form of anthrax - 500 mg twice a day for 60 days.

In the treatment elderly patients the lowest possible dose of ciprofloxacin should be used, based on the severity of the disease and the clearance of creatinine (for example, when creatinine clearance is 30-50 ml / min, the recommended dose of ciprofloxacin is 250-500 mg every 12 hours).

Children:

For treatment of complications of cystic fibrosis of the lungs caused by Pseudomonas aeruginosa, in children aged 5 to 17 years, 20 mg / kg body weight is administered orally 2 times / day. (maximum dose of 1500 mg). The duration of treatment is 10-14 days.

For prevention and treatment of pulmonary form of anthrax appoint inside 15 mg / kg body weight 2 times / day (do not exceed the maximum single dose of 500 mg and a daily dose of 1000 mg).

The drug should be taken immediately after a suspected or confirmed infection.

The total duration of taking ciprofloxacin in the pulmonary form of anthrax is 60 days.

Dosing for violations of kidney or liver function:

Adults:

Impaired renal function:

With a clearance of creatinine from 31 to 60 ml / min / 1.73 m² or its concentration in the blood plasma from 1.4 to 1.9 mg / 100 ml, the maximum dose of ciprofloxacin for oral administration should be 1000 mg per day.
With a creatinine clearance of 30 ml / min / 1.73 m² or less, or a plasma concentration of 2 mg / 100 ml or more, the maximum dose of ciprofloxacin taken orally should be 500 mg per day.

Impaired renal function + hemodialysis:

Dosing regimen - with creatinine clearance of 30 ml / min / 1.73 m² or less, or a plasma concentration of 2 mg / 100 ml or more, the maximum dose of ciprofloxacin for oral administration should be 500 mg per day;
In days of hemodialysis ciprofloxacin take after this procedure.

Impaired renal function + peritoneal dialysis:

In outpatients, 1 tablet of 500 mg of ciprofloxacin (or 2 tablets of 250 mg).

Impaired liver function

A dose adjustment is not required.

Impaired renal and hepatic function

The dosing regimen is similar to that for renal dysfunction.

Children

The dosage regimen in children with renal and hepatic insufficiency was not studied.

Duration of application

The duration of therapy depends on the severity of the disease and its clinical and bacteriological course. It is important to continue treatment for at least 3 days after the disappearance of the fever or other clinical symptoms of the disease.

Average duration of treatment:

1 day with acute uncomplicated gonorrhea.
During the entire neutropenia period in patients with weakened immunity.
Maximum 2 months with osteomyelitis.
7-14 days for other infections.

In infections caused by streptococci, due to the risk of late complications, treatment should continue for at least 10 days.

For infections caused by chlamydia, therapy should also be conducted for at least 10 days.

If, due to the severity of the condition or for other reasons, the patient is deprived of the ability to take the pill, it is recommended that parenteral therapy be given with an infusion solution of ciprofloxacin, and after the improvement of the condition, switch to the tablet form of the drug

Patients with severe renal dysfunction should be given a drug in a half dose.

Table of recommended doses of the drug for patients with chronic renal failure.

Creatinine clearance ml / mg	Dose
>50	The usual dosing regimen
30-50	250-500 mg 1 time in 12 hours
5-29	250-500 mg once every 18 hours
Patients on hemolytic or peritoneal dialysis	After dialysis, 250-500 mg per day. Take the drug immediately after the hemodialysis session.

Side effects:

The following adverse reactions are classified as follows: "very often" (≥ 10), "often" (≥1 / 100, <1/10), "infrequently" (≥1 / 1000, <1/100), "rarely" (≥1 / 10000, <1/1000), "very rarely" (<10000), "frequency is unknown".

In clinical studies of ciprofloxacin, the following adverse reactions were most frequently observed:

From the digestive system:

Often: nausea, diarrhea.

Infrequently: pain in the regionabdomen; vomiting; flatulence; anorexia; changes in liver tests - alanine aminotransferase (ALT) and aspartate aminotransferase (ACT), alkaline phosphatase; jaundice; hyperbilirubinemia.

Rarely: candidiasis of the oral cavity, jaundice, including cholestatic, pseudomembranous colitis.

Rarely: candidiasis, hepatitis, necrosis of liver tissue (in extremely rare cases progressing to life-threatening liver failure), life-threatening pseudomembranous colitis with possible fatal outcome, pancreatitis.

From the skin:

Infrequently: rash.

On the part of the hematopoiesis system:

Infrequently: eosinophilia.

Rarely: anemia, leukopenia (granulocytopenia), leukocytosis, an increase or decrease in prothrombin, thrombocytopenia, thrombocytosis, neutropenia.

Rarely: hemolytic anemia, pancytopenia (including life-threatening), agranulocytosis, in extremely rare cases, life-threatening bone marrow depression.

From the side of the urinary system:

Infrequently: increased levels of creatinine and urea nitrogen.

From the musculoskeletal system:

Infrequently: arthralgia.

Rarely: myalgia (pain in the muscles), swelling of the joints.

Rarely: myasthenia gravis, tendinitis (predominantly Achilles tendons), partial or complete rupture of tendons (predominantly Achilles), worsening of myasthenia gravis symptoms, arthritis, muscle weakness, exacerbation of myasthenia gravis symptoms.

From the central nervous system:

Infrequently: headache, dizziness, sleep disorders, anxiety, confusion.

Rarely: migraine, hallucinations, sweating, paresthesia (including peripheral paralysis), anxiety, nightmares, depression, tremors, convulsions, hyperesthesia, agitation, disorientation, dysesthesia, hypoesthesia, vertigo.

Rarely: large convulsive attacks, unstable gait, psychosis, increased intracranial pressure, ataxia, increased muscle tone, muscle cramps, impaired coordination of movements.

Frequency unknown: peripheral neuropathy and polyneuropathy.

From the skin:

Infrequently: itching, urticaria, maculopapular rash.

Rarely: petechia, erythema multiforme, erythema nodosa, persistent rashes on the skin.

From the sense organs:

Infrequently: a taste disorder.

Rarely: noise in the ears, temporary hearing impairment, visual impairment (diplopia, color perception disorder), hearing loss.

Rarely: parosmia, anosmia.

Other:

Infrequently: asthenia (feeling of weakness, fatigue), candidiasis.

Rarely: peripheral edema, hyperglycemia, pain in the extremities, back pain, pain in the chest.

Rarely: increased activity of amylase, lipase.

From the cardiovascular system:

Rarely: tachycardia, a feeling of "tide" of blood to the face, lowering of blood pressure, fainting, vasodilation.

Rarely: vasculitis.

Frequency unknown: prolongation of Q-T interval, ventricular arrhythmias (including "pirouette" type).

Allergic reactions:

Rarely: anaphylactic reactions, fever, angioedema.

Rarely: anaphylactic shock, skin rash, serum-like reactions, Stevens-Johnson syndrome (malignant exudative erythema), Lyell's syndrome (toxic epidermal necrolysis).

From the respiratory system:

Rarely: dyspnea, laryngeal edema, respiratory failure (including bronchospasm).

From the skin:

Rarely: reaction photosensitivity.

From the side of the urogenital system:

Rarely: acute renal failure, renal dysfunction, vaginal candidiasis, hematuria, crystalluria, interstitial nephritis.

In addition, the following adverse events were noted: cerebral thrombosis, polyuria, albuminuria, urinary retention. The association of these undesirable phenomena with the use of ciprofloxacin is not reliably confirmed.

Overdose:

In the case of an overdose of ingestion in several cases, a reversible toxic effect on the renal parenchyma was noted. Therefore, in case of an overdose, in addition to standard measures (gastric lavage, the use of emetics, the introduction of a large amount of fluid, the creation of an acidic urine reaction), it is also recommended to monitor the kidney function and take magnesium and calcium containing antacids, which reduce the absorption of ciprofloxacin. The specific antidote is not known. It is necessary to carefully monitor the patient's condition, make gastric lavage, carry out usual emergency measures, ensure sufficient fluid intake.With the help of hemo- and peritoneal dialysis, only a small amount (less than 10%) of the drug can be excreted.

Interaction:

With the simultaneous use of didanosine with ciprofloxacin, the effect of ciprofloxacin is reduced by the formation of ciprofloxacin complexes with aluminum and magnesium salts contained in Didanosine.

Simultaneous reception of ciprofloxacin with theophylline may lead to an increase in the concentration of theophylline in the blood plasma, due to competitive inhibition in the binding sites of cytochrome P450, which leads to an increase in the half-life of theophylline and an increased risk of toxic effects associated with theophylline.

Simultaneous administration of sucralfate, antacids, preparations with a large buffer capacity (eg, antiretroviral drugs), as well as preparations containing ions of aluminum, zinc, iron or magnesium, can cause a decrease in absorption of ciprofloxacin, therefore ciprofloxacin should be taken either 1-2 hours before or 4 hours after taking these drugs.

This restriction does not apply to antacids belonging to the class of H2-receptor blockers.

The simultaneous use of ciprofloxacin, dairy products or beverages enriched with minerals (eg milk, yogurt, calcium-fortified orange juice) should be avoided, since the absorption of ciprofloxacin may decrease. However, calcium, which is part of other foods, does not significantly affect the absorption of ciprofloxacin.

With the combined use of ciprofloxacin and omeprazole, there may be a slight decrease in the maximum concentration (C_max) of the drug in the blood plasma and a decrease in the area under the "concentration-time" curve (AUC).

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

With the simultaneous use of ciprofloxacin and anticoagulants (including warfarin), the bleeding time is prolonged.

With the simultaneous use of ciprofloxacin and cyclosporine, the nephrotoxic effect of the latter is enhanced. With simultaneous therapy with ciprofloxacin and cyclosporine, a short-term increase in the concentration of creatinine in the blood plasma was observed.In such cases, the concentration of creatinine in the blood should be determined twice a week.

In some cases, the simultaneous use of ciprofloxacin and glibenclamide can enhance the effect of glibenclamide (hypoglycemia).

Co-administration of uricosuric drugs, including probenecid, slows the rate of ciprofloxacin excretion by the kidneys (up to 59%) and increases the concentration of ciprofloxacin in the blood plasma.

With the simultaneous administration of ciprofloxacin, tubular transport (renal metabolism) of methotrexate may be slowed, which may be accompanied by an increase in the concentration of methotrexate in the blood plasma. This may increase the likelihood of side effects of methotrexate. In this regard, for patients receiving co-therapy with methotrexate and ciprofloxacin, careful monitoring should be established.

Metoclopramide accelerates the absorption of ciprofloxacin, shortening the time period necessary to achieve its maximum concentration in the blood plasma. In this case, the bioavailability of ciprofloxacin does not change.

As a result of a clinical study involving healthy volunteers with the simultaneous use of ciprofloxacin and tizanidine,an increase in the concentration of tizanidine in blood plasma: an increase in C_max in 7 times (from 4 to 21 times), increase in AUC by 10 times (from 6 to 24 times). With increasing tizanidine concentration in the blood serum, hypotensive and sedative side effects are associated. Thus, the simultaneous use of ciprofloxacin and tizanidine is contraindicated. Ciprofloxacin can be used in combination with other antibiotics. As was shown in studies in vitro, the combined use of ciprofloxacin and P-lactam antibiotics, as well as aminoglycosides, was accompanied by a predominantly additive and indifferent effect; relatively rarely there was an increase in the effect of both drugs and very rarely an attenuation.

Possible combinations of drugs with ciprofloxacin include:

Against Pseudomonas spp.	azlocillin, ceftazidime
Against Streptococcus spp.	mezlocillin, azlocillin, other effective beta-lactam antibiotics
Against Staphylococcus spp.	beta-lactam antibiotics, especially isoxazolylpenicillins, vancomycin
Against anaerobes	metronidazole, clindamycin

When used simultaneously with drugs that extend the Q-T interval (antiarrhythmic IA and III classes), the Q-T interval can be extended.The simultaneous use of duloxetine and potent inhibitors of the isoenzyme CYP450 1A2 (such as fluvoxamine) may lead to an increase in BMD and C_maxduloxetine. Despite the lack of clinical data on the possible interaction with ciprofloxacin, it is possible to foresee the likelihood of such interaction with the simultaneous use of ciprofloxacin and duloxetine. The simultaneous use of ropinirole and ciprofloxacin, a moderate inhibitor of the isoenzyme CYP450 1A2, leads to an increase in C_maxand MIC of ropinirole by 60% and 84%, respectively. It is necessary to monitor the side effects of ropinirole during its combined use with ciprofloxacin and for a short time after completion of the combination therapy. With simultaneous application of clozapine and ciprofloxacin at a dose of 250 mg for 7 days, an increase in serum concentrations of clozapine and N-desmethylclozapine by 29% and 31%, respectively (correction of the dosage regimen of clozapine during its simultaneous use with ciprofloxacin and for a short time after completion of combination therapy) ";

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

Special instructions:

It was found that ciprofloxacin, like other drugs of this class, causes arthropathy of large joints in animals. When analyzing the current data on the safety of ciprofloxacin in children under 18 years of age, most of whom have cystic fibrosis of the lung, there is no association between cartilage damage and joints with drug administration. It is not recommended to use ciprofloxacin in children for the treatment of other diseases, in addition to treatment of complications of cystic fibrosis of the lungs (in children aged 5 to 17 years) associated with Pseudomonas aeruginosa and for the treatment and prevention of pulmonary anthrax form (after suspected or proven infection with Bacillus anthracis).

For outpatient treatment of patients with pneumonia caused by bacteria of the genus Pneumococcus, ciprofloxacin Do not use as a first-choice drug In some cases, adverse reactions from the central nervous system may occur after the first use of the drug. In very rare cases, psychosis may manifest as suicidal attempts. In these cases, the use of ciprofloxacin should be stopped immediately.

Patients with epilepsy, episodes of seizures in history, vascular diseases and organic brain damage due to the threat of development of adverse reactions from the central nervous system ciprofloxacin should be prescribed only for "vital indications", in those cases when the expected clinical effect exceeds the possible risk of side effects of the drug.

If a severe or prolonged diarrhea occurs during treatment or after treatment with ciprofloxacin, the diagnosis of pseudomembranous colitis should be ruled out, which requires immediate discontinuation of the drug and the appointment of appropriate treatment. Contraindicated in the use of drugs that suppress the intestinal peristalsis. Patients, especially those suffering from liver disease, may experience cholestatic jaundice, as well as a temporary increase in the activity of "liver" transaminases and alkaline phosphatase.

Compliance with the appropriate dosing regimen is required when administering the drug to patients with renal and hepatic insufficiency.

Sometimes, after taking the first dose of ciprofloxacin, allergic reactions can occur, rarely anaphylactic shock.Taking ciprofloxacin in these cases should be stopped immediately and appropriate treatment should be performed.

In elderly patients, previously treated with glucocorticosteroids, there may be cases of rupture of the Achilles tendon.

If pain occurs in tendons or when the first signs of tendonitis appear, treatment should be discontinued due to the fact that individual cases of inflammation and even rupture of tendons during treatment with fluoroquinolones are described.

During the treatment with ciprofloxacin, contact with direct sunlight should be avoided, since photosensitivity reactions may occur when taking ciprofloxacin. Treatment should be discontinued if symptoms of photosensitivity are observed (for example, changes in skin that resemble sunburn).

It is known that ciprofloxacin is a moderate inhibitor of the isoenzyme CYP1A2. Caution should be exercised with the simultaneous use of ciprofloxacin and drugs metabolized by this isoenzyme, such as theophylline, methylxanthine, caffeine, t. an increase in the concentration of these drugs in the serum can cause corresponding side effects.

To avoid the development of crystalluria, exceeding the recommended daily dose is inadmissible, adequate fluid intake (with normal diuresis) and maintaining an acidic urine reaction is also necessary.

For genital infections presumably caused by strains of Neisseria gonorrhoeae resistant to fluoroquinolones, local information on ciprofloxacin resistance should be taken into account and the susceptibility of the causative agent in laboratory tests should be confirmed.

Effect on the ability to drive transp. cf. and fur:Patients receiving ciprofloxacin, you should be careful when driving a car and doing other potentially dangerous activities that require increased attention and speed of psychomotor reactions.

Form release / dosage:Film-coated tablets, 250 and 500 mg.

Packaging:

Cyfran® 250 mg

For 10 tablets in a planar cell pack of aluminum foil. One or ten packages in a cardboard box with instructions for use.

Cyfran® 250 mg

For 10 tablets in a planar cell box made of aluminum foil and PVC. One package in a cardboard box with instructions for use.

Cyfran® 500 mg

For 10 tablets in a planar cell box made of aluminum foil and PVC. One package in a cardboard box with instructions for use.

Storage conditions:

Store at a temperature not higher than 25 ° C, protected from moisture.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiry date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N014412 / 02

Date of registration:19.12.2008

The owner of the registration certificate:Ranbaxy Laboratories LimitedRanbaxy Laboratories Limited India

Manufacturer: & nbsp

RANBAXY LABORATORIES, Ltd. India

Representation: & nbspRABBAYS LABORATORY LIMITEDRABBAYS LABORATORY LIMITED

Information update date: & nbsp20.10.2015

Illustrated instructions

Instructions

Cyphran® (Cifran®)